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1.
2.
Tetsuji Terazawa Takeshi Kato Masahiro Goto Katsuya Ohta Shingo Noura Hironaga Satake Yoshinori Kagawa Hisato Kawakami Hiroko Hasegawa Kazuhiro Yanagihara Tatsushi Shingai Ken Nakata Masahito Kotaka Masayuki Hiraki Ken Konishi Shiro Nakae Daisuke Sakai Yukinori Kurokawa Toshio Shimokawa Taroh Satoh 《The oncologist》2021,26(1):17-e47
Lessons Learned
- Panitumumab monotherapy showed favorable efficacy and feasibility in the treatment of frail or elderly patients with RAS wild‐type unresectable colorectal cancer.
- It is especially effective for left‐sided tumors; therefore, panitumumab as first‐line treatment could be an additional therapeutic option for frail elderly patients, particularly in those who are unsuitable for upfront oxaliplatin‐based or irinotecan‐based combination regimens.
3.
Comparison of cerebral activation between motor execution and motor imagery of self-feeding activity
Moemi Matsuo Naoki Iso Kengo Fujiwara Takefumi Moriuchi Daiki Matsuda Wataru Mitsunaga Akira Nakashima Toshio Higashi 《中国神经再生研究》2021,16(4):778
Motor imagery is defined as an act wherein an individual contemplates a mental action of motor execution without apparent action. Mental practice executed by repetitive motor imagery can improve motor performance without simultaneous sensory input or overt output. We aimed to investigate cerebral hemodynamics during motor imagery and motor execution of a self-feeding activity using chopsticks. This study included 21 healthy right-handed volunteers. The self-feeding activity task comprised either motor imagery or motor execution of eating sliced cucumber pickles with chopsticks to examine eight regions of interest: pre-supplementary motor area, supplementary motor area, bilateral prefrontal cortex, premotor area, and sensorimotor cortex. The mean oxyhemoglobin levels were detected using near-infrared spectroscopy to reflect cerebral activation. The mean oxyhemoglobin levels during motor execution were significantly higher in the left sensorimotor cortex than in the supplementary motor area and the left premotor area. Moreover, significantly higher oxyhemoglobin levels were detected in the supplementary motor area and the left premotor area during motor imagery, compared to motor execution. Supplementary motor area and premotor area had important roles in the motor imagery of self-feeding activity. Moreover, the activation levels of the supplementary motor area and the premotor area during motor execution and motor imagery are likely affected by intentional cognitive processes. Levels of cerebral activation differed in some areas during motor execution and motor imagery of a self-feeding activity. This study was approved by the Ethical Review Committee of Nagasaki University(approval No. 18110801) on December 10, 2018. 相似文献
4.
Hosokawa Shinobu Ichihara Eiki Harada Daijiro Kuyama Shoichi Inoue Koji Gemba Kenichi Ichikawa Hirohisa Kato Yuka Oda Naohiro Oze Isao Tamura Tomoki Kozuki Toshiyuki Umeno Takahiro Kubo Toshio Hotta Katsuyuki Bessho Akihiro Maeda Yoshinobu Kiura Katsuyuki 《International journal of clinical oncology / Japan Society of Clinical Oncology》2022,27(7):1139-1144
International Journal of Clinical Oncology - The role of pembrolizumab in the treatment of poor performance status (PS) patients remains unclear. We conducted a phase II trial to investigate the... 相似文献
5.
Masaki Sato Kei Inai Mikiko Shimizu Hisashi Sugiyama Toshio Nakanishi 《Congenital heart disease》2019,14(2):167-175
Objective: The recognition of fluid retention is critical in treating heart failure (HF).
Bioelectrical impedance analysis (BIA) is a well-known noninvasive method; however,
data on its role in managing patients with congenital heart disease (CHD) are limited.
Here, we aimed to clarify the correlation between BIA and HF severity as well as the
prognostic value of BIA in adult patients with CHD.
Design: This prospective single-center study included 170 patients with CHD admitted between 2013 and 2015. We evaluated BIA parameters (intra- and extracellular water, protein, and mineral levels, edema index [EI, extracellular water-to-total body water ratio]), laboratory values, and HF-related admission prevalence.
Results: Patients with New York Heart Association (NYHA) functional classes III-IV had a higher EI than those with NYHA classes I-II (mean ± SD, 0.398 ± 0.011 vs 0.384 ± 0.017, P < .001). EI was significantly correlated with brain natriuretic peptide level (r = 0.51, P < .001). During the mean follow-up period of 7.1 months, KaplanMeier analysis showed that a discharge EI > 0.386, the median value in the present study, was significantly associated with a future increased risk of HF-related admission (HR = 4.15, 95% CI = 1.70-11.58, P < .001). A body weight reduction during hospitalization was also related to EI reduction.
Conclusions: EI determined using BIA could be a useful marker for HF severity that could predict future HF-related admissions in adult patients with CHD. 相似文献
Design: This prospective single-center study included 170 patients with CHD admitted between 2013 and 2015. We evaluated BIA parameters (intra- and extracellular water, protein, and mineral levels, edema index [EI, extracellular water-to-total body water ratio]), laboratory values, and HF-related admission prevalence.
Results: Patients with New York Heart Association (NYHA) functional classes III-IV had a higher EI than those with NYHA classes I-II (mean ± SD, 0.398 ± 0.011 vs 0.384 ± 0.017, P < .001). EI was significantly correlated with brain natriuretic peptide level (r = 0.51, P < .001). During the mean follow-up period of 7.1 months, KaplanMeier analysis showed that a discharge EI > 0.386, the median value in the present study, was significantly associated with a future increased risk of HF-related admission (HR = 4.15, 95% CI = 1.70-11.58, P < .001). A body weight reduction during hospitalization was also related to EI reduction.
Conclusions: EI determined using BIA could be a useful marker for HF severity that could predict future HF-related admissions in adult patients with CHD. 相似文献
6.
Yasmine Abouleila Kaoru Onidani Ahmed Ali Hirokazu Shoji Takayuki Kawai Chwee Teck Lim Vipin Kumar Shinobu Okaya Ken Kato Eiso Hiyama Toshio Yanagida Tsutomu Masujima Yoshihiro Shimizu Kazufumi Honda 《Cancer science》2019,110(2):697-706
Recently, there has been increased attention on the analysis of circulating tumor cells (CTCs), also known as liquid biopsy, owing to its potential benefits in cancer diagnosis and treatment. Circulating tumor cells are released from primary tumor lesions into the blood stream and eventually metastasize to distant body organs. However, a major hurdle with CTC analysis is their natural scarcity. Existing methods lack sensitivity, specificity, or reproducibility required in CTC characterization and detection. Here, we report untargeted molecular profiling of single CTCs obtained from gastric cancer and colorectal cancer patients, using live single cell mass spectrometry integrated with microfluidics‐based cell enrichment techniques. Using this approach, we showed the difference in the metabolomic profile between CTCs originating from different cancer groups. Moreover, potential biomarkers were putatively annotated to be specific to each cancer type. 相似文献
7.
Yoshiaki Maru Kunishige Onuma Masako Ochiai Toshio Imai Yoshitaka Hippo 《Cancer science》2019,110(3):858-866
Inactivation of the Adenomatous polyposis coli (APC) gene is an initiating and the most relevant event in most sporadic cases of colorectal cancer, providing a rationale for using Apc‐mutant mice as the disease model. Whereas carcinogenesis has been observed only at the organism level, the recent development of the organoid culture technique has enabled long‐term propagation of intestinal stem cells in a physiological setting, raising the possibility that organoids could serve as an alternative platform for modeling colon carcinogenesis. Indeed, it is demonstrated in the present study that lentivirus‐based RNAi‐mediated knockdown of Apc in intestinal organoids gave rise to subcutaneous tumors upon inoculation in immunodeficient mice. Reconstitution of common genetic aberrations in organoids resulted in development of various lesions, ranging from aberrant crypt foci to full‐blown cancer, recapitulating multi‐step colorectal tumorigenesis. Due to its simplicity and utility, similar organoid‐based approaches have been applied to both murine and human cells in many investigations, to gain mechanistic insight into tumorigenesis, to validate putative tumor suppressor genes or oncogenes, and to establish preclinical models for drug discovery. In this review article, we provide a multifaceted overview of these types of approaches that will likely accelerate and advance research on colon cancer. 相似文献
8.
9.
Ayako Nakamura-Ishizu Keiyo Takubo Hiroshi Kobayashi Katsue Suzuki-Inoue Toshio Suda 《The Journal of experimental medicine》2015,212(12):2133-2146
Hematopoietic stem cells (HSCs) depend on the bone marrow (BM) niche for their maintenance, proliferation, and differentiation. The BM niche is composed of nonhematopoietic and mature hematopoietic cells, including megakaryocytes (Mks). Thrombopoietin (Thpo) is a crucial cytokine produced by BM niche cells. However, the cellular source of Thpo, upon which HSCs primarily depend, is unclear. Moreover, no specific molecular pathway for the regulation of Thpo production in the BM has been identified. Here, we demonstrate that the membrane protein C-type lectin-like receptor-2 (CLEC-2) mediates the production of Thpo and other factors in Mks. Mice conditionally deleted for CLEC-2 in Mks (Clec2MkΔ/Δ) produced lower levels of Thpo in Mks. CLEC-2–deficient Mks showed down-regulation of CLEC-2–related signaling molecules Syk, Lcp2, and Plcg2. Knockdown of these molecules in cultured Mks decreased expression of Thpo. Clec2MkΔ/Δ mice exhibited reduced BM HSC quiescence and repopulation potential, along with extramedullary hematopoiesis. The low level of Thpo production may account for the decline in HSC potential in Clec2MkΔ/Δ mice, as administration of recombinant Thpo to Clec2MkΔ/Δ mice restored stem cell potential. Our study identifies CLEC-2 signaling as a novel molecular mechanism mediating the production of Thpo and other factors for the maintenance of HSCs.Maintenance of hematopoietic stem cells (HSCs) within the adult BM is crucial for the healthy production of hematopoietic cells (Orkin and Zon, 2008). HSCs reside in a specialized microenvironment in the BM called the niche (Schofield, 1978). Along with cell-intrinsic programs, the niche influences the cell fate of HSCs, which in turn govern the homeostasis of the hematopoietic system (Nakamura-Ishizu et al., 2014a). The HSC niche is chiefly composed of nonhematopoietic cells, including immature osteoblasts (OBLs; Arai and Suda, 2007), endothelial cells (ECs; Butler et al., 2010; Ding et al., 2012), perivascular cells (Sugiyama et al., 2006; Ding et al., 2012), mesenchymal stem cells (MSCs; Méndez-Ferrer et al., 2010), sympathetic nervous cells (Katayama et al., 2006), adipocytes (Naveiras et al., 2009), and nonmyelinating Schwann cells (Yamazaki et al., 2011). Nonetheless, mature hematopoietic cells such as macrophages/monocytes (Chow et al., 2011), osteoclasts (Kollet et al., 2006), and regulatory T cells (Fujisaki et al., 2011) also regulate HSCs, albeit mainly in an indirect manner, through the modulation of nonhematopoietic niche cells. Recently, mature megakaryocytes (Mks) were described as hematopoietic progeny that directly regulate HSC quiescence (Heazlewood et al., 2013; Bruns et al., 2014; Zhao et al., 2014; Nakamura-Ishizu et al., 2014b); one of the mechanisms underlying Mk niche function is the production of the cytokine thrombopoietin (Thpo) by Mks themselves (Nakamura-Ishizu et al., 2014b). However, among the Mk-related niche factors reported to date, no molecular mechanism that is specific to Mks has been identified.Thpo is a crucial cytokine for both the maturation of Mks and the maintenance of quiescent HSCs (Zucker-Franklin and Kaushansky, 1996; Qian et al., 2007; Yoshihara et al., 2007). Thpo is produced in multiple organs, including the liver, kidney, spleen, and muscle (Nomura et al., 1997). Baseline production of serum Thpo is thought to be maintained by the liver and regulated in response to inflammatory stress or changes in glycosylation of aged platelets (Kaser et al., 2001; Stone et al., 2012; Grozovsky et al., 2015). Serum Thpo levels also fluctuate according to circulating platelet number: platelets sequester Thpo via the myeloproliferative leukemia virus oncogene (c-Mpl), the receptor for Thpo (Kuter and Rosenberg, 1995; de Graaf et al., 2010), thereby lowering Thpo levels. Thus, platelet number is not as tightly regulated by Thpo production as erythrocyte number is by erythropoietin production (Fandrey and Bunn, 1993). It is likely that BM HSCs depend on Thpo, which is produced in the BM by niche cells. Depletion of circulating platelets by neuraminidase does not affect HSCs (Bruns et al., 2014), indicating that serum Thpo up-regulation through thrombocytopenia does not affect HSC maintenance. Moreover, HSCs reside near bone-lining OBLs and mature Mks, which both support HSCs by producing Thpo (Yoshihara et al., 2007; Nakamura-Ishizu et al., 2014b). However, the main cellular source of Thpo, upon which BM HSCs depend, and the molecular signaling pathway that mediates BM Thpo production remain elusive.Recent studies showed that signals mediated through C-type lectin-like domain-containing receptors (CLEC-4H1 and CLEC-4H2; also known as Ashwell–Morell receptor) stimulate Thpo production in hepatocytes through recognition of desialylated platelets (Grozovsky et al., 2015). Platelets and Mks express CLEC-2 (Suzuki-Inoue et al., 2006, 2007), which is among the top 25 genes specifically expressed on Mks (Senis et al., 2007). Activation of platelet CLEC-2 through binding to sialylated podoplanin is essential for the segregation of lymphatic and blood vessels during development (Bertozzi et al., 2010; Suzuki-Inoue et al., 2010). CLEC-2–podoplanin signaling also functions in maintenance of lymphocyte- and dendritic cell–related responses in the stroma of lymph nodes (Acton et al., 2012, 2014; Herzog et al., 2013).The significance of CLEC-2 expression on Mks in BM hematopoiesis, and whether it is involved in Thpo production in Mks, has not been previously explored. Here, we demonstrate that Mk-specific deficiency of CLEC-2 disrupts HSC quiescence and alters HSC potential as a result of defective Mk niche function. Moreover, we demonstrate that CLEC-2 signaling is involved in various molecular pathways for production of niche factors, including Thpo in Mks. Through the identification of CLEC-2, a novel Mk-specific factor, our data elucidate the organ-dependent production and function of Thpo and reinforce the idea that Mks contribute to a niche that regulates HSC quiescence. 相似文献
10.
Tamotsu Yabumoto Sohee Shin Tsuneo Watanabe Yusuke Watanabe Toru Naka Kazuo Oguri Toshio Matsuoka 《Journal of Physical Therapy Science》2015,27(9):3023-3025
[Purpose] Strength training is recommended for children with cerebral palsy. However, it
is difficult for moderately impaired children with cerebral palsy, who require crutches
for ambulation, to participate in this type of training. The purpose of this study was to
investigate whether whole-body vibration training is an effective method of strengthening
in a moderately impaired child with cerebral palsy. [Subject and Methods] This report
describes an 8-year-old Japanese boy with cerebral palsy, who was ambulatory with
crutches. The subject participated in physical therapy twice a week for 5 weeks.
Whole-body vibration training was selected to complement the standing practice. The
patient’s crutch-walking ability, gross motor function, and spasticity were evaluated.
[Results] The number of steps and walking duration were reduced in a 5-m walk test with
crutches and gross motor function was improved. Further, the spasticity was reduced.
[Conclusion] Whole-body vibration training is an effective physical therapy intervention
in moderately impaired children with cerebral palsy, who are unable to walk without
crutches.Key words: Cerebral palsy, Whole-body vibration, Walking ability 相似文献