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Soh Katayanagi,
Osamu Konno,
Daiki Ono,
Takayoshi Yokoyama,
Takeshi Suda,
Sumito Hoshino,
Kazushige Ito,
Yu Takagi,
Akihiko Tsuchida,
Tatsuya Aoki,
Hiromi Serizawa, Motohide Shimazu
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ABSTRACT: A 49-year-old man was admitted to another hospital with the complaint of difficulty in defecating. He underwent laparotomy, and investigation of the biopsy revealed a huge intraperitoneal tumor. He began to take imatinib in April 2008 following a diagnosis of gastrointestinal stromal tumor (GIST), but the tumor increased in size. He was referred to our hospital for oral administration of sunitinib to reduce the tumor size. The tumor was 30 cm in diameter, and there were several peritoneal metastases around the liver. He began to take sunitinib in February 2009. The tumor increased in size from August 2010 but a partial remission was noted. We performed cytoreductive surgery in April 2011 as palliative care, but the tumor size increased again in October. We performed cytoreductive surgery again, but he died in December 2011. Although cytoreductive surgery for GIST is a potential treatment option, we suggest supportive care.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2012; 39(12):1935-7.
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Kiminori Takano, Motohide Shimazu,
Taizo Hibi,
Yasushi Hasegawa,
Masahiro Shinoda,
Shigeyuki Kawachi,
Minoru Tanabe,
Koichi Aiura,
Masakazu Ueda,
Rie Irie,
Yuko Kitagawa
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ABSTRACT: We report a patient with Castleman’s disease arising from the gallbladder neck, which caused difficulty in making the differential
diagnosis against gallbladder malignancies. A 50-year-old woman presented to our institution with epigastric pain. An abdominal
computed tomography scan (CT) and magnetic resonance cholangiopancreatography (MRCP) study showed a 20-mm tumor located in
the gallbladder neck for which malignancy could not be completely ruled out. For the definitive diagnosis and treatment, cholecystectomy
was performed. In the operation, the main tumor and resection margins of the cystic duct were submitted for frozen section.
The tumor was composed of a proliferation of lymphoid tissue with no signs of dysplasia. The ductal margin was free of tumor.
The final histopathological diagnosis was unicentric Castleman’s disease, a hyaline vascular variant that developed in the
gallbladder. The patient is currently in good condition without any signs of recurrence 28months after the operation. This
is the first detailed report of Castleman’s disease of the gallbladder. Making a correct diagnosis was very difficult before
the operation, and only a surgical approach enabled confirmation of the diagnosis for this patient.
Clinical Journal of Gastroenterology 04/2012; 3(1):57-60.
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Gastrointestinal endoscopy 03/2012; 75(5):1099; discussion 1099-1100. · 6.71 Impact Factor
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ABSTRACT: Single nucleotide polymorphism (SNP) of the genes for ATP-binding cassette transporters is related to the side effects of anticancer drugs and that of drug metabolism-related enzyme genes is involved in the activation of gemcitabine (GEM).
Forty eight patients treated with adjuvant GEM chemotherapy after pancreatic cancer resection was examined for the SNP of multidrug-resistance 1 (MDR1) 2677, MDR1 3435, breast cancer resistance protein (BCRP) 421, ribonucleotide reductase M1 (RRM1)(-)524, RRM1(-)37 and deoxycytidine deaminase (CDA) 208. We divided the patients according to normal group: patients homozygous for a wild-type allele or heterozygous for a mutant allele and mutant group: those homozygous for a mutant allele. Both groups were compared regarding the outcome and the occurrence and severity of side effects.
MDR1 2677, MDR1 3435, BCRP421, RRM1(-) 524, RRM1(-) 37 and CDA mutant groups comprised 37.5, 31.3, 0, 12.5, 4.2 and 4.2%, respectively. The occurrence of >G3 side effects was the most frequent in the MDR1 2677 mutant group at 39%. The disease-free survival and overall survival tended to be longer in the MDR1 2677 mutant group.
A correlation between the SNP of MDR1 2677 and drug response in patients receiving GEM chemotherapy.
Hepato-gastroenterology 12/2011; 59(117):1609-13. · 0.66 Impact Factor
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Soh Katayanagi, Motohide Shimazu,
Osamu Konno,
Satoshi Kikuchi,
Takeshi Suda,
Sumito Hoshino,
Kazushige Itoh,
Hiromi Serizawa,
Yu Takagi,
Akihiko Tsuchida,
Tatsuya Aoki
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ABSTRACT: A 69-year-old man underwent distal gastrectomy in September 2007 for type 2 gastric cancer with liver metastasis (S5) in LM area (p-T2N3aM1, Stage IV). After the operation, we performed chemotherapy. But the liver metastasis was enlarged, so we performed a partial hepatectomy in July 2008. After hepatectomy, liver metastases appeared on S6 and S7 in February 2009. So we performed the fifth-line chemotherapy with paclitaxel. The effect of paclitaxel was not so good. Therefore, SBRT was performed for the liver metastases (S6/7 and S7) in December 2009 and February 2010. After SBRT, he had no recurrent tumor. SBRT was one of the effective treatments for liver metastases from gastric cancer.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2011; 38(12):2097-9.
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ABSTRACT: The normal pancreas has an abundant blood flow, in contrast to pancreatic cancer, which is a hypovascular tumor. During hypoxia under a hypovascular environment, the transcription factor hypoxia-inducible factor-1α (HIF-1α) is activated. High HIF-1α expression reduces sensitivity to gemcitabine (GEM) which is used as a treatment for pancreatic cancer. The objective of this study was to clarify HIF-1α expression in pancreatic cancer and the association of its effects to GEM treatment. We used the human pancreatic ductal carcinoma cell lines AsPC-1 and BxPC-3 to evaluate cell proliferation, HIF-1α protein expression and sensitivity to GEM in a hypoxic environment of 1% O2 in 48 pancreatic cancer patients who received adjuvant GEM treatment after pancreatectomy. We divided the patients according to HIF-1α expression and the presence of single nucleotide polymorphisms, and we based our evaluation on the adverse events associated with GEM chemotherapy and patient outcome. The hypoxic environment promoted cell proliferation, induced HIF-1α expression and increased GEM resistance, especially in AsPC-1 cells, which included a mutant homozygote for HIF-1α(C1772T). There were no significant differences between the HIF-1α(-) and HIF-1α(+) groups in either adverse events or patient outcomes. HIF-1α enhanced neo-microvascularity in a hypoxic environment and increased drug resistance. The period until recurrence was shorter in the patients with a strong HIF-1α expression, than that in those with a weak HIF-1α expression.
Oncology Reports 09/2011; 26(6):1399-406. · 1.84 Impact Factor
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Magnus J Hansson,
Saori Morota,
Li Chen,
Nagahisa Matsuyama,
Yoshiaki Suzuki,
Satoshi Nakajima,
Tadashi Tanoue,
Akibumi Omi,
Futoshi Shibasaki, Motohide Shimazu,
Yukio Ikeda,
Hiroyuki Uchino,
Eskil Elmér
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ABSTRACT: The mitochondrial permeability transition (mPT) is considered to be a major cause of cell death under a variety of pathophysiological conditions of the central nervous system (CNS) and other organs. Pharmacological inhibition or genetic knockout of the matrix protein cyclophilin D (CypD) prevents mPT and cell degeneration in several models of brain injury. If these findings in animal models are translatable to human disease, pharmacological inhibition of mPT offers a promising therapeutic target. The objective of this study was to validate the presence of a CypD-sensitive mPT in adult human brain and liver mitochondria. In order to perform functional characterization of human mitochondria, fresh tissue samples were obtained during hemorrhage or tumor surgery and mitochondria were rapidly isolated. Mitochondrial calcium retention capacity, a quantitative assay for mPT, was significantly increased by the CypD inhibitor cyclosporin A in both human brain and liver mitochondria, whereas thiol-reactive compounds and oxidants sensitized mitochondria to calcium-induced mPT. Brain mitochondria underwent swelling upon calcium overload, which was reversible upon calcium removal. To further explore mPT of human mitochondria, liver mitochondria were demonstrated to exhibit several classical features of the mPT phenomenon, such as calcium-induced loss of membrane potential and respiratory coupling, as well as release of the pro-apoptotic protein cytochrome c. We concluded that adult viable human brain and liver mitochondria possess an active CypD-sensitive mPT. Our findings support the rationale of CypD and mPT inhibition as pharmacological targets in acute and chronic neurodegeneration.
Journal of neurotrauma 01/2011; 28(1):143-53. · 4.25 Impact Factor
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Kazuhiko Kasuya,
Takao Itoi,
Takaaki Matsudo,
Bunsoh Kyo,
Yasushi Endo,
Takahisa Ikeda,
Yuichi Nagakawa,
Yoshiaki Suzuki, Motohide Shimazu,
Tatsuya Aoki,
Akihiko Tsuchida
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ABSTRACT: We describe the surgical method of cases showing a distended gallbladder. Because the most important thing does not cause biliary tract injury, it is to find orientation carefully. The frequency of incidental gallbladder cancer was in 7 (0.7%) of the 983. Only cholecystectomy is necessary to be performed for Tis or T1 cancer, and surgery has to be changed to radical surgery for T2 cancer or deeper invasion. Laparoscopic cholecystectomy is already an established standard operation. In the presence of acute or severe chronic inflammation, special attention should be paid to these points.
ISRN surgery. 01/2011; 2011:827465.
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Kazuhiko Kasuya,
Katsutoshi Sugimoto,
Bunsoh Kyo,
Yuichi Nagakawa,
Takahisa Ikeda,
Yasuharu Mori,
Tatehiko Wada,
Minako Suzuki,
Takeshi Nagai,
Takao Itoi, Motohide Shimazu,
Tatsuya Aoki,
Akihiko Tsuchida
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ABSTRACT: For hepatic tumors that cannot be identified on routine ultrasonography (US), we marked the target area using real-time virtual sonography (RVS) with indocyanine green (ICG)-ethanol (1:100) during surgery, and performed hepatic resection while observing the fluorescence. EXPERIMENT: An ICG-ethanol mixture locally injected into mouse liver was retained in the same area for more than 4 h. The same mixture locally injected into pig liver at a depth of 3 cm could be observed using an infrared camera.
An ICG-ethanol mixture (500 μl) was locally injected under RVS guidance into a metastatic hepatic tumor that was visible only on magnetic resonance imaging (MRI), and hepatic resection was performed while Photodynamic Eye (PDE) images were being observed. The metastatic lesion (3 mm in diameter in a pathological specimen) could be successfully resected.
This method was useful for resecting US-invisible hepatic tumors.
Journal of hepato-biliary-pancreatic sciences. 12/2010; 18(3):380-5.
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Takao Itoi,
Kazuhiko Kasuya,
Atsushi Sofuni,
Fumihide Itokawa,
Takayoshi Tsuchiya,
Toshio Kurihara,
Nobuhito Ikeuchi,
Mami Takeuchi,
Takeshi Nagano,
Hitoshi Iwamoto,
Eigoro Yamanouchi, Motohide Shimazu,
Akihiko Tsuchida
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ABSTRACT: Magnetic compression anastomosis (MCA) is a revolutionary, minimally invasive method of performing choledochoenterostomy or choledochocholedochostomy without using surgical techniques in patients with biliary stricture or obstruction. Herein, we describe a case series of MCA for severe biliary stricture or obstruction, which could not be treated with conventional therapies.
Two patients with biliary obstruction were treated using MCA for choledochocholedochostomy and choledochoenterostomy at Tokyo Medical University Hospital and Tokyo Medical University Hachioji Medical Center. Endoscopically, a samarium-cobalt (Sm-Co) rare-earth magnet was placed at the superior site of obstruction through the percutaneous transhepatic biliary drainage route and another Sm-Co magnet was placed at the inferior site of obstruction. A comprehensive computer-aided literature search for MCA was performed up to September 2009 by using MEDLINE and EMBASE.
MCA techniques enabled complete anastomosis in both cases without procedure-related complications.
The MCA technique is a revolutionary method of performing choledochocholedochostomy and choledochoenterostomy interventionally in patients with biliary obstruction, for whom the conventional endoscopic procedure is not available, or in candidates who are deemed unsuitable for surgery.
Journal of hepato-biliary-pancreatic sciences. 12/2010; 18(3):357-65.
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ABSTRACT: A jejunum partial resection was performed on a 49-year-old female for jejunum leiomyosarcoma of 7 cm in 1990. She was resected four times for recurrent tumors from 1993 to 2004. We started an internal use of imatinib in 2003, because we could get a diagnosis of GIST. After the surgery of 2004, she stopped taking the internal use of imatinib, but an intraabdominal recurrence occurred in 2006 and she restarted taking the internal use of imatinib.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(12):2322-4.
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ABSTRACT: ABO-incompatible (ABOi) living donor liver transplantation (LDLT) in adult patients has been controversial because of the high risk of antibody-mediated rejection (AMR) mediated by preformed anti-ABO antibodies. However, outcomes have recently improved owing to various treatment advances.
This review article describes the history and current progress in ABOi liver transplantation, mainly from the viewpoint of the Japanese experience.
The typical clinical manifestations of AMR are hepatic necrosis and intrahepatic biliary complication. The outcomes of early ABOi LDLT were poor, especially in older children and adult cases. Since we first introduced portal vein infusion therapy into adult ABOi LDLT in 1998, local graft infusion therapy has emerged in Japan as a crucial breakthrough to overcome the ABO blood group barrier. From 2003, rituximab prophylaxis has been widely used with local graft infusion, and has resulted in markedly improved patient survival. The novel approach of intravenous immunoglobulin induction may become another option to suppress AMR. Continued patient enrollment and controlled trials will allow further validation of these treatments.
The outcome of ABOi LDLT is now similar to that of blood-type-matched transplantation in Japan. However, infection is the major cause of morbidity and mortality after ABOi LDLT. Thus, evaluation of the patients' immune status and adjustment of immunosuppression will be the way forward in the future.
European Journal of Clinical Investigation 10/2010; 40(10):943-9. · 3.02 Impact Factor
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ABSTRACT: Recently, a second-generation photosensory agent for photodynamic therapy (PDT), mono-L: -aspartyl chlorine e6 (NPe6), which degrades rapidly in vivo, has been developed. We evaluated its feasibility and efficacy for treatment in biliary tract carcinoma.
A transmittance of semiconductor laser light (664 nm), sensitivity of a human biliary tract carcinoma cell line, and disorder to normal tissue including Glissonian constructs and adjacent hepatocytes were investigated.
The transmittance of the laser was 85-91% through yellow clear bile and that of the bile including 50 microg/ml NPe6 was 17-48%. The effective concentration of NPe6 which showed LD50 for a cell line was 12.5 microg/ml, and that of LD95 was 25 microg/ml. NPe6 in the supernatant reduced laser transmissiveness, but it had little influence on the antitumor effect in supernatant with or without NPe6. The NOZ cell-tumor volume was reduced significantly 14 days after irradiation in the PDT group (PDT 69.9 +/- 44.6 mm(3) vs control 296.3 +/- 239.9 mm(3) P < 0.05). No severe hepatic disorder including Glisson components was observed by the histological findings.
NPe6 PDT was effective in carcinomas even in the presence of bile, and causes no serious complication for the liver and Glisson structure. Therefore, NPe6 PDT will be a useful candidate as a new therapy for biliary tract carcinomas.
Journal of hepato-biliary-pancreatic sciences. 05/2010; 17(3):313-21.
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ABSTRACT: Humanized antibodies vary and have certain effects, but they are expensive and require repeated administration. We developed cells which constantly express a humanized antibody, and we performed anticancer humanized antibody therapy involving cell transplantation. Genes with the same amino acid sequence as that of the variable region of trastuzumab (Herceptin) as the humanized anti-HER2 monoclonal antibody were produced by overlap-PCR and were connected to the anti-human CD16 antibody [anti-HER2+anti-CD16 single-chain antibody (anti-HER2+CD16 scAb)]. For transplantation, stem cell-like cells that are immunologically tolerant and do not transform into cancer [mouse embryo fibroblast cell line C3H10T1/2 (10T1/2)] were used. The antibody was incorporated into 10T1/2 (antibody-expressing cells) using the pMX-IRES-EGFP retroviral vector. Cell supernatants and human monocytes were exposed to the human breast cancer strain HTB131 expressing HER2, and the in vitro antibody-dependent cell-mediated cytotoxicity (ADCC) effects were evaluated. After the transplantation of antibody-expressing and HTB131 cells into SCID mice, human monocytes were intermittently administered, and the in vivo ADCC effects were evaluated. We found that the ex vivo dead cell rate was 15.4% for Herceptin, 5.6% for anti-HER2+CD16 scAb, 1.5% for anti-CD16 scAb, and 2.1% for the control, demonstrating the antitumor effects of anti-HER2+CD16 scAb. In an antibody-expressing cell transplantation model, the inhibitory effects of this antibody on HTB131 cell establishment were observed. In conclusion, the establishment of breast cancer cells in the peritoneum was inhibited by the transplantation of antibody-expressing cells. Since this method requires cell transplantation only once, the drug cost may be reduced.
International Journal of Molecular Medicine 02/2010; 25(2):209-15. · 1.98 Impact Factor
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Roland Månsson,
Saori Morota,
Magnus J Hansson,
Ichiro Sonoda,
Yoshihiro Yasuda, Motohide Shimazu,
Ayumu Sugiura,
Shigeru Yanagi,
Hitoshi Miura,
Hiroyuki Uchino,
Eskil Elmér
Hepatology 01/2010; 51(1):347-8; author reply 349-50. · 11.66 Impact Factor
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Kazushige Ito,
Takashi Ogata,
So Katayanagi,
Tomohisa Nomura,
Tetsuo Ishizaki,
Yoshihiro Yasuda,
Ichiro Sonoda,
Yoshiaki Suzuki,
Tetsuo Sumi,
Akihiko Tsuchida,
Tatsuya Aoki, Motohide Shimazu
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ABSTRACT: S-1 is a key drug for advanced, recurrent gastric cancer. It is difficult to administer S-1 for inoperable gastric cancer with stenosis. We report that a simple suspension method allows administration of S-1 for improved quality of life. The patient was a 65-year-old woman. She consulted a doctor regarding her poor food intake, and had a medical examination with chest-abdominal CT and gastrofiberscopy. She was diagnosed as type 4 gastric cancer with esophageal invasion. It was difficult for her to drink a cup of water due to the stenosis, but we could insert a 6 Fr-Elemental Diet (ED) tube into her stomach. S-1 was dissolved by the simple suspension method. She received combination chemotherapy of S-1 100mg/body (day 1-21) and CDDP 80 mg/body (day 8). After two courses, her intake was much improved; she was able to eat rice porridge and was discharged with improved quality of life. S-1 suspension with ED tube was effective for advanced gastric cancer with stenosis.
Gan to kagaku ryoho. Cancer & chemotherapy 01/2010; 37(1):135-8.
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ABSTRACT: Upon hypoxia, erythrocytes utilize hemoglobin (Hb) to trigger activation of glycolysis through its interaction with band 3. This process contributes to maintenance of ATP, a portion of which is released extracellularly to trigger endothelium-dependent vasorelaxation. However, whether the ATP release results either from metabolic activation of the cells secondarily or from direct regulation of the gating through Hb allostery remains unknown. This study aimed to examine if stabilization of T-state Hb could induce steady-state and hypoxia-induced alterations in glycolysis and the ATP release from erythrocytes. Treatment of deoxygenated erythrocytes with a nitric oxide (NO) donor generated alpha-NO Hb that is stabilized T-state allostery. Under these circumstances, the release of ATP was significantly elevated even under normoxia and not further enhanced upon hypoxia. These events did not coincide with activation of glycolysis of the cells, so far as judged by the fact that intracellular ATP was significantly decreased by the NO treatment. Collectively, the present study suggests that hypoxia-induced ATP release is triggered through mechanisms involving R-T transition of Hb, and the gating process might occur irrespective of hypoxia-responsive regulation of glycolysis.
Advances in experimental medicine and biology 01/2010; 662:109-14. · 1.09 Impact Factor
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ABSTRACT: Expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT) have been reported to be associated with tumor response to 5-fluorouracil (5-FU).
We investigated correlations of clinicopathological factors with protein expression levels of TS, DPD, OPRT in colorectal cancer (CRC). The subjects were 202 patients who had undergone CRC resection.
There was a negative correlation between DPD and OPRT protein levels, but no correlation of TS levels with either OPRT or DPD levels. The DPD levels in women was significantly lower than that in men. The DPD level was significantly lower in colonic tumors than in rectal tumors, while the OPRT level was significantly higher in colonic tumors than in rectal tumors. The TS level did not correlate with any clinicopathological factors.
DPD and OPRT protein levels in CRC suggest that female gender and colonic tumors are positive prognostic factors in patients who receive chemotherapy with 5-FU.
Chemotherapy 01/2010; 56(2):120-6. · 1.82 Impact Factor
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ABSTRACT: A 74-year-old female was performed distal gastrectomy (f-T3N0H0P0CY0M0, Stage II) for gastric cancer in 2003. After 14 months, CT scan showed a metastasis in S7 segment of the liver. We performed chemotherapies until seventh-line and radio-frequency ablation (RFA). It finally got a long-term survival of 36 months postoperatively. RFA may be one of the useful therapies of liver metastasis from gastric cancer.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2009; 36(12):2321-3.
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Toshihide Tajima,
Nobuhito Goda,
Natsuko Fujiki,
Takako Hishiki,
Yasumasa Nishiyama,
Nanami Senoo-Matsuda, Motohide Shimazu,
Tomoyoshi Soga,
Yasunori Yoshimura,
Randall S Johnson,
Makoto Suematsu
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ABSTRACT: Coordinated recovery of hepatic glucose metabolism is prerequisite for normal liver regeneration. To examine roles of hypoxia inducible factor-1alpha (HIF-1alpha) for hepatic glucose homeostasis during the reparative process, we inactivated the gene in hepatocytes in vivo. Following partial hepatectomy (PH), recovery of residual liver weight was initially retarded in the mutant mice by down-regulation of hepatocyte proliferation, but occurred comparably between the mutant and control mice at 72h after PH. At this time point, the mutant mice showed lowered blood glucose levels with enhanced accumulation of glycogen in the liver. The mutant mice exhibited impairment of hepatic gluconeogenesis as assessed by alanine tolerance test. This appeared to result from reduced expression of PGK-1 and PEPCK since 3-PG, PEP and malate were accumulated to greater extents in the regenerated liver. In conclusion, these findings provide evidence for roles of HIF-1alpha in the regulation of gluconeogenesis under liver regeneration.
Biochemical and Biophysical Research Communications 08/2009; 387(4):789-94. · 2.48 Impact Factor