Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment

BACKGROUND: After development of hormone-refractory metastatic disease, prostate cancer is incurable. The recent history of chemotherapy has shown that with difficult disease targets, combinatorial therapy frequently offers the best chance of a cure. In this study we have examined the effects of a combination of zoledronic acid (ZOL), a new-generation bisphosphonate, and docetaxel on LuCaP 23.1, a prostate cancer xenograft that stimulates the osteoblastic reaction when grown in the bone environment. METHODS: Intra-tibial injections of LuCaP 23.1 cells were used to generate tumors in the bone environment, and animals were treated with ZOL, docetaxel, or a combination of these. Effects on bone and tumor were evaluated by measurements of bone mineral density and histomorphometrical analysis. RESULTS: ZOL decreased proliferation of LuCaP 23.1 in the bone environment, while docetaxel at a dose that effectively inhibited growth of subcutaneous tumors did not show any effects in the bone environment. The combination of the drugs significantly inhibited the growth of LuCaP 23.1 tumors in the bone. CONCLUSION: In conclusion, the use of the osteolysis-inhibitory agent ZOL in combination with docetaxel inhibits growth of prostate tumors in bone and represents a potential treatment option

Bal arılarında stress protein tepkileri: kovandaki her bir arının strese tepkilerinin ölçülmesi kullanışlı mı

Eusociality provides honey bees a broad repertoire of responses, through a colony’s division of labor, to maintain hive homeostasis in the countenance of environmental perturbations. The hive dynamics instrumented by workers must be balanced against losses during periods of stress. Stress proteins, a component of the cellular stress response that is already characterized in species from bacteria to man, provide molecular protection against many stressors at the organismal level of biological organization. A capacious stress protein literature reveals several general patterns. Exposure to sublethal stress increases cellular stress protein concentrations and improves survival to subsequent stress. While promoting survival during periods of stress, over-expression of stress proteins during development may diminish expression of performance traits important later in life under different circumstances. The relatively few studies that have investigated stress responses in bees reveal relationships with abiotic stress (i.e. temperature, toxins) and oxidative stress associated with flight and alcohol consumption. Given the economic importance of the honey bee and the need to better understand how agricultural factors (e.g., hive management practices, pesticides, natural enemies) affect colony performance, investigations of the association between the stress response and performance traits in individual bees should be pursued in the future.Amaç: Bu derlemenin amacı bal arılarında stres proteinlerinin çalışma mekanizması, stres proteinlerinin stres zamanında bal arılarında hücresel-moleküler ve organizma seviyesinde nasıl bir tolerans sağladığı, her bir arının kovanda bir biyo-gösterge olabileceğini tartışmaktır. Tartışma: Bal arılarında ileri derecede sosyal yapı çevresel faktörlere ve kovandaki dengelerin kurulmasında koloni işbölümü sayesinde çok geniş bir tepki olanağı sağlamaktadır. Işçi arılar tarafından sağlanan kovan dinamikleri koloni kayıp zamanlarındaki strese karşı dengelenmelidir. Stres proteinleri çevredeki çok farklı stres faktörlerine karşı hücresel-moleküler tepki mekanizmasının önemli bir parçasıdır. Bal arısı kolonisi grup olarak çok farklı çevre koşullarında özelleşmiş rekabetçilere karşı rekabet edip yaşamaya devam edebilmesi için kovan içindeki iklimsel dengeyi de korurlar. Bunu yayılmacı arılar nektar yerine su toplayarak buharlaşma ile çok sıcak havalarda kovanda soğutma yaparak sağlar. Nectar stresi bal arılarında çiçeklere yayılma davranışı ve diğer nektar toplayan canlılar arasında bir yarışmanın sonucudur. Bu durumda yayılmacı arılar her ne kadar maksimum net enerji hedefleselerde çiçekleri paylaşımda da bir işbölümü olduğu ve bunun rekabeti azalttığı görülmektedir. Bakteriden insana kadar tanımlanmış ve moleküler hücre stres tepki mekanizmasının bir parçası olan stres proteinleri biyolojik organizasyonda organizma seviyesinde stres faktörlerine karşı koruma sağlamaktadır. Literatürde yaygın stres proteini birçok genel yapı göstermektedir. Ölümcül olmayan stres hücre seviyesinde stres proteinlerinin konsantrasyonunu artırmakta ve arkasından gelecek strese karşı yaşama direncini artırmaktadır. Fakat üretilen stres proteinlerinin canlı açısından bir bedeli bulunmaktadır. Bir taraftan stres koşullarında fazla üretilen stres proteinleri yaşama gücünü artırırken gelişme döneminde yaşamın daha sonraki evrelerinde farklı koşullar altında önemli olan bazı başarı karakterlerinin kaybedilmesine neden olabilir. Bir kaç çalışma stres proteinlerinin cansız faktörlerle (sıcaklık, zehirler) alkol tüketimi ve uçuşla ilişkili oksijen stresi arasındaki ilişkilerini araştırmıştır. Sıcaklık stresi bal arılarında sinir sisteminde bozukluk ve kısa süreli hafızanın kaybedilmesine ve yayılmacı arıların besinin yerini bulmasını engellemektedir. Pestisit olarak zararlı organizmalara karşı kullanılan kimyasallar merkez sinir sistemi fonksiyonu, deri değiştirme ve üreme gibi fizyolojik gelişmeleri bozmaktadır. Elde edilen veriler pestisitlerin ölümcül dozun altında olması durumunda bile tozlaşma için önemli olan kolonideki yayılmacı arı sayısını azalttığnıı göstermektedir. Ek olarak permethrin, coumaphos, diazin gibi kimyasaların bal arılarında öğrenmeyi engellediği bilinmektedir. Son zamanlarda (yeni nesil pyrethroids, böcek büyüne düzenleyicileri gibi) hedefe özel çevreye dost ve güvenli görülen tarımsal kimyasalların bal arılarında davranışı nasıl etkilediği konusunda çok az bilgi bulunmaktadır. Örneğin, Dicofol’un çoğu böceklere karşı zehirli olmadığı kabul edilir fakat bal arılarında kullanıldığı zaman öğrenme seviyesinde önemli derecede kayıp görülmüştür. Sonuç: Sonuçta böceklere karşı kullanılan kimyasallar tarımsal ilaçlar ekolojik açıdan doğru olmayan, zararlıların direnç geliştrmesine, ikincil zararlıların çok sayıda artmasına, hedef olmayan canlılarda olumsuz etkilere, kalıntı sorunlarına, ve üzerinde uygulanan canlılara zrar vermektedir. Bu bakımdan stres oluşturması nedeniyle benzer şekilde farklı konsantrasyonlarda alkol solüsyonları ile çalışmalar yapılmaktadır. Ölümcül dozun altındaki tarımsal kimysallar kovanda direk olarak arıları öldürmeyebilir, fakat işçi arıları, ana arıyı ve erkek arıları olumsuz etkileyerk koloninin veriminin azalmasına neden olabilir. Bal arılarının ekonomik önemi (farklı mevsimlerde sıcaklık, besinin durumu, kovanların gezginci arıcılıkta taşınması, kolonilerin rutin kontrolleri, körük kullanımı, koloni bakım-besleme, pestisitler, doğal düşmanlar) nedeni ile tarımsal faktörlerin koloni performansını nasıl etkilediği, her bir arıda başarı karakterleri ve stres tepkileri arasındaki ilişkinin belirlenmesi gelecekte araştırılması gereken bir konudu

Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment-2

<p><b>Copyright information:</b></p><p>Taken from "Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment"</p><p>BMC Cancer 2006;6():15-15.</p><p>Published online 17 Jan 2006</p><p>PMCID:PMC1360086.</p><p>Copyright © 2006 Brubaker et al; licensee BioMed Central Ltd.</p>ured twice a week and blood was drawn weekly for determination of serum PSA levels. Mean ± SEM is plotted.: Docetaxel administration significantly decreased tumor volume compared to that of the control group. : Docetaxel decreased PSA levels significantly compared to those in the control animals

Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment-1

<p><b>Copyright information:</b></p><p>Taken from "Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment"</p><p>BMC Cancer 2006;6():15-15.</p><p>Published online 17 Jan 2006</p><p>PMCID:PMC1360086.</p><p>Copyright © 2006 Brubaker et al; licensee BioMed Central Ltd.</p>treatment significantly increased bone volume compared to that of the control group (p = 0.0164, *). %BV/TV of the ZOL group was increased in comparison to the control group but the changes did not reach significance (p = 0.0839). . Blood was drawn weekly from each treatment group, control (■), ZOL (●), Docetaxel (▼), or ZOL + docetaxel (○), and analyzed for PSA levels (ng/ml). The combination of ZOL + docetaxel decreased PSA levels significantly compared to those in the control animals. . Tumor volume as a percentage of the total volume was determined by bone histomorphometrical analysis for the four treatment groups. The ZOL and ZOL + docetaxel treatments decreased tumor volume significantly (p = 0.027, 0.0002, respectively *) compared to that of the control group. The combination of ZOL and docetaxel resulted in decreased tumor volume in comparison to animals receiving ZOL alone; however, these results did not reach significance (p = 0.111)

Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment-0

<p><b>Copyright information:</b></p><p>Taken from "Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment"</p><p>BMC Cancer 2006;6():15-15.</p><p>Published online 17 Jan 2006</p><p>PMCID:PMC1360086.</p><p>Copyright © 2006 Brubaker et al; licensee BioMed Central Ltd.</p>on is also visible with ZOL and ZOL + docetaxel, these tibiae exhibit decreased periosteal activity compared to the control and docetaxel-treated tibiae. . Sections stained with Goldner reagent show marrow or tumored areas in pink and bone in green. The growth plate is marked with the letter G. The ZOL- (C) and ZOL + docetaxel-treated groups (E) exhibit substantial increases in bone volume and decreases in tumor volume compared to the control (B) and docetaxel-treated (D) groups. . BMD was measured for the non-tumored and tumored legs of all four treatment groups. BMD was higher in tumored tibiae than in non-tumored tibiae, but there were no significant differences among the four treatment groups

Inhibition of Androgen-Independent Prostate Cancer by Estrogenic Compounds Is Associated with Increased Expression of Immune-Related Genes 1

Abstract The clinical utility of estrogens for treating prostate cancer (CaP) was established in the 1940s by Huggins. The classic model of the anti-CaP activity of estrogens postulates an indirect mechanism involving the suppression of androgen production. However, clinical and preclinical studies have shown that estrogens exert growth-inhibitory effects on CaP under low-androgen conditions, suggesting additional modes whereby estrogens affect CaP cells and/or the microenvironment. Here we have investigated the activity of 17B estradiol (E2) against androgen-independent CaP and identified molecular alterations in tumors exposed to E2. E2 treatment inhibited the growth of all four androgen-independent CaP xenografts studied (LuCaP 35V, LuCaP 23.1AI, LuCaP 49, and LuCaP 58) in castrated male mice. The molecular basis of growth suppression was studied by cDNA microarray analysis, which indicated that multiple pathways are altered by E2 treatment. Of particular interest are changes in transcripts encoding proteins that mediate immune responses and regulate androgen receptor signaling. In conclusion, our data show that estrogens have powerful inhibitory effects on CaP in vivo in androgendepleted environments and suggest novel mechanisms of estrogen-mediated antitumor activity. These results indicate that incorporating estrogens into CaP treatment protocols could enhance therapeutic efficacy even in cases of advanced disease. Neoplasia (2006) 8, 862-87

Inhibition of Androgen-Independent Prostate Cancer by Estrogenic Compounds Is Associated with Increased Expression of Immune-Related Genes

The clinical utility of estrogens for treating prostate cancer (CaP) was established in the 1940s by Huggins. The classic model of the anti-CaP activity of estrogens postulates an indirect mechanism involving the suppression of androgen production. However, clinical and preclinical studies have shown that estrogens exert growth-inhibitory effects on CaP under low-androgen conditions, suggesting additional modes whereby estrogens affect CaP cells and/or the microenvironment. Here we have investigated the activity of 17β estradiol (E2) against androgen-independent CaP and identified molecular alterations in tumors exposed to E2. E2 treatment inhibited the growth of all four androgen-independent CaP xenografts studied (LuCaP 35V, LuCaP 23.1AI, LuCaP 49, and LuCaP 58) in castrated male mice. The molecular basis of growth suppression was studied by cDNA microarray analysis, which indicated that multiple pathways are altered by E2 treatment. Of particular interest are changes in transcripts encoding proteins that mediate immune responses and regulate androgen receptor signaling. In conclusion, our data show that estrogens have powerful inhibitory effects on CaP in vivo in androgen-depleted environments and suggest novel mechanisms of estrogen-mediated antitumor activity. These results indicate that incorporating estrogens into CaP treatment protocols could enhance therapeutic efficacy even in cases of advanced disease