Non-thiazolidinedione antihyperglycemic agents. 2: alpha-Carbon substituted-beta-phenylpropanoic acids.

Buckle, D. R.; Cantello, B. C. C.; Cawthorne, M. A.; Coyle, P. J.; Dean, D. K.; Faller, A.; Haigh, D.; Hindley, R. M.; Lefcott, L. J.; et al. Dep. Medicinal Chem., Smithkline Beecham Pharmaceuticals, Surrey, UK. Bioorganic & Medicinal Chemistry Letters (1996), 6(17), 2127-2130. Publisher: Elsevier, CODEN: BMCLE8 ISSN: 0960-894X. Journal written in English. CAN 125:238227 AN 1996:573179 CAPLUS (Copyright (C) 2009 ACS on SciFinder (R)) Abstract The thiazolidine-2,4-dione ring of insulin-sensitizing antidiabetic agents can be replaced by ?-acyl-, ?-alkyl- and ?-(aralkyl)-carboxylic acids. The inclusion of an addnl. lipophilic moiety affords compds., equipotent to BRL 48482.

Non-thiazolidinedione antihyperglycemic agents. 1: Alpha-Heteroatom substituted-beta-phenylpropanoic acids.

A review with 22 refs. The 5-benzylthiazolidine-2,4-dione moiety of insulin sensitizing antidiabetic agents can be replaced by a range of ?-heteroatom functionalized ?-phenylpropanoic acids. ?-Oxy-carboxylic acids show potent antidiabetic activity and one compd., the ?-ethoxyacid (SB 213068), is one of the most potent antihyperglycemic agents yet reported.

Rapid sympatric ecological differentiation of crater lake cichlid fishes within historic times

Background: After a volcano erupts, a lake may form in the cooled crater and become an isolated aquatic ecosystem. This makes fishes in crater lakes informative for understanding sympatric evolution and ecological diversification in barren environments. From a geological and limnological perspective, such research offers insight about the process of crater lake ecosystem establishment and speciation. In the present study we use genetic and coalescence approaches to infer the colonization history of Midas cichlid fishes (Amphilophus cf. citrinellus) that inhabit a very young crater lake in Nicaragua-the ca. 1800 year-old Lake Apoyeque. This lake holds two sympatric, endemic morphs of Midas cichlid: one with large, hypertrophied lips (~20% of the total population) and another with thin lips. Here we test the associated ecological, morphological and genetic diversification of these two morphs and their potential to represent incipient speciation.
Results: Gene coalescence analyses [11 microsatellite loci and mitochondrial DNA (mtDNA) sequences] suggest that crater lake Apoyeque was colonized in a single event from the large neighbouring great lake Managua only about 100 years ago. This founding in historic times is also reflected in the extremely low nuclear and mitochondrial genetic diversity in Apoyeque. We found that sympatric adult thin- and thick-lipped fishes occupy distinct ecological trophic niches. Diet, body shape, head width, pharyngeal jaw size and shape and stable isotope values all differ significantly between the two lip-morphs. The eco-morphological features pharyngeal jaw shape, body shape, stomach contents and stable isotopes (d15N) all show a bimodal distribution of traits, which is compatible with the expectations of an initial stage of ecological speciation under disruptive selection. Genetic differentiation between the thin- and thick-lipped population is weak at mtDNA sequence (FST = 0.018) and absent at nuclear microsatellite loci (FST < 0.001).
Conclusions: This study provides empirical evidence of eco-morphological differentiation occurring very quickly after the colonization of a new and vacant habitat. Exceptionally low levels of neutral genetic diversity and inference from coalescence indicates that the Midas cichlid population in Apoyeque is much younger (ca. 100 years or generations old) than the crater itself (ca. 1 800 years old). This suggests either that the crater remained empty for many hundreds of years after its formation or that remnant volcanic activity prevented the establishment of a stable fish population during the early life of the crater lake. Based on our findings of eco-morphological variation in the Apoyeque Midas cichlids, and known patterns of adaptation in Midas cichlids in general, we suggest that this population may be in a very early stage of speciation (incipient species), promoted by disruptive selection and ecological diversification.

Raman microscopy in the diagnosis and prognosis of surgically resected nonsmall cell lung cancer

The main curative therapy for patients with nonsmall cell lung cancer is surgery. Despite this, the survival rate is only 50%, therefore it is important to more efficiently diagnose and predict prognosis for lung cancer patients. Raman spectroscopy is useful in the diagnosis of malignant and premalignant lesions. The aim of this study is to investigate the ability of Raman microscopy to diagnose lung cancer from surgically resected tissue sections, and predict the prognosis of these patients. Tumor tissue sections from curative resections are mapped by Raman microscopy and the spectra analzsed using multivariate techniques. Spectra from the tumor samples are also compared with their outcome data to define their prognostic significance. Using principal component analysis and random forest classification, Raman microscopy differentiates malignant from normal lung tissue. Principal component analysis of 34 tumor spectra predicts early postoperative cancer recurrence with a sensitivity of 73% and specificity of 74%. Spectral analysis reveals elevated porphyrin levels in the normal samples and more DNA in the tumor samples. Raman microscopy can be a useful technique for the diagnosis and prognosis of lung cancer patients receiving surgery, and for elucidating the biochemical properties of lung tumors. (C) 2010 Society of Photo-Optical Instrumentation Engineers. [DOI: 10.1117/1.3323088]

Will Antiangiogenic Agents be a Future for Mesothelioma Therapy?

Background: Malignant mesothelioma (MM) is an aggressive disease that is diagnosed mostly in locally advanced or metastatic stage. In this condition chemotherapy with the combination cisplatin and pemetrexed or ralitrexed represents the standard treatment as supported by a phase III study. However, chemotherapy has very limited effect on the improvement of survival of patients and very few of the MM patients survive more than 2 years. A better understanding of molecular mechanisms and pathways involved in angiogenesis in MM is the basis for the development of new drugs targeted against these pathways responsible for the proliferation and survival of tumor cells.