2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent

2-Hydroxypropyl-β-cyclodextrin (HP-β-CyD) is a cyclic oligosaccharide that is widely used as an enabling excipient in pharmaceutical formulations, but also as a cholesterol modifier. HP-β-CyD has recently been approved for the treatment of Niemann-Pick Type C disease, a lysosomal lipid storage disorder, and is used in clinical practice. Since cholesterol accumulation and/or dysregulated cholesterol metabolism has been described in various malignancies, including leukemia, we hypothesized that HP-β-CyD itself might have anticancer effects. This study provides evidence that HP-β-CyD inhibits leukemic cell proliferation at physiologically available doses. First, we identified the potency of HP-β-CyD in vitro against various leukemic cell lines derived from acute myeloid leukemia (AML), acute lymphoblastic leukemia and chronic myeloid leukemia (CML). HP-β-CyD treatment reduced intracellular cholesterol resulting in significant leukemic cell growth inhibition through G₂/M cell-cycle arrest and apoptosis. Intraperitoneal injection of HP-β-CyD significantly improved survival in leukemia mouse models. Importantly, HP-β-CyD also showed anticancer effects against CML cells expressing a T315I BCR-ABL mutation (that confers resistance to most ABL tyrosine kinase inhibitors), and hypoxia-adapted CML cells that have characteristics of leukemic stem cells. In addition, colony forming ability of human primary AML and CML cells was inhibited by HP-β-CyD. Systemic administration of HP-β-CyD to mice had no significant adverse effects. These data suggest that HP-β-CyD is a promising anticancer agent regardless of disease or cellular characteristics.     

Vesnarinone Represses the Fibrotic Changes in Murine Lung Injury Induced by Bleomycin

We investigated the potential usefulness of vesnarinone, a novel cytokine inhibitor, for the treatment of lung fibrosis using a murine model of bleomycin (BLM)-induced pulmonary fibrosis. Mice were fed a control diet (n=42), or a diet containing low (n=42) or high (n=42) dose of vesnarinone. Dietary intake of vesnarinone minimized the BLM toxicity as reflected by significant decreases in numbers of inflammatory cells, KC, and soluble TNF receptors in the bronchoalveolar lavage fluid. A quantitative evaluation of histology demonstrated significantly mild lung parenchymal lesions in BLM-treated mice fed with diet containing high dose of vesnarinone than in the control diet group. Consistent with the histopathology, hydroxyproline levels in lung tissue from BLM-treated mice fed with diet containing vesnarinone were significantly lower than that from mice fed with control diet. We concluded that vesnarinone inhibits BLM-induced pulmonary fibrosis, at least in part, by the inhibition of acute lung injuries in the early phase.     

A new species of Petrochromis (Perciformes: Cichlidae) from Lake Tanganyika

Based on morphological and molecular analyses of a Petrochromis fish (Cichlidae) from the southern end of Lake Tanganyika, this fish is considered a taxonomic species distinct from the six known congeners. A new scientific name is proposed for this fish. A key to the seven Petrochromis species is included.     

Function of nuchal humps of a cichlid fish from Lake Tanganyika: inferences from morphological data

Nuchal humps occur in various fish groups, but their functions are rarely studied. Both sexes of Cyphotilapia gibberosa, a cichlid fish endemic to Lake Tanganyika, possess nuchal humps. This study morphologically analysed the humps of this species to assess the primary factors responsible for hump development. Semi-landmarks showed that the size of male humps positively correlated with body condition, and thicknesses of hypodermises implied that the humps were larger in males than in females. These facts suggest that sexual selection on male humps is intense. Semi-landmarks showed that the humps were less prominent in females than in males, and that the transformation of nuchal humps with growth (becoming more prominent) ceased at medium body size in females. These facts suggest that sex recognition likely plays a role in the evolution of the uniform humps of large females, because, according to this hypothesis, a morphologically moderate hump may be favoured. If male humps also function as a sex recognition trait, the transformation of nuchal humps is expected to cease at a certain body size, as did female humps. However, the male humps became continuously more prominent from the smallest to the largest individuals examined. The body size at which hump transformation stops or at which extreme hump shape interferes with sex recognition may be outside of the size range of the present samples. A prominent nuchal hump may also function as a species recognition trait, because sympatric cichlid species do not develop nuchal humps as prominent as this species. In short, the present morphological analyses do not contradict the hypotheses that C. gibberosa individuals recognise conspecifics and their sex from the shapes of the nuchal humps, and that females prefer males with larger humps.     

Taxonomic status of the six-band morph of Cyphotilapia frontosa (Perciformes: Cichlidae) from Lake Tanganyika, Africa

Six- and seven-band morphs have been identified in a cichlid, Cyphotilapia frontosa, that is endemic to Lake Tanganyika. These color morphs have allopatric distributions; the six-band morph is widespread in the northern half of the lake while the seven-band morph is restricted to Kigoma on the east coast of the lake. Because no specimens of the seven-band morph have been available for taxonomic study except for the holotype of C. frontosa, the taxonomic status of these morphs has not been discussed. In a recent survey at the lake, 21 specimens of the seven-band morph were collected. A comparison of these with existing collection specimens of the six-band morph showed significant differences in morphometric and meristic characters; however, because all characters largely overlapped between these morphs, they are regarded as conspecific.     

A taxonomic review ofXenotilapia sima andX. boulengeri (Cichlidae; Perciformes) from Lake Tanganyika

Two cichlid fishes from Lake Tanganyika,Xenotilapia sima Boulenger, 1899 andX. boulengeri (Poll, 1942) are often confused owing to insufficient information on the diagnostic morphological characters for each species. Morphological and morphometric analyses showed thatX. sima differs fromX. boulengeri in having a greater number of teeth and anal and pectoral fin soft rays, thicker caudal peduncle, larger eyes, and a shorter snout and anal fin base.     

Neolamprologus cancellatus, a new cichlid fish from Lake Tanganyika, Africa

Neolamprologus cancellatus, a new cichlid species, is described on the basis of eight specimens from the Zambian coast of Lake Tanganyika. The new species is characterized by a subtruncate caudal fin and a body that is slender (depth 22.3–25.2% in standard length) and easily distinguishable from its congeners by having 7–8 anal fin spines, 34–37 scales in longitudinal line, 33 total vertebrae, and a gridlike body pattern on a pale brownish body color. This species is only known to inhabit the shallow (2–7 m depth), rocky bottom of Wonzye Point in the southern part of the lake.     

Systematics of Tanganyikan cichlid fishes (Teleostei: Perciformes)

The relationships among 53 genera of Tanganyikan cichlid fishes were analyzed based on internal and external morphological features. Comparison of the morphological cladistic tree with a previously proposed classification showed 5 of 12 tribes to be nonmonophyletic. Sixteen tribes were recognized, the changes in classification being that Trematocarini was treated as a junior synonym of Bathybatini; 5 new tribes were established for each of the following genera, Benthochromis, Boulengerochromis, Ctenochromis benthicola, Cyphotilapia, and Greenwoodochromis; Ctenochromis horei was transferred from Haplochromini to Tropheini; and Gnathochromis pfefferi was transferred from Limnochromini to Tropheini. The revised classification was supported by previously proposed molecular trees.