Details of a Researcher - Nakamura, Rieko

Papers - Nakamura, Rieko

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Report of a case successfully treated with chemo-radiation against local recurrence after gastric cancer surgery

Igarashi Takahiro, Saikawa Yoshiro, Kumagai Koshi, Nakamura Rieko, Takahashi Tsunehiro, Takeuchi Yuya, Kitagawa Yuko

Japanese Journal of Cancer and Chemotherapy 36 ( 8 ) 1363 - 1366 2009.08

ISSN 0385-0684

A 68-year-old male was diagnosed as type 2 gastric cancer in the upper part of the stomach, then diagnosed as cT2 (MP) N0M0H0P0, cStage I B. Total gastrectomy and splenectomy with D2 lymph node dissection were performed. Final diagnosis including pathology was pT1 (SM) N1M0H0P0, pStage IB, and with his informed consent, an anti-cancer drug, UFT, was given as postoperative adjuvant therapy. Four months after the surgery, a 35-mm sized tumor recurring around the distal region of pancreas was detected by abdominal computed tomography (ACT). Then, combination chemo-radiotherapy using S-1, cisplatin and radiation (50 Gy) was performed. One year after the initial surgery, ACT showed a complete response (CR) of the recurred tumor, while outpatient chemotherapy with S-1+CPT-11 and S-1+paclitaxel was continuously performed, because of elevated CEA. Two years after initial surgery, the CEA value was elevated to 28.4 ng/mL, and so S-1 +docetaxel was applied. The patient is still alive with no sign of lesion recurrence by CT 3 years after initial surgery. Outpatient chemotherapy helped the patient maintain good quality of life. In addition, initial therapy for the recurred tumor including radiation proved to be a powerful way to control local growth of gastric cancer, even if hematogenous/lymphatic spreading of gastric cancer cells might be difficult to suppress with such chemo-radiotherapy.

Dynamic alteration of gene expression induced by anticancer-agent exposure in gastric cancer cell lines

Takahashi Tsunehiro, Saikawa Yoshiro, Nakamura Rieko, Kumagai Koshi, Takeuchi Hiroya, Kubota Tetsuro, Kitagawa Yuko

Oncology Reports 21 ( 2 ) 451 - 459 2009

ISSN 1021-335X

The prognosis for advanced gastric cancer remains very poor due to the limited effectiveness of chemotherapy agents. The range in efficacy of these chemotherapy agents is likely the result of various factors including gene expression. In addition, the emergence of drug resistance during chemotherapy can result in the undesirable outcome of patients experiencing the side effects of chemotherapy without benefiting in terms of tumor response. Gene expression profiling provides a unique opportunity to gain insight into the development of different types of gastric cancer. We applied the TaqMan low density array to investigate the expression of 96 genes in four gastric cancer cell lines (TMK-1, MKN-45, MKN-74 and CDDP-resistant MKN-74). The cell lines displayed different patterns of gene expression alteration after exposure to the chemotherapeutic drugs cisplatin and 5-fluorouracil. We also established that cisplatin-resistant MKN-74 cells do not show the same gene expression patterns as the parental MKN-74 cell line at 0, 8 and 24 h after CDDP exposure. This study reveals the underlying complexity of biological and pathological events and could, perhaps, contribute to new experimental protocols or treatments that would achieve a consistent and desirable outcome of chemotherapy.

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Phase II Study of Chemoradiotherapy With S-1 and Low-Dose Cisplatin for Inoperable Advanced Gastric Cancer

Saikawa Yoshiro, Kubota Tetsuro, Kumagai Koshi, Nakamura Rieko, Kumai Koichiro, Shigematsu Naoyuki, Kubo Atsushi, Kitajima Masaki, Kitagawa Yuko

International Journal of Radiation Oncology Biology Physics 71 ( 1 ) 173 - 179 2008.05

ISSN 0360-3016

Purpose: The results of a pilot study using S-1/low-dose cisplatin/radiotherapy led us to hypothesize that the initial chemoradiotherapy regimen would induce a 70% efficacy rate with a 10% pathologic complete response rate. Patients and Methods: Only patients with unresectable or incurable advanced gastric cancer were eligible. The patients received induction S-1 and cisplatin therapy with radiotherapy followed by chemotherapy alone. Results: Of the 30 patients recruited and assessed, 29 were eligible for clinical evaluation of measurable lesions. The response rate was 65.5%, with 19 with a partial response, 8 with no change, and 2 with progressive disease of 29 patients. Of the 30 patients recruited, 10 (33.3%) underwent stomach resection and D2 LN dissections. The pathologic complete response rate was 13.3% (4 patients), and the R0 resection rate was 100% (10 patients). The survival analysis showed a median survival time of 25 months. Grade 3 toxicity occurred in 66.7% for leukocytopenia, 33.3% for thrombocytopenia, 23.3% for nausea and appetite loss, and 6.7% for anemia, diarrhea, and renal dysfunction. Although all the patients had been hospitalized with a poor performance status with a giant tumor, 97% (29 of 30) could be discharged after the first cycle, resulting in an improvement in quality of life. Conclusion: Chemoradiotherapy could be a powerful regimen for controlling tumor progression in advanced gastric cancer, improving patients' quality of life with tolerable toxicity. A complete histologic response rate of >10% would be expected, even for large tumors with metastatic lesions.

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Development of 36 clones producing human monoclonal antibodies specific to cancer cells and their ability to inhibit cancer cell growth

Nakamura Rieko, Saikawa Yoshiro, Hosokawa Saiko, Fukuda Kazumasa, Kumai Koichiro, Kubota Tetsuro, Kitajima Masaki, Kitagawa Yuko

Anticancer Research 28 ( 3 A ) 1651 - 1657 2008.05

ISSN 0250-7005

The development of a specific antibody for cancer therapy could enable a potent strategy for overcoming cancer. As ideal immunotherapy, a human monoclonal antibody (HuMoAb) might have a useful antitumor effect without any lethal toxicities. Thirty-six unique clones producing HuMoAbs were successfully developed using tumor infiltrating lymphocytes collected from 28 patients with several malignant solid tumors. The 36 tumor-specific immunoglobins were found among 9,450 clones after 43 fusions by the conventional hybridoma method. Among these 36 HuMoAbs, 9 had a remarkable tumor-specific reaction and no reaction with normal tissues, as determined with quantum dots-streptavidin and a fluorescence microscope. The inhibition of cell proliferation by the HuMoAbs was evaluated with the MTT assay. Over 40% cell growth inhibition was confirmed with 4 of the 36 HuMoAbs. Two of the antibodies had highly-specific reactivity to carcinomatous lesions with strong growth inhibition and up to 94.3% inhibition of the control growth. In conclusion, 36 clones with HuMoAbs that have specific reactions with cancer cells were successfully established. These HuMoAbs might be utilized as either anticancer or drug delivery agents.

Clinical experience of second-line chemotherapy with S-1/CPT-11 for highly advanced gastric cancer

Kumagai Koshi, Saikawa Yoshiro, Nakamura Rieko, Takahashi Tsunehiro, Kubota Tetsuro, Kumai Koichiro, Kitagawa Yuko, Kitajima Masaki

Gan to kagaku ryoho. Cancer & chemotherapy 35 ( 2 ) 245 - 250 2008.02

ISSN 0385-0684

We have performed chemoradiation with S-1 and low-dose CDDP as an initial treatment for 27 patients with incurable or unresectable highly advanced gastric cancer since 2002. Twelve out of 27 patients received combination chemotherapy of S-1 and CPT-11 as the second-line chemotherapy. On this regimen, S-1 was administered orally at a dose of 80 mg-120 mg daily, and CPT-11 at a dose of 60 mg/m(2) once in 2 or 3 weeks for outpatients. Clinical effects after therapy showed a response rate of 30.0%. Considering the prognostic outcome of the regimen, the one-year survival rate of the therapy was 66.7%, and the median survival time was more than 1 year, suggesting second-line chemotherapy will be one of the beneficial regimens in gastric cancer patients. Although 4 patients showed grade 3 bone marrow suppression (33.3%), they were all able to continue the therapy, after recovering from toxicity by means of G-CSF and/ or cessation of chemotherapy. The incidence and level of toxicity accompanying subjective symptoms, however, were relatively low, and the regimen was useful as an outpatient treatment maintaining good quality of life and improving their prognosis. Treatment with an appropriate regimen at an appropriate time will enable these patients to have good quality of life and survival.

Retrospective analysis of treatment for advanced gastric cancer with peritoneal dissemination

Nakamura Rieko, Saikawa Yoshiro, Wada Norihito, Yoshida Masashi, Kubota Tetsuro, Kumai Koichiro, Kitajima Masaki, Kitagawa Yuko

Gan to kagaku ryoho. Cancer & chemotherapy 34 ( 11 ) 1827 - 1831 2007.11

ISSN 0385-0684

Recent development and clinical application of novel anticancer agents like S-1 have been reported to show a good outcome against gastric cancer (GC) with peritoneal dissemination (P). In our study, a retrospective analysis of the treatment for GC with P was performed. Since 1989, a chemosensitivity test with MTT assay (MTTA) using surgical specimen was performed to choose chemotherapy after surgery, resulting in good prognosis in patients who received drugs which were determined effective by the MTTA. Since 1999, S-1 was introduced as adjuvant chemotherapy, and, since 2002, initial treatment with S-1/CDDP was used for GC with P, suggesting a better prognostic outcome compared with previous results with ineffective chemotherapy or surgery alone. In conclusion, prognosis of GC with P has been improving by effective regimens with novel anticancer agents like S-1. Further research and clinical trials will be necessary to achieve a more satisfactory outcome with the treatment of GC with P.

A patient with gastric cancer and liver metastases successfully treated with combination chemotherapy including S-1

Nakamura Rieko, Saikawa Yoshiro, Kumagai Koushi, Kiyota Tsuyoshi, Ohashi Masaki, Yoshida Masashi, Kubota Tetsuro, Kumai Koichiro, Kitajima Masaki

International Journal of Clinical Oncology 12 ( 4 ) 295 - 299 2007.08

ISSN 1341-9625

We report the case of a 62-year-old man with advanced gastric cancer and multiple liver metastases who was successfully treated with combined chemotherapy including S-1. The patient was clinically diagnosed with stage IV (T3 N2 H1 P0) disease and was initially treated with 100 mg/body per day S-1 administered orally for 21 days and 10 mg/body per day cisplatin (CDDP) infused on days 1-5, 8-12, and 15-19. This chemotherapy resulted in significant reduction of the liver and gastric tumors. After receiving additional CDDP/S-1 administration as an outpatient, the patient's liver masses disappeared as shown on abdominal computed tomography (CT). With the patient's desire and informed consent, he underwent curative surgery with total gastrectomy, D1+α lymph node dissection, and partial resection of liver S4. After discharge without any surgical complication, CT revealed regrowth of the S4 liver mass, and combined docetaxel and CDDP was selected as second-line chemotherapy with local radiation therapy against the hepatic metastasis. Additionally, a third regimen with irinotecan and S-1 was given. At 2 years 7 months after the initial treatment, no sign of cancer (including liver metastasis and peritoneal dissemination) has been identified by radiological follow-up examinations.

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Retrospective analysis of prognosis for scirrhous-type gastric cancer

Nakamura Rieko, Saikawa Yoshiro, Wada Norihito, Yoshida Masashi, Kubota Tetsuro, Kumai Koichiro, Kitajima Masaki

International Journal of Clinical Oncology 12 ( 4 ) 291 - 294 2007.08

ISSN 1341-9625

Background. Scirrhous gastric cancer is biologically aggressive, and the prognosis is poor even with curative surgery. We compared outcomes with different therapies in order to identify prognostic factors. Methods. Records for 83 patients, who were treated between 1991 and 2004, were evaluated for survival and stage, treatment, and clinicopathological factors. Results. Cumulative 5-year overall survival was 10.2% for all 83 patients, including 27 (32.5%) patients with stage II/III disease and 56 (67.4%) with stage IV disease. The 5-year overall survival rate and median survival time for patients with stage II/III disease after curative surgery were 24.3% and 1150 days. For patients with stage IV disease, 2-year and 5-year survival rates after initial surgery were 13.7% and 0% and median survival was 250 days. In contrast, preoperative chemotherapy for advanced, unresectable disease produced 2-year and 3-year overall survival rates of 53.6% and 26.8% and medican survival was 910 days. Conclusion. Aggressive surgery alone does not seem to improve outcome, but preoperative chemotherapy might be beneficial and should be investigated further.

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Endoscopic classifications as diagnostic factors of peptic ulcer and early gastric cancer - A possible reason why Helicobacter pylori infection causes gastric ulcers along lesser curvature

Yoshida M., Saikawa Y., Hosoda S., Kumai K., Kubota T., Ishikawa H., Nakamura T., Nakamura R., Kameyama K., Takahashi S., Kurihara N., Kitajima M.

Alimentary Pharmacology and Therapeutics 24 ( SUPPL.4 ) 303 - 310 2006.12

ISSN 0269-2813

Background: Endoscopic classifications were reported to reflect the pathophysiology of gastric mucosa. However, relationship between gastric lesions and classifications has not been examined well. Aim: To investigate the relationship between endoscopic classifications and cancers or ulcers. Methods: In this study, 487 patients undergoing upper gastrointestinal endoscopy in Takahashi Clinic and 257 patients with early gastric cancer in Keio University Hospital were enrolled. Results: Incidence of reflux oesophagitis was higher in Helicobacter pylori-negative patients. K-form was better in the H. pylori-positive patients. Most cancers in the patients with the closed-type or reflux oesophagitis were of undifferentiated types. Incidences of ulcers were highest in C-2 and C-3 in which the borders of atrophy cross the medial oblique muscle bundle, the border circular muscle bundle or both, and 94% of ulcers in C-2 and C-3 stomach were located along the lesser curvature. Conclusion: The predominant existence of undifferentiated types in patients with reflux oesophagitis or closed-type stomach can be useful information for early diagnosis of cancers. The relationship between the Kimura-Takemoto classification and ulcer location may explain why H. pylori infection is related to ulcer formation along the lesser curvature.

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Endoscopic classifications as diagnostic factors of peptic ulcer and early gastric cancer - A possible reason why Helicobacter pylori infection causes gastric ulcers along lesser curvature

Yoshida M., Saikawa Y., Hosoda S., Kumai K., Kubota T., Ishikawa H., Nakamura T., Nakamura R., Kameyama K., Takahashi S., Kurihara N., Kitajima M.

Alimentary Pharmacology and Therapeutics Symposium Series 2 ( 1 ) 303 - 310 2006.07

ISSN 1746-6334

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A recent trial of chemo-radiation with S-1 against gastric cancer

Saikawa Yoshiro, Kiyota Tsuyoshi, Nakamura Rieko, Wada Norihito, Yoshida Masashi, Kubota Tetsuro, Kumai Koichiro, Shigematsu Naoyuki, Kubo Atsushi, Kitajima Masaki

Gan to kagaku ryoho. Cancer & chemotherapy. 33 Suppl 1 99 - 105 2006.06

ISSN 0385-0684

A recent development of novel anticancer agents like S-1, CPT-11 or taxanes has improved a therapeutic outcome for advanced gastric cancer, while conventional anticancer agents showed less anticancer effect against gastric cancer. The present main drug in Japan is S-1, which is easily used for outpatient with a high efficacy rate and low toxicity, also shows better effect in combination with other anticancer drugs than S-1 alone. In the present article, we demonstrated significant meaning of additional radiation therapy with anticancer drugs like S-1. With novel anticancer drugs like S-1, we will expose a clinical advantage and appropriateness for chemo-radiation therapy against gastric cancer discussed in the present references according to chemo-radiation therapy. Although chemo-radiation therapy has been recognized as one of the standard therapies for gastric cancer in Western countries, radiation therapy was selected in Japan for palliation therapy of recurrent disease or a terminal cancer to improve patients' QOL. On the other hand, we demonstrated in our trial of chemo-radiation therapy with S-1/low-dose CDDP/radiation (TSLDR), which was applied to initial treatment against highly advanced Stage IV gastric cancer and revealed the usefulness of the regimen in anticancer effect and toxicity. In addition, chemo-radiation therapy including novel anticancer agents like S-1 will be discussed based on various kinds of view points, expecting a better clinical outcome of multimodal therapies against advanced gastric cancer.

Metastatic gastric cancer from malignant fibrous histiocytoma

Akatsu Yukako, Saikawa Yoshiro, Kubota Tetsuro, Kiyota Tsuyoshi, Nakamura Rieko, Akatsu Tomotaka, Takahashi Tsunehiro, Yoshida Masashi, Otani Yoshihide, Kumai Koichiro, Kitajima Masaki

Surgery Today 36 ( 4 ) 385 - 389 2006.04

ISSN 0941-1291

Metastatic gastric cancer originating from malignant fibrous histiocytoma (MFH) is rare. To our knowledge, only nine other cases have been reported. We report the case of a 75-year-old man who underwent a distal gastrectomy for advanced gastric carcinoma, 2 years after resection of an MFH from the left side of his back. We based our preliminary diagnosis of primary advanced gastric carcinoma on the results of a preoperative biopsy specimen, which suggested either poorly differentiated adenocarcinoma or nonepithelial cell-originating malignant disease-like lymphoma. The resected stomach contained a large ulcerative tumor in the antral section, which was positive for Kp-1 and S-100 by immunohistochemical staining, confirming a pathological diagnosis of metastatic MFH of the stomach. He died of recurrence in the mediastinal space 16 months after the gastrectomy. Our analysis of this and previous cases suggests that resection may be inappropriate for patients with gastric metastasis of MFH because of the extremely high malignant potential of this tumor.

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Role of the MTT chemosensitivity test in the prognosis of gastric cancer patients after postoperative adjuvant chemotherapy

Nakamura Rieko, Saikawa Yoshiro, Kubota Tetsuro, Kumagai Atsushi, Kiyota Tsuyoshi, Ohashi Masaki, Yoshida Masashi, Otani Yoshihide, Kumai Koichiro, Kitajima Masaki

Anticancer Research 26 ( 2 B ) 1433 - 1437 2006.03

ISSN 0250-7005

The clinical usefulness of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) chemosensitivity test (MTT assay; MTTA) in the selection of anticancer drugs against advanced gastric cancer (AGC) was evaluated. MTTA is widely used to predict patient responses to particular drugs, allowing for the selection of appropriate chemotherapeutic drugs and the avoidance of ineffective chemotherapeutic drugs, thereby improving patient survival. Since 1989, we have accumulated MTTA efficacy data from AGC patients. In this study, the present clinical roles of MTTA and the data from 202 patients with stage III or IV gastric cancer analyzed for survival outcome following surgery, with or without postoperative chemotherapy, evaluated by MTTA, are discussed. The patients were divided into 3 groups; an adapted group found to be sensitive to chemotherapy by MTTA, a non-adapted group found to be insensitive to chemotherapy by MTTA and a group that received no chemotherapy. For stage III gastric cancer patients, the adapted group had a statistically better survival rate compared to the other groups, while for stage IV patients, there was no difference in survival rate between any of the groups. However, further classification of stage IV patients as to the presence or absence of peritoneal dissemination (P) showed that the adapted group with P showed better prognoses than the other groups with P. The analysis of data collected since 2000 revealed that the 11 patients in the taxane-adapted group, who received chemotherapeutic regimens that included taxanes and were found to be sensitive to taxanes by MTTA, demonstrated better survival than the taxane non-adapted group (n=11) (p=0.045). In conclusion, MTTA results predicted patient prognoses, based on the selection of appropriate chemotherapy.

Preoperative combination chemotherapy with TS-1 is effective in a case gastric cancer with peritoneal dissemination

Nakamura Rieko, Saikawa Yoshiro, Kubota Tetsuro, Nakamura Tetsuya, Akatsu Yukako, Takahashi Tsunehiro, Yoshida Masashi, Otani Yoshihide, Kumai Koichiro, Kitajima Masaki

Gan to kagaku ryoho. Cancer & chemotherapy 32 ( 9 ) 1323 - 1326 2005.09

ISSN 0385-0684

We report a case of peritoneal cancer dissemination with Type 4 gastric cancer, successfully treated with combination chemotherapy with TS-1. The patient was a 59-year-old female, who complained of abdominal distension with pain, weight loss, and poor appetite. She was diagnosed as unresectable Type 4 gastric cancer, T3N2MOHOP1CY1M0, Stage IV with massive ascites (cytology: Class V). After 2 courses of combined chemotherapy with TS-1 and cisplatin (CDDP), primary tumor reduction was confirmed and no cancer cells were detected from a pathological investigation with biopsied specimens by endoscopy. As additional therapy for remained ascites, intraperitoneal administration of paclitaxel and docetaxel was performed, resulting in a remarkable decrease of ascites with cytological disappearance of cancer cells. The patients underwent total gastrectomy with lymph node dissection, pathological diagnosis of primary site and lymph nodes showed grade 2 effect, and no cancer cells were detected in ascites and peritoneum, microscopically. While she died of peritoneal recurrence after the surgery, the case suggested the clinical advantage of controlling the advanced cancer-bearing state by combination chemotherapy with TS-1, instead of surgery.

Is chemoradiation effective or harmful for stage VI gastric cancer patients?

Saikawa Yoshiro, Kubota Tetsuro, Takahashi Tsunehiro, Akatsu Yukako, Nakamura Rieko, Yoshida Masashi, Shigematsu Naoyuki, Otani Yoshihide, Kumai Koichiro, Hibi Toshifumi, Kitajima Masaki

Oncology Reports 13 ( 5 ) 865 - 870 2005.05

ISSN 1021-335X

We aim to clarify beneficial effect of pre-operative radiation with chemotherapy in highly advanced gastric cancer patients, evaluating histological response, toxicity and patients' quality of life (QOL). We used pre-operative radiation with S-1 and low-dose cisplatin to treat 8 patients with highly advanced gastric cancer (clinical stage IV) in a pilot study. Clinical staging after therapy showed 5 PRs (partial response), 2 NCs (no change), and 1 PD (partial disease) following evaluation of the primary tumor and suspicious metastatic lesions in the lymph nodes, esophagus, liver, and peritoneum, for a response rate of 62.5% (5/8 cases). Of 8 patients, 6 underwent surgery, and 2 of these 6 patients had a histologically complete response (grade 3 effect) and 3 patients had a partial response (grade 2 effect), suggesting that a high histological response (5/6 cases; 83.3%) is expected by the chemoradiation. The survival analysis showed that 5 out of the 8 patients died within 10 months after initiating therapy, while 3 patients are alive without recurrence at 15, 18, and 30 months after therapy, suggesting a relatively good outcome for clinical stage IV gastric cancer. All cases showed grade 2-4 bone marrow suppression toxicity and/or grade 0-2 gastrointestinal toxicity, while 5 out of 8 patients (62.5%) showed improvement in appetite loss at the end of the therapy, indicating that the patients' quality of life (QOL) was preserved. Chemoradiation may be a powerful regimen for obtaining histological response with tolerable toxicity and improved QOL in highly advanced gastric cancer patients.

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