TD-DFT investigation on the electronic spectra of novel N-methylmaleimides linked with indolizine ring system

The major electronic absorption features in visible region were computationally investigated for a series of novel N-methylmaleimide derivatives. The newly synthesized compounds through the reaction of indolizines with N-methylmaleimides exhibited their maxima ranging 587?634 nm in solution at room temperature. Time dependent density functional theory (TD-DFT) calculations were performed in order to elucidate their structure?color relationship, as well as to assess its performance using a variety of exchange-correlation (XC) functionals and basis sets. 4-(Indolizin-3-yl)-1-methyl-2,5-dioxo-1H-pyrrole-3-carbonitrile (referred to 3a hereafter), a representative of the new compounds, was analyzed in detail on its intramolecular push?pull electronic structure. As a consequence of systematic evaluation of computational strategies for 3a, we found that the theoretical λmax obtained by PCM-TD-DFT/6-31+G(d, p)//DFT/6-311G(2d, 2p) level of theory, which was consistently employed throughout this study, has converged within 2 nm deviation from λmax of the most elaborated level considered. Among some of the molecules with near-planarity structure, unusual discrepancies between the theoretical and the experimental λmax were observed, which should be attributed to the well-known TD-DFT limitation to describe multi-configurational or charge transfer (CT) excitations

Structural requirement of leucine for activation of p70 S6 kinase

AbstractThe addition of leucine induced activation of p70S6k in amino acid-depleted H4IIE cells. Whereas the activation of p70S6k by leucine was transient, the complete amino acid stimulated p70S6k more persistently. The effect of leucine on p70S6k was sensitive to rapamycin, but less sensitive to wortmannin. Using various amino acids and derivatives of leucine, we found that the chirality, the structure of the four branched hydrocarbons, and the primary amine are required for the ability of leucine to stimulate p70S6k, indicating that the structural requirement of leucine to induce p70S6k activation is very strict and precise. In addition, some leucine derivatives exhibited the ability to stimulate p70S6k and the other derivatives acted as inhibitors against the leucine-induced activation of p70S6k

Retroperitoneal liposarcoma presenting a indirect inguinal hernia

A 60-year-old man was admitted to our hospital with a right inguinal swelling that had been growing in size without any pain for 7 months. We diagnosed the growth as a right inguinal hernia and operated on him. The growth, however, was found to be a tumor it situated along the spermatic cord and testicular vessels. We diagnosed it as a lipoma. The tumor was resected near part of the internal inguinal ring. Histopathological diagnosis showed well-differentiated liposarcoma of the sclerosing type. Postoperative computed tomography (CT) revealed a large residual tumor in the retroperitoneum. We believed that the tumor was a retroperitoneal liposarcoma and that it developed in the inguinal region. The residue of the liposarcoma was resected onto the right inguinal tract. A periodic follow up has been performed and no evidence of recurrence or metastasis has been seen in the 4 years and 9 months since the second surgery. No adjuvant therapy was performed. Inguinal liposarcomas are relatively rare and in most cases these tumors are thought to originate in the spermatic cord. The origin of the tumor is believed to be the retroperitoneum</p

A novel PI3K inhibitor iMDK suppresses non-small cell lung Cancer cooperatively with A MEK inhibitor

The PI3K–AKT pathway is expected to be a therapeutic target for non-small cell lung cancer (NSCLC) treatment. We previously reported that a novel PI3K inhibitor iMDK suppressed NSCLC cells in vitro and in vivo without harming normal cells and mice. Unexpectedly, iMDK activated the MAPK pathway, including ERK, in the NSCLC cells. Since iMDK did not eradicate such NSCLC cells completely, it is possible that the activated MAPK pathway confers resistance to the NSCLC cells against cell death induced by iMDK. In the present study, we assessed whether suppressing of iMDK-mediated activation of the MAPK pathway would enhance anti-tumorigenic activity of iMDK. PD0325901, a MAPK inhibitor, suppressed the MAPK pathway induced by iMDK and cooperatively inhibited cell viability and colony formation of NSCLC cells by inducing apoptosis in vitro. HUVEC tube formation, representing angiogenic processes in vitro, was also cooperatively inhibited by the combinatorial treatment of iMDK and PD0325901. The combinatorial treatment of iMDK with PD0325901 cooperatively suppressed tumor growth and tumor-associated angiogenesis in a lung cancer xenograft model in vivo. Here, we demonstrate a novel treatment strategy using iMDK and PD0325901 to eradicate NSCLC

Gastric function preserving esophagectomy for esophageal cancer

Although, the gastric roll is widely used for reconstruction after an esophagectomy for esophageal cancer, adverse effects such as the post operative disturbance of oral intake and the reflux of gastric juice have been reported. A function preserving surgical procedure, which is similar to that for stomach and colon cancer, has been developed for esophageal cancer. Gastric function can be preserved by using the intestine as the reconstructive organ after an esophagectomy. In this report, we described the procedure for an esophagectomy with pedunculated jejunal or right colonic interposition, collectively termed as a gastric function preserving esophagectomy (GPE). We believe that this procedure is minimally invasive with a low risk of postoperative digestive symptoms and weight loss

Amino acid signaling in the intestine : The roles of glutamine, leucine and arginine

Amino acids have an influence on the function of organs, glands, tendons and arteries. Some of them play crucial roles in the control of gene expression by controlling the initiation phase of mRNA translation. Furthermore, recent studies have revealed that some kinds of amino acids directly participate in important signal transduction in the immune system. Glutamine, leucine and arginine play crucial roles in intestinal growth, integrity, and function through cellular signaling mechanisms. In this paper, we review amino acid signal transduction in the intestinal function

A case report of isolated presacral squamous cell carcinoma developed four years after gastrectomy

Chemoradiation therapy and a transsacral resection were performed to treat isolated squamous cell carsinoma that occurred in presacral tissues in the pelvis four years after gastrectomy due to early gastric cancer, with the prognosis continuing to be favorable. The patient was a 57-year-old woman, who came to our hospital having symptoms of anemia four years after gastrectomy. After a rectal examination, a tumor mass the size of a sparrowegg was discovered on the left rectal wall. An abdominal CT showed a tumor, 3.7cm × 3.7cm in size, on the outer left wall of the upper rectum. After a CT-guided biopsy, squamous cell carcinoma was detected. Irradiation (total 40 Gy) and chemotherapy (MMC+5-FU) were performed, mass shrinkage was confirmed, and a transsacral tumor resection was performed. According to the histopathological examination, a very small but viable cancer was found to be remaining. 4 years after the tumor removal, no recurrence has been discovered. Squamous cell carcinoma in the pelvis often originates from the vagina. However, the patient didn\u27t have any malignant findings from a genital examination at the time the symptoms appeared, and this case was diagnosed as isolated squamous cell carcinoma. A transsacral approach to remove such a tumor is considered to be useful because it is relatively low invasion and preserves anal functions

Skin Tube Reconstruction for Esophageal Defects due to Postoperative Complications: Applying a skin flap in esophageal resection and reconstruction

Numerous improvements and advances in operational methods and techniques have occurred in the area of reconstruction for esophageal cancer. Patients with thoracic esophageal cancer who have previously had a gastrectomy usually undergo reconstruction using the colon and small intestine. The incidence of organ necrosis is not necessarily low after reconstruction with those organs. Generally, the main types of skin flaps and musculocutaneous flaps used for cervical and other esophageal reconstructions are deltopectoral (DP) flaps, pedicled musculocutaneous latissimus dorsi flaps and free anteriolateral thigh flaps. This kind of reconstruction is low invasive, relatively simple, and also causes very few fatal post-operative complications. Therefore, it is considered to be an effective reconstruction choice for the following types of patients: poor risk patients, patients whose gastrointestinal (GI) tract cannot be used for their reconstruction for some reason, and patients having a second reconstruction due to complications caused by organ necrosis after their first GI tract reconstruction

肝転移を伴う胆嚢腺内分泌細胞癌の一例

症例は50歳代,女性.20XX 年1月ごろより前屈での心窩部付近の疼痛と右季肋部違和感を認めていた.同年3月初旬に疼痛が増強したため近医を受診し,CTで胆嚢に造影効果のある腫瘤と肝内の腫瘤陰影が認められた.肝転移を伴う胆嚢癌が疑われ,精査加療目的に当院へ紹介された.当院での画像検査でも胆嚢底部から体部にかけて約4.5cm大の隆起性病変を認めた.胆嚢底部では漿膜面が腫瘤に引き込まれ陥入している像を認め,肝床と一部で接しており境界不明瞭ではあったが,肝実質内への浸潤像は認めなかった.肝S4に約2cm大のリング状に造影される腫瘤を認め,肝転移が疑われた.ERCPでは胆嚢頸部,胆嚢管,総胆管への浸潤は認めなかった.胆汁細胞診はClass Vであった.単発の肝転移以外には遠隔転移を認めず,主要血管への浸潤も認めないため肝S4a+5切除,胆嚢摘出術,リンパ節郭清を施行した.切除標本では,病変は約4.5cm大の乳頭・結節型であり漿膜外まで浸潤していた(T3).組織学的には腺管構造を呈する腺癌とシナプトフィジン,クロモグラニンAが陽性の内分泌細胞癌が混在していた.肝転移巣は約2cmの結節・浸潤型であり,組織学的には同様にCD56強陽性,シナプトフィジン,クロモグラニンA陽性となる内分泌細胞癌が認められた(M1).リンパ節転移は認めなかった(N0).病理診断は腺内分泌細胞癌,UICC Stage-IVBであった.本症例は孤立性の肝転移を伴った胆嚢癌であったが,肝転移がS4であり,通常の胆嚢癌手術の切除範囲内であり,大きなリスクもなかったため,切除手術を行った.術後,gemcitabineとcisplatinによる補助化学療法を行った.A 57 year-old-female was referred to our hospital, because of an epigastric pain and discomfort for 2 months. Contrast-enhanced CT showed the tumor in the gallbladder body with a liver tumor in S4. An ERCP and other examinations showed no evidence of invasion to bile duct, vessels and other distant metastasis. It was diagnosed as the gallbladder cancer with a solitary liver metastasis. Preoperatively, we assessed that the curative operation might be possible. Then, we performed subsegmentectomy of liver S4a+5, cholecystectomy, and lymphadenectomy. The gallbladder cancer invasion remained extra serosa and no direct invasion to the liver tissue. Immuno-histochemical examinations showed that the tumor contained tubular adenocarcinoma and endocrine cell carcinoma with synaptophysin and chromogranin A positive. Also, the metastasis in liver S4 showed almost same results in synaptophysin, chromogranin A and CD56 positive. According to those results, she was diagnosed as mixed adeno - neuroendocrine carcinoma and Stage-IVB. Although she recovered uneventfully, she developped other liver metastases, 4 months after surgery. The chemotherapy including gemcitabine and cisplatin was introduced. Clinical cases of mixed adenoneuroendocrine carcinoma of gallbladder have been rarely reported. We present this case with a review of literatures