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Molecular genetic analysis of organogenesis in vitro with temperature-sensitive mutants
Munetaka Sugiyama 한국식물생명공학회 2014 Plant biotechnology reports Vol.8 No.1
About 20 years ago, molecular genetic analysis of tissue culture responses with temperature-sensitive mutants of Arabidopsis was launched in the laboratory of Prof. Atsushi Komamine as a new approach to mechanisms of plant organogenesis in vitro. In this and later studies, many interesting mutants were isolated and characterized, which led to the identification of unexpected genes as important players involved in organogenesis in vitro. The present article provides an overview of the outcomes from thesemolecular genetic studies derived from Komamine’s work.
Munetaka Takekuma 대한부인종양학회 2024 Journal of Gynecologic Oncology Vol.35 No.2
Cer vical cancer represents a global public health issue, particularly burdening many low-incomeand middle-income countries. Effective inter ventions, such as vaccination against thehuman papillomavirus and screening, render cer vical cancer a preventable disease [1]. By implementing these inter ventions, the incidence of cer vical cancer can be reduced,simultaneously enhancing the quality of life for cancer sur vivors, particularly those in theearly stages. Currently, the standard treatment for cer vical cancer is surger y with radicalhysterectomy (RH), which can lead to complications such as urinar y incontinence. The SHAPE trial results have been published in the New England Journal of Medicine [2], generatingenthusiasm among patients with early-stage cer vical cancer and gynecologic oncologists. The trial demonstrated that less invasive surger y is non-inferior to standard surger y for low-riskpatients. The trial results demonstrate that a lot of patients with early-stage cer vical cancer cansur vive with a good quality of life in clinical practice. However, I am composing this articledue to certain concerns regarding this trial. First, there are concerns related to the quality assurance of the surgical procedures. This trial excels in terms of external validity, specifically in terms of study generalization. However, doubts arise when considering whether the trial was conducted with adequateinternal validity. A crucial issue related to this trial is the quality assurance of the trial inter vention, i.e.,surgical therapy. To what extent was quality assurance implemented for RH or surgicaltherapy? Upon reviewing the trial results, in the RH group, there were 9 cases (2.7%) withpositive vaginal margins, which is higher than the expected occurrence rate. The studyincluded low-risk patients alone based on preoperative assessment. Considering thefrequency of positive vaginal margins when performing RH on the eligible trial participants,questions arise regarding the quality assurance of surgical therapy. For quality assurance,an audit of surgical therapy is crucial, and central review through photographs (or videos)should be considered mandator y. In particular, did the trial manager ensure that thecomponents deemed essential for RH, as outlined in the trial protocol, were appropriatelyperformed in the standard treatment group? According to the protocol, the followingprocedures are specified for RH: the en block removal of the uterus, cer vix, medial one-thirdof parametria, 2 cm of the uterosacral ligaments, and upper 1–2 cm of the vagina, the ligationof uterine arteries lateral to the ureters, and the unroofing of ureters from the ureterovesical junction. If these techniques were not adequately conducted, the trial could not evaluate itsoriginal research question, which means the trial may inadvertently compare “hysterectomy-mimicked RH” to simple hysterectomy. In the SHAPE trial, only photographic images of thesurgical specimen were requested for quality assurance [2], which may not be sufficient. Considering these factors, although the external validity is somewhat lacking, it might havebeen prudent to conduct the trial by limiting participating facilities and surgeons to enhancethe internal validity. Secondly, there are concerns about the primar y endpoint and non-inferiority margin. The primar y endpoint was changed from pelvic relapse-free sur vival to pelvic recurrence rateat 3 years (PRR3) due to the ver y low event rate. However, the choice of the primar y endpointas PRR3 raises concerns. Can we assert the establishment of surrogacy for the essentialultimate goal of cancer treatment, i.e., overall sur vival, based on PRR3? It is questionablewhether sufficient obser vation has been conducted for cases with an obser vation period<3 years. Furthermore, the outcomes may var y depending on the number of patients lostwithin the 3-year period and how they were labeled in the process of analysis. Additionall...
Munetaka Takekuma,Shiho Kuji,Aki Tanaka,Nobutaka Takahashi,Masakazu Abe,Yasuyuki Hirashima 대한부인종양학회 2015 Journal of Gynecologic Oncology Vol.26 No.3
Objective: The concept of platinum sensitivity and cross-resistance among platinum agents are widely known in the management of recurrent ovarian cancer. The aim of this study was to evaluate two hypotheses regarding the validity of the concept of platinum sensitivity and non-cross-resistance of cisplatin analogue with cisplatin in recurrent cervical cancer. Methods: In this retrospective study, the clinical data of patients with recurrent cervical cancer, who had a history of receiving cisplatin based chemotherapy (including concurrent chemoradiotherapy [CCRT] with cisplatin) and who received second-line chemotherapy at the time of recurrence between April 2004 and July 2012 were reviewed. Results: In total, 49 patients―34 squamous cell carcinomas (69.4%) and 15 non-squamous cell carcinomas (30.6%)―were enrolled. The median age was 53 years (range, 26 to 79 years). Univariate and multivariate analysis showed that a platinum free interval (PFI) of 12 months has a strong relationship with the response rate to second-line chemotherapy. Upon multivariate analysis of survival after second-line platinum-based chemotherapy, a PFI of 12 months significantly influenced both progression-free survival (hazard ratio [HR], 0.349; 95% confidence interval [CI], 0.140 to 0.871; p=0.024) and overall survival (HR, 0.322; 95% CI, 0.123 to 0.842; p=0.021). In patients with a PFI of less than 6 months, the difference of progression-free survival between patients with re-administration of cisplatin (3.0 months) and administration of cisplatin analogue (7.2 months) as second-line chemotherapy was statistically significant (p=0.049, log-rank test). Conclusion: The concept of platinum sensitivity could be applied to recurrent cervical cancer and there is a possibility of noncross- resistance of cisplatin analogue with cisplatin.
Yawara Eguchi,Munetaka Suzuki,Hajime Yamanaka,Hiroshi Tamai,Tatsuya Kobayashi,Sumihisa Orita,Kazuyo Yamauchi,Miyako Suzuki,Kazuhide Inage,Kazuki Fujimoto,Hirohito Kanamoto,Koki Abe,Masaki Norimoto,Tom 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.3
Study Design: Retrospective observational study. Purpose: We considered the relationship between spinal alignment and skeletal muscle mass on clinical outcomes following a surgery for lumbar spinal stenosis (LSS). Overview of Literature: There are no reports of preoperative factors predicting residual low back pain following surgery for LSS. Methods: Our target population included 34 women (mean age, 74.4 years) who underwent surgery for LSS. Prior to and 6 months after the surgery, systemic bone mineral density and lean soft tissue mass were measured using dual-energy X-ray absorptiometry. Skeletal muscle mass index (SMI) was calculated as the sum of the arm and leg lean mass in kilograms divided by height in meters squared. The spinal alignment was also measured. Clinical outcomes were evaluated using the Japanese Orthopedic Association scoring system, leg and low back pain Visual Analog Scale, and Roland–Morris Disability Questionnaire (RDQ). Additionally, we examined the bone mineral density, skeletal muscle mass, and spinal alignment before and after the surgery. We used the Spearman correlation coefficient to examine the associations among clinical outcomes, preoperative muscle mass, and spinal alignment. Results: Sarcopenia (SMI <5.46) was observed in nine subjects (26.5%). Compared with normal subjects (SMI >6.12), RDQ was significantly higher in subjects with sarcopenia (p =0.04). RDQ was significantly negatively correlated with SMI (r =−0.42, p <0.05). There was a significant positive correlation between postoperative RDQ and pelvic tilt (PT; r =0.41, p <0.05). SMI and PT were significantly negatively correlated (r =−0.39, r <0.05). Conclusions: Good postoperative outcomes were negatively correlated with low preoperative appendicular muscle mass, suggesting that postoperative outcomes were inferior in cases of decreased appendicular muscle mass (sarcopenia). Posterior PT due to decreased limb muscle mass may contribute to postoperative back pain, showing that preoperatively reduced limb muscle mass and posterior PT are predictive factors in the persistence of postoperative low back pain.