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1.
Genetic alteration in carcinoid tumors of the lung. 总被引:1,自引:0,他引:1
Kenji Sugio Toshihiro Osaki Tsunehiro Oyama Mitsuhiro Takenoyama Takeshi Hanagiri Masaru Morita Koji Yamazaki Akira Nagashima Hisashi Nakahashi Yoshihiko Maehara Kosei Yasumoto 《Annals of thoracic and cardiovascular surgery》2003,9(3):149-154
Surgically resected specimens of 13 carcinoid tumors of the lung including nine typical carcinoids and four atypical carcinoids, and eight salivary gland type carcinomas (six mucoepidermoid carcinomas and two adenoid cystic carcinomas) were analyzed regarding p53 expression, loss of heterozygosity (LOH) in chromosome 3p, 9p, and K-ras mutation. The overexpression of p53 was identified in four atypical carcinoid tumors, one mucoepidermoid carcinoma, and one adenoid cystic carcinoma, however, none of typical carcinoids showed p53 immunoreactivity. LOH in 3p14 was demonstrated in three of seven informative cases in all tumors. LOH in 9p was demonstrated in two of five informative cases in all tumors. Two of three cases with LOH at 3p14 had a poor prognosis, one of which also had LOH at 9p. No mutation of the K-ras gene was observed in any of these tumors. These data thus indicate that p53 overexpression might distinguish atypical carcinoid tumors from typical tumors and might therefore be useful as an adjunct modality in the differential diagnosis of pulmonary carcinoid tumors. The presence of LOH at 3p14 or 9p may thus help to identify lung cancer patients with a poor prognosis. 相似文献
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T Yamada T Saito Y Matsue Y Honda T Fuchigami M Fujii M Ross 《Electroencephalography and clinical neurophysiology》1992,84(6):492-498
Using a conditioning-test paradigm, we studied the recovery function of tibial nerve somatosensory evoked potentials (SEPs) conditioned by preceding peroneal nerve stimulation. The inter-stimulus intervals (ISIs) ranged from 0 to 400 msec, where 0 msec indicated simultaneous arrival of tibial and peroneal nerve volleys at the L1 spine. The recovery curve was W-shaped, showing two peaks of SEP suppression, maximum at 6 msec ISI (1st phase) and 50-75 ISI msec (2nd phase). In the 1st phase suppression, we found distinct differences in wave forms between 0-2 msec ISI and 4-6 msec ISI. At 0-2 msec ISI, P40-N50-P60 amplitude decreased and latencies shortened, while P31 and N35 were unchanged. At 4-6 msec ISI, all peaks, possibly excluding P31, were markedly depressed. We attribute the former change to an "occlusive effect" and the latter to an "inhibitory effect," each mediated via a central synaptic network between the two nerves. The attenuation of the 2nd but not the 1st phase suppression by peroneal nerve block distal to the stimulating electrodes provided evidence that the 2nd phase suppression resulted primarily from interfering afferent signals generated by peroneal nerve peripheral receptors, activated by foot movement. 相似文献
4.
CDX2 expression is progressively decreased in human gastric intestinal metaplasia, dysplasia and cancer. 总被引:1,自引:0,他引:1
Qiang Liu Ming Teh Kosei Ito Nilesh Shah Yoshiaki Ito Khay Guan Yeoh 《Modern pathology》2007,20(12):1286-1297
Intestinal metaplasia is a key event in multistep gastric carcinogenesis. CDX2, a master regulator of intestinal phenotype, was shown to play a tumor-suppressive role in colon cancer. However, it was reported to be expressed in nearly all gastric intestinal metaplasia and many gastric cancers. As CDX2 is differentially expressed in normal stomach and intestine, we sought to relate the CDX2 expression to gastrointestinal differentiation along gastric carcinogenesis. The expression of CDX2 protein in gastric intestinal metaplasia, dysplasia and cancer was examined and related to their gastrointestinal differentiation. CDX2 expression was significantly decreased in incomplete intestinal metaplasia, which expresses both gastric mucins (MUC5AC and MUC6) and intestinal mucin (MUC2), compared with complete intestinal metaplasia, which expresses intestinal mucin (MUC2) only. Although incomplete intestinal metaplasia morphologically resembles colon, its CDX2 expression was apparently lower than that in the normal colon. Moreover, CDX2 expression was progressively reduced in gastric dysplasia and cancer. The CDX2 expression in gastric cancer was also inversely correlated with the expression of gastric mucins. As incomplete intestinal metaplasia is associated with higher risk of gastric cancer, its lower CDX2 expression compared with that in complete intestinal metaplasia and normal colon epithelium resolved the current contradiction between the tumor-suppressive role of CDX2 in the colon and the high prevalence of CDX2 in intestinal metaplasia. Further decrease of CDX2 expression in gastric dysplasia and cancer suggests that CDX2 plays a similar anticarcinogenic role in intestinal metaplasia as it does in colon. Intestinal metaplasia or dysplasia with low expression of CDX2 may serve as predictive markers for gastric cancer. 相似文献
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S Shiobara M Ueda M Harada T Mori K Matsue S Nakao K Kondo M Ootsuka K Iwabuchi T Matsuda 《Journal of Japan Haematological Society》1989,52(1):55-62
A 27-year-old male with acute lymphoblastic leukemia in the first relapse received allogeneic marrow graft from an HLA-identical sister on April 28, 1978. We studied in vitro immunologic parameters such as T cell surface phenotypes, proliferative response to PHA and Con A; T cell suppressor and helper function for in vitro immunoglobulin production stimulated with pokeweed mitogen serially after the transplantation. Despite a low OKT4/OKT8 ratio for more than 5 yrs after marrow grafting, proliferative response to PHA recovered to normal 4 yrs and 9 months post-transplant. In contrast, proliferative response to Con A did not recover. T cell suppressor function induced by Con A had recovered at 3 yrs 6 months; however helper T cell function took longer to recover. These findings suggest differences in functional recovery of T cell subsets following allogeneic marrow transplantation. 相似文献
7.
Takeshi Hanagiri Ichiro Yoshino Mitsuhiro Takenoyama Tomoko So Hiroshi Fujie Satoru Imabayashi Ryozo Eifuku Takashi Yoshimatsu Toshihiro Osaki Ryoichi Nakanishi Yuji Ichiyoshi Akira Nagashima Kikuo Nomoto Kosei Yasumoto 《Cancer science》1998,89(2):192-198
Lung cancer-specific cytotoxic T lymphocytes (CTL) were induced by repeated stimulations of regional lymph node lymphocytes (RLNL) in lung cancer patients with either autologous or HLA-A-locus-matched tumor cells. To investigate the effect of interleukin-12 (IL-12), IL-12 was added during the stimulation of RLNL from HLA A24 / adenocarcinoma patients with either autologous tumor cells or HLA A24-positive adenocarcinoma cells (PC-9) in combination with, or instead of interleukin-2 (IL-2), and then the cytotoxic activity, cytokine production and populations of the lymphocyte subsets were examined. The addition of IL-12, or the substitution of IL-2 by IL-12 was found to enhance the cytotoxic activity and the cytokine production (IFN-γ, GM-CSF) of the CTL as compared with IL-2 alone. The cytotoxic activity and cytokine production were both partially inhibited by anti-MHC-class I monoclonal antibody. The CTL thus induced by IL-12 had a higher proportion of CD3+ /CD56+ cells than the CTL induced with IL-2 alone. The positively selected CD8+ /CD56– lymphocytes showed PC-9-specific cytotoxic activity, because the population did not show any cytotoxicity to K562 or A549 (HLA-A26/A30). However, the CD3+ /CD56+ lymphocytes were cytotoxic to both PC-9 and K562. In conclusion, IL-12 is considered to be a useful cytokine for both the induction of lung-cancer specific CTL and the augmentation of non-MHC-restricted cytotoxicity against tumor cells, and may be applicable for adoptive immunotherapy using CTL. 相似文献
8.
Hisashi Nagahara Koshi Mimori Mitsuhiko Ohta Tohru Utsunomiya Hiroshi Inoue Graham F Barnard Masaichi Ohira Kosei Hirakawa Masaki Mori 《Clinical cancer research》2005,11(4):1368-1371
PURPOSE: Somatic mutations of the epidermal growth factor receptor (EGFR) gene may predict the sensitivity of non-small cell lung carcinoma to gefitinib. However, no mutations have been reported for colorectal carcinoma. We therefore analyzed EGFR mutations in colorectal adenocarcinomas by the combined use of laser microdissection and sequencing of genomic DNA. EXPERIMENTAL DESIGN: We examined 11 representative colorectal adenocarcinoma cell lines and 33 clinical samples of colorectal carcinoma. In the clinical cases, we carefully dissected only carcinoma cells from frozen sections by laser microdissection. After DNA extraction and PCR, we examined EGFR mutations by sequencing genomic DNA. RESULTS: None of 11 colorectal carcinoma cell lines exhibited somatic mutations, but 4 of 33 clinical tumors (12%) exhibited mutations in the EGFR kinase domain. This may be the first report of somatic mutations in colorectal adenocarcinoma. CONCLUSIONS: Our findings suggest that a distinct minority of colorectal adenocarcinomas exhibit somatic mutations of EGFR, and these tumors may be susceptible to gefitinib treatment. 相似文献
9.
Yoshika Nagata Takeshi Hanagiri Mitsuhiro Takenoyama Takashi Fukuyama Makiko Mizukami Tetsuya So Yoshinobu Ichiki Masakazu Sugaya Kenji Sugio Kosei Yasumoto 《Clinical cancer research》2005,11(14):5265-5272
PURPOSE: A large number of tumor-associated antigens have been used in vaccination trials for mainly melanomas. Our purpose of this study is to identify a novel tumor antigen useful for immunotherapy of lung cancer patients. EXPERIMENTAL DESIGN: Analysis of an autologous tumor-specific CTL clone F2a that was established from regional lymph node lymphocytes of a patient with lung cancer (A904) by a mixed lymphocyte-tumor cell culture. RESULTS: F2a recognized and killed autologous tumor cells (A904L), whereas it did not respond to autologous EBV-transformed B cells, phytohemagglutinin-blastoid T cells, and K562 cells. cDNA clone 31.2 was isolated by using cDNA expression cloning method as a gene encoding antigen. This gene was identical to the reported gene whose function was unknown. The antigen encoded by the cDNA was recognized by the CTL in a HLA-Cw*0702-restricted manner. Furthermore, a 9-mer peptide at positions 659 to 685 in cDNA clone 31.2 was identified as a novel epitope peptide. The CTL recognized some allogeneic cancer cell lines with HLA-Cw*0702 as well as some HLA-Cw*0702-negative cell lines when transfected with HLA-Cw*0702, thus indicating that the identified antigen was a cross-reactive antigen. CONCLUSIONS: Although exact mechanism to process the encoded protein and present the antigen in the context of HLA class I remains to be elucidated, the CTL recognized some of tumor cells in the context of HLA-Cw*0702 but did not recognize a variety of normal cells and also autologous EBV-transformed B cells. These results indicated that the antigen identified in this study may therefore be a possible target of tumor-specific immunotherapy for lung cancer patients. 相似文献
10.
Kan Yonemori Yasutoshi Kuboki Kosei Hasegawa Takashi Iwata Hidenori Kato Kazuhiro Takehara Yasuyuki Hirashima Hisamori Kato Chaitali Passey Jeppe Klint Buchbjerg Jeffrey R. Harris Camilla
Mondrup Andreassen Leonardo Nicacio Ibrahima Soumaoro Keiichi Fujiwara 《Cancer science》2022,113(8):2788
New treatments, particularly second‐line options, are needed to improve outcomes for patients with recurrent/metastatic cervical cancer (r/mCC). Tisotumab vedotin (TV) is an antibody–drug conjugate directed to tissue factor, a transmembrane protein commonly expressed in cancer cells, to deliver cytotoxic monomethyl auristatin E. This single‐arm, open‐label phase 1/2 trial evaluated the consistency of safety and efficacy outcomes of TV in Japanese patients with r/mCC to bridge the current findings with those reported in previous trials in non‐Japanese patients in the United States and Europe. In part 1 (dose escalation; N = 6), patients with advanced solid tumors received TV 1.5 or 2.0 mg/kg once every 3 weeks to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Part 2 (dose expansion; N = 17) evaluated the RP2D in r/mCC patients with 1–2 prior lines of therapy. In part 1, no dose‐limiting toxicities were observed, the MTD was not reached, and TV 2.0 mg/kg was established as the RP2D. In part 2, the most common treatment‐emergent adverse events were anemia (58.8%), nausea (58.8%), alopecia (47.1%), epistaxis (47.1%), and diarrhea (35.3%); adverse events of special interest were bleeding (76.5%), ocular events (35.3%), and peripheral neuropathy (17.6%), and were mostly grade 1/2. In part 2, confirmed objective response rate was 29.4%, median duration of response was 7.1 months, and median time to response was 1.2 months. In Japanese patients with r/mCC, TV demonstrated a manageable and tolerable safety, pharmacokinetics, and efficacy profile consistent with that observed in non‐Japanese patients. 相似文献