Purpose: Circulating tumor DNA (ctDNA) is an attractive source for liquid biopsy to understand molecular phenotypes of a tumor non-invasively, which is also expected to be both a diagnostic and prognostic marker. PIK3CA and KRAS are among the most frequently mutated genes in epithelial ovarian cancer (EOC). In addition, their hotspot mutations have already been identified and are ready for a highly sensitive analysis. Our aim is to clarify the significance of PIK3CA and KRAS mutations in the plasma of EOC patients as tumor-informed ctDNA. Methods: We screened 306 patients with ovarian tumors for somatic PIK3CA or KRAS mutations. A total of 85 EOC patients had somatic PIK3CA and/or KRAS mutations, and the corresponding mutations were subsequently analyzed using a droplet digital polymerase chain reaction in their plasma. Results: The detection rates for ctDNA were 27% in EOC patients. Advanced stage and positive peritoneal cytology were associated with higher frequency of ctDNA detection. Preoperative ctDNA detection was found to be an indicator of outcomes, and multivariate analysis revealed that ctDNA remained an independent risk factor for recurrence (p=0.010). Moreover, we assessed the mutation frequency in matched plasma before surgery and at recurrence from 17 patients, and found six patients had higher mutation rates in cell-free DNA at recurrence compared to that at primary diagnosis. Conclusion The presence of ctDNA at diagnosis was an indicator for recurrence, which suggests potential tumor spread even when tumors were localized at the time of diagnosis.

Objective: Maternal embryonic leucine zipper kinase (MELK) is receiving an attention as a therapeutic target in various types of cancers. In this study, we aimed to evaluate the prognostic significance of MELK expression in ovarian cancer using clinical samples, and assessed the efficacy of a small molecule MELK inhibitor, OTS167, using patient-derived ovarian cancer cells as well as cell lines. Methods: Expression levels of MELK in 11 ovarian cancer cell lines were confirmed by western blotting. Inhibitory concentration of OTS167 was determined by colorimetric assay.MELK messenger RNA (mRNA) expression was evaluated in 228 ovarian cancer patients by quantitative polymerase chain reaction. Growth inhibition of OTS167 was also evaluated using freshly-isolated primary ovarian cancer cells including spheroid formation condition. Results: MELK mRNA expression was significantly higher in ovarian cancer than in normal ovaries (p<0.001), and high MELK mRNA expression was observed in patients with advanced stage, positive ascites cytology and residual tumor size. Patients with high MELK mRNA expression showed shorter progression-free survival (p=0.001). Expression of MELK was also confirmed in 10 of 11 ovarian cancer cell lines tested, and the half maximal inhibitory concentration of MELK inhibitor, OTS167, ranged from 9.3 to 60 nM. Additionally, OTS167 showed significant growth inhibitory effect against patient-derived ovarian cancer cells, regardless of their tumor locations, histologic subtypes and stages. Conclusions We demonstrated MELK as both a prognostic marker and a therapeutic target for ovarian cancer using clinical ovarian cancer samples. MELK inhibition by OTS167 may be an effective approach to treat ovarian cancer patients.

Objective：The purpose of this study was to evaluate the effectiveness of a four-week short-term intensive rehabilitation on ataxia in patients with ambulatory spinocerebellar degeneration (SCD), using the Scale for the Assessment and Rating of Ataxia (SARA) total score and sub-score.Methods：This study included 23 SCD patients；we considered those with a SARA gait score of＜3 points. Our program included a one-hour training session with individualized instructions and a one-hour self-balance training session. Additionally, occupational or speech-language-hearing therapy was performed for one hour daily. Our program was conducted five days weekly for four weeks. We assessed the SARA total score and sub-score findings immediately, before the first and after the last interventions.Results：The SARA total, gait, stance, and heel-shin scores showed more significant improvement after intervention than before intervention (p＜0.05). The other SARA sub-scores were not significantly different between “before and after” interventions.Conclusion：The four-week short-term intensive rehabilitation on ataxia in patients with ambulatory spinocerebellar degeneration improved the SARA total score and ataxia of the trunk and lower limbs.

Objective：The purpose of this study was to evaluate the effectiveness of a four-week short-term intensive rehabilitation on ataxia in patients with ambulatory spinocerebellar degeneration (SCD), using the Scale for the Assessment and Rating of Ataxia (SARA) total score and sub-score.Methods：This study included 23 SCD patients；we considered those with a SARA gait score of＜3 points. Our program included a one-hour training session with individualized instructions and a one-hour self-balance training session. Additionally, occupational or speech-language-hearing therapy was performed for one hour daily. Our program was conducted five days weekly for four weeks. We assessed the SARA total score and sub-score findings immediately, before the first and after the last interventions.Results：The SARA total, gait, stance, and heel-shin scores showed more significant improvement after intervention than before intervention (p＜0.05). The other SARA sub-scores were not significantly different between “before and after” interventions.Conclusion：The four-week short-term intensive rehabilitation on ataxia in patients with ambulatory spinocerebellar degeneration improved the SARA total score and ataxia of the trunk and lower limbs.

A 70-year-old man with continuous diarrhea for over 1 month consulted a primary care doctor. He was treated with oral antibiotics and probiotics but his condition worsened. He developed generalized edema and was referred to our hospital. Abdominal ultrasound and computed tomography (CT) scan findings were suggestive of colon cancer with accompanying liver metastasis. Total colonoscopy and endoscopy for pathological diagnosis led to a diagnosis of cancer of the sigmoid colon accompanied with liver metastasis or liver abscess. We planned to perform sigmoidectomy with simultaneous resection of the liver lesion. However, we considered that he was not particularly fit to undergo two concurrent surgeries. Therefore, based on his physical condition, we planned to first do a sigmoidectomy. Before surgery, the fever persisted and a repeat CT scan showed deterioration of the liver lesion. We diagnosed the liver lesion as abscess and performed percutaneous transhepatic abscess drainage (PTAD). Three days after PTAD, we then performed sigmoidectomy. Subsequently, the liver abscess resolved and gradually disappeared. At 5 years after surgery, there has been no recurrence of the cancer or abscess.

As a serine hydrolase, monoacylglycerol lipase (MAGL) is principally responsible for the metabolism of 2-arachidonoylglycerol (2-AG) in the central nervous system (CNS), leading to the formation of arachidonic acid (AA). Dysfunction of MAGL has been associated with multiple CNS disorders and symptoms, including neuroinflammation, cognitive impairment, epileptogenesis, nociception and neurodegenerative diseases. Inhibition of MAGL provides a promising therapeutic direction for the treatment of these conditions, and a MAGL positron emission tomography (PET) probe would greatly facilitate preclinical and clinical development of MAGL inhibitors. Herein, we design and synthesize a small library of fluoropyridyl-containing MAGL inhibitor candidates. Pharmacological evaluation of these candidates by activity-based protein profiling identified