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1.
A series of A-ring pyrrole compounds of duocarmycin bearing 4'-methoxy-beta-heteroarylacryloyl groups were synthesized and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. Most of the 4'-methoxy-beta-heteroarylacrylates displayed in vitro anticellular activity equivalent to that of 4'-methoxycinnamates. Among the 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxy-beta-heteroarylacrylates, compound 15b having a (4-methoxy-3,5-pyrimidinyl)acryloyl as segment-B (Seg-B) showed remarkably potent in vivo antitumor activity and low peripheral blood toxicity compared with the A-ring pyrrole derivatives having the trimethoxyindole skeleton in Seg-B, which were equal to 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxycinnamates. Moreover, these 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxy-beta-heteroarylacrylates had high aqueous solubility. 相似文献
2.
Functional connectivity between amygdala and facial regions involved in recognition of facial threat
Motohide Miyahara Tokiko Harada Ted Ruffman Norihiro Sadato Tetsuya Iidaka 《Social cognitive and affective neuroscience》2013,8(2):181-189
The recognition of threatening faces is important for making social judgments. For example, threatening facial features of defendants could affect the decisions of jurors during a trial. Previous neuroimaging studies using faces of members of the general public have identified a pivotal role of the amygdala in perceiving threat. This functional magnetic resonance imaging study used face photographs of male prisoners who had been convicted of first-degree murder (MUR) as threatening facial stimuli. We compared the subjective ratings of MUR faces with those of control (CON) faces and examined how they were related to brain activation, particularly, the modulation of the functional connectivity between the amygdala and other brain regions. The MUR faces were perceived to be more threatening than the CON faces. The bilateral amygdala was shown to respond to both MUR and CON faces, but subtraction analysis revealed no significant difference between the two. Functional connectivity analysis indicated that the extent of connectivity between the left amygdala and the face-related regions (i.e. the superior temporal sulcus, inferior temporal gyrus and fusiform gyrus) was correlated with the subjective threat rating for the faces. We have demonstrated that the functional connectivity is modulated by vigilance for threatening facial features. 相似文献
3.
4.
Junji Kato Yoshihiro Mogi Yutaka Kohgo Rishu Takimoto Masayoshi Kobune Hiroyuki Hisai Tokiko Nakamura Kohichi Takada Yoshiro Niitsu 《Journal of gastroenterology》1998,33(6):855-859
Blood levels of inflammatory-related cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, are
elevated in patients with alcoholic liver diseases. We investigated the effects of these cytokines and ethanol on the expression
of hepatic asialoglycoprotein receptors (AGPRs) in a human hepatoblastoma cell line, HepG2. An [125I]-asialo-orosomucoid binding assay showed significant increases in surface AGPR numbers in HepG2 cells by treatment with
IL-1β, IL-6, and TNF-α, to levels which were approximately 130% of the values in untreated control cells. However, the enhanced
AGPR numbers induced by treatment with these cytokines were markedly suppressed, to 70%–80% of the number in the untreated
cells, by treatment with ethanol. Immunological detection of AGPR with a specific antibody demonstrated that the modulation
of surface AGPR numbers was correlated with the cellular expression levels of AGPR. These results suggest that, although IL-1β,
IL-6, and TNF-α stimulate the synthesis of hepatic AGPR, ethanol suppresses the expression of AGPR augmented by these cytokines.
This leads to an increase in serum asialo-orosomucoid levels caused by the disordered catabolism mediated by AGPR in patients
with alcoholic liver disease.
(Received Dec. 5, 1997; accepted May 22, 1998) 相似文献
5.
Ooi J Iseki T Takahashi S Tomonari A Nagayama H Ishii K Ito K Sato H Takahashi T Shindo M Sekine R Ohno N Uchimaru K Nagamura F Shirafuji N Tojo A Tani K Asano S 《British journal of haematology》2002,118(1):140-143
We performed a clinical comparison of unrelated cord blood transplantation (UCBT) and unrelated bone marrow transplantation in adult acute leukaemia patients in complete remission (CR) who received the same conditioning regimen, graft-versus-host disease (GvHD) prophylaxis and supportive treatment. The incidence of acute GvHD was almost the same between the two groups, but the haematopoietic recovery was delayed and the incidence of chronic GvHD was higher in the UCBT group. The probability of 2 year disease-free survival was similar between the two groups. These results suggest that adult acute leukaemia patients in CR without a suitable donor should be considered as candidates for UCBT. 相似文献
6.
Takahiro Niimi Tokiko Nakai Keiju Aokage Kenta Tane Tomohiro Miyoshi Joji Samejima Saori Miyazaki Tetsuro Taki Naoya Sakamoto Shingo Sakashita Reiko Watanabe Motohiro Kojima Kenji Suzuki Masahiro Tsuboi Genichiro Ishii 《Cancer science》2022,113(4):1497
Extratumoral lymphatic permeation (ly‐ext) has been reported as an independent poor prognostic factor for lung adenocarcinoma, but whether or not the number of ly‐ext foci is associated with prognosis and its relationship to the immune microenvironment is unclear. We counted the number of ly‐ext foci on pathological slides from patients with completely resected lung adenocarcinoma with ly‐ext, and divided them into two groups: a group with a high number of ly‐ext foci (ly‐ext high) and one with a low number of ly‐ext foci (ly‐ext low). Among the patients with ly‐ext, only a high number of ly‐ext foci was an independent poor prognostic factor. The 3‐year recurrence‐free survival (RFS) rate of the ly‐ext high group was significantly lower than that of the ly‐ext low group (14.7% vs. 50.0%, P < 0.01). Then, we analyzed the immune microenvironment of pT1 lung adenocarcinoma with ly‐ext (13 cases of ly‐ext high and 11 cases of ly‐ext low tumor) by immunohistochemistry using antibodies for stem cell markers (aldehyde dehydrogenase 1 A1 and CD44), tumor‐promoting mucin (MUC1), tumor‐infiltrating lymphocytes (CD4, CD8, FOXP3, and CD79a), and tumor‐associated macrophages (CD204). The number of CD8+ TILs within the primary lesion was significantly lower and the number of FOXP3+ TILs within the primary lesion was significantly higher in the ly‐ext high group (P < 0.05 and P < 0.01, respectively). Our results indicated that a high number of ly‐ext foci was an independent poor prognostic factor. Moreover, tumors with high numbers of ly‐ext foci had a more immunosuppressive microenvironment. 相似文献
7.
CD19-targeting liposomes containing imatinib efficiently kill Philadelphia chromosome-positive acute lymphoblastic leukemia cells 总被引:2,自引:0,他引:2
Harata M Soda Y Tani K Ooi J Takizawa T Chen M Bai Y Izawa K Kobayashi S Tomonari A Nagamura F Takahashi S Uchimaru K Iseki T Tsuji T Takahashi TA Sugita K Nakazawa S Tojo A Maruyama K Asano S 《Blood》2004,104(5):1442-1449
Patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) have poor prognosis despite intensive therapeutic intervention. Recently, imatinib, a BCR-ABL tyrosine kinase inhibitor, has been proven to be an effective treatment for Ph(+) ALL, but nearly all patients rapidly acquire resistance. High-dose imatinib administration might overcome this resistance; however, systemic toxicities would likely limit this approach. Therefore, a new delivery system allowing for the specific targeting of imatinib is urgently needed. Because almost all Ph(+) ALL cells express CD19 on their surface, we have developed an immunoliposome carrying anti-CD19 antibody (CD19-liposomes). The internalization efficiency of the CD19-liposomes approached 100% in all Ph(+) ALL cells but was very low in CD19(-) cells. The cytocidal effect of imatinib-encapsulated CD19-liposomes (imatinib-CD19-liposomes) on Ph(+) ALL cell lines and primary leukemia cells from patients with Ph(+) ALL was much greater than that of imatinib with or without control liposomes. Importantly, the imatinib-CD19-liposomes did not affect the colony formation of CD34(+) hematopoietic cells, even at inhibitory concentration of free imatinib. Taken together, these data clearly demonstrate that the imatinib-CD19-liposomes induced specific and efficient death of Ph(+) ALL cells. This new therapeutic approach might be a useful treatment for Ph(+) ALL with fewer side effects than free imatinib. 相似文献
8.
Ooi J Takahashi S Tomonari A Tsukada N Konuma T Kato S Kasahara S Sato A Monma F Nagamura F Iseki T Tojo A Asano S 《Bone marrow transplantation》2009,43(6):455-459
We analyzed the disease-specific outcomes of adult ALL treated with cord blood transplantation (CBT) after myeloablative conditioning. Between October 2000 and November 2007, 27 adult patients with ALL were treated with unrelated CBT. All patients received four fractionated 12 Gy TBI and chemotherapy as myeloablative conditioning. The median age was 36 years, the median weight was 57 kg and the median number of nucleated cells was 2.47 x 10(7)/kg. All patients received a single and HLA-mismatched cord blood unit. The cumulative incidence of neutrophil recovery at day 30 and platelet recovery at day 200 was 92.6 and 92.3%, respectively. With a median follow-up of 47 months, the probability of EFS at 5 years was 57.2%. The 5-year cumulative incidence of TRM and relapse was 3.7 and 27.4%, respectively. These results suggest that unrelated CBT after myeloablative conditioning could be safely and effectively used for adult patients with ALL. 相似文献
9.
Takaaki Konuma Satoshi Takahashi Jun Ooi Akira Tomonari Nobuhiro Tsukada Seiko Kato Aki Sato Fumihiko Monma Senji Kasahara Tokiko Nagamura-Inoue Kaoru Uchimaru Tohru Iseki Arinobu Tojo Takuhiro Yamaguchi Shigetaka Asano 《Annals of hematology》2009,88(6):581-588
Increasing recipient age is a well-known risk factor for graft-versus-host disease (GVHD) and treatment-related mortality
(TRM) and has a negative impact on allogeneic hematopoietic stem cell transplantation. Since the incidence of severe GVHD
after cord blood transplantation (CBT) is lower than that after transplants using bone marrow or mobilized peripheral blood
grafts from adult cells, we should expect better outcomes from CBT in older patients. To evaluate the feasibility and efficacy
of myeloablative unrelated CBT in patients aged between 50 and 55 years, we performed a retrospective comparison of 100 patients
with acute leukemia who received cord blood grafts at our institution. Nineteen older patients (median age, 52; range, 50–55)
and 81 younger patients (median, 36; range, 16–49) received a myeloablative conditioning regimen including 12 Gy of total
body irradiation and chemotherapy. GVHD prophylaxis included cyclosporine with (n = 96) or without (n = 4) methotrexate. There were no significant differences in the incidences of grades II to IV acute GVHD, extensive-type
chronic GVHD, TRM, and the probability of overall and disease-free survival between these groups. These results suggest that,
in patients with acute leukemia, myeloablative CBT might be as safe and effective in patients aged between 50 and 55 years
as in younger patients. 相似文献
10.
Yasuhiro Katsumata Masayoshi Harigai Yasushi Kawaguchi Chikako Fukasawa Makoto Soejima Tokiko Kanno Katsuji Nishimura Takayuki Yamada Hisashi Yamanaka Masako Hara 《BMC musculoskeletal disorders》2010,11(1):13