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ABSTRACT: Anaplastic lymphoma kinase-positive (ALK+) large B-cell lymphoma (LBCL) is a rare subtype of non-Hodgkin B-cell lymphoma that exhibits a more aggressive clinical course and poorer prognosis than the typical diffuse large B-cell lymphoma. In this study, we report the case of a 67-year-old man with left cervical lymph node swelling. Aspiration cytology revealed many clusters of cohesive, large, and solitary cells. The tumor cells had abundant cytoplasm and large round-to-oval nuclei with prominent nucleoli. The Giemsa staining specimens exhibited amorphous global bodies adjacent to some clusters. Histologically, large tumor cells occupied the lymph nodes in a sinusoidal pattern, and immunohistochemically, these cells were cytokeratin-, CD19- , CD20- , CD79a- , CD3- , CD30- , CD138+ , IgG- , IgA+ , and ALK+ . Chromogenic in situ hybridization revealed restricted immunoglobulin light-chain expression. Fluorescent in situ hybridization demonstrated translocation of the ALK gene. The tumor cells were negative for Epstein-Barr virus and human herpesvirus 8. It is important to differentiate ALK+LBCL from metastatic carcinoma and other lymphoma subtypes with similar histological features to ensure a proper treatment strategy and prediction of prognosis. Diagn. Cytopathol. 2013;. © 2013 Wiley Periodicals, Inc.
Diagnostic Cytopathology 03/2013; · 1.16 Impact Factor
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The Breast Journal 01/2013; · 1.64 Impact Factor
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Takashi Miyatake,
Yutaka Ueda,
Akiko Morimoto,
Takayuki Enomoto,
Sumiyuki Nishida,
Toshiaki Shirakata,
Yoshihiro Oka,
Akihiro Tsuboi,
Yusuke Oji,
Naoki Hosen, Shin-Ichi Nakatsuka,
Satoshi Morita,
Junichi Sakamoto,
Haruo Sugiyama,
Tadashi Kimura
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ABSTRACT: OBJECTIVE: The aim of the present study was to analyze the long-term survival effects of WT1 peptide vaccine, in addition to its anti-tumor effects and toxicity. METHODS: A phase II clinical trial was conducted during the period of 2004-2010 at Osaka University Hospital, Osaka, Japan. The patients who had gynecologic malignancies progressing against previous treatments received WT1 peptide vaccine intradermally at 1-week intervals for 12 weeks. The vaccination was allowed to further continue, unless the patient's condition became significantly worse due to the disease progression. RESULTS: Forty out of 42 patients, who met all the inclusion criteria, underwent WT1 peptide vaccine. Among these 40 patients, stable disease was observed in 16 cases (40 %). Skin toxicity of a grade 1, 2 and 3 occurred in 25 cases (63 %), 9 cases (23 %) and a single case (3 %), respectively, and liver toxicity of grade 1 in a single case (3 %). The overall survival period was significantly longer in cases positive for the WT1 peptide-specific delayed-type hypersensitivity (DTH) reaction after the vaccination, compared to those negative for the DTH reaction (p = 0.023). Multivariate Cox proportional hazards analysis demonstrated that the adjusted hazard ratio for the negative DTH reaction was 2.73 (95 % CI 1.04-7.19, p = 0.043). CONCLUSION: WT1 peptide vaccine may be a potential treatment, with limited toxicity, for gynecologic malignancies that have become resistant to conventional therapies. Larger scale of clinical studies is required to establish the efficacy of the WT1 peptide vaccine for gynecologic malignancies.
Journal of Cancer Research and Clinical Oncology 11/2012; · 2.56 Impact Factor
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ABSTRACT: Retroperitoneal cysts are a rare disease. Most retroperitoneal cysts of vascular origin have been reported as hemangiomas. However, according to the recent classification of vascular anomalies accepted by the International Society for Study of Vascular Anomalies (ISSVA), these previously reported retroperitoneal hemangiomas should rather have been classified as vascular malformations.
A 65-year-old woman visited our hospital complaining of a sense of unexplained abdominal fullness. Magnetic resonance imaging suggested a uterine leiomyoma and bilateral ovarian cystic tumors. However, abdominal surgery revealed normal bilateral ovaries, but huge cystic masses in the retroperitoneum. Postoperative histological diagnosis of the retroperitoneal cysts demonstrated that they were venous malformations.
This is a rare case in which large cystic retroperitoneal venous malformations were preoperatively diagnosed as ovarian cystic tumors. Retroperitoneal hemangiomas should be renamed as vascular malformations following the ISSVA classification.
Archives of Gynecology 06/2012; 286(4):1011-4. · 0.91 Impact Factor
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Toshiaki Shirakata,
Yoshihiro Oka,
Sumiyuki Nishida,
Naoki Hosen,
Akihiro Tsuboi,
Yusuke Oji,
Ayako Murao,
Hidetaka Tanaka, Shin-Ichi Nakatsuka,
Hidenori Inohara,
Haruo Sugiyama
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ABSTRACT: Wilms' tumor (WT1) protein is one of the most promising target antigens for cancer immunotherapy. In fact, clinical responses, such as growth stabilization or shrinkage of tumor with immunological responses, have been reported in patients vaccinated with WT1 peptide. Here, we performed WT1 peptide-based immunotherapy for a patient with chemotherapy-resistant salivary gland cancer, whose histologic type was carcinoma ex pleomorphic adenoma. The patient with its pulmonary metastasis, refractory to chemotherapy, was intradermally injected with 3 mg of WT1 peptide emulsified with Montanide ISA51 adjuvant at one-week intervals for 12 weeks. The considerably rapid growth of tumor was inhibited after WT1 vaccination, and stable disease, lasting three months, was achieved. Concomitantly, immunological responses, i.e. an increase in frequencies of WT1 tetramer(+) CD8(+)T cells and delayed type hypersensitivity response, were detected after the vaccination. These results indicate the potential of WT1 peptide-based immunotherapy for the treatment of chemotherapy-resistant salivery gland cancer.
Anticancer research 03/2012; 32(3):1081-5. · 1.73 Impact Factor
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ABSTRACT: Malignant transformation is rarely seen in the disease course of mature cystic teratoma (MCT) of the ovary. Adenocarcinoma arising from MCT is especially rare. We herein present the case of a premenopausal woman with a mucinous borderline-like tumor arising from a MCT. Based on the histological transition between the borderline-like tumor and gastrointestinal elements of the MCT, we consider that the tumor derived from teratomatous gastrointestinal epithelium. Immunohistochemistry showed that the proliferating mucinous cells were diffusely positive for cytokeratin 20 and partially positive for cytokeratin 7. MUC5AC was partially positive, whereas MUC2 and MUC6 were positive in a small number of tumor cells. The immunophenotype of cytokeratins and mucins in the present case was compatible with malignant transformation of the teratomatous gastrointestinal epithelium.
Journal of Obstetrics and Gynaecology Research 02/2012; 38(2):471-5. · 0.94 Impact Factor
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ABSTRACT: The patient is a 75-year-old man with axillary lymphadenopathy presenting an indurated papule on his buttock. Touch imprint cytology of the biopsied axillary lymph node revealed the monotonous appearance of medium-sized tumor cells. The nuclei had a slightly irregular contour, finely dispersed chromatin, and a conspicuous nucleolus. Some tumor cells had intracytoplasmic microvacuoles. Immunohistochemistry of the imprint specimens showed that the tumor cells were positive for CD56 and CD123. Histological diagnosis of the lesion was blastic plasmacytoid dendritic cell neoplasm (BPDCN). Epstein-Barr virus-encoded RNAs were not detected in the tumor cells. Neither immunoglobulin heavy chain genes nor T- cell receptor genes was clonally rearranged. BPDCN should be strongly considered during the differential diagnosis of CD56-positive neoplasms of the skin. We demonstrated a possible contribution of the cytomorphological and immunohistochemical findings of the touch imprint specimens to the diagnosis of BPDCN. Diagn. Cytopathol. 2012; © 2012 Wiley Periodicals, Inc.
Diagnostic Cytopathology 01/2012; · 1.16 Impact Factor
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Shin-Ichi Nakatsuka,
Isao Taguchi,
Tadasuke Nagatomo,
Michiaki Yamane,
Kenji Sugio,
Ryuichi Yoshino,
Kazuko Oku,
Teruaki Nagano,
Hayato Kimura,
Kazuya Nakajo,
Gaku Kawabata
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ABSTRACT: Carcinomas rarely arise from the urethral diverticulum. In this report, we present a case of clear cell adenocarcinoma arising from the urethral diverticulum. A 42-year-old woman complained of bloody discharge and lower back pain. Imaging studies showed a tumor involving the region surrounding the urethra and cystourethroscopy showed papillary and villous tumors in the urethral diverticula. Cytology of the urine sediment showed papillary or spherical clusters of atypical cells, some of which had clear abundant cytoplasm and formed mirror ball-like clusters, suggesting adenocarcinoma. Although histological diagnosis was indeterminate by biopsy and transurethral resection (TUR) because of absence of stromal invasion, surgically resected specimen via cysturethrectomy revealed that the tumor was clear cell carcinoma. Urinary cytological findings and immunohistochemical analysis for CD15, Ki-67, and p53 might be useful for accurate diagnosis of clear cell adenocarcinoma that arises from the urethral diverticulum when sufficient materials are not available by biopsy and TUR.
CytoJournal 01/2012; 9:11.
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ABSTRACT: Low-grade cribriform cystadenocarcinoma (LGCCA) is a rare tumor of the salivary gland that exhibits clinically indolent behavior. In this paper, we present a case of invasive adenocarcinoma of the accessory parotid gland in a young male that exhibited histology suggestive of an association of LGCCA. A 27-year-old man presented with a subcutaneous tumor in his left cheek. The tumor was separated from the parotid gland and located on the masseter muscle. The tumor was resected, and the postoperative histological diagnosis was adenocarcinoma, not otherwise specified (ANOS). The tumor exhibited papillary-cystic and cribriform proliferation of the duct epithelium and obvious stromal infiltration. Some tumor nests were rimmed by myoepithelium positive for smooth muscle actin, p63, and cytokeratin 14, indicating the presence of intraductal components of the tumor. Tumor cells exhibited mild nuclear atypia, and some of them presented an apocrine-like appearance and had cytoplasmic PAS-positive/diastase-resistant granules and hemosiderin. Other cells had foamy cytoplasm with microvacuoles. Immunohistochemistry revealed that the almost all of the tumor cells were strongly positive for S-100. These histological findings suggest the possibility that ANOS might arise secondarily from LGCCA. This is an interesting case regarding the association between ANOS and LGCCA in oncogenesis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1226764594634693.
Diagnostic Pathology 12/2011; 6:122. · 1.64 Impact Factor
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ABSTRACT: Extragonadal germ cell tumors rarely arise from the brain stem. In this report, the authors present a rare case of germinoma developing in the medulla oblongata. A 31-year-old woman complained of intractable hiccups, hoarseness, and swallowing disturbance. Magnetic resonance imaging showed a tumor located on the dorsal part of the medulla oblongata without any abnormalities in the pineal body and suprasellar regions. Histological diagnosis of surgically resected tumor was germinoma. Tumor cells were positive for alkaline phosphatase, c-kit, octamer-binding transcription factor 3/4, cytokeratin, and epithelial membrane antigen in immunohistochemistry. The patient received adjuvant chemotherapy and irradiation to the residual tumor and cerebral ventricles. The patient is alive without recurrence 6 months after the surgery.
International Journal of Surgical Pathology 12/2011; 20(3):276-9. · 1.00 Impact Factor
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ABSTRACT: A case of multifocal nodular oncocytic hyperplasia (MNOH) of the bilateral parotid gland is presented. An 80-year-old woman was admitted to hospital because of painless swellings in bilateral parotid regions. Histologically, the nodular lesion had incomplete capsules and engulfed the surrounding parotid gland at the periphery. The lesions were mostly composed of clear cells, while the peripheries of the lesions had typical oncocytic cells with abundant fine granules. The histological existence of the clear cell component in the lesions led to misdiagnoses of other clear cell neoplasms. However, this case had multiple nodules in bilateral glands. No evidence of malignant histological findings was found. Moreover, the clear cells, as well as the oncocytic cells, were demonstrated to have mitochondria and glycogen in their cytoplasm using special staining. Based on these findings, the diagnosis of this case was MNOH in the parotid gland. We also discuss the differential diagnosis for clear cell lesions.
Pathology - Research and Practice 06/2011; 207(7):452-5. · 1.21 Impact Factor
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ABSTRACT: Our patient was an 86-year-old man who had worked as a lathe operator for 40 years. He had no history of tuberculosis, pyothorax, or autoimmune disease. He had not been exposed to asbestos. He was asymptomatic, but an imaging study showed gradually increasing pleural plaques. A biopsy specimen of a pleural lesion showed sclerosis of the pleura and diffuse infiltration of small- to medium-sized B lymphocytes. Polymerase chain reaction-based analysis detected monoclonal rearrangement of immunoglobulin heavy-chain genes. Histologic diagnosis was extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma). The lymphoma was negative for Epstein-Barr virus. We report a rare case of a metal worker with MALT lymphoma arising in the pleura with pleural fibrous plaques. It is speculated that MALT lymphoma might develop in the background of pneumoconiosis. Inflammatory and/or immunologic reactions to metal particles might contribute to the oncogenesis of this tumor.
Annals of diagnostic pathology 05/2011; 16(3):224-9.
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ABSTRACT: This is the first report of adalimumab-associated pulmonary cryptococcosis. A 56-year-old female with rheumatoid arthritis without a history of pulmonary disease was simultaneously administered adalimumab (40 mg/2 wks), methotrexate (4 mg/wk), and isoniazid (200 mg/day). Five months later, chest radiography revealed a small spiculated pulmonary nodule, and the laboratory test results, including levels of tumor markers and plasma β-D-glucan, were within normal ranges. Since the lesion continued to grow, even after discontinuing adalimumab, it was surgically resected. Grocott staining of the tissue sample revealed black-brown fungi, identified as Cryptococcus neoformans in culture. The patient now remains well, without adalimumab therapy.
Annals of thoracic and cardiovascular surgery : official journal of the Association of Thoracic and Cardiovascular Surgeons of Asia. 01/2011; 17(4):390-3.
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Junya Nakamura,
Sayaka Aoyagi,
Isamu Nanchi, Shin-Ichi Nakatsuka,
Erika Hirata,
Shohei Shibata,
Mari Fukuda,
Yumiko Yamamoto,
Ikuyo Fukuda,
Naoya Tatsumi, [......],
Toshiaki Shirakata,
Naoki Hosen,
Akihoro Tsuboi,
Yoshihiro Oka,
Riichiro Nezu,
Masaki Mori,
Yuichiro Doki,
Katsuyuki Aozasa,
Haruo Sugiyama,
Yusuke Oji
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ABSTRACT: A high level protein synthesis is one of the characteristics of cancer cells. The aim of this study is to show the contribution of eukaryotic elongation factor 2 (eEF2), which plays an essential role in the polypeptide chain elongation step, in the tumorigenesis of gastrointestinal cancers. In the present study, we demonstrated by using immunohistochemistry that eEF2 protein was overexpressed in 92.9% (13 of 14) of gastric and 91.7% (22 of 24) of colorectal cancers. No mutations were found in any of the exons of the eEF2 gene in six gastric and six colorectal cancers. Knockdown of eEF2 by eEF2-specific short-hairpin RNA (shEF2) inhibited cancer cell growth in two gastric cancer cell lines, AZ-521 and MKN28, and one colon cancer cell line, SW620. Flow cytometric analysis showed that knockdown of eEF2 induced G2/M arrest and resulted in inactivation of Akt and cdc2 (a G2/M regulator) and activation of eEF2 kinase (a negative regulator of eEF2) in these cancer cells. Conversely, forced expression of eEF2 in AZ-521 cells significantly enhanced the cell growth through promotion of G2/M progression in cell cycle, activated Akt and cdc2, and inactivated eEF2 kinase. Furthermore, forced expression of eEF2 in these cancer cells enhanced in vivo tumorigenicity in a mouse xenograft model. These results showed that overexpressed eEF2 in gastrointestinal cancers promoted G2/M progression and enhanced their cell growth in vitro and in vivo. These results also suggested a novel linkage between translational elongation and cell cycle mechanisms, implying that the linkage might play an important role to orchestrate the deregulated translation and cell cycle mechanisms for promotion of the development of gastrointestinal cancers.
International Journal of Oncology 06/2009; 34(5):1181-9. · 2.40 Impact Factor
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Yusuke Oji,
Yayoi Kitamura,
Eriko Kamino,
Aiko Kitano,
Noriyoshi Sawabata,
Masayoshi Inoue,
Masahide Mori, Shin-ichi Nakatsuka,
Nao Sakaguchi,
Kaori Miyazaki, [......],
Naoki Hosen,
Akihiro Tsuboi,
Riichiro Nezu,
Hajime Maeda,
Yoshihiro Oka,
Ichiro Kawase,
Katsuyuki Aozasa,
Meinoshin Okumura,
Shinichiro Miyoshi,
Haruo Sugiyama
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ABSTRACT: There are urgent needs to develop methods for early detection of nonsmall cell lung cancer (NSCLC) because of its increasing incidence and poor prognosis. Here, we analyzed the production of IgG antibody (WT1 Ab) against WT1 (Wilms' tumor gene) protein that was overexpressed in the majority of NSCLC. Enzyme-linked immuno-sorbent assay showed that WT1 Ab was produced in all of 91 NSCLC patients and 70 healthy individuals and that WT1 Ab titers were significantly higher in NSCLC patients compared with healthy individuals. When the cut-off level of WT1 Ab titers were fixed at mean + 3SD of those in healthy individuals, 26.4% of NSCLC patients had WT1 Ab titers over the cut-off level, and positive rates of WT1 Ab at each clinical stage were 25.0, 30.8 and 38.4% in stage I, II and III NSCLC, respectively. When WT1 Ab was combined with CEA or CYFRA for detection of NSCLC, positive detection rates increased from 25.0 to 34.1 and 31.8%, respectively, in stage I and from 38.4 to 69.2 and 46.1%, respectively, in stage III, but not changed in stage II. Western blot analysis showed that dominant subclass of WT1 Ab was Th1-type IgG2. Interestingly, elevation of WT1 Ab titers was significantly associated with longer disease-free survival in patients with stages I-III NSCLC. These results showed that WT1 Ab could be a useful marker for early detection of NSCLC and its prognostic prediction. These results also suggested that WT1-specific immune responses played an important role in anti-cancer immunity in NSCLC.
International Journal of Cancer 03/2009; 125(2):381-7. · 5.44 Impact Factor
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Hideaki Ohta,
Yoshiko Hashii,
Akihiro Yoneda,
Sachiko Takizawa,
Shigenori Kusuki,
Sadao Tokimasa,
Masahiro Fukuzawa,
Akihiro Tsuboi,
Ayako Murao,
Yoshihiro Oka,
Yusuke Oji,
Katsuyuki Aozasa, Shin-ichi Nakatsuka,
Haruo Sugiyama,
Keiichi Ozono
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ABSTRACT: Immunotherapy using a Wilms tumor (WT1) peptide has been undergoing clinical trials for adulthood leukemia and solid cancer with promising results. In this study, the authors used WT1 peptide vaccination to treat a 6-year-old girl with metastatic alveolar rhabdomyosarcoma. She received weekly intradermal injection with HLA-A*2404-restricted, 9-mer WT1 peptide against residual bone disease. After 3 months her bone disease disappeared, concurrent with an increase in the frequency of WT1-specific cytotoxic T lymphocytes (CTLs). A high proportion of WT1-specific CTLs with effector or effector memory phenotype were detected in peripheral blood of this patient. She is currently still on continued WT1 peptide immunotherapy in a disease-free condition for 22 months. WT1 peptide-based immunotherapy should be a promising option for high-risk rhabdomyosarcoma in childhood.
Pediatric Hematology and Oncology 02/2009; 26(1):74-83. · 0.89 Impact Factor
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Shuichi Izumoto,
Akihiro Tsuboi,
Yoshihiro Oka,
Tsuyoshi Suzuki,
Tetsuo Hashiba,
Naoki Kagawa,
Naoya Hashimoto,
Motohiko Maruno,
Olga A Elisseeva,
Toshiaki Shirakata, [......],
Sumiyuki Nishida,
Satoshi Ohno,
Ichiro Kawase,
Jun Hatazawa, Shin-Ichi Nakatsuka,
Katsuyuki Aozasa,
Satoshi Morita,
Junichi Sakamoto,
Haruo Sugiyama,
Toshiki Yoshimine
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ABSTRACT: The object of this study was to investigate the safety and clinical responses of immunotherapy targeting the WT1 (Wilms tumor 1) gene product in patients with recurrent glioblastoma multiforme (GBM).
Twenty-one patients with WT1/HLA-A*2402-positive recurrent GBM were included in a Phase II clinical study of WT1 vaccine therapy. In all patients, the tumors were resistant to standard therapy. Patients received intra-dermal injections of an HLA-A*2402-restricted, modified 9-mer WT1 peptide every week for 12 weeks. Tumor size, which was obtained by measuring the contrast-enhanced area on magnetic resonance images, was determined every 4 weeks. The responses were analyzed according to Response Evaluation Criteria in Solid Tumors (RECIST) 12 weeks after the initial vaccination. Patients who achieved an effective response continued to be vaccinated until tumor progression occurred. Progression-free survival and overall survival after initial WT1 treatment were estimated.
The protocol was well tolerated; only local erythema occurred at the WT1 vaccine injection site. The clinical responses were as follows: partial response in 2 patients, stable disease in 10 patients, and progressive disease in 9 patients. No patient had a complete response. The overall response rate (cases with complete or partial response) was 9.5%, and the disease control rate (cases with complete or partial response as well as those in which disease was stable) was 57.1%. The median progression-free survival (PFS) period was 20.0 weeks, and the 6-month (26-week) PFS rate was 33.3%.
Although a small uncontrolled nonrandomized trial, this study showed that WT1 vaccine therapy for patients with WT1/HLA-A*2402-positive recurrent GBM was safe and produced a clinical response. Based on these results, further clinical studies of WT1 vaccine therapy in patients with malignant glioma are warranted.
Journal of Neurosurgery 06/2008; 108(5):963-71. · 2.96 Impact Factor
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European Journal Of Haematology 08/2007; 79(1):88-90. · 2.61 Impact Factor
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Yoshihiko Hoshida,
Jing-Xian Xu,
Shigeki Fujita,
Itsuko Nakamichi,
Jun-Ichiro Ikeda,
Yasuhiko Tomita, Shin-Ichi Nakatsuka,
Jun-Ichi Tamaru,
Atsushi Iizuka,
Tsutomu Takeuchi,
Katsuyuki Aozasa
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ABSTRACT: Individuals with rheumatoid arthritis (RA) with or without methotrexate (MTX) medication occasionally develop lymphoproliferative disorders (MTX-LPD and non-MTX-LPD, respectively). The hyperimmune state of RA itself or the immunosuppressive state induced by MTX administration might contribute to development of LPD. Our objective was to characterize MTX-LPD in comparison to non-MTX-LPD and sporadic LPD in patients with RA.
We compared MTX-LPD to non-MTX-LPD and sporadic LPD by evaluating 48 cases of MTX-LPD, 28 non-MTX-LPD, and 150 sporadic LPD.
Later onset age of LPD and female predominance were evident in patients with RA-LPD compared to sporadic LPD. The interval between the diagnosis of RA and LPD in MTX-LPD (median 132 mo) was significantly shorter than that in non-MTX-LPD (240 mo). The frequency of diffuse large B cell lymphoma (DLBCL) and positive rate of Epstein-Barr virus (EBV) in RA-LPD was significantly higher than in sporadic LPD (57.9% vs 42.7%, 27.6% vs 9.9%, respectively). After withdrawal of MTX, 11 of the MTX-LPD cases showed a spontaneous regression of tumors. The 5-year survival rate in RA-LPD (59.2%) was significantly worse than that in sporadic LPD (74.6%).
The majority of cases of RA-LPD show similar clinicopathological characteristics irrespective of MTX medication, except for spontaneous regression of LPD after withdrawal of MTX in MTX-LPD, and a shorter interval between the diagnosis of RA and LPD in MTX-LPD than in non-MTX-LPD. RA-LPD cases showed younger age of onset, female predominance, unfavorable prognosis, and higher frequencies of DLBCL and EBV positivity compared to sporadic LPD.
The Journal of Rheumatology 03/2007; 34(2):322-31. · 3.69 Impact Factor
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Tatsuo Iiyama,
Keiko Udaka,
Sachihiko Takeda,
Tamotsu Takeuchi,
Yoshihiro C Adachi,
Yuji Ohtsuki,
Akihiro Tsuboi, Shin-ichi Nakatsuka,
Olga A Elisseeva,
Yusuke Oji,
Manabu Kawakami,
Hiroko Nakajima,
Sumiyuki Nishida,
Toshiaki Shirakata,
Yoshihiro Oka,
Taro Shuin,
Haruo Sugiyama
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ABSTRACT: Tumor-specific immunotherapy with a Wilms' tumor 1 (WT1) peptide has been on clinical trial for leukemia, myelodysplastic syndrome, breast and lung cancers and is producing promising results. In this study, we treated three patients with renal cell carcinoma with an anchor modified, HLA-A*2402 binding WT1 peptide which was emulsified in Freund's incomplete adjuvant. In two patients tumor growth was suppressed and clinical response was evaluated as stable disease by the RECIST criteria after 3 months of weekly immunizations. Notably, development of new metastases has stopped in these patients for a prolonged period. No deleterious side effects were observed. Peptide-specific T cells were expanded in PBMCs of the patients and a substantial fraction of them bore the surface phenotype consistent with a CD8+ cytotoxic effector population. Although established tumors did not regress further, considering the component of the vaccine, i.e. peptide alone, the stabilization effect suggested the potential of WT1 peptide to develop into a more effective vaccine. To our knowledge, this is the first report of WT1 immunotherapy for renal cell carcinoma. Hopefully, the results will stimulate more extensive clinical studies.
Microbiology and Immunology 02/2007; 51(5):519-30. · 1.30 Impact Factor
