1.Хавдрын үүдэл эсийн зохицуулгад “sonic hedgehog” дохиоллын үүрэг
Batsaikhan Bat-Erdene ; Mitsuo Shimada ; Nobuhiro Kurita ; Takashi Iwata ; Hirohiko Sato ; Kozo Yoshikawa ; Jun Higashijima
Innovation 2013;7(3):7-9
Cancer stem cells (CSCs) play an important role in cancer development, its main functions are self-renewing capacity, chemoresistance and tumorigenic
capacity. The aim of this study is to clarify the possible role of Shh signaling in regulation of CSCs.
METHODS:
Normal cancer cells (HCT-116) were cultured with serum medium and cancer stem-like cells (CSCs) were obtained from serum-free medium after incubation for
14 days. After cell culturing was done RNA extraction and cDNA transcription of NCs and CSCs (HCT-116). The expressions mRNA of surface markers (CD44,
EpCAM), stemness genes (Oct-4, Nanog), Shh signaling (Ptch1, SMO), and shh pathway downstream gene (Gli1), EMT markers (E-Cadherin, Vimentin) and TJ
genes (Claudin-4, Occludin) were determined by real time RT-PCR before and after administration of cyclopamine (2, 5 μM).
RESULTS:
The expressions of surface markers (CD44, EpCAM) and stemness genes (Oct-4, Nanog) were significantly highly expressed in CSCs. Shh signaling pathway
Ptch1, SMO and downstream gene Gli1 were significantly higher in CSCs than in NCs. Epithelial marker E-Cadherin was reduced in CSCs, mesenchymal marker
Vimentin was up-regulated in CSCs. The expressions of Claudin-4 and Occludin were significantly higher in CSCs compared with NCs. SMO, Gli1 and Vimnetin were significantly inhibited after administration of cyclopamine (2, 5μM), but E-Cadherin was up-regulated in CSCs. Tight junction proteins were significantly inhibited by cyclopamine (2, 5μM). Although CD-44, Oct-4 and Nanog were inhibited in CSCs after administration of cyclopamine, these alterations were statistically significant in different genes respectively, but EpCAM was not inhibited.
CONCLUSION:
EMT, TJ and CSCs markers were affected by Shh signaling pathway in CSCs. Shh signaling pathway may play in an important role of regulation of CSCs.
2.Acupuncture and the Autonomous Reflex (3)
Kazushi Nishijo ; Kazuhiro Yazawa ; Hidetoshi Mori ; Keishi Yoshikawa ; Tomomi Sakai ; Kozo Nemoto
Journal of the Japan Society of Acupuncture and Moxibustion 1982;31(4):342-349
Using the peripheral-visceral reflex, one of the peripheral-autonomous reflexes as a clue we grappled with the problem of clarifying or explaining the acupuncture-moxibustion therapeutic effect meridians, acupoints, etc. At this time using principaly the peripheral-cardiac reflex and the circulatory function as an index, a survey examination concerning the differences in peripeheral responses with acupuncture and moxibustion was conducted.
Method:
Subjects: 32 healthy female and male adults between the ages of 22-40.
Method of Observing Physiological Phenomena:
Changesd in heartbeat were observed using an electrocardiograph (manufactured by Fukuda Electronics Inc.) and a polygraph (Nihon KODEN, Inc.). The pulse wave, respiration curve, etc., were simultaneously measured and recorded on the polygraph. Based on the above the patient was alowed to recline until the heart beat stabilized then stimulation was administered.
Area and Method of Stimulation: The point of stimulation in all but 2 cases was HC-4. In 2 cases 14 points over the entire body were used. Moxibustion stimulation involved 3 cones of moxa weighing 3.65mg. each. For acupuncture stimulation 1.3 TSUN No. 3 silver needles (manufactured by Aoki) were inserted to a depth of 2cm. and pecking at a rate of once per second administered for 30 seconds.
Results: The results of acupuncture-moxibustion stimulation at left HC-4 were that with acupuncture the heart beat decreases and with moxibustion stimulation quickens. In the individual 32 cases when these opposite responses of decreased pace with acupuncture, increased pace with moxibustion occured there was indicated a significant occurence with a danger rate of 1%.
3.Reversible Cerebral Damage Following Bilateral Ascending Aorta-Internal Carotid Artery Bypass Operation for Aortitis Syndrome: A Case Report.
Yoshiro YOSHIKAWA ; Kanji KAWACHI ; Kiyoshi INOUE ; Yoichi KAMEDA ; Kozo KANEDA ; Yoshiaki KONDO ; Hiroji HAGIHARA ; Soichiro KITAMURA
Japanese Journal of Cardiovascular Surgery 1992;21(3):274-277
Aortitis is an inflammatory arteriopathy that often progresses to obliteration of multiple large arteries. Surgical treatment for obstructive lesions due to aortitis syndrome therefore is difficult in many cases. The patient was a 23-year-old female who at the age of 19 had been diagnosed as aortitis syndrome with cerebral vessel involvement, and she subsequently received steroids. She increasingly experienced syncopal attacks, and was indicated for surgical treatment. Angiography revealed obstruction of the left common carotid and left subclavian arteries, and severe stenosis of the right common carotid and right vertebral arteries. She underwent bilateral ascending aorta-carotid artery bypass operation with 7mm ring-supported EPTFE grafts. After the operation she developed clinical signs of temporary brain damage due to hyperperfusion syndrome, but she now completely recovered and maintains a good clinical condition.
4. Хавдрын үүдэл эсийн зохицуулгад “sonic hedgehog” дохиоллын үүрэг
Batsaikhan BAT-ERDENE ; Mitsuo SHIMADA ; Nobuhiro KURITA ; Takashi IWATA ; Hirohiko SATO ; Kozo YOSHIKAWA ; Jun HIGASHIJIMA.
Innovation 2013;7(3):7-9
Cancer stem cells (CSCs) play an important role in cancer development, its main functions are self-renewing capacity, chemoresistance and tumorigeniccapacity. The aim of this study is to clarify the possible role of Shh signaling in regulation of CSCs.METHODS:Normal cancer cells (HCT-116) were cultured with serum medium and cancer stem-like cells (CSCs) were obtained from serum-free medium after incubation for14 days. After cell culturing was done RNA extraction and cDNA transcription of NCs and CSCs (HCT-116). The expressions mRNA of surface markers (CD44,EpCAM), stemness genes (Oct-4, Nanog), Shh signaling (Ptch1, SMO), and shh pathway downstream gene (Gli1), EMT markers (E-Cadherin, Vimentin) and TJgenes (Claudin-4, Occludin) were determined by real time RT-PCR before and after administration of cyclopamine (2, 5 μM).RESULTS:The expressions of surface markers (CD44, EpCAM) and stemness genes (Oct-4, Nanog) were significantly highly expressed in CSCs. Shh signaling pathwayPtch1, SMO and downstream gene Gli1 were significantly higher in CSCs than in NCs. Epithelial marker E-Cadherin was reduced in CSCs, mesenchymal markerVimentin was up-regulated in CSCs. The expressions of Claudin-4 and Occludin were significantly higher in CSCs compared with NCs. SMO, Gli1 and Vimnetin were significantly inhibited after administration of cyclopamine (2, 5μM), but E-Cadherin was up-regulated in CSCs. Tight junction proteins were significantly inhibited by cyclopamine (2, 5μM). Although CD-44, Oct-4 and Nanog were inhibited in CSCs after administration of cyclopamine, these alterations were statistically significant in different genes respectively, but EpCAM was not inhibited.CONCLUSION:EMT, TJ and CSCs markers were affected by Shh signaling pathway in CSCs. Shh signaling pathway may play in an important role of regulation of CSCs.
5.Usefulness of Virtual 3D image analysis in laparoscopic gastrectomy for trainee surgeons
Masaaki Nishi ; Kozo Yoshikawa ; Jun Higashijima ; Takuya Tokunaga ; Toshihiro Nakao ; Chie Takasu ; Shohei Eto ; Hiroki Teraoku ; Mistuo Shimada
Innovation 2014;8(4):114-115
Background: Laparoscopic gastrectomy has several difficult points including,
lymph node dissection and resection of several blood vessels for trainee surgeons.
Recently, preoperative evaluation of vasculature based three-dimensional (3D)
imaging technique resulted in a significantly improved clinical outcome in
abdominal surgery. The aim of this study is to investigate the usefulness of the 3D
image in laparoscopic gastrectomy for trainee surgeons.
Method: We adopted a multiphase CT protocol to acquire 3 image sets (arterial,
portal, and equilibrium phases). 3D-reconstruction of gastric vasculature was
made using data from a contrast enhanced MDCT and SYNAPSE VINCENT
software. Whole pancreas, spleen, gastric vasculature were extracted from MDCT
scans and traced. Thirty three patients, who underwent laparoscopic gastrectomy
for gastric cancer during the period between Jan 2013 and May 2014 were
examined in this study. Four trainees performed a 19 laparoscopic gastrectomy,
while 14 laparoscopic gastrectomy were conducted by the two trainers. The
surgical outcomes in both groups and the pattern of gastric vasculatures were
evaluated.
Result: 3D imaging technique showed a correct positional relationship between
the stomach, gastric vessels, pancreas and spleen. Surgical outcome including
estimated blood loss, and operative time in trainee group were not significantly
different compared to trainer group. 3D imaging technique showed a correct
positional relationship between the stomach, gastric vessels, pancreas and spleen.
Regarding vascular pattern detected by 3D imaging, the origins of IPA were RGEA
in 12 cases (36%), GDA in 8 cases (24%).bifurcation of RGEA and GDA in7 cases
(21%), and not detected in 1 case (3%), respectively. The types of confluence of
IPV were RGEV in 16 cases (48%), ASPDV in 10 cases (30%), and not detected
in 7 cases (21%), respectively.
Conclusions: 3D imaging technique might contribute to successful laparoscopic
gastrectomy. Preoperative 3D-simulation techniques enabled trainee surgeons to
easily and safely perform laparoscopic gastrectomy.
6.Redo CABG Using Lateral Minimally Invasive Direct Coronary Artery Bypass Technique-Selection of Grafts, Bypass Inflow and Bypass Routes-
Yoshihiro Hayata ; Tetsuji Kawata ; Hidehito Sakaguchi ; Nobuoki Tabayashi ; Yoshiro Yoshikawa ; Shigeo Nagasaka ; Takashi Ueda ; Takehisa Abe ; Kozo Morita ; Shigeki Taniguchi
Japanese Journal of Cardiovascular Surgery 2003;32(5):318-321
We performed redo coronary artery bypass grafting (CABG) using lateral MIDCAB for 3 patients with severe symptomatic ischemia in the left circumflex system alone. When the descending thoracic aorta had no atherosclerotic lesions on chest CT, it was selected as the inflow of the bypass. According to the location of the target artery, we undertook sequential or T-composite off-pump bypass using the radial artery through a left lateral thoracotomy. On the other hand, when the descending aorta was diseased, the left axillary artery was chosen as the inflow of the bypass. We selected the saphenous vein as a conduit to obtain sufficient graft length. A proximal anastomosis was made through a left infraclavicular incision, and then a distal anastomosis was done through a left lateral thoracotomy without cardiopulmonary bypass. Moreover, care was taken not to kink the grafts. The postoperative course was uneventful in all patients. Lateral MIDCAB technique was useful for redo revascularization to the circumflex system. We believe that selection of bypass conduits, routes, and bypass inflow according to the individual patient is essential for the procedure.
7. Usefulness of Virtual 3D image analysis in laparoscopic gastrectomy for trainee surgeons
Masaaki NISHI ; Kozo YOSHIKAWA ; Jun HIGASHIJIMA ; Takuya TOKUNAGA ; Toshihiro NAKAO ; Chie TAKASU ; Shohei ETO ; Hiroki TERAOKU ; Mistuo SHIMADA
Innovation 2014;8(4):114-115
Background: Laparoscopic gastrectomy has several difficult points including,lymph node dissection and resection of several blood vessels for trainee surgeons.Recently, preoperative evaluation of vasculature based three-dimensional (3D)imaging technique resulted in a significantly improved clinical outcome inabdominal surgery. The aim of this study is to investigate the usefulness of the 3Dimage in laparoscopic gastrectomy for trainee surgeons.Method: We adopted a multiphase CT protocol to acquire 3 image sets (arterial,portal, and equilibrium phases). 3D-reconstruction of gastric vasculature wasmade using data from a contrast enhanced MDCT and SYNAPSE VINCENTsoftware. Whole pancreas, spleen, gastric vasculature were extracted from MDCTscans and traced. Thirty three patients, who underwent laparoscopic gastrectomyfor gastric cancer during the period between Jan 2013 and May 2014 wereexamined in this study. Four trainees performed a 19 laparoscopic gastrectomy,while 14 laparoscopic gastrectomy were conducted by the two trainers. Thesurgical outcomes in both groups and the pattern of gastric vasculatures wereevaluated.Result: 3D imaging technique showed a correct positional relationship betweenthe stomach, gastric vessels, pancreas and spleen. Surgical outcome includingestimated blood loss, and operative time in trainee group were not significantlydifferent compared to trainer group. 3D imaging technique showed a correctpositional relationship between the stomach, gastric vessels, pancreas and spleen.Regarding vascular pattern detected by 3D imaging, the origins of IPA were RGEAin 12 cases (36%), GDA in 8 cases (24%).bifurcation of RGEA and GDA in7 cases(21%), and not detected in 1 case (3%), respectively. The types of confluence ofIPV were RGEV in 16 cases (48%), ASPDV in 10 cases (30%), and not detectedin 7 cases (21%), respectively.Conclusions: 3D imaging technique might contribute to successful laparoscopicgastrectomy. Preoperative 3D-simulation techniques enabled trainee surgeons toeasily and safely perform laparoscopic gastrectomy.
8.Non-Randomized Confirmatory Trial of Laparoscopy-Assisted Total Gastrectomy and Proximal Gastrectomy with Nodal Dissection for Clinical Stage I Gastric Cancer: Japan Clinical Oncology Group Study JCOG1401.
Kozo KATAOKA ; Hitoshi KATAI ; Junki MIZUSAWA ; Hiroshi KATAYAMA ; Kenichi NAKAMURA ; Shinji MORITA ; Takaki YOSHIKAWA ; Seiji ITO ; Takahiro KINOSHITA ; Takeo FUKAGAWA ; Mitsuru SASAKO
Journal of Gastric Cancer 2016;16(2):93-97
Several prospective studies on laparoscopy-assisted distal gastrectomy for early gastric cancer have been initiated, but no prospective study evaluating laparoscopy-assisted total gastrectomy or laparoscopy-assisted proximal gastrectomy has been completed to date. A non-randomized confirmatory trial was commenced in April 2015 to evaluate the safety of laparoscopy-assisted total gastrectomy and laparoscopy-assisted proximal gastrectomy for clinical stage I gastric cancer. A total of 245 patients will be accrued from 42 Japanese institutions over 3 years. The primary endpoint is the proportion of patients with anastomotic leakage. The secondary endpoints are overall survival, relapse-free survival, proportion of patients with completed laparoscopy-assisted total gastrectomy or laparoscopy-assisted proximal gastrectomy, proportion of patients with conversion to open surgery, adverse events, and short-term clinical outcomes. The UMIN Clinical Trials Registry number is UMIN000017155.
Anastomotic Leak
;
Asian Continental Ancestry Group
;
Conversion to Open Surgery
;
Gastrectomy*
;
Humans
;
Japan*
;
Laparoscopy
;
Medical Oncology*
;
Non-Randomized Controlled Trials as Topic
;
Prospective Studies
;
Stomach Neoplasms*
9.The Clinical Studies of the Protective Effects of Acupuncture on the Habitual Tonsilitis
Keishi Yoshikawa ; Kazushi Nisijo ; Kazuhiro Yazawa ; Hidetoshi Mori ; Tomomi Sakai ; Kozo Nemoto ; Kiyomi Gennai ; Kazuo Sasaki ; Akihiro Ogata ; Kyoko Oda ; Toshikazu Shima ; Kiyokazu Kubota ; Hiroshi Mineta ; Hideko Kamio ; Akemi Yamamoto
Journal of the Japan Society of Acupuncture and Moxibustion 1982;31(4):372-380
We administered electro-acupuncture with the purpose of preventing repeated attacks of repetitive tonsillities.
The majority of the 77 subjects were kindergarden and elementary shool children, who had high fiver more then 4 times a year.
The treatment method was as follows: 1Hz low frequency stimulation between Co 4 and lu 6 (and this bilateral) for 20 to 30 minutes.
The treatment interval was once a week, with 3 weeks constituting a treatment course.
And depending on the results of 1 course, the treatment was repeated or not. 53 patients followed 1 course, 24 patients followed 2 course.
The evaluaton of the results is based on a 1 year observation period.
RESULTS:
-9 patients (11.68%) didn't got any high fever.
-49 patients (63.63%) noticed a decrease of the high fever frequency [39 patients (50.64%) got less then 3 times a year a high fever.]
-19 patients (24.67%) didn't notice any effect [6 patients (7.79%) got tonsillectomy.]
This study showed the usefulness of acupuncture and as it's a general and easy to apply therapy, we can consider acupuncture as a first choice therapy for the prevention off repetitive tosillitis.
10.Kampo and Cancer Immunity in the Era of Immune Checkpoint Inhibitors
Mitsuo SHIMADA ; Yuji MORINE ; Tetsuya IKEMOTO ; Kozo YOSHIKAWA ; Chie TAKASU
Kampo Medicine 2019;70(2):162-166
Kampo medicine is well known to play an important role in cancer therapy, especially as a supportive therapy. We literally investigated the significance of Kampo medicine on antitumor effect including our data in the era that cancer immunotherapy using immune checkpoint inhibitors is a main stream. Up to now, many reports have been published regarding the mechanism of Kampo medicine on augmentation of immunity, particularly innate immunity. Regarding the effect of Kampo medicine on cancel of immune suppression by cancer, a few reports have been published including our data that juzentaihoto reduced regulatory T cell ratio in advanced pancreas cancer patients. Interestingly, a certain kind of Kampo medicine has possibility to induce immune tolerance in murine cardiac transplant model through increased regulatory T cells, and to suppress intestinal inflammation by anticancer drug by functioning immune checkpoint (PD-1). We hope that Kampo medicine would be proved to possibly regulate immune function from the viewpoint of immune checkpoint in the near future.