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SummarySomatic cell reprogramming using the microRNAs miR200c, miR-302s, and miR-369s leads to increased expression of cyclin-dependent kinase inhibitors in human colorectal cancer (CRC) cells and suppressed tumor growth. Here, we investigated whether these microRNAs inhibit colorectal tumorigenesis in CPC;Apc mice, which are prone to colon and rectal polyps. Repeated administration of microRNAs inhibited polyp formation. Microarray analysis indicated that c-MAF, which reportedly shows oncogene-like behavior in multiple myeloma and T-cell lymphoma, decreased in tumor samples but increased in microRNA-treated normal mucosa. Immunohistochemistry identified downregulation of c-MAF as an early tumorigenesis event in CRC, with low c-MAF expression associated with poor prognosis. Of note, c-MAF expression and p53 protein levels were inversely correlated in CRC samples. c-MAF knockout led to enhanced tumor formation in azoxymethane/dextran sodium sulfate–treated mice, with activation of cancer-promoting genes. c-MAF may play a tumor-suppressive role in CRC development.

Fusobacterium nucleatum (Fn) is frequently found in colorectal cancers (CRCs). High loads of Fn DNA are detected in CRC tissues with microsatellite instability-high (MSI-H), or with the CpG island hypermethylation phenotype (CIMP). Fn infection is also associated with the inflammatory tumor microenvironment of CRC. A subtype of CRC exhibits inflammation-associated microsatellite alterations (IAMA), which are characterized by microsatellite instability-low (MSI-L) and/or an elevated level of microsatellite alterations at selected tetra-nucleotide repeats (EMAST). Here we describe two independent CRC cohorts in which heavy or moderate loads of Fn DNA are associated with MSI-H and L/E CRC respectively. We also show evidence that Fn produces factors that induce γ-H2AX, a hallmark of DNA double strand breaks (DSBs), in the infected cells.

Colorectal cancer (CRC) is the third most common cancer worldwide, and surgical treatment remains the first-line treatment to provide a cure. In addition to the aging population, obesity, low physical activity, and smoking habits increase CRC risk. Despite advances in surgical techniques, chemotherapy, and radiotherapy, colorectal cancer remains the second leading cause of cancer-related deaths worldwide. For early-stage CRC, endoscopic treatment, including endoscopic mucosal resection and endoscopic submucosal dissection, has been performed. However, lymph node dissection is an integral part of surgical treatment for advanced-stage cancer because of the high incidence of lymph node metastasis. Conventional open surgery has evolved into laparoscopic and robotic surgery. Although prospective studies have confirmed the safety and feasibility of laparoscopic surgery for CRC, relevant treatment models of transverse colon cancer and rectal cancer still need to be further explored and validated. Furthermore, multidisciplinary treatment is needed to cure CRC completely. This review aimed to provide an update on recent advances in the surgical treatment of CRC.

Background Hyponatremia and syndrome of inappropriate antidiuretic hormone (SIADH) is a potentially fatal adverse effect of antidepressants (ADs) and antipsychotics (APs), although its frequency and onset time have not been well documented. Objective To analyze the frequency and onset time of AD- or AP-induced hyponatremia/SIADH. Methods We used plural data-mining techniques to search the US Food and Drug Administration Adverse Event Reporting System (FAERS) database for reports on hyponatremia/SIADH induced by psychotropic drugs from January 2004 to June 2020. For each item, we assessed the reporting odds ratio, 95% CI, median onset time, and Weibull distribution parameters. Results We identified 36 422 reports related to hyponatremia/SIADH. Signals were detected for all psychotropic drugs that we analyzed, except for clozapine. The median onset time of total AD-induced hyponatremia/SIADH was shorter than that of AP. For all ADs and APs except clozapine, hazards were considered to be the early failure type. In contrast, the hazard of clozapine was considered to be the random failure type. The limitations of this study included several reporting biases and the presence of confounding variables, particularly age. Conclusion and Relevance Most ADs and APs were found to be associated with a risk for hyponatremia/SIADH. In addition, sufficient attention should be paid to signs of hyponatremia/SIADH in the early phase when most ADs and APs are administered. These data are potentially useful for determining AD- or AP-induced hyponatremia/SIADH in the early stage and for preventing its further aggravation into a serious condition.

Background: MiR-1291 has an anti-tumor effect in carcinoma of kidney, esophagus, pancreas, and prostate. However, it’s role in colorectal cancer (CRC) has not been elucidated.Methods: In this study, we explored the effect of miR-1291 in CRC cells (HCT116, DLD-1, and HT29) in vitro, and performed a tumor growth inhibitory assay in a mouse therapeutic model using DLD-1 cells. Flow cytometric analysis and Western blotting were performed to examine a role of miR-1291 in cell cycle regulation. We performed luciferase reporter assay to verify the interaction between DCLK1 and miR-1291 in HCT116 cells. Cancer stemness was evaluated by identifying the expression of BMI1 and CD133, as well as performing sphere formation assay. Results: We found that miR-1291 significantly suppressed the proliferation, invasion, cell mobility, and colony formation capability of CRC cell lines. MiR-1291 caused altered expression of the cell cycle-regulatory proteins, representatively CDK inhibitors p21WAF1/CIP1 and p27KIP1 or CDK4. Moreover, intravenous administration of miR-1291 loaded on the super carbonate apatite delivery system significantly inhibited a tumor growth in the DLD-1 xenograft mouse model. A luciferase reporter assay showed that miR-1291 directly bound the 3’ UTR sequence of DCLK1 and suppressed its expression at both the mRNA and protein levels in HCT116 expressing the DCLK1 protein. In addition, miR-1291 suppressed cancer stem cell (CSC) markers BMI1 and CD133 as well as sphere formation ability in HCT116 cells. Conclusions: Taken together, these findings indicate that miR-1291 has an anti-tumor effect by modulating multiple functions, including cell cycle, invasiveness, and cancer stemness. Our data suggest that miR-1291 could be a promising nucleic acid medicine against CRC.

Black Americans (BA) have higher incidence and higher mortality rates for colorectal cancers (CRC) as compared to White Americans (WA). While there are several identified risk factors associated with the development of CRC and evidence that high levels of adequate screening can reduce differences in incidence for CRC between BA and WA, there remains little data regarding patient co-morbid contributions towards survival once an individual has CRC. Here we set out to identify patient risk factors that influenced overall survival in a cohort of 293 BA and 348 WA with colon cancer. Amid our cohort, we found that patients' age, tobacco usage, and pre-diagnosed medical conditions such as hypertension and diabetes were associated with shorter overall survival (OS) from colon cancer. We identified pre-diagnosed hypertension and diabetes among BA were responsible for one-third of the colon cancer mortality disparity compared with WA. We also identified long-term regular use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, was associated with shorter OS from colon cancer among WA >65 years of age, but not younger WA patients or any aged BA patients. Our results raise the importance of not only treating the colon cancer itself, but also taking into consideration co-morbid medical conditions and NSAID usage to enhance patient OS. Further evaluation regarding adequate treatment of co-morbidities and timing of NSAID continuance after cancer therapy will need to be studied.

Background: Cancer stem cells (CSCs) are drug-tolerant and cause distant metastasis and recurrence in various cancers, including colorectal cancer (CRC). Thus, CSC-targeted therapy may be an effective curative approach in CRC. MiR-1291 has an anti-tumor effect in carcinoma of kidney, esophagus, pancreas, and prostate. However, there is no report about the effect of miR-1291 on CRC.Methods: In this study, we took CSC marker DCLK-1 as a target gene, and screened promising miRNAs that may suppress DCLK-1 by using TargetScan Human. We performed luciferase reporter assay, quantitative real-time PCR analysis, and Western blot analysis to verify the interaction between DCLK-1 and miR-1291 in CRC cells. We also confirmed the function of miR-1291 on cancer stemness by identifying the expression of Bmi1 and CD133 in CRC cells by quantitative real-time PCR analysis, Western blot analysis, and flow cytometric analysis, as well as performing sphere formation assay. We also explored the effect of miR-1291 on cell proliferation, invasion, and wound-healing, colony formation, and cell cycle regulation. Results: We found a 7-base seed sequence of miR-1291 that matches the 3’ UTR sequence of DCLK-1 using TargetScan Human. A luciferase reporter assay showed that miR-1291 directly bound the 3’ UTR sequence of DCLK-1 and suppressed its expression at both the mRNA and protein levels. In addition, miR-1291 suppressed CSC markers Bmi1 and CD133 as well as sphere formation ability in CRC cells. Moreover, miR-1291 significantly suppressed the proliferation, invasion, wound-healing, and colony formation capability of colon cancer cell lines. MiR-1291 caused altered expression of the cell cycle-regulatory proteins representatively, CDK inhibitors p21WAF1/CIP1 and p27KIP1. Conclusions: Taken together, these findings indicate that miR-1291 has an anti-tumor effect by modulating multiple functions, including, cancer stemness, cell cycle, and invasiveness. Our data suggest that miR-1291 could be a promising nucleic acid medicine against CRC.

Molecular hydrogen ameliorates pathological states in a variety of human diseases, animal models, and cell models, but the effects of hydrogen on cancer have been rarely reported. In addition, the molecular mechanisms underlying the effects of hydrogen remain mostly unelucidated. We found that hydrogen enhances proliferation of four out of seven human cancer cell lines (the responders). The proliferation-promoting effects were not correlated with basal levels of cellular reactive oxygen species. Expression profiling of the seven cells showed that the responders have higher gene expression of mitochondrial electron transport chain (ETC) molecules than the non-responders. In addition, the responders have higher mitochondrial mass, higher mitochondrial superoxide, higher mitochondrial membrane potential, and higher mitochondrial spare respiratory capacity than the non-responders. In the responders, hydrogen provoked mitochondrial unfolded protein response (mtUPR). Suppression of cell proliferation by rotenone, an inhibitor of mitochondrial ETC complex I, was rescued by hydrogen in the responders. Hydrogen triggers mtUPR and induces cell proliferation in cancer cells that have high basal and spare mitochondrial ETC activities.

A 54-year-old female patient was hospitalized with a chief complaint of anal discomfort. Based on biopsy results, she was diagnosed with highly differentiated adenocarcinoma, and colonoscopy findings indicated a type 3 rectal tumor. We observed a right pelvic kidney on enhanced abdominal CT. We began a laparoscopic operation but converted to an open operation after resecting the right pelvic renal artery by mistake. After low anterior resection, urologists performed angioplasty of the right renal pelvic artery. The patient was discharged on postoperative day 16, after the preservation of right renal function had been confirmed. This case strongly suggests that it is important to understand the positional relationship of the inferior mesenteric and renal arteries by preoperative assessment using either 3-D CT angiography or magnetic resonance angiography.

Sox2 is known as the undifferentiated cell marker. Recent studies have shown that Sox2 may also be involved in the maintenance of cancer stem cells (CSCs) in skin and bladder cancers. In this study, we aimed to clarify the role of Sox2 in colorectal CSCs. Sox2 expression was measured in colon cancer cells and colorectal clinical samples by qRT-PCR and western blot analysis. To visualize the active Sox2 mRNA production, we generated a Sox2 promoter-dependent DsRed fluorescence emission system. Colon cancer cell lines and colorectal tumor tissues generally expressed the Sox2 protein. Knockdown of Sox2 by siRNA led to increased proliferative activity in Caco2 cells. Kaplan-Meier survival curves showed that the group with high Sox2 mRNA expression had a worse prognosis for relapse-free survival (RFS) than the low expression group (P = 0.045, median follow-up 60.0 months). Time-lapse image analysis revealed that most DsRed+ cells exhibited typical asymmetric cell division and had higher CSC marker expressions. The DsRed+ cells exhibited chemoresistance and they grew slower in vitro, yet they established rather larger tumors in vivo. Our data suggest that Sox2 may be a potential biomarker for colorectal CSCs.

This paper deals with a dual decomposition-based distributed model predictive control (MPC) technique for power management of a microgrid with mass introduction of photovoltaic (PV) energy supplies. The PV power has large uncertainty because it depends on weather conditions. To keep stable power supply to the microgrid, both accurate prediction of PV power supplies and efficient energy management based on the prediction are essential. We propose a method for microgrid management by combining the dual decomposition-based MPC and the PV power prediction. The dual decomposition is a technique for solving an optimization problem in a distributed manner. We demonstrate the effectiveness of the proposed method by a numerical simulation.

A 54-year-old female patient was hospitalized with a chief complaint of anal discomfort. Based on biopsy results, she was diagnosed with highly differentiated adenocarcinoma, and colonoscopy findings indicated a type 3 rectal tumor. We observed a right pelvic kidney on enhanced abdominal CT. We began a laparoscopic operation but converted to an open operation after resecting the right pelvic renal artery by mistake. After low anterior resection, urologists performed angioplasty of the right renal pelvic artery. The patient was discharged on postoperative day 16, after the preservation of right renal function had been confirmed. This case strongly suggests that it is important to understand the positional relationship of the inferior mesenteric and renal arteries by preoperative assessment using either 3-D CT angiography or magnetic resonance angiography.

We report a case of human epidermal growth factor receptor 2 (HER2) -positive advanced gastric cancer effectively treated via capecitabine, cisplatin, and trastuzumab (XPT) chemotherapy followed by curative gastrectomy. The patient was a 66- year-old man with type 2 gastric cancer in the greater curvature of the gastric angle. Biopsy revealed that the tumor was a well or moderately differentiated adenocarcinoma, and immunohistochemistry showed positive expression of HER2(3+). Chest and abdominal computed tomography(CT)showed a liver tumor 21×9 mm in size in the caudate lobe and swollen lymph nodes in the paragastric, para-aortic, and left supraclavicular regions. After 4 courses of XPT, a clinical complete response was obtained. The patient received additional 13 courses of trastuzumab and capecitabine and underwent Billroth I distal gastrectomy with D2 lymph node dissection and resection of the para-aortic and left supraclavicular lymph nodes. Liver metastasis was not detected. No residual cancer cells were found in the stomach or lymph nodes except for the left supraclavicular lymph nodes. Pathological classification according to the Japanese Classification of Gastric Carcinoma, 14 th edition, was ypT0, ypN0, ypM1(LYM), Grade 2, ypStage IV. The patient developed a post-operative anastomotic leakage that required drainage via laparotomy, but was discharged 76 days after surgery in good condition.

王子製紙（株）日南工場（宮崎県日南市）は富士セロックスオフィスサプライ（株）と協力のもと，PPC用紙ダンボールケースのパレット積載工程に水溶性接着液吐出装置（以下ロッキンポップシステム）を開発し実用化した。このシステムの導入により，パレット輸送時の荷崩れと外装箱の汚れを防ぐため長年にわたり多用されてきたストレッチフイルムの使用量を半減し，廃棄処理にかかる顧客のコストを大幅に削減することが可能となった。ロッキンポップシステムは，段ボールケースの搬送ライン上でケース天面に無色透明の特殊な接着液を線状に定量塗布し，この状態で積載することによってケース天面と上段ケース底面の間が接着される仕組みとなっている。接着したケースはパレット搬送時に生じる横方向の力に対しては強靭な耐性を発揮する反面，垂直方向には剥離しやすく使用時には容易に取り外すことが可能であり，接着面の跡も残らないため外観を損なうことがない。またロッキンポップシステム本体はコンパクトに設計されており，ノズルの本数や位置を変更することにより各サイズの製品に対応できる。ロッキンポップシステムは王子製紙（株）日南工場のPPC用紙生産ラインで開発し03年4月より本稼動し，その後同社春日井工場に同年12月，王子特殊紙製紙江別工場には04年3月と順次展開している。今後はエンジニアリング部門である王子エンジニアリングを通じて当システムを王子グループのみならず同業他社に対しても積極的に普及し，PPC用紙業界の環境負荷軽減に貢献していきたいと考えている。

Mucoceles of the appendix are a group of mucus‑filled lesions causing obstructive dilation of the ileocecal appendix. We report a rare case of giant appendiceal mucocele. A 48‑year‑old woman with no discomfort was admitted to our hospital after a mass was det ected in the right lower quadrant of the abdomen. The patient underwent right hemicole ctomy on the basis of the clinical diagnosis of a possible appendiceal tumor. The final pathologic diagnosis was mucocele of the appendix. (J Nippon Med Sch 2014; 81: 110―113

The electron mobilities, μe, and electron-ion recombination rate constants, kr, in dense gaseous Ar and Kr with a small amount of N2 or CH4 as a molecular impurity have been measured as a function of electric field strength using a pulse radiolysis dc-conductivity method combined with a new decay-curve analysis method in which a space-charge effect is taken into account to obtain more accurate values of kr. The energy of electrons in recombination is controlled experimentally in two ways; one is heating-up by the electric field and the other is cooling-down by inelastic collisions with additive molecules. A large deviation of kr from the Debye theory obtained in the present experiment has been discussed in terms of the electron mean free paths and electron energies based on recent theories.

A 75-year-old man was diagnosed as gall bladder carcinoma by postoperative histological examination following laparoscopic cholecystectomy. He underwent the second surgery of resection of liver bed and port sites with lymph node dissection. Isolated hepatic metastasis of 20 mm in diameter was found in S4/8 by MRI 18 months postoperatively, and stereotactic radiotherapy (52.8 Gy/4 Fr) was done for the metastatic lesion. The lesion could not be detected by CT 7 months after the radiotherapy, and thereafter no local recurrence has been observed for 24 months. However, lymph node metastasis of #9 was diagnosed 31 months postoperatively. Liniac radiotherapy (60 Gy/20 Fr)was performed and stable disease has been obtained for 9 months. The patient is alive at present of 43 months after surgery without any other site of the disease, and his quality of life is well maintained. Stereotactic radiotherapy showed an excellent local therapeutic effect without any serious complications, suggesting that this is a potent modality for isolated liver metastasis of gall bladder carcinoma.