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Shinya Yamashita,
Hirofumi Yamamoto,
Koshi Mimori,
Naohiro Nishida,
Hidekazu Takahashi,
Naotsugu Haraguchi,
Fumiaki Tanaka,
Kohei Shibata,
Mitsugu Sekimoto,
Hideshi Ishii,
Yuichiro Doki,
Masaki Mori
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ABSTRACT: MicroRNA-372 (miR-372) is reportedly shown to be an oncogene in human testicular germ cell tumors and gastric cancers, but its expression in colorectal cancer (CRC) is not yet determined. This study investigated the clinical significance of miR-372 expression in CRC.
qRT-PCR was used to evaluate miR-372 in 144 CRC patients, and large tumor suppressor 2 (LATS2) expression was also examined as the likely target gene of miR-372. In vitroassays were performed to evaluate the biological function of miR-372.
Multivariate analysis indicated that high miR-372 expression was an independent prognostic factor (p = 0.006). High miR-372 expression was associated with synchronous liver metastasis (p = 0.035). We found an inverse relationship between miR-372 and LATS2 by qRT-PCR (p = 0.007) and immunohistochemistry (p = 0.042) using CRC tissue samples. Furthermore, pre-miR-372 led to a decrease in the LATS2 protein and an increase in proliferative activity of LoVo cells. We also found a significant association between low LATS2 expression and liver metastasis (p = 0.042).
This study suggested that miR-372 was a novel independent prognostic factor in CRC. Our data suggest that LATS2 may serve as one of the target genes of miR-372 in clinical CRC tissues.
Oncology 03/2012; 82(4):205-12. · 2.27 Impact Factor
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ABSTRACT: Recent evidence has shown that altered patterns of microRNA (miRNA) expression correlate with various human cancers. We investigated the clinical significance of miR-10b and its involvement in chemotherapeutic resistance to 5-fluorouracil (5-FU), which is a key component of common chemotherapy regimens in colorectal cancer.
Quantitative RT-PCR was used to evaluate the clinicopathologic significance of miR-10b expression in 88 colorectal cancer cases. We also investigated the chemotherapeutic sensitivity to 5-FU in miR-10b-overexpressing colorectal cancer cells. To explore the mechanism of chemoresistance in miR-10b transfected cells, we examined whether miR-10b inhibits the pro-apoptotic BH3-only Bcl-2 family member BIM(BCL2L11), a key mediator of chemotherapy-induced cell death.
High level miR-10b expression was found to be significantly associated with high incidence of lymphatic invasion (P = 0.0257) and poor prognosis (P = 0.0057). Multivariate analysis indicated that high miR-10b expression is an independent prognostic factor for survival. In vitro studies revealed that miR-10b directly inhibits pro-apoptotic BIM, and the overexpression of miR-10b confers chemoresistance in colorectal cancer cells to 5-FU.
MiR-10b is a novel prognostic marker in colorectal cancer. Moreover, the expression of miR-10b is a potential indicator of chemosensitivity to the common 5-FU-based chemotherapy regimen.
Annals of Surgical Oncology 02/2012; 19(9):3065-71. · 4.17 Impact Factor
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Hajime Hirose,
Masataka Ikeda,
Norikatsu Miyoshi,
Ho Min Kim,
Miho Okano,
Mamoru Uemura, Shinya Yamashita,
Ichiro Takemasa,
Tsunekazu Mizushima,
Hirofumi Yamamoto,
Hideshi Ishii,
Mitsugu Sekimoto,
Yuichiro Doki,
Masaki Mori
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ABSTRACT: A 57-year-old man was diagnosed as having advanced rectal cancer that was suspected for a prostatic gland invasion. CPT-11 plus UFT/LV-based chemoradiotherapy (CRT) was administered. A total radiation dose was 50.4 Gy. After completion of CRT, rectal tumor has shrunken, but Virchow's lymph node metastasis was found on PET CT scan. Therefore, the main rectal tumor was resected first, and chemotherapy was then planned. After an abdominoperineal resection, mFOLFOX6 was started. We have stopped mFOLFOX6 after 9 courses because of grade 3 peripheral neuropathy. FOLFIRI was administered thereafter for 27 courses until the confirmation of the shrinkage of the Virchow's lymph node. With a request from the patient, the chemotherapy was stopped for 7 months. Virchow's lymph node has re-grown. We restarted chemotherapy with FOLFOX + bevacizumab regimen. Although the re-grown Virchow's lymph node was unresectable, a tumor in the rectum was resected for a control of local symptom. We, then, introduced a sequential systemic chemotherapy. After that, we could continue the treatment for 38 months without spoiling the QOL. The patient is alive and come to see us as an outpatient.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(12):2545-7.
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Yoshinori Kagawa,
Masataka Ikeda, Shinya Yamashita,
Ho Min Kim,
Hajime Hirose,
Ichiro Takemasa,
Tsunekazu Mizushima,
Hirofumi Yamamoto,
Mitsugu Sekimoto,
Yuichiro Doki,
Masaki Mori
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ABSTRACT: A 54-year-old male had huge pre-sacral recurrent mass (54 × 41 mm) at the level of S1 sacral bone six months after he underwent a high anterior resection for advanced rectal cancer. He was considered inoperable although he had no distant metastasis. We planned a surgical resection for the recurrent tumor after the chemo-radiation therapy (radiation + CPT-11, UFT, Leucovorin). The tumor had a good response (33 × 29 mm) for CRT allowing a dissection area between sacral bone and posterior tumor margin. The surgical resection was performed. We dissected recurrent tumor and sacral bone below S2 and preserved S1 nerve roots under direct vision in order to prevent complications such as walking disorder and spinal fluid leakage. The operative time was 870 minutes and the blood loss was 3,600 g. There were no intraoperative complications. Macroscopically, surgical margin was well secured and a pathological examination of resected specimen revealed microfoci of cancer cells. The post operative hospital stay was 36 days. The patient is alive without any evidence of recurrence 72 months after surgery. He has no walking disability, and a good quality of life.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(12):2617-9.
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Shinya Yamashita,
Masataka Ikeda,
Ho Min Kim,
Hajime Hirose,
Yoshinori Kagawa,
Ichiro Takemasa,
Tsunekazu Mizushima,
Hideshi Ishii,
Hirofumi Yamamoto,
Mitsugu Sekimoto,
Yuichiro Doki,
Masaki Mori
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ABSTRACT: We report a case of lateral lymph node metastasis of submucosal rectal cancer. A 54-year-old man was pointed out with stool occult blood reaction positive. Screening colonoscopy revealed an 18 mm 0-Is rectal cancer in Rb 6 cm from anal verge. Endoscopic mucosal resection (EMR) was performed. Tumor appeared to be well treated, but pathological findings demonstrated the tumor invasion into submucosally (1,300 µm) with lymphovascular invasion ie ly (+) and v (+). Laparoscopic low anterior resection was then performed and no metastasis of lymph nodes (pSM, N0/stage I) was found. But he suddenly had an elevation of CEA (4 ng/mL to 26 ng/mL) after 14 months and following MRI and PET-CT revealed a recurrence in a right lateral lymph node (#283). Chemoradiation therapy (CRT) with CPT-11, UFT and LV was performed. After CRT, lateral lymph nodes and para aortic lymph nodes dissection were performed. Despite of the chemotherapy, he died after 13 months from a recurrence of lateral lymph node metastasis.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(12):2629-31.
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Ho Min Kim,
Masataka Ikeda,
Miho Okano,
Norikatsu Miyoshi,
Hajime Hirose, Shinya Yamashita,
Ichiro Takemasa,
Tsunekazu Mizushima,
Hirofumi Yamamoto,
Mitsugu Sekimoto,
Yuichiro Doki,
Masaki Mori
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ABSTRACT: We report a case of 57-year-old woman suffering from advanced sigmoid colon cancer with adrenal and para-aortic lymph node recurrence. Sigmoidectomy was performed for sigmoid colon cancer in January 2002. Pathological staging was Stage II (pT3, pN0, pM0, Cur A). She received a UFT + CPT-11 regimen as preoperative chemotherapy for liver metastasis (S2, S7) from December 2002. A partial liver resection (S2, S7) was performed for liver metastasis in July 2003, and the UFT + CPT-11 was introduced as adjuvant chemotherapy. However, adrenal and para-aortic lymph node recurrence was detected in February 2007, and mFOLFOX6 was performed as preoperative chemotherapy. Right adrenalectomy and para-aortic lymph node dissection was performed in July 2007. mFOLFOX6 as postoperative chemotherapy was done, mFOLFOX6 + bevacizumab was started because of CEA increase. The chemotherapy was performed for 23 courses and temporarily stopped due to adverse reactions, such as peripheral neuropathy (grade 2), general fatigue (grade 1), and nausea (grade 1). She had no recurrence for almost 3 years after a resection of adrenal and para-aortic lymph node metastasis.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2010; 37(12):2548-50.
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ABSTRACT: We report a case of hemobilia developing after RFA for hepatocellular carcinoma. A 75-year-old woman with hepatitis C was diagnosed as hepatocellular carcinoma (d=15 mm) located in subsegment 7. Laboratory data on admission are AFP 37.3 ng/mL, PIVKA-II 20 mAU/mL, GOT/GPT 84/52 IU/L, T-Bil 1.1 mg/dL, Alb 3.8 g/dL, Plt 8.9x104/microL, and PT 11.8 seconds (INR 1.28) "Child classification A". Under general anesthesia, percutaneous RFA (Cool-tip radionics 10 minutes) was performed. Tumor appeared to be well treated, but on day 5 after the procedure, the patient had sudden upper abdominal pain, followed by the elevation of total bilirubin conc. (3.3 mg/dL) and decrease of Hb. Abdominal ultrasonography showed a debris-like shadow in the gall bladder. Hemobilia was confirmed because endoscopic examination revealed blood contaminated bile from the papilla Vater. Since spontaneous thrombolysis is known to occur in the bile, the patient was only followed by MRI. Symptoms were subsided in a week without any treatment. Obstructive jaundice due to hemobilia is a rare complication of RFA, and may be followed without any treatment.
Gan to kagaku ryoho. Cancer & chemotherapy 11/2009; 36(12):2368-70.
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Katsutoshi Nakano, Shinya Yamashita,
Itsuro Soma,
Nobuyasu Hayashi,
Naozumi Higaki,
Masakazu Murakami,
Hirohito Hayashida,
Kazuomi Kan,
Takao Ichihara,
Masato Sakon,
Masahiro Ayata
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ABSTRACT: A 52-year-old man was admitted for detailed examination of a mass with extensive calcification in the tail of the pancreas by fluoro-deoxy glucose-positron emission tomography/computed tomography (FDG-PET/CT). Abdominal CT and magnetic resonance imaging (MRI) findings showed a calcified tumor 5 cm in diameter with a smooth surface. The tumor mainly showed calcification at it center and a partially solid element around it margin which was enhanced in the early phase. With no definiture preoperative diagnossi, we performed distal pancreatectomy and splenectomy. Pathological and immunohistochemical studies revealed a nonfunctioning islet cell tumor with calcification. A nonfunctioning islet cell tumor with central calcification formation as it grew to a maximum diameter of 7 cm is rare. When diagnosing pancreatic tumors it must be kept in mind that some nonfunctioning islet cell tumors of the pancreas can show nontypical features such as calcification formation.
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 10/2009; 106(10):1494-9.
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ABSTRACT: We report a case of advanced unresectable pancreatic cancer (cT4N1M0/stage IVa). The patient was a 68-year-old man. Chemo-radiation therapy (CRT) with GEM (1,000 mg/body) was administered once a week on days 1, 8 and 15 for 3 weeks. The radiotherapy dose was 45 Gy (1.5 Gy x 2/day, 15 days). After CRT, the patient was treated with a GEM+ UFT-E combination chemotherapy. When that was done, CT scan revealed metastases of umbilicus (Sister Mary Joseph's nodule) and the liver. Microwave Coagulation Therapy for the liver metastasis and tumorectomy for metastasis of umbilicus were performed. But he died after 4 months from the therapies.
Gan to kagaku ryoho. Cancer & chemotherapy 12/2008; 35(12):2112-4.
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ABSTRACT: We report a case of advanced unresectable pancreatic cancer with multiple liver metastases (cT4N x M1, stage IVb). The patient is a 68-year-old man. Serum DUPAN-2 was 15,800 U/mL. Abdominal CT scan revealed the body and tail of pancreatic cancer and multiple liver metastases. Chemo-radiation therapy (CRT) with GEM 1000 mg/body was given once a week on days 1, 8 and 15 for 3 weeks. The radiotherapy dose was 45 Gy (1.5 Gy x 2/day, 15 days). Hematological side effect such as anemia (grade 3) and thrombopenia (grade 2) appeared, but could be well controlled. Abdominal CT scan revealed no change in size, but serum DUPAN-2 decreased up to 4590 U/mL. After CRT, the patient was treated thereafter by the combination chemotherapy with GEM and S-1. After 7 months, CT scan revealed no change in tumor size.
Gan to kagaku ryoho. Cancer & chemotherapy 12/2007; 34(12):2010-2.
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ABSTRACT: We present a case of a 70-year-old man with an anamnesis of intra-cerebral bleeding that resulted in right half of the body paralysis and right diaphragm paralysis, The present clinical history indicated hepatocellular carcinoma (HCC) caused by hepatitis C and liver cirrhosis during a regular hospital visit, and the patient had a total of 4 TAEs enforced from three years before. A 4 x 3.5 cm neoplasm at the left adrenal was detected by CT inspection this time. The diagnosis was a metastatic adrenal gland tumor from HCC. Since HCC is controlled by TAE, the metastatic lesions were not found in other organs and were isolated, of 10 cm or less in size. Hence, laparoscopic adrenalectomy was performed in March, 2006. He started having a meal from the 2nd day after the operation. He left the hospital on the 9th day. Pathologial diagnosis was a metastatic adrenal gland tumor from moderately differentiated hepatocellular carcinoma. When observing the adaptation standard strictly to the high-risk case, it was thought that the metastatic tumor extraction under laparoscopic surgery could become a low stress cure in consideration of QOL being useful as a local treatment for cancer.
Gan to kagaku ryoho. Cancer & chemotherapy 12/2006; 33(12):1765-7.
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ABSTRACT: We report a case of advanced hepatocellular carcinoma (HCC). A 73-year-old man with positive HBV and HCV underwent a partial hepatectomy (S6 and S5) twice and transcatheter arterial (chemo) embolization (TAE) four times, thereafter. During these treatments, HCC became intractable and the patient complained of general fatigue. The liver function was Child's classification A, and serum AFP was 6,737 ng/ml. Abdominal CT scan revealed recurrent lesions in the right hepatic lobe and left adrenal gland. The catheter for hepatic arterial infusion chemotherapy was inserted from the left femoral artery. Arterial chemotherapy with 5-fluorouracil (5-FU 750 mg) and cisplatin (CDDP 10 mg) was performed every two weeks. During 6 courses of this regimen, a significant side effect did not appear. Abdominal CT revealed no change in size, but serum AFP decreased up to 794 ng/ml and the general fatigue subsided. After 2 months, serum AFP began to increase and became 1454 ng/ml. The regimen of arterial chemotherapy was changed to epirubicin (EPI 40 mg every two weeks) and UFT-E (300 mg/day for four weeks), followed by a week off. An appetite loss (grade 2) appeared, but it could be well controlled. Serum AFP decreased again, up to 54 ng/ml. A good QOL was kept for about one year after the initiation of hepatic arterial infusion chemotherapy.
Gan to kagaku ryoho. Cancer & chemotherapy 12/2006; 33(12):1928-30.
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ABSTRACT: In colorectal cancer, hepatic and pulmonary metastases are the most common and most important prognostic factors. Surgical resection is the first choice of treatment for hepatic and pulmonary metastases if completely resectable. However, only a few patients survived long term after metastatectomy. We present the two cases, in which surgical resection for pulmonary and/or hepatic metastases from colorectal cancer resulted in long-term survival for more than ten years without recurrence.
Gan to kagaku ryoho. Cancer & chemotherapy 12/2006; 33(12):1971-3.
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ABSTRACT: A male in his eighties underwent abdominoperineal resection under the diagnosis of adenocarcinoma associated with anal fistula (P0, H0, n (-), A1, stage II, ly0, v0). Ten years after the surgery, a painful lymph node swelling was noticed in the left inguinal region. Biopsy specimen showed adenocarcinoma consisting of severe dysplastic cells. Radiotherapy was performed in the pelvic region at a total dose of 50 Gy (2 Gy/day). After the radiotherapy, left inguinal and pelvic lymph nodes markedly shrank and became painless. After one month, the chemotherapy with UFT (UFT 300 mg/day) was started. One year thereafter, para-aortic lymph nodes were found to be enlarged, but a good quality of life was obtained without elevation of tumor markers.
Gan to kagaku ryoho. Cancer & chemotherapy 12/2006; 33(12):1977-9.
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ABSTRACT: We report a patient with a case of advanced rectal cancer with unresectable liver metastasis, who received the combination of systemic chemotherapy of 5-FU/l-LV and external radiation therapy. He was alive for 21 months. He had been able to maintain a good quality of life without any complaints of the primary rectal tumor.
Gan to kagaku ryoho. Cancer & chemotherapy 12/2006; 33(12):1980-2.
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ABSTRACT: We report a case of a 54-year-old man with unknown primary squamous cell carcinoma in the bilateral neck. The patient was treated with chemotherapy and radiation therapy, because his right common carotid artery was invaded by the right neck tumor, and a complete curative operation was not considered possible. We chose instead combination chemotherapy with nedaplatin, adriamycin and 5-fluorouracil (NAF), because it was reported that NAF was available for advanced squamous cell carcinoma of the esophagus. After 3 cycles of NAF chemotherapy, the patient showed a partial response of approximately an 86% decrease in the right neck tumor for over three months. In addition to NAF, radiation therapy was performed. In the CT findings after chemotherapy and radiation therapy, the patient showed a complete response in the bilateral neck tumors. Unknown primary squamous cell carcinoma in the neck has been treated by combination therapy consisting of chemotherapy, radiation therapy and surgery. The regime of 5-fluorouracil and cisplatin is said to be an effective treatment for unknown primary squamous cell carcinoma in the neck. Based on our experience, NAF would be available as chemotherapy for unknown primary squamous cell carcinomas in the neck.
Gan to kagaku ryoho. Cancer & chemotherapy 09/2005; 32(8):1149-51.
