Concise total syntheses of (–)-jorunnamycin A and (–)-jorumycin enabled by asymmetric catalysis

The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over the past four decades for their exceptionally potent anticancer activity, in addition to strong gram-positive and -negative antibiotic character. Synthetic strategies toward these complex polycyclic compounds have relied heavily on electrophilic aromatic chemistry, such as the Pictet-Spengler reaction, that mimics their biosynthetic pathways. Herein we report an approach to two bis-THIQ natural products, jorunnamycin A and jorumycin, that instead harnesses the power of modern transition-metal catalysis for the three major bond-forming events and proceeds with high efficiency (15 and 16 steps, respectively). By breaking from biomimicry, this strategy allows for the preparation of a more diverse set of non-natural analogs

EGFR Inhibitor Enhances Cisplatin Sensitivity of Oral Squamous Cell Carcinoma Cell Lines

Epidermal growth factor receptor (EGFR) is involved in multiple aspects of cancer cell biology. EGFR has already been identified as an important target for cancer therapy, with various kinds of EGFR inhibitors currently used in treatment of several human cancers. Recently, EGFR and its downstream signaling pathways were identified as being associated with cisplatin sensitivity. In addition, EGFR inhibitors have shown significant promise for patients who failed cisplatin-based therapy. In this study, we investigated whether treatment with an EGFR inhibitor improves cisplatin sensitivity in oral squamous cell carcinoma (OSCC) cell lines. The effects of a combination of AG1478, a specific EGFR tyrosine kinase inhibitor, with cisplatin were evaluated in cultured OSCC cell lines and cisplatin-resistant sublines. Higher expression of EGFR and p-EGFR was found in the two cisplatin-resistant cell lines compared with the corresponding parental cell lines. In addition, augmented inhibition of OSCC cell growth by the combination of AG1478 with cisplatin was found in both cell lines. These results suggest that the combination of an EGFR inhibitor and cisplatin may be useful as a rational strategy for the treatment of patients with oral cancer with acquired cisplatin resistance

Concise total syntheses of (–)-jorunnamycin A and (–)-jorumycin enabled by asymmetric catalysis

The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over the past four decades for their exceptionally potent anticancer activity, in addition to strong gram-positive and -negative antibiotic character. Synthetic strategies toward these complex polycyclic compounds have relied heavily on electrophilic aromatic chemistry, such as the Pictet-Spengler reaction, that mimics their biosynthetic pathways. Herein we report an approach to two bis-THIQ natural products, jorunnamycin A and jorumycin, that instead harnesses the power of modern transition-metal catalysis for the three major bond-forming events and proceeds with high efficiency (15 and 16 steps, respectively). By breaking from biomimicry, this strategy allows for the preparation of a more diverse set of non-natural analogs

The Effect of Aerobic Exercise Training Frequency on Arterial Stiffness in a Hyperglycemic State in Middle-Aged and Elderly Females

The frequency of aerobic exercise training in reducing the increase in arterial stiffness during acute hyperglycemia, a risk factor for cardiovascular disease, is unknown. The aim of the study was to determine the aerobic exercise training frequency on arterial stiffness in a hyperglycemic state in middle-aged and elderly females. Twenty healthy elderly people were randomly assigned to a two-times-a-week (T2, n = 10) and four-times-a-week (T4, n = 10) exercise group. All participants exercised for 35 min per session, which consisted of jogging exercises with a heart rate intensity of 65%. Brachial-ankle (ba), and heart-brachial (hb) pulse wave velocity (PWV) were measured before, 4 and 8 weeks after intervention; before the oral ingestion of 75-g of glucose; and 30, 60, and 90 min after ingestion. The baPWV before and 4 weeks after the intervention increased in both groups (p < 0.05), but only increased 8 weeks after intervention in the T2 group. hbPWV was unchanged before, 4 and 8 weeks after intervention in both groups. These findings show that frequent aerobic exercise suppresses the increase in arterial stiffness following glucose intake. The results of this study can be used to support the implementation of exercise programs for middle-aged and elderly patients

Synthesis and Intramolecular Diels-Alder Reaction of 4-Trimethylsiloxy-1, 3, 8-nonatriene

Oxy-Cope rearrangement of 4-vinyl-1, .6-heptadien-4-ol [1] at 330°C gave 1, 8-nonadien-4one [4] along with 2, 8-nonadien-4-one [5]. The ketone [4] was converted to the title compound [2] as a mixture of (E)- and (Z)-isomers, by the treatment with LDA and, trimethylsilyl chloride. Alternatively the nonatriene [2] was prepared selectively by the anionic oxy-Cope rearrangement of [1] followed by quenching with trimethylsilyl chloride. Intramolecular Diels-Alder reaction of [2] afforded only cis-3 a-trimethylsiloxy-2, 3, 3 a, 6, 7, 7 a-hexahydro-1 H-indene [3], irrespective of the stereochemistry of [2]

Impact of double-balloon rectal catheter use in external-beam radiotherapy for prostate cancer.

[Backgrounds]Prostate motion and rectal sparing are important treatment strategy issues in external-beam radiotherapy for localized prostate cancer. To address these issues, we prospectively investigated the feasibility of using a double-balloon rectal catheter. [Methods]The rectal catheter has inner and outer balloons that wedge the anus between them. Computed tomography (CT) examinations with and without the catheter were conducted in seven patients with localized prostate cancer treated by external-beam radiotherapy. The rectal wall sparing effect was evaluated using virtual three-dimensional conformal radiotherapy plans in each arm. To evaluate interfractional prostate motion, each patient underwent a series of four CT examinations consisting of a planning CT followed by three additional series of CT with and without a catheter during the course of radiotherapy. [Results]Virtual plans demonstrated the reduction of the dose to the rectum by expanding the posterior wall to lie outside the high- to intermediate-dose area when a catheter was applied. Interfractional prostate motion in the anteroposterior direction was effectively reduced by catheter usage; the mean ± standard deviation (SD) of the displacement was 1.3 ± 0.9 mm with a catheter as compared to 2.8 ± 1.8 mm without a catheter (P = 0.014), and the maximum displacement was successfully suppressed to 3 mm with a catheter compared to 6 mm without a catheter. Systematic and random components were also reduced with the catheter. [Conclusion]These results suggest the feasibility and clinical applicability of the double-balloon rectal catheter