758 research outputs found
Abstract 2497: Differential requirement of amino acids on cell survival of ovarian cancer cells
No full textAbstract
Amino acids (AAs) are traditionally classified into nutritionally essential AAs (EAAs) or nonessential AAs (NEAAs) for animals and humans. Recent studies have demonstrated that not only EAAs but also NEAAs play important roles on energy metabolisms in cancer cells. However, which AAs are indispensable for human cancer cell survival has not been fully elucidated. The purposes of this study were 1) to determine the indispensable AAs for ovarian cancer (OVC) cells and 2) to investigate the relationship between the AAs synthetase and cancer cell survival.
Firstly, OVC cell lines were cultured with different medium in which each AA was depleted and cancer cell survival was examined. Among 17 OVC cell lines, EAAs were required in 12 cell lines, whereas others did not require EAAs for cell survival. Interestingly, cancer cell lines which required EAA also required at least one NEAAs, including arginine, cystine, glutamine, serine and tyrosine. Although extracellular glutamine has been known to be a critical factor for cancer cell survival and growth, 3 OVC cell lines did not require extracellular glutamine. Hence, we next examined glutamine synthetase (GS) gene, which is a critical enzyme for production of endogenous glutamine from glutamate. In OVC cell lines which did not require extracellular glutamine, GS expression level was positively correlated with cell survival rate under glutamine-depleted condition. Furthermore, we found that the expression of GS protein was negative in 38 of 645 primary OV tumors (5.9 %). Taken together, these results suggest that GS-down-regulated OVC cells require extracellular glutamine for their survival. Therefore, uptake inhibition of extracellular glutamine or reduction of extracellular glutamine level may be a novel therapeutic strategy for patients with ovarian cancer with “GS down-regulation”, as well as development of an AA-based precision medicine of OVC.
Citation Format: Akiko Furusawa, Jun Inoue, Hitoshi Tsuda, Naoyuki Miyasaka, Johji Inazawa. Differential requirement of amino acids on cell survival of ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2497. doi:10.1158/1538-7445.AM2017-2497</jats:p
Revisiting Shimoda's “Shuuchaku-Kishitsu” (Statothymia): A Japanese View of Manic-Depressive Patients
No full textAlthough the empiric paradigm is now dominant in academic research, in Japan quite a few psychiatric clinicians still take phenomenological-anthropological approaches into consideration, especially when they address manic-depressive illness with typical endogenous features. This is because Shimoda's concept of “shuuchaku-kishitsu” (statothymia) has been widely accepted, together with other phenomenological views of continental origin. In the present paper the author first delineates Shimoda's concept which is based on observations of patients' personality features and the characteristics of their emotionality. He then attempts to refine this concept in spatiotemporal terms, presenting the view that in patients the past self tends to adhere to the present self (the term “shuuchaku” means “adhering to” or “preoccupied with”). He also considers that patients tend to incorporate “soto” (outer space) into “uchi” (inner space), where they believe that symbiotic relations are preserved. Finally, he argues the clinical significance of the presented views in the cultural milieu in which Japanese psychiatric practices are situated.</jats:p
Marine Benthic Algae from the Leeward Hawaiian Group
No full text"Reprinted from ATOLL RESEARCH BULLETIN NO. 115 THE PACIFIC SCIENCE BOARD NATIONAL ACADEMY OF SCIENCES - NATIONAL RESEARCH COUNCIL"The following is an account of all the marine benthic algae accumulated by the author from various collectors from six of the nine islands in the Leeward Hawaiian Group (Nihoa, Necker, French Frigate Shoals, Lisianski, Pearl and Hermes Reef, Kure). The islands comprising this group consist of remnants of nine former high islands which at present make up low volcanic islands, reefs, and atolls. They extend approximately 1300 miles Northwest from Kauai and are located between 23º 05' N. and 28º 25' N. latitude and 161º 58' W. and 178º 25' W. longitude. Also included in this paper are the corrected specific epithets of three species of Liagora and one species of Halimeda which were reported inaccurately from Laysan Island (Tsuda, 1965) and Midway Island (Buggeln, 1965)
The Orientation of the Frog's Egg
No full textThe classical experiments of Pflüger on the segmenting frog's egg, and the important conclusions drawn by Roux from a study of the same egg, have made it very desirable to have an accurate knowledge of the relation existing between the early segmenting egg and the position of the embryo with respect to the egg.
Our work in relation to the orientation of the embryo has covered the ground somewhat more extensively than that of any previous author, since we have made use of the methods employed by all of them.
Our results will be considered under three headings:
1st. Normal development and location of blastopore.
2nd. Results obtained by injury to definite portions of the early embryo.
3rd. Results obtained from embryos whose development had been modified by artificial means.
A word of personal explanation ought to be added. The senior author is responsible for Sections I, II, IV, and V of the present paper. The work recorded in these was done in the spring of 1893.
Section II is the record of the results obtained by Umè Tsuda while a student in the Biological Laboratory of Bryn Mawr College. This work was done during the winter of 1891-2 j the account written in the spring of 1892. Only very slight alterations have been made in this portion preparatory to publication
Abstract 1792: Immune system pathway activation for prediction of the response to neoadjuvant chemotherapy in triple-negative breast cancer
No full textAbstract
Background: Triple-negative breast cancer patients (TNBCs) who receive neoadjuvant chemotherapy (NAC) generally show a response to NAC, but about 5% experience progressive disease (PD). Although TNBCs that respond to NAC have been well-studied, reports about TNBCs with PD during NAC are absent. We aimed to compare kinase activity profiles of TNBCs of both groups to identify a biological predictor of NAC non-responders.
Methods: Tyrosine kinase activity profiles of lysates of fresh frozen cancer tissues from NAC non-responders and responders, the latter represented by TNBCs who did not receive NAC, were determined with a peptide microarray system (Cancer Res. 2009; 69(14):5987-95). Tumor infiltrating lymphocytes (TILs) were counted in these tissues.
Results: Among 740 TNBCs, 20 NAC non-responders were identified. For the 7 samples from PD confirmed patients and 10 TNBCs not receiving NAC, no correlation was observed between NAC response and age, menopausal status, tumor size or axillary lymph node status. Kinase activity measurements showed large differences in overall tyrosine kinase activity between responders and non-responders. 35 peptides had significantly (p &lt; 0.05) higher phosphorylation in the responder group. Kinases that phosphorylate these peptides (upstream kinases) were identified from literature. Among others, the immune related kinases Zap70, Syk and JAK2 were identified as upstream kinases. Pathway analysis yielded evidence for increased activity in the responder group in immune-related pathways and in pathways involved in development and signal transduction. Responders had a significantly higher (p = 0.0053) TILs count.
Conclusion: Kinases related to the immune system are less activated in NAC non-responders. The low TILs count in the non-responders confirmed that activation of the immune system in non-responders is lower than in NAC responders. These data merit a further investigation of the use of kinase activity profiling either alone or in combination with TIL scoring for the prediction of the response to NAC in TNBC with a larger patient cohort.
Citation Format: Takeshi Sawada, Riet Hilhorst, Savithri Rangarajan, Masayuki Yoshida, Kenji Tamura, Rinie van Beuningen, Rob Ruijtenbeek, Hitoshi Tsuda, Fumiaki Koizumi. Immune system pathway activation for prediction of the response to neoadjuvant chemotherapy in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1792. doi:10.1158/1538-7445.AM2017-1792</jats:p
Studies on Heat-Resistant Non-Goagulating Substances of Serum Part 1. Changes in heat-resistant non-coagulating substances of the serum in the rabbits injected with extracts of human cancer tissue and gastric mucosa of benign disease and various factors involved
No full textIt is well known that the serum of cancer pationt possesses a specific coagulability to heat. By estimating heat-resistant non-coagulating substances of the serum in the rabbits previously injected with cancer tissue extract and benign gastric mucosa extract by Tsuda-Okujima's method the author pursued changes in these substances as well as inves tigated the relationship between the erythrocyte count, leucocyte count, and plasma protein content. The following are the results. 1. Rabbits given intravenous injection of cancer tissue extract to the ear-lobe show marked differences from those similatly injected with benign mucosa extract. 2. Observation for a long period of time is possible when extract is given intraperitoneal, and those injected with cancer tissue extract show a marked increase in heat-resistent non-coagulating substances when compared with those injected with benign mucosa extract. 3. There is a certain relationship between the change of the erythrocyte count and that of the hemoglobin content, namely, between the degree of anemia and the change of heatresistant non-coagulating substances in serum, but in the strict sense it is not a parallel relationship. 4. Between the leucocyte count and heat-resistant noncoagulating substance not any relatinoship can be recognized. 5. No completely parallel relationship can be recognized between the plasma protein content and heat-resistant noncoagulating substance. 6. Likewise no parallel relationship can be seen between tyrosine excreted in urine and heat-resistant non-coagulating substance
Radiofrequency ablation therapy for primary breast cancer: expectations and problems as a novel breast conservation therapy
No full textImages Of Class- Spaces
No full textAbstractIn this paper the author characterizes images of class- spaces (as defined by Ishii, Tsuda and Kunugi, Proc. Japan Acad. 44, (1968), 897-903) under almost-open maps, bi-quotient maps, pseudoopen maps and quotient maps.</jats:p
Reading the Binary Oppositious in Soseki Natsume's Meian (Light and Darkness)
No full text40020040028application/pdfThis essay considers Soseki Natsume's novel Meian(1916), unfinished at the author's death, and tries to illuminate the binary structure underlying the text. Although the title itself, Light and Darkness in English, refers to such a binary opposition, the structure of the binary in the book is not so evident. This essay carefully picks up some examples of the contra-distinctive plots in Meian, and concludes that the author intentionally set them there. Once the binary structures are set, however, they show vulnerability and fragility, opening up the door to a deconstructive moment.
From the perspective of the structural characteristics peculiar to this text, we trace the ways in which the author tries to mend Tsuda, the antagonist, who is described as a modern man, suffering from not only a bodily disease (haemorrhoids) but also mental corruption. We analyze the four treatments the author gives for Tsuda's malady. The first is implemented by Kobayashi, Tsuda's friend. The second is from a beggar, whom Tsuda catches a glimpse of. The third is from a letter written by an unknown person whom Tsuda feels a queer sympathy with, in spite of a disparity in their status. He at first finds all three apparently alienated and far away from himself. But, in the end, he is obliged to recognize that he has something in common with them, even that he is close to them. Tsuda's treatment is gradually implemented by this acknowledgement that he is even close to those whom he despised till then.
As the final treatment for Tsuda, he must confront Kiyoko, who left him for another man, and determine what she really thinks and who she really is. These questions are still a total enigma to Tsuda, who cannot forget Kiyoko even though he is married to another woman. This essay tries to take over this enigma from the author who did not finish the novel, and, in the light of the structural pattern of the text, to explain to derive the final answer that Tsuda may conclude. Even in the final treatment, in Kiyoko, he will have to acknowledge two conflicting elements, innocence and art, and to accept the way that they are reconciled in her personality.departmental bulletin pape
Abstract 4274: The contribution of deleterious germ-line mutations of susceptibility genes to ovarian, fallopian tube, and peritoneal cancers in Japanese
No full textAbstract
Different ethnic groups present specific morphological features in ovarian cancer (OC). High-grade serous OC is more frequently found in Caucasian women, in contrast clear cell OC is more frequently found in East Asian women. Although inherited mutations of BRCA1 or BRCA2 (BRCA1/2) and other genes are known to predispose to OC, the contributions of these inherited mutations on disease burden is not well characterized in Japanese OC patients. Using a comprehensive genetic testing panel, the aim of our study was to identify the prevalence of pathogenic germ-line mutations of candidate genes associated with genetic predisposition to OC in Japanese patients with ovarian, fallopian tube, or peritoneal cancer.Samples from 236 individuals with unselected ovarian, fallopian tube, or peritoneal cancer, which were obtained from the Keio Women’s Health Biobank (KWB) from the School of Medicine at Keio University (Tokyo, Japan), were used for this study. Germ-line DNA was enriched using the SureSelect XT Target Enrichment System (Agilent Technologies) designed for 75 or 79 genes as a custom OC panel, followed by sequencing using MiSeq (Illumina). Detected variants, including point mutations, small indels, and a gross deletion, were classified according to the American College of Medical Genetics and Genomics (ACMG) recommendations. Furthermore, BRCA1/2 variants were interpreted using resources from Myriad Genetic Laboratories.Forty-two (17.8%) OC patients had germ-line mutations of cancer predisposition genes. BRCA1/2 pathological germ-line mutations were found in 27 cases (11.4%) while six cases (2.5%) had a mutation in a mismatch repair gene (MLH1, MSH2, MSH6, or PMS2). Furthermore, ten cases (4.2%) had germ-line mutations in the RAD51D, ATM, MRE11A, FANCC, or GABRA2 genes. Of patients with a BRCA1/2 mutation (n=27), we found that the most common histological subtype was high-grade serous OC, but we also found two cases with clear cell carcinoma. Of 42 cases with an inherited mutation, we found that 25% (6/24) had no family history of cancer, and 78% (31/41) were under 60 years old at diagnosis.We found that approximately 18% of unselected Japanese patients with ovarian, fallopian tube, or peritoneal cancer were associated with inherited mutations of cancer-predisposing genes. Our study demonstrates that comprehensive genetic testing is informative for all women with ovarian, fallopian tube, and peritoneal cancers to establish personalized clinical management and genetic counseling, irrespective of the patient's histological subtypes, ages or family histories.
Citation Format: Akira Hirasawa, Issei Imoto, Takuya Naruto, Tomoko Akahane, Wataru Yamagami, Nobuyuki Susumu, Hitoshi Tsuda, Daisuke Aoki. The contribution of deleterious germ-line mutations of susceptibility genes to ovarian, fallopian tube, and peritoneal cancers in Japanese [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4274. doi:10.1158/1538-7445.AM2017-4274</jats:p
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