Drug-Selected Human Lung Cancer Stem Cells: Cytokine Network, Tumorigenic and Metastatic Properties

Background: Cancer stem cells (CSCs) are thought to be responsible for tumor regeneration after chemotherapy, although direct confirmation of this remains forthcoming. We therefore investigated whether drug treatment could enrich and maintain CSCs and whether the high tumorogenic and metastatic abilities of CSCs were based on their marked ability to produce growth and angiogenic factors and express their cognate receptors to stimulate tumor cell proliferation and stroma formation. Methodology/Findings: Treatment of lung tumor cells with doxorubicin, cisplatin, or etoposide resulted in the selection of drug surviving cells (DSCs). These cells expressed CD133, CD117, SSEA-3, TRA1-81, Oct-4, and nuclear β-catenin and lost expression of the differentiation markers cytokeratins 8/18 (CK 8/18). DSCs were able to grow as tumor spheres, maintain self-renewal capacity, and differentiate. Differentiated progenitors lost expression of CD133, gained CK 8/18 and acquired drug sensitivity. In the presence of drugs, differentiation of DSCs was abrogated allowing propagation of cells with CSC-like characteristics. Lung DSCs demonstrated high tumorogenic and metastatic potential following inoculation into SCID mice, which supported their classification as CSCs. Luminex analysis of human and murine cytokines in sonicated lysates of parental- and CSC-derived tumors revealed that CSC-derived tumors contained two- to three-fold higher levels of human angiogenic and growth factors (VEGF, bFGF, IL-6, IL-8, HGF, PDGF-BB, G-CSF, and SCGF-β). CSCs also showed elevated levels of expression of human VEGFR2, FGFR2, CXCR1, 2 and 4 receptors. Moreover, human CSCs growing in SCID mice stimulated murine stroma to produce elevated levels of angiogenic and growth factors. Conlusions/Significance: These findings suggest that chemotherapy can lead to propagation of CSCs and prevention of their differentiation. The high tumorigenic and metastatic potentials of CSCs are associated with efficient cytokine network production that may represent a target for increased efficacy of cancer therapy. © 2008 Levina et al

The effects of genotype and week of lactation on milk yield, udder dimensions and linear body measurements of non-dairy ewes

One hundred and ninety two records were taken weekly for twenty four (24) weeks from West African Dwarf (WD), the Yankasa (YN) and the West African Dwarf X Yankasa crossbred (XB) sheep . The traits evaluated were milk yield (MK), linear body measurements (LB) such as height at withers, (HT), body length (BL), heart girth (HG), shoulder width (SW), Tail length (TA), Neck length (NL), Neck circumference (NC), Face length (FA), Hind leg length (HL), Foreleg length (FL), Face length (FA), Ear length (EA), Head width (HW) and Rump height (RH) together with the following Udder dimensions (UD): Udder circumference (UC), Teat length (TL) and Teat circumference (TC). There was significant (P<0.05) influence of genotype on MK, WHT, HT, BL, TA, FL, HL, FA, EA and RH. The WD ewes produced more milk than either the YN or XB ewes. Average daily milk yield (ml) was 122.25, 90.88 and 108.8. The YN genotype was superior in all LBs except SW and NC than the WD and XB in the three genotypes. Height at withers was 59.08, 69.21 and 61.81 cm; BL 48.54, 55.08 and 54.49 cm and RH 62.88, 75.11 and 68.46 cm for WD, YN and XB ewes respectively. Since milk offtake is related to body weight and some linear body measurements, selection for WT, HG, SW, NL, NC, UC and TL in WD ewes could lead to higher milk and mutton production. Keywords: West African Dwarf, Yankasa, Yankasa x West African Dwarf, milk yield, weight, linear body measuremen

Milk yield and rectal temperature in West African Dwarf goats as affected by wattle and litter size

This study was conducted to investigate milk yield and rectal temperature in West African Dwarf (WAD) goats as affected by wattle and litter size. A total of 28 lactating does were used for the experiment. 13 does had wattle (bilateral) while 15 had no wattle. 14 does had twin birth while the other 14 had single birth. The goats were fed at 5% body weight with combination of concentrate and grass (Panicum maximum and Pennisetum purpureum) in ratio 50:50 twice per day in the morning and evening (zero grazing). The lactating does were hand milked once per day (08.00) and thrice per week for the period of 12 weeks. The goats were housed in cross ventilated pens with slatted floor. Rectal temperature was taken after milking of each animals using digital thermometer. Data collected were analysed using SAS (2010) in a randomized complete block design. The results showed that wattle and litter size had significant effect on milk yield and rectal temperature in WAD goats. Wattled animals produce significantly (P<0.05) higher milk yield of 297.72 g/day compared to their nonwattled counterparts (255.11 g/day). Animals with wattle however had higher rectal temperature of 39.35ºC compared to animals without wattle (39.23ºC). Also twin littered does produced daily milk milk yield of 292.74 g/day significantly (P<0.05) higher than single littered counterparts (257.04 g/day). The interaction between wattle and litter size showed that there was no significant difference in daily milk yield in wattled animals regardless of the litter size. However, in non-wattle animals, does with twin birth produced daily milk yield of 283 g/day significantly (P<0.05) higher than 235 g/day for does with single birth. Also, wattled does with single birth had significantly (P<0.05) higher rectal temperature of 39.43ºC when compared with wattled does with twin birth. However, in nonwattle animals, does with single birth had significantly lower rectal temperature of 39.18ºC as compared with does with twin birth (39.29ºC). It was concluded that WAD goats with wattle and twin birth produces more milk than those without wattle and single birth. Therefore, WAD goats with wattle should be selected for lactation purpose especially those with twin birth.Keywords: wattle, litter size, WAD goats, milk yield, rectal temperatur

Composition and specific gravity of milk of West African Dwarf sheep as affected by stage of lactation and parity

Twelve matured lactating ewes weighing between 16 and 24 kg live weight were used to evaluate the effects of stage of lactation and parity on milk composition and specific gravity of milk of West African Dwarf (WAD) sheep in a semi-intensive system of management. Stage of lactation was divided into 4: early, mid, late and very late respectively with 3 weeks interval. The animals were of parities 1 and 2 and were allowed to graze on an established paddock in the University Farm for 5 hours and supplemented with concentrate (17% CP, 5% BW) daily. Animals were hand milked once daily at 8.00 am for 12 weeks. Stage of lactation significantly (P < 0.05) affected specific gravity of milk while parity did not have any significant effect. Daily milk mass and daily milk volume decreased linearly from early to very late stage of lactation; 158.276 to 34.411 g and 156.054 to 34.410 cm3 respectively. Average composition of milk components were 3.78%, 4.49%, 0.76%, 4.99%, 9.02% and 14.00% for protein, lactose, ash, fat, solid non-fat and total solids respectively. Stage of lactation significantly (P<0.001) affected milk protein, lactose, fat, solid non-fat and total solid except ash. However, parity did not significantly affect any of these milk constituents. The contents of total solids, solid non-fat, fat and protein were positively correlated with. On the other hand, phenotypic correlations between lactose, protein and fat were negative. It was concluded that stage of lactation exerts significant influence on specific gravity and composition of milk of WAD sheep while parity did not.Keywords: stage of lactation, parity, specific gravity, ewe milk, compositio