Unusual abscesses associated with colon cancer: report of three cases

Three cases of colon cancer accompanied by unusual abscess formation are reported. Case I : A 77-year-old man was diagnosed with a paracolic abscess formation behind the cecum and a swollen appendix by computed tomography (CT) scan. Case II : An 85-year-old woman was diagnosed with an abscess formation of the right iliopsoas muscle, a swollen appendix, and a thickened right colon wall by CT scan. After antibiotic therapy failed, both patients underwent ileocecal resection urgently under suspicion of appendicitis, but cecal cancer around the entrance to the appendix caused secondary appendicitis in both cases. Case III : A 50-year-old woman was diagnosed with sigmoid colon cancer with an abscess formation in the pelvic cavity concomitant with ovarian tumor. A Hartmann procedure was performed, and a pathological examination revealed that a subserosal abscess behind the sigmoid colon cancer perforated the rectum with abscess formation. All cases were definitively diagnosed intraoperatively. The cancer recurred in cases I and III. We emphasize that precise surgical evaluation has an important role in the diagnosis of these complicated diseases. In addition, surgery affords the patient the best chance of recovery, and in these advanced cases radical treatment is recommended as early as possible

Response Rate Is Associated with Prolonged Survival in Patients with Advanced Non-small Cell Lung Cancer Treated with Gefitinib or Erlotinib

Introduction:Gaining a higher response rate (RR) has usually been determined as a primary end point in phase II trials evaluating the efficacy of new molecular targeted drugs. However, a relationship between clinical response and survival benefit has not been well studied in the patients treated with molecular targeted agents.Methods:Prospective trials of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) monotherapy in non-small cell lung cancer were extracted from MEDLINE, EMBASE, and the annual meetings in 2007 of the American Society of Clinical Oncology, European Cancer Conference, and World Conference on Lung Cancer.Correlation between clinical response and survival was examined using linear regression analysis. We also tried to compare the significance of RR as surrogate markers for survival with that of disease control rate (DCR) by calculating the area under their receiver operating characteristic (ROC) curves.Results:We identified 24 phase II trials and 4 phase III trials with a total of 6171 patients and 30 treatment arms, including 22 arms for the gefitinib group and 8 arms for the erlotinib group. Both RR and DCR strongly correlated with median survival time (MST; p < 0.0001 and p = 0.003, respectively). In an ROC analysis, the area under the ROC curve predicting MST prolongation by RR was 0.918, which was higher than the area under the ROC curve by DCR.Conclusions:We found a significant relationship between RR and MST in clinical trials with EGFR-TKIs. RR could be an independent surrogate marker for MST in the current response criteria in the clinical trials of EGFR-TKIs

A guiding role of the Arabidopsis circadian clock in cell differentiation revealed by time-series single-cell RNA sequencing

Circadian rhythms and progression of cell differentiation are closely coupled in multicellular organisms. However, whether establishment of circadian rhythms regulates cell differentiation or vice versa has not been elucidated due to technical limitations. Here, we exploit high cell fate plasticity of plant cells to perform single-cell RNA sequencing during the entire process of cell differentiation. By analyzing reconstructed actual time series of the differentiation processes at single-cell resolution using a method we developed (PeakMatch), we find that the expression profile of clock genes is changed prior to cell differentiation, including induction of the clock gene LUX ARRYTHMO (LUX). ChIP sequencing analysis reveals that LUX induction in early differentiating cells directly targets genes involved in cell-cycle progression to regulate cell differentiation. Taken together, these results not only reveal a guiding role of the plant circadian clock in cell differentiation but also provide an approach for time-series analysis at single-cell resolution

Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Beyond Progressive Disease: A Retrospective Analysis for Japanese Patients with Activating EGFR Mutations

IntroductionIt is not determined whether the continuous use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is reasonable for patients with activating EGFR mutations, who have progressed with the drug.MethodsWe retrospectively analyzed the data from 2002 to 2010 of consecutive patients who had advanced non–small-cell lung cancer (NSCLC) harboring activating EGFR mutations and showed radiological disease progression after EGFR-TKI treatment as the first-line or second-line setting. We classified them into two groups: continuous EGFR-TKI and switching to chemotherapy, and compared the clinical outcomes. Multivariate analysis for survival was performed including age, sex, Eastern Cooperative Oncology Group performance status (0–1/ 2–4), brain metastasis, EGFR mutations (deletions in exon 19 versus L858R), continuous EGFR-TKI (yes/no), and initiation of EGFR-TKI (first versus second).ResultsA total of 551 NSCLC patients were screened for EGFR mutations in the period, and 186 patients had activating EGFR mutations. To explore the potential use of EGFR-TKI beyond progressive disease (PD), 64 patients were selected and analyzed. There were 13 men and 51 women, and median age was 65.5 years (range, 42–86). Among them, 31 patients had deletions in exon 19, and 33 had point mutation of L858R in exon 21. Thirty-nine patients were continuing EGFR-TKI beyond PD; 25 patients were switched to cytotoxic chemotherapy alone. The median overall survival was 32.2 months in the patients continuing EGFR-TKI, and 23.0 months in the patients switching to chemotherapy, presenting a significant difference between the two groups (p = 0.005). Cox analysis showed that continuous EGFR-TKI after PD (hazards ratio 0.42, 95% confidence interval: 0.21–0.83, p = 0.013) was associated with improved survival.ConclusionContinuous use of EGFR-TKI beyond PD may prolong overall survival compared with switching to cytotoxic chemotherapy in patients with activating EGFR mutations. A prospective study will be needed to confirm our results

Effect of Vandetanib on Lung Tumorigenesis in Transgenic Mice Carrying an Activating Egfr Gene Mutation

Vandetanib (ZactimaTM) is a novel, orally available inhibitor of both vascular endothelial growth factor receptor-2 (VEGFR-2) and epidermal growth factor receptor (EGFR) tyrosine kinase. In the present study, a line of transgenic mice with a mouse Egfr gene mutation (delE748-A752) corresponding to a human EGFR mutation (delE746-A750) was established. The transgenic mice developed atypical adenomatous hyperplasia to adenocarcinoma of the lung at around 5 weeks of age and died of lung tumors at approximately 17 weeks of age. In the mice treated with vandetanib (6mg/kg/day), these lung tumors disappeared and the phosphorylations of EGFR and VEGFR-2 were reduced in lung tissues to levels comparable to those of non-transgenic control mice. The median overall survival time of the transgenic mice was 28 weeks in the vandetanib-treated group and 17 weeks in the vehicle-treated group. Vandetanib significantly prolonged the survival of the transgenic mice (log-rank test, p＜0.01); resistance to vandetanib occurred at 20 weeks of age and the animals died from their lung tumors at about 28 weeks of age. These data suggest that vandetanib could suppress the progression of tumors harboring an activating EGFR mutation

カンケイ ドウブツ アオゴカイ Perinereis aibuhitensis キョダイ ヘモグロビン ノ グロビンサ ニ フクマレル ケウナ SSケツゴウ

The extracellular hemoglobin (Hb) from the polychaete Perinereis aibuhitensis consists of four types of 144 globins and two types of 36 linker chains，having a molecular mass of about 3,500 kDa. There are two types of globin subunits: monomer chain a and disulfide-bondedt rimer AbB. The amino acid sequences of the four globin chains (a，A ，b ，B ) were already reported，previously (Yamanaka，M. et al. Natural Science Research of Tokushima University, 19, 63-92, 2005). The site of disulfide bonds in the globin subunits have been investigated. Each globin chain contains an intrachain disulfide bond between N-terminal and C-terminal Cys residues. In addition，the interchain disulfide bonds were found between chains A and b，and b and B. Therefore，it is elucidated that the chain b is situated at the center of disulfide-bonded trimer，such as A-b-B.The sites of disulfide-bonds determined all could be suitably fitted to the tree dimensional structure of each subunit in a model without stretching or twisting. It was also confirmed that there is no free Cys residue in Peinereis globins. The positions of Cys residues of Perinereis globin sequences were compared wIth those of other 27 chains derived from the homologous Hbs. Among 31 sequences，Cys residues were distributed in six sites. The sites 1 and 2 are located at the N-terminal region of amino acid sequences，the sItes 3 and 4 at the central region，and the sites 5 and 6 at C-terminal region. Furthermore，the Cys distribution was categorized into eight patterns. Perinereis Hb has four patterns I，IV，VII，VIII，be ing lack of the central sites 3 and 4. It should be noted that the pattern II includes the unique globins from Hbs of Lamellibrachia，Riftia and Oligobrachia that carry H2S to the symbiotic bacteria，suggesting that these globin chains might carry H2S in vivo. The phylogenetic tree of 31 globin chains derived from the giant Hbs is divided into two families A and B， as already poited out by us Previously. The family A indudes pattern I-V，whereas the family B includes V- VIII