Divergent Total Synthesis of Azalamellarins D and N

Lamellarins are polycyclic marine alkaloids with potent cytotoxic activities against cancer cell lines. A divergent synthesis of azalamellarins D and N, lactam congeners of the marine natural products lamellarins D and N, has been achieved via the pentacyclic 14-bromo-8,9-dihydro-benzo[7,8]indolizino[3,2-c]- quinolin-6(5H)-one intermediate. The pentacyclic intermediate can be synthesized from methyl 1-(benzensulfonyl)-3-bromo-1H-pyrrole-2-carboxylate via the Suzuki–Miyaura cross-coupling and intramolecular direct arylation as key reactions

Constituents of Casuarina equisetifolia J.R.& G.Forst. 2

From the leaves of Casuarina equisetifolia J.R.& G.Forst. betulin, glutinone, glutinyl acetate, β-sitosterol-β-D-glucoside, and gallicin were newly isolated. These compounds were identified by the comparison of their physical and spectral data with those of their respective authentic samples or with those described in the literature. The compounds isolated from this plant were examined for the piscicidal, germination inhibitory, and antifungal activities

Identification of colorectal cancer patients with tumors carrying the <it>TP53 </it>mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy

<p>Abstract</p> <p>Background</p> <p>Although postoperative chemotherapy is widely accepted as the standard modality for Dukes' stage C or earlier stage colorectal cancer (CRC) patients, biomarkers to predict those who may benefit from the therapy have not been identified. Previous <it>in vitro </it>and clinical investigations reported that CRC patients with wild-type p53 gene (<it>TP53)</it>-tumors benefit from 5-fluorouracil (5-FU) based chemotherapy, while those with mutated <it>TP53</it>-tumors do not. However, these studies evaluated the mutation-status of <it>TP53 </it>by immunohistochemistry with or without single-strand conformation polymorphism, and the mutation frequency was different from study to study. In addition, the polymorphic status at p53 codon 72, which results in arginine or proline residues (R72P) and is thought to influence the function of the protein significantly, was not examined.</p> <p>Methods</p> <p>To evaluate the significance of the <it>TP53 </it>mutation as a molecular marker to predict the prognosis of CRC patients, especially those who received postoperative chemotherapy, we examined the mutation by direct sequencing from fresh CRC tumors and evaluated the R72P polymorphism of the mutated <it>TP53 </it>by a combined mutant allele- and polymorphic allele-specific polymerase chain reaction (PCR).</p> <p>Results</p> <p>The <it>TP53 </it>mutation occurred in 147 (70%) of 211 Japanese CRC tumors. The mutation was observed in 93 (63%) tumors on the R72 allele and in 54 (37%) tumors on the P72 allele. Although the alterations to <it>TP53 </it>have no prognostic significance for CRC patients overall, we found that Dukes' stage C CRC patients who did not receive postoperative chemotherapy and carried the mutated <it>TP53</it>-R72 showed significantly longer survival times than those with the mutated <it>TP53</it>-P72 when evaluated by overall survival (<it>p = 0.012</it>).</p> <p>Conclusion</p> <p>Using a combined mutant allele- and polymorphic allele-specific PCR, we defined the codon 72 polymorphic status of the <it>TP53 </it>mutated allele in Japanese CRC patients. We raised a possibility that Dukes' stage C colorectal cancer patients with tumors carrying <it>TP53 </it>mutation, especially the P72 allele, benefited from 5-FU based postoperative chemotherapy.</p

Clinical predictors for inappropriate initial diagnosis.

<p>AID: appropriate initial diagnosis; IID: inappropriate initial diagnosis; SBP: systolic blood pressure; HR: heart rate; RR: respiratory rate; HTN: hypertension; HL: hyperlipidemia; DM: diabetes mellitus; IHD: ischemic heart disease; CVA: cerebrovascular accident; TA: true aneurysm; DA: dissection aneurysm; AV: aortic valvular disease; WI: Walk-in visit to the emergency room; SP: sudden pain; MP: migrating pain. Comp: complication; PAO: peripheral arterial occlusion; DC: disturbed consciousness; AR: aortic regurgitation; Tampo: tamponade; CM: coronary malperfusion; HP: hemiplegia; CHF: congestive heart failure; AECG: acute electrocardiagram changes; CECG: chronic ECG changes; MW: mediastinal widening; Car M: cardiomegaly; CHF (X-p): CHF on chest X-p; Classic: classic aortic dissection. Before 2002 indicates the comparison between before 2002 and after 2003.</p><p>Clinical predictors for inappropriate initial diagnosis.</p

Predictors for DD.

<p>ED: early diagnosis; DD: delayed diagnosis. Other abbreviations are as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0141929#pone.0141929.t002" target="_blank">Table 2</a>.</p><p>Predictors for DD.</p