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Climb That Tree
Luke 19:1-10
(v1) And Jesus entered and passed through Jericho.
(v2) And, behold, there was a man named Zaccheus, which was the chief among the
publicans, and he was rich.
(v3) And he sought to see Jesus Who He was, and could not for the press, for he was little
of stature.
(v4) And he ran before, and climbed up into a sycamore tree to see Him, for He was to pass
that way.
(v5) And when Jesus came to the place, He looked up, and saw him, and said unto Him,
Zaccheus, make haste, and come down, for today I must abide at thy house.
(v6) And he made haste, and came down, and received Him joyfully.
(v7) And when they saw it, they all murmured, saying, That he was gone to be guest with a
man that is a sinner.
(v8) And Zaccheus stood, and said unto the Lord, Behold, Lord, the half of my goods I give
to the poor, and if I have taken anything from any man by false accusation, I restore him
(v9) And Jesus said unto him, This day is salvation come to this house, for so much as he also is a son of Abraham.
(v10)For the Son of Man is come to seek and to save that which was lost.
We are told in verse 4 that Zaccheus climbed a sycamore tree, in order that he might get a view of Jesus. It is interesting, to say the least, that a rich man, especially one who was despised, would humble and debase himself to the point of ridicule to climb a tree. He could have hired a kid to do it for him. Or he could have muttered to himself, �Forget it, I�ll just go home. It�s not worth my time or trouble.� The fact this man was willing to climb that tree and the results that followed bring home a powerful point, and here it is:
If You Want To Meet Jesus At Your Point Of Need, You�ve Got To Climb Your Own Tree
In other words, you�ve got to seek the Lord, and you�ve got to exercise your own faith. You can�t expect other people to do your praying for you, while you hardly pray yourself. It�s going to take effort on your part. No, I am not talking about doing it in your own strength. But it is going to require laying down some things like pride, self will, your own agenda, and so forth. I don�t think Zaccheus climbed that tree like a monkey. I also don�t believe that a Divine wind blew him up that tree and placed him on the limb where he needed to be. I�m going to go out on a limb- figuratively speaking- and say that he probably broke a sweat. He may have broken many a sweat that day, especially if he was out of shape- like most of us. The thought of climbing a tree, any tree, does not set well with me. If Jesus were to walk down the main street of my town, and I was not able to see Him, would I be willing to climb the nearest tree? I would rather sit on someone�s shoulders, all 6'4" and 270+ pounds of me. Hold still, Mom, Jesus is getting closer. Quit complaining, you�re causing a scene. You carried me for nine months, you ought to be able to carry me on your shoulders for a few minutes.
Zaccheus did not have any shoulders to sit on because nobody liked him. So try to picture him climbing that tree. Picture him as he reaches upward to that lowest limb. Picture him as he uses his muscles, muscles that may not have been used in a long time, to pull himself up. Picture him as he tries to get a foothold on the tree. Picture him as beads of sweat form on his face. Picture him as he positions himself on the limb, inching himself forward ever so precariously. Picture the blisters forming on his hands, hands that were only used to holding large sacks of silver. Picture his nice expensive robe being torn. Try to imagine the thoughts that may have raced across his mind. Is this worth it? I�ll bet people are looking and laughing at me. I�ll never make it, it�s too hard. What was I thinking?
Despite the odds against him, what kept Zaccheus going? Why would he risk ridicule, humiliation, blood, sweat, and splinters? It was because he wanted to see Jesus. His desire to see the Lord was what motivated him to climb that tree. It motivated him to shake off any complacency and any attitude that would suggest, �I wish I could see Jesus, but I guess it�s not for me.� It motivated him to physically exert himself. It motivated him to be laughed at on his way to accomplishing that goal. And in the end he found that it was well worth it. �Zaccheus, come down immediately. I must stay at your house today.�
Are we motivated to see Jesus? Not just when we get to Heaven, although this is something we all should strive for, but are we motivated to do our part in order to meet Jesus at our point of need? Are we motivated to do some climbing, if necessary? Just as Zaccheus had to stretch to reach that lowest limb, are we willing, or motivated to stretch our faith to grab hold of His promises? At some point, while he was climbing that tree, Zaccheus had to realize that he could not let go, or he would fall. With that in mind, are we clinging to Christ? Are we saying with our attitudes, our actions, our faith, �Lord, You�re all I�ve got to hold onto. Your Word is all I have to keep me from falling. Your cross is all I want� ?
Friend, are you willing to do some climbing? Are you willing to climb from the bottom of discouragement? Are you willing to climb upward from hopelessness? Are you willing to stretch your faith? Are you willing to let your �religious clothes�get torn? What are �religious clothes�? Religious clothes are what characterizes you on the outward. It is how you want people to see you in their minds- always in a positive way. You see, we wear clothing for different reasons. One reason is to protect ourselves from the elements- wind, rain, freezing temperatures, and so forth. Another reason is to cover ourselves, to hide a scar or wound. We also dress to impress; we want people to have a favorable opinion of our clothing style. And we dress to attract. Men dress to attract women, and women dress to attract men.
We wear religious clothing for much the same reasons. I am not speaking of the nice set of clothing we wear on Sunday mornings. I am speaking of the image with which we try to project ourselves to others. We are either trying to protect ourselves from being hurt; or we are trying to cover up old wounds; or we are trying to impress others and draw attention to the incredible amount of faith we seem to have (we know how to use all the right words). For example, a man with a bravado attitude uses that as a buffer against rejection and humiliation. It seems that nothing bothers him. He is actually wearing religious clothing. At home, out of sight of everyone, he sits alone, lonely and confused, hoping that someone will pick up the phone and give him a call. A lady who always acts happy and carefree is trying to hide a lifetime of hurts. That is religious clothing. A young married couple attends church regularly. At every service he manages to slip his arm around his wife while they listen to the sermon. Often they hear compliments such as, �You two make a lovely couple.� But what the people don�t know, and what the young couple is trying to hide is that there are serious problems at home. We�re talking about religious clothing.
These examples are not meant to denigrate anybody. Each one of us has been guilty of wearing religious clothes at times. At church we put our best foot forward. We don�t like to expose our vulnerability. We know how to interject a hearty �Amen!� or �Hallelujah!� while we are miserable inside. We can sing with the rest of the congregation, �I�m So Glad I�m A Part Of The Family Of God� while being jealous of that brother or sister who is being blessed. We can excuse ourselves and pull our clothing around us tighter. �That�s just the way I am.� But if you�re going to climb, you might tear your clothes. Your vulnerability might show through. People might realize that you actually don�t have it all together. Some of your family or friends might think that you�re going a little too far. �It�s OK if you want to go to church, but once a week is enough. What�s the idea of going to the Bible studies and prayer meetings?�
I think that Peter is a good example of someone whose religious clothes were torn. When he began to sink in the Sea of Galilee, it didn�t concern him that he was a man that had faith. He didn�t consider himself the most spiritual disciple at that moment. I think some fear was showing through his clothes. �Lord, save me!� Wait a minute, Peter, don�t lose control. Have you forgotten that the other disciples are in the ship watching you? What might his response have been? I don�t care what they think! I need Jesus or I�m going to drown! I seriously doubt that of all the thoughts that may have bombarded his mind at that horrific moment, Gee, I wonder if my hands are folded reverently enough was among them.
If his religious clothes were torn that day, they were certainly ripped to shreds on that night he discovered he could not stand for Jesus. Earlier he had stood with his thumbs in his spiritual lapels and announced, �Lord, even if all men deny You, I�ll stand with You, even if it means death.� Instead he found himself broken, weeping bitterly because he had failed in that in which he had boasted he would do.
Do I downgrade Peter? Not at all; I�ve been where Peter was. �Did you hear what so-and-so did ? I would never do that.� While there are sins and crimes that are especially heinous, we must always guard against having a judgmental, self righteous attitude.
Did Zaccheus worry about dirtying or tearing his clothes? Personally, I don�t think so. I would not be surprised if the very first thing he did was to �gird up his loins�. If there was a long distance to run, the runner would tuck his robe between his legs and then tighten it around his waist like a belt. This would enable his legs to have free mobility. I think the same would be true for climbing a tree.
Zaccheus wanted to see Jesus, but there were at least four things he was not expecting. Considering that there may have been other trees in the vicinity, 1.) He did not expect Jesus to stop at his tree, but He did. We are told that Zaccheus climbed a sycamore tree, not the sycamore tree. Of all the trees Jesus could have stopped at, He stopped at the one Zaccheus climbed. Coincidence? There are a lot of things that happen in our lives that seem like coincidence, but are actually the hand of a Sovereign, loving Heavenly Father. The Bible says that Jesus came to �the place�. As far as Zaccheus was concerned, it was just �a tree�, but as far as Jesus was concerned it was �the place.� Never confuse �a tree� with �the place�. Never underestimate the places God will lead you on your journey of destiny. You may think of your employment as simply �a job�. But to the Lord it might be �the place� where He wants to use you to minister to others, or teach you to love people with His kind of love. When they crucified Christ, to them it was just �a tree� to nail Him upon. But in the Father�s order, it was �the place� of eternal redemption for all who will believe in Jesus� sacrifice as the only cure for sin.
Considering the people Jesus may have already met and ministered to on His way through Jericho, 2.) Zaccheus did not expect Him to know him by name, but He did. In Bible times names meant something. Your name not only identified you, it also defined you. �Is not he rightly named Jacob? For he hath supplanted me these two times?� (Genesis 27:35) The name Jacob meant �supplanter� or �deceiver�. �Thou shalt call His Name Jesus, for He shall save His people from their sins.� (Matthew 1:21) So what does the name Zaccheus mean? Believe it or not, it comes from a Hebrew word which means �pure�. Taken further, it means, �to be transparent or clean� [Strong�s Exhaustive Concordance; Hebrew #2140, #2141] Zaccheus pure? Transparent? Clean? The tax collector who swindled people? It can be safely said that he was not living up to his name. So when Jesus called to him, who was He referring to? I know this sounds like a dumb question, of course He was calling to Zaccheus- the only Zaccheus sitting up in a tree. To better rephrase the question, which Zaccheus was He calling to? Was He calling to the swindler/tax collector? Or was He calling to the one whose name meant �transparent and clean�?
Now we would say, �Of course He was calling to the crooked tax collector.� But let me remind you that Jesus does not see others the same way we do. He does not see us the same way we see ourselves. We see ourselves the way we are, flawed, imperfect, in need of repair. Or we see ourselves through vaunted eyes. We see others often with a biased eye, especially when their reputation precedes them. But whether it�s us or others, Jesus always sees the finished product. He sees a person that He shed His blood for and died and rose again to redeem from everlasting destruction. He sees a person that He has purchased for Himself. In other words, His view of us is not limited to what we are or where we are at this moment. (Now be sure if there is anything to be corrected, He will not hesitate to point it out. He is not overlooking where we are now.) He sees the end product, what He created us to be. Yes, he saw Jacob, the deceiver and manipulator. But He also looked ahead and saw Israel, the mighty prince.
Therefore, in the case of Zaccheus, He saw the crooked tax collector. But I also believe that He looked beyond that and saw the Zaccheus He created him to be, transparent and clean. And Zaccheus proved this when he later told Jesus, �Lord, I�ll give half of my money to the poor, and if I have defrauded anybody by any means, I will restore that person fourfold.� That�s being transparent and clean.
So if you are climbing your tree, don�t be surprised if He calls you by name. And don�t worry, He is looking ahead to the finished product, and not just seeing the work in progress.
Considering the places Jesus could have gone, 3.) Zaccheus did not expect Him to go to his house, but He did. It was not that Jesus just happened to stop at that sycamore tree, and just happened to look up, and by a stretch of coincidence just happened to call out the right name. It was all in Divine order, not an order that simply makes the best out of an awkward situation. But it was an order firmly set in place even before the worlds were created. Remember that Jesus came to the place. What Zaccheus did not know was that he was merely keeping an appointment made eons before.
As you climb your tree, remember that Almighty God has already made the appointment to meet you. He has already designated �the place�. It could be the place of repentance. It could be the place of humility. It could be the place of broken-ness. It could be the place of tears. Whatever or wherever the place, it will be where God wants to meet you. It won�t be of your choosing. But it will be there where He will meet you at your point of need. And it will be there where He will show Himself strong on your behalf.
Considering all the results that could have happened when Zaccheus met Jesus, 4.) He did not expect salvation to come to his household, but it did. I don�t believe that while he was making his way up that tree Zaccheus was saying to himself, �If I could just make it up this tree to see Jesus, He will see me, come to my house, and everybody in my household will get saved.� I doubt that he was even thinking of his own spiritual well-being. His motive was simply to see Jesus.
As for ourselves, we have all been guilty of trying to manipulate our unsaved loved ones to the altar. We have used all manner of methods, from preaching at them their damnable, worldly ways, to making sure our Gospel music was playing louder when they were around, to putting Scripture verses in their lunch for work, those verses that pertained to Salvation and Hell and getting right with God before it was too late. Now I am not disparaging the sincerity of these efforts, and others like them. But did we forget about walking in love, having a meek and quiet spirit, and just simply living a godly life before them? What Zaccheus did- and he didn�t realize it- was to demonstrate that if we will seek for Jesus with all our hearts, He in turn will take care of our families, providing them with what we in and of ourselves could never provide; namely, a one-on-one relationship with God; forgiveness of sins; peace of heart and mind; freedom from sin and its tyranny; and health and healing for the body.
And so all these things that Zaccheus did not expect reveals another powerful point that deserves mentioning:
If We Will Put Forth The Effort To Climb Our Tree, Not Only Will Jesus Do What We Expect Him To, He Will Also Do What We Are Not Expecting.
He is a God of surprises. We look for Him to answer our prayers through the front door, but instead He comes through the back door, or through a window, or down the chimney.
We have talked much about Zaccheus, and now I would like to turn a corner and focus for a little while on the tree itself. There are some facts about this tree that I hope you will find interesting.
First of all, it had to be the right type of tree, to accommodate this little man. It could not be too high to climb, like a palm tree. It could not be too small, like a sapling. It could not be covered with thorns, or poison ivy, or poison oak, or poison sumac. It could not be a tree made hollow by rot and disease, with limbs that might break under his weight.
Let me ask you, are you climbing the right kind of tree? I�m not talking about the trees growing in your backyard. Have you invested all your faith and hope in the Cross of Christ? In the Finished Work He did there? Or have you been trying to climb that �palm tree� of lofty ideals and good intentions? You know that you�ll never get there, yet every time you fall down, you get back up and try again. A good sentiment, maybe, but how many times will you have to fall out of that tree before you come to your senses? Are you trying to climb the �sapling� of your plans for your life? God created you for great and good things, and the weight of your potential will never be held by your own agenda. Have you been snared by the thorns and poison of sin, with no hope of ever being free? Listen, my friend, the Man called Jesus was wounded for your transgressions; He was bruised for your iniquities. He paid the price for sin with His own blood. He became your Substitute and thereby forever guaranteed that salvation- deliverance for the total man, spirit, soul. mind, and body- would be available to you, regardless of your race or station in life. All you have to do is place your faith in the Atoning Work Christ has done on your behalf.
Secondly, this tree had to be in the right place, where Jesus was to pass by. What good would it have done if that tree were one-hundred yards away?
Friend, is your heart in the right place? You�re not going to see Jesus if your heart is still in the world. Is your faith in the right place? If your faith is in yourself you will be �far off� when Jesus passes by. And it is not up to Him to travel down your pathway; you need to get over to His.
Thirdly, it was a common, ordinary tree. Perhaps Zaccheus had passed by it every day and never gave it a second thought. Because our human minds are finite, we think that, in order for the Lord to perform a miracle on our behalf, He must use miraculous ways and methods. Yet the Scriptures are loaded with events where the opposite was the case. When the advancing Egyptian army was closing in on the Israelites, God did not defeat them with thunderings and lightning bolts thrown from above; He did it with a common, ordinary shepherd�s staff. When a giant threatened and intimidated, and took the morale out of an entire group of fighting men, God did not use another giant to defeat him, but a common, ordinary shepherd boy with a common, ordinary stone. When mankind was under the grip and the dominion of sin, God did not set him free with armies and guns and tanks and battalions, but He started with a common, ordinary Baby, born in a common, ordinary manger. I say a common, ordinary Baby, not to belittle Who He was, God incarnate, born of a virgin, but only to show that God�s ways are truly higher than our ways. In our human minds we would think, �How can a baby save humanity?�
Fourthly, this tree did not magically grow out of the ground as Zaccheus was frantically searching for a way to see Jesus. The seed had been planted many years before. It began as a sapling and had to endure storms and heat just like any other sapling. Someone took care to water it, fertilize around it, weed it, and prune it. At exactly the time when it was needed, it was there, strong and sturdy enough for a man to climb on.
Mom and Dad, Grandma and Grandpa, are you planting seeds of faith, hope, and love in your youngsters? Are you instilling those values that will benefit them as they grow up? The ability to make the right choices in life will not magically appear, just like that tree did not magically appear for Zaccheus. That ability comes as we are rooted and grounded in Christ. Parents and grandparents, are you living Jesus before your young people? Do they know you to be people of faith and prayer? Are you people of integrity? Can you honestly say that you would be pleased and proud for your young people to follow your example? Are you talking about Jesus to them? If so, what are you telling them? Are you telling them that He loves them so much He went to the Cross and died for them, shedding His blood, and rose from the dead on the third day? Are you telling them that He is the best Friend a boy or girl could ever have? Are you telling them that He cares and cries along with them when they scrape their knee? When other kids laugh at them? When they have a hard test at school? When they find their first pimple? Or when Mommy and Daddy don�t love each other anymore, and they think it�s their fault? What are you teaching them about Jesus? Do you tell them that the days of miracles have long since passed away, that if you want to succeed you must look to yourself, and just do the best you can do?
Yes there is much to glean from this simple tree. But there is an even greater message that I believe the Lord has shown me about this. I see mankind, too small to �see� God, too small to reach out and touch Him. When I say �small�, I�m not speaking of physical height or lack thereof. I�m speaking of mankind shortened and stymied by sin. And because of the sin problem all he can see is his own wretchedness and evil, his total unworthiness to even have a glimmer of hope of ever becoming right with the Creator of the Universe. Man tried all he knew how to do. He tried keeping the commandments, but found that, although he excelled in one area, he was sadly wanting in other areas, thus making him a failure of the total package. He tried being a good humanitarian, but found out that his good deeds were not good enough to heal the void in his soul. He even tried living for himself, indulging in unhealthy and ungodly pleasures. But when things could not get any more hopeless, there was a tree provided and mankind was told, �If, by faith, you will climb this tree, you will be able to see God, and your life will be forever changed.�
That tree, of course, is the Cross of Christ. There was no hope for mankind prior to the Cross. Mankind was totally unable and inept to make himself right with God, just as Zaccheus was unable to see Jesus on his own. The message of the Cross was preached by men of God like Isaiah, who foresaw the Suffering Servant, by Whose bloody stripes we would be healed. And when I speak of �climbing� the Cross, I�m not speaking of having one hand on the Cross and another hand on our good efforts. I�m speaking of wrapping our faith totally in what Christ did there on our behalf.
Before I go any further, I see a parallel between Zaccheus� tree and Jesus Himself that I would like to share. I believe the Holy Spirit has opened to me some nuggets of truth. Shortly before, I made the observation that this tree did not just magically appear out of the ground, but was planted just like any other tree, and had to weather all the obstacles that any tree would encounter. The Bible says of Him, For He shall grow up before him as a tender plant, and as a root out of a dry ground (Isaiah 53:2a). [He] was in all points tempted like as we are, yet without sin (Hebrews 4:15b). Jesus endured all the stuff that everyday life brings, and it was heaped on Him even more. The one exception-and this is huge-was that He never sinned.
Someone can remark, �Yes, but He was not born with the sin germ.� This is true, but bear in mind that when He was tempted (and He was tempted more often than just the 40 days on the mountain), the devil was not tempting God Incarnate, the Word made flesh, he was tempting Jesus the Man, the One Who hungered and thirsted, and got angry, and got tired. If He had given in to Satan one iota, He would not have been able to offer Himself on the Cross as the spotless Lamb. It would have been just like you or I hanging on the cross- one sinner dying for the rest of the sinners. But He lived a sinless life while here on earth and was able to offer Himself up as the Perfect Sacrifice.
I spoke of Zaccheus� tree as being there at just the right time, sturdy and strong enough to hold his weight.. The Bible tells us in Galatians 4:4, But when the fulness of the time was come, God sent forth His Son, made of a woman, made under the law. The Old Testament saints had looked forward to a coming Redeemer; the prophets had prophesied of His coming. At just the right time in history He was born of a virgin, and because He lived a sinless life, He was able to bear the weight of sin upon Himself
Well, there it is. A little man- little in stature as well as in the estimation of the townspeople- climbed an ordinary tree so that he could get a better glimpse of the Carpenter passing his way. And yet the results were extraordinary and far exceeded this little man�s expectations. Sinner friend, do you want to see this Man? If so, wrap your faith totally in what He has done for you on the Cross. Stop looking to yourself, your good deeds to make you right with God. Child of God, do you want to see Him at your point of need? If so, wrap your faith totally in what He has done for you on the Cross. Stop looking to yourself, your good deeds to make you more right with God.
So start climbing this Tree. The Lord Jesus Christ has made the appointment to meet you there. Don�t miss Him.
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Home » Breaking News!, News » American Idol 2011: Weekly Winners and Losers
American Idol 2011: Weekly Winners and Losers
Weekly American Idol 2011 winners and losers predictions.
Tonight the top 13 American Idol 2011 contestants take the stage and sing for America. There are no more judges' picks. No more wildcards. Now you sing and if America likes you and votes for you then you move on and if not, you don't. With the top 13 are all performing tonight I have selected my top three potential winners and losers. These are the three contestants I think have the best shot at being great tonight and the three that could be a disaster. Which category does Pia Toscano fall into?
Top three winners for tonight's American Idol show:
Scotty McCreery: Scotty knows who he is and he knows where he lives. Tonight he is performing "The River" by Garth Brooks and while that is not much of a stretch or risk for him, it is perfect for him. There is something to be said for knowing who you are and delivering that week in and week out. I think this song suits Scotty McCreery perfectly and I look for him to be great at it.
Paul McDonald: Paul is singing Ryan Adams' "Come Pick Me Up" which is a great song about a man desperate for a connection. It suits Paul's distinct voice perfectly. He has the ability to connect with the audience and he sings from the gut. This song could be amazing.
Lauren Alaina: Lauren is one of those singers that is wise/talented well beyond her 16 years. She has that country/rock thing down perfectly and tonight she takes on "Any Man of Mine" by Shania Twain. It is a perfect choice for her. It will let her have some fun, kick up her heels and it has some big parts in it where she can hit some high notes and show off her voice. I think tonight Lauren Alaina will make a statement that she is a contestant to be reckoned with.
Top three losers for tonight's American Idol show:
James Durbin: There is no doubting that James Durbin has a lot of vocal talent and while he may rely a little too often on hitting that high note, he has the ability to really be powerful. I think tonight he has chosen a bad song for him as he performs "Maybe I'm Amazed" by Paul McCartney. For starters there are few singers as iconic as McCartney so any time you tackle them, it is rough and there are few McCartney songs that are as beloved as "Maybe I'm Amazed." Short of him finding a way to make it wholly original and his own it will likely seem shallow and pale next to the original.
Naima Adedapo: Naima is going to sing Rihanna's "Umbrella." This potentially poses all kinds of problems for her. First off, it is a recent hit so it is very much affiliated with Rihanna and she risks doing what is essentially a karaoke version of the song. Second, the song has been covered by a million different singers so it will be hard for her to find a way to make it her own. Naima is kind of the odd one of the group so maybe she will give it some kind of old school flavor, but I think this song is a big risk and may not pay off for her.
Pia Toscano: Last week I suggested that Pia Toscano could win American Idol and I think she still has the ability to do so. Tonight she is singing "All By Myself" by Celine Dion. She has the voice to pull off this big song, but in doing so she might start to box herself into a corner where she is known as the big ballads girl. This is also one of those songs that a lot of people are familiar with and like and she could fall flat and try to over-sing it. She showed us last week that she could hit the high notes, I just have my worries that she may try to repeat that performance and fall flat.
So there you have it. My six picks for people who I think will either shine tonight on American Idol or who will fall flat. Tune in tonight at 8pm on FOX for a two hour American Idol 2011 to find out if I have any idea what I am talking about.
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This has been a great winter for skating on the Way Park rink. It is busy after school and at night, on vacation days and weekends, with parents and kids playing pick-up hockey games, tykes pushing chairs for balance, teens practicing figure eights, grandparents on foot escorting beginning skaters, and college students arriving to play broomball.
Friendly cooperation (hockey games are often restricted to one end of the rink) keeps the various skaters safe. The city regularly floods the rink after clearing the most recent snow, which at times this winter has made piles high enough that from across the park skaters appear as heads and shoulders floating through the air.


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Sunday, April 22, 2012
I found some little cute puppies at the toy store yesterday. I couldn't resist 59 cents each. I needed a little miniature time today. We've had a busy weekend. I am enjoying some quite time while my husband takes the kids thrifting. Ahhh. Deep breath. Quiet... Now to enjoy further quiet....
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Snail Post Live Video of "Blood" from The Obelisk All-Dayer
Posted in Bootleg Theater on January 4th, 2017 by JJ KoczanIf you'll allow me a sentimental moment: I remember quite clearly standing in front of the stage at Kimo's in San Francisco in 2010 and singing along with Snail's Mark Johnson and Matt Lynch to the titular hook of their 2009 return album, Blood (review here). It was among the greatest joys of the day to do so again this past August at The Obelisk All-Dayer at the Saint Vitus Bar in Brooklyn. Some time passed between the two events, obviously, and Snail have put out two more records in the meantime in 2012's Terminus (review here) and 2015's Feral (review here) and shifted from a four-piece back to the original trio of Johnson on guitar, Lynch on bass and drummer Marty Dodson, but still, it was something special.
When I announced The Obelisk All-Dayer was a thing that was happening, Snail were among the first acts who got in touch with me, offering to make their way across the continent for what would be their first East Coast appearance ever in a history that stretched as far back as their 1993 self-titled debut (review here). The generosity of that gesture was unbelievable, but the truth of the matter is I'd already dreamed of having Snail involved in the show, as Feral was so decisively their best album to-date and those songs ones I very, very much wanted to see brought to life onstage. I'm hardly an impartial observer at this point, but they were even better in Brooklyn than they'd been six years earlier in California.
The video below for "Blood" was recorded at The Obelisk All-Dayer and takes footage captured by the esteemed Frank Huang and Jennifer Hendrix and manipulates it with some additional psychedelic weirdness suited to the overall vibe. But listen to the sound as well. Snail were so on-point that I was just blown away, and as I watch "Blood," I can only keep my fingers crossed they follow this up with a companion clip for "Thou Art That," or, you know, a tape release of the whole set. Either way. No pressure. Ha.
I've included the full-stream of Feral at the bottom of this post also. I know you've heard it, but hell, you should hear it again.
And please enjoy:
Snail, "Blood" at The Obelisk All-Dayer official live video
Happy New Year! The high point of 2016 (for us) was getting to play The Obelisk All-Dayer in Brooklyn. Matt combined footage from a variety of sources and the board tracks and created a really trippy video of our performance of 'Blood.' Check it out! See if you can find the footage of a person giving blood at a blood bank…
Video and Sound Production: Matt Lynch
Footage courtesy of Frank Huang and Jennifer Hendrix. Photos by Jennifer Hendrix.
Special Thanks to: Jennifer Hendrix, Frank Huang, JJ Koczan and The Obelisk and all the folks who came to rock.


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Doctor Who: Podshock Live Show Reviewing 'A Christmas Carol' Scheduled
Doctor Who: Podshock will be once again be taking to the net on Boxing Day, Sunday (26 December 2010) for a live-over-the-net show reviewing the latest episode (special) of Doctor Who, A Christmas Carol.
He's back… and it's about time! We return with our live-over-the-net review, this time talking about and reviewing the Doctor Who adventure starring Matt Smith as the Doctor premiering on BBC One and BBC America on the 25th of December, Doctor Who: A Christmas Carol.
The Latest Sonic Newsdriver is Out for 10 December 2010
The latest episode of The Sonic Newsdriver has been released. Be warned, there is some singing in it. Sorry. It is sonic after all. As always, it contains selected Doctor Who related news for you to digest sonically. Short and sweet, just like a Jelly Baby -- only sonic.
Sonic Newsdriver (10 December 2010) -
The Sonic Newsdriver 20101210
Selected Doctor Who related news delivered sonically.
For Earth-date: Friday, the 10th of Dec. 2010
Happy Birthday Doctor Who-sein, Doctor Who Get Smart and Lancaster, BBC iPlayer? There's an App for That!, If Adventure Has Name..., We Have a Date for Christmas... Again, The Mazes Are Landing Soon, It's All About Triumph of Intellect and Romance over Brute Force and Cynicism, Doctor Who in 3D?, and more!
Doctor Who: A Christmas Carol Blu-Ray and DVD Release Date
Even though we are still a couple weeks away from the airing of Doctor Who: A Christmas Carol (coming to BBC (6pm) and BBC America (9pm) on the 25th of December), we already have a release date for the special on Blu-ray and DVD.
Just in time for Gallifrey 22, the special is slated for release on the 15th of February. So much for giving it as a Valentine's Day gift. Along with the special, the accompanying 'Doctor Who: Confidential' on it and 'Doctor Who at the Proms 2010' will be included as bonus material.
We can also assume that the special will be available on iTunes the day after it is shown on BBC America, so figure on it being there on Boxing Day.
You're Going to Need a Bigger Boat - Doctor Who: A Christmas Carol
The BBC Press Office released more information about the upcoming Doctor Who Christmas special for 2010, titled, A Christmas Carol. The special will be transmitted on the BBC and BBC America on Christmas Day.
BBC - Press Office - Doctor Who: A Christmas Carol introduction:
Doctor Who: A Christmas Carol Promo Photo
There are a bunch of articles I've been meaning to write since last week, unfortunately I have been fighting off a nasty bug I probably picked up at our anniversary event a week ago. And no, that would not be 'Bug' as in Pete's nickname who was there.
With that said, this may be old news, but only if you haven't seen it already. Below is a publicity photo for the upcoming 2010 Doctor Who Christmas special, A Christmas Carol that the BBC released recently.
@BBCAmerica had tweeted a slightly alternate version here.
Doctor Who: A Christmas Carol Trailer (video)
The first official trailer for the 2010 Doctor Who Christmas special, A Christmas Carol.
(This version is iPhone/iPad compatible.)
24th of March 2010 Edition of the Sonic Newsdriver
The Sonic Newsdriver 20100324
Selected Doctor Who related news delivered sonically.
For Earth-date: Wednesday, the 24th of Mar. 2010
Two Promo Trailers, A Date with the Doctor, Rumoured Christmas Special and Series 32, What's Up Doc?, Down with the Government, Easter Plans, I-CON 29, and more.
Hosted by Louis Trapani
Series 6(2 Doctor 11,31,Fnarg2) and Press Pack
I got another Birthday Treat as Series 6 has been confirmed for next year, Speaking at Thursday's Press Launch, New Series Producer, Piers Wenger, has confirmed that Series Six of Doctor Who has been commissioned and that Matt Smith will return as The Doctor, as well as starring in a Christmas Special later in the year. There is currently no confirmation whether the new companion, Amy Pond (Karen Gillan), will return or not.
Series Five Press Pack
This is part of the Information released to the press as part of the usual Programme launch press pack. It includes two interviews one with Matt Smith and one with Karen Gillan.
Doctor Who: Podshock - Episode 176
"And so it came to pass on Christmas Day, that the human race did cease to exist."
Doctor Who: Podshock - Episode 176
Running Time: 1:18:41
Live show reviewing Doctor Who: The End of TIme, Part 1 with live feedback, and more (part 2 of 2).
Hosted by Louis Trapani, James Naughton and Dave Cooper.
Video: BBC America End of Time Part 2 Promo and David Tennant and Russell T Davies
More new videos coming from BBC America. A promo for the upcoming Doctor Who: The End of TIme, Part 2, plus one of David Tennant and Russell T Davies speaking of their departures.
The End of Time, Part 2 Promo
Video: Extended Inside Look at The End Of Time, Part 1
An 'Inside Look' segment from BBC America on Doctor Who: The End of Time, Part 1.
Thanks to @mcfangirl
Doctor Who: Podshock - Episode 175
"Blimey, trying to make an Ood laugh…"
Doctor Who: Podshock - Episode 175
Running Time: 1:18:08
Live show reviewing Doctor Who: The End of TIme, Part 1 with live feedback, and more (part 1 of 2).
Hosted by Louis Trapani, James Naughton and Dave Cooper.
Will End of Time Break Waters of Mars Record for BBC America?
The End of Time comes to BBC America tonight, well part 1 of it at least. Will it top the best figures BBC America received last week with the airing The Waters of Mars special? Time will tell. 1.1 million viewers turned into BBC America (of those that can receive it of course) to see The Waters of Mars making it the highest rated show ever on BBC America.
Tonight at 9pm (EST), Doctor Who returns to the cable/satellite channel with The End of Time, Part 1. Here's a taste of the episode below.
How do you rate Doctor Who: The End of Time, Part 1? (5=Fantastic)
Paul Cornell's 12 Blogs of Christmas - Doctor Who Style
Paul Cornell has a series on his blog, The 12 Blogs of Christmas this holiday season.
In the latest entry, The 12 Blogs of Christmas: Eleven. Millennium Eve he features some of his fellow Doctor Who folk… included are Russell T Davies, Steven Moffat, Gary Russell, Murray Gold, James Moran, Noel Clarke, even a familiar name from Doctor Who: Podshock is there too.
In it, we are recounting what we were doing ten years ago as we rang in the new millennium.
Actually, it is quite humbling to be sharing such company on the same page. I thank Paul, he is a lovely person and friend. As I said in my piece included in Paul's blog, take nothing for granted.


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BCS Playoffs: Round 1
With our alternative to the BCS offered up, nothing else to do than to let it play out. Food expert/football junkie Dave Faries, take it away ...
Given its record in other matters, it's unlikely Congress can solve the BCS mess and put in place a viable playoff system. And it's very clear the NCAA can't work things out. Hell, they're the ones who changed a nice, easy 1-A/1-AA system to Football Bowl Subdivision and Football Championship Subdivision or something.
Which is why we sat down over a dozen or so drinks and slapped together the most equitable playoff system yet proposed (though we haven't actually researched that statement).
It's a 20 team bracket that emphasizes conference and divisional champions in the FBS ... or is it the other one? This includes champion teams from the smaller 1-A conferences, leaving six at-large bids.
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The at-large bids are bared upon AP ranking, strength of conference, strength of conference and finishing position within the conference (so you can't select a 3rd place team over a 2nd place). Independents with a top 15 ranking will receive a bid.
Seeding is based on AP ranking and strength of conference. Seeds 13-20 go into "play in" brackets. And all games will be played at neutral bowl sites.
To accomplish this, we scale back the regular season to 11 games and end it in early December at the latest. So unless a champion comes out of the play in bracket, the title winner will play 4 tournament games. By emphasizing conference wins, this system would--hopefully--lead to more meaningful non-conference match ups. The loss wouldn't hurt as much.
So--while we're stuck now watching Temple battle 6-6 UCLA in the Safebank Bowl or Minnesota take on Iowa St. in the Insight, our playoff begins with:
In Charlotte, Clemson knocks off Troy, 31-10--pretty much as expected. Clemson advances to take on top seed Alabama.
LSU came from behind to beat Arizona, 35-27. LSU now travels to El Paso to meet 4th seeded Cincinnati
In a shocker, Central Michigan topped Pitt, 21-17. The mighty whoevers face 3rd seed TCU.
And Nebraska's 17-3 win over East Carolina in Mobile now pits them in a rematch against 2nd seeded Texas.
Upcoming Events
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Our sites: Home
of The Napoleonic Wars Collection Military Music Sound Clip Gallery Products and Services: British Army Products 1793-1815 British Army Products 1816-1856 If you enjoy reading the types of articles on our website, show your support by making your book purchases through here: |
Articles - Reenactments and Units - Book Reviews - Quizzes - Replicas - Links - Chart of British Regiments - Sound Clips - Prints for Sale - Animated GIF Battles - Chronology of Events - Video Clips Songs of the War of
1812 The following are words to a number of songs Mr Graves has uncovered which are appropiate to the War of 1812 period. A tune to some of the songs have yet to be uncovered. The British Bayoneteers Eyes right, my jolly field boys, Great guns have shot and shell, boys, The English arm is strong, boys, (Tune: "The British Grenadiers") General, Glorious, Great, Granny Born-dear The war is commenc'd, Some soldiers are freezing, The Tickler, Philadelphia, 8 January 1813
Why, soldiers, why, 'Tis but in vain, Dates from 1729 The Girl I Left Behind Me I'm lonesome since I crossed the hill, Oh, ne'er shall I forget the night Dates from 1758 Lochaber No More Farewell to Lochaber and farewell, my
Jean, Then glory, my Jean, maun plead my excuse,
When wild war's deadly blast was blawn, For gold the merchant ploughs the main,
As I was a-walking down by the Lock
Hospital Then beat the drums slowly and play the
fifes lowly, Had she but told me when she did disorder
me, Got six of my comrades to carry my coffin, On top of his tombstone these words they
are written,
Hark! I hear the Colonel crying, The Major cries, "Boys, are yez
ready?" The mother crys, "Boys, do not wrong
me, Oh, Molly, dear, you're young and tinder, Oh, Molly, darling, grieve no more,
Le matin, des le point du jour, Ils nous font mettre dans les rangs, Nos sergents et nos officiers Qu'en a compose la chanson
A landlady of France, But when the bandy officer She filled him out a bumper
Nous avons un Major We have a major
"Don't you hear your General say,
Fifty I got for selling me coat, Twice tried for selling me coat, Yankee Doodle Father and I went down to camp, And there we see a thousand men, Yankee doodle, etc. And there we see a swamping gun, Yankee doodle, etc. And every time they shoot it off, Yankee doodle, etc.
The first time I deserted I thought myself
free A court-martial, a court-martial, a
court-martial was then, The next time I deserted I thought myself
free A court-martial, a court-martial, a
court-martial then sat, He put his hand in his pocket and pulled
out ten pounds, (Broadsheet, c. 1800)
Hark, now the drums beat up again, Over the hills and o'er the main, All gentlemen that have a mind, Over the hills and o'er the main ... Over rivers, bogs and springs, Over the hills and o'er the main ... We then shall lead more happy lives, Over the hills and o'er the main ... George Farquhar, "The Recruiting Officer," 1706 The Bold Canadian Come all ye bold Canadians, The Yankees did invade us, Come all ye bold Canadians, Trad., current to 1812-1813. Canadian Boat Song Tom Moore, 1805 Faintly as tolls the evening chime Why should we yet our sail unfurl? Utawa's tide! this trembling moon, Copyright Access Heritage Inc (formerly The Discriminating General) 1998 |


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Tamoxifen enhances the cytotoxic effects of nelfinavir in breast cancer cells
DOI: 10.1186/bcr2602
© Brüning et al.; licensee BioMed Central Ltd. 2010
Received: 1 March 2010
Accepted: 1 July 2010
Published: 1 July 2010
The HIV protease inhibitor nelfinavir is currently under investigation as a new anti-cancer drug. Several studies have shown that nelfinavir induces cell cycle arrest, endoplasmic reticulum stress, autophagy, and apoptosis in cancer cells. In the present article, the effect of nelfinavir on human breast cancer cells is examined and potential combination treatments are investigated.
The effects of nelfinavir and tamoxifen on the human breast cancer cell lines MCF7, T47 D, MDA-MB-453, and MDA-MB-435 were tested by analysing their influence on cell viability (via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay), apoptosis (annexin binding, poly(ADP-ribose) polymerase cleavage), autophagy (autophagy marker light chain 3B expression), endoplasmic reticulum stress (binding protein and activating transcription factor 3 expression), and the occurrence of oxidative stress (intracellular glutathione level).
Nelfinavir induced apoptosis in all four breast cancer cell lines tested, although the extent of autophagy and endoplasmic reticulum stress varied among the cell lines. The concentration of nelfinavir needed for an efficient induction of apoptosis in breast cancer cells could be reduced from 15 μg/ml to 6 μg/ml when combined with tamoxifen. At a concentration of 6 μg/ml, tamoxifen substantially enhanced the endoplasmic reticulum stress reaction in those cell lines that responded to nelfinavir with binding protein (BiP) upregulation (MCF7, T47D), and enhanced autophagy in cell lines that responded to nelfinavir treatment with autophagy marker light chain 3B upregulation (MDA-MB-453). Although tamoxifen has been described to be able to induce oxidative stress at concentrations similar to those applied in this study (6 μg/ml), we observed that nelfinavir but not tamoxifen reduced the intracellular glutathione level of breast cancer cells within hours of application by up to 32%, suggesting the induction of oxidative stress was an early event and an additional cause of the apoptosis induced by nelfinavir.
The results demonstrate that nelfinavir may be an effective drug against breast cancer and could be combined with tamoxifen to enhance its efficacy against breast cancer cells. Moreover, the cytotoxic effect of a tamoxifen and nelfinavir combination was independent of the oestrogen receptor status of the analysed breast cancer cells, suggesting a potential benefit of a combination of these two drugs even in patients with no hormone-responsive tumours. We therefore recommend that clinical studies on nelfinavir with breast cancer patients should include this drug combination to analyse the therapeutic efficacy as well as the safety and tolerability of this potential treatment option.
Breast cancer is the most frequent cancer in the female population [1]. Although tremendous progress in the treatment of breast cancer has been achieved during past decades, it is still the principal cause of cancer death for females worldwide [1, 2].
Tamoxifen is a selective oestrogen receptor antagonist, and since its introduction in cancer therapy has become the standard treatment option for hormone-responsive breast cancer patients [2–5]. Not all breast cancer patients, however, benefit from an endocrine therapy with tamoxifen [3]. Interestingly, several hormone receptor-independent effects of tamoxifen have been described, leading to apoptosis when higher concentrations of tamoxifen are applied [6, 7]. A combination therapy of tamoxifen with other drugs that cause synergistic anti-tumour effects might therefore be an interesting option in the therapy of breast carcinomas.
Nelfinavir (Viracept®; Pfizer, Groton, CT, USA) is an HIV protease inhibitor that has long been an essential component of the antiviral combination highly active antiretroviral therapy. Several recent in vitro studies have indicated that nelfinavir has potential anti-tumoral effects [8, 9], and clinical studies on nelfinavir are ongoing to confirm its efficacy against human cancers in vivo [10–13]. Nelfinavir exerts pleiotropic effects on cancer cells, including induction of apoptosis, necrosis, and autophagy [9, 14, 15]. Nelfinavir is believed to either cross-react with a protease of the cytoplasmic proteasomal protein degradation machinery or with endoplasmic reticulum-resident proteases [15, 16]. In both cases, this protease inhibition can lead to the accumulation of misfolded proteins that cause the unfolded protein response or endoplasmic reticulum stress response [17–19]. These pathways are primarily associated with a transient cell cycle arrest and upregulation of molecular chaperones such as binding protein (BiP) and other members of the heat shock family, in order to repair and prevent further cell damage [18]. A prolonged or irreparable stress reaction, however, eventually switches from a repair and survival mechanism to cell death executed by apoptosis [20, 21]. This nonclassical cell death mechanism has recently become of interest because of its ability to act even on otherwise chemoresistant human cancer cells [15, 22].
Since the orally available drugs tamoxifen and nelfinavir have anti-tumoral properties, a combination of these medications might be an intriguing option in the therapy of breast cancer patients. However, no data regarding their potential synergistic effects are yet available. We therefore tested the effect of nelfinavir and tamoxifen with regard to the influence on apoptosis, endoplasmic reticulum stress, autophagy, and oxidative stress in breast cancer cells with different oestrogen receptor status.
Materials and methods
Cells and cell culture
The breast cancer cell lines T47 D (ATCC HTB 133; oestrogen receptor-positive), MCF7 (ATCC HTB 22; oestrogen receptor-positive), MDA-MB-453 (ATCC HTB 131; oestrogen receptor-negative), and MDA-MB-435 S (ATCC HTB 129; oestrogen receptor-negative) - all kindly provided by G Saretzki (Newcastle, UK) - were cultured in RPMI-1640 medium supplemented with 10% foetal calf serum and antibiotics at 37°C in a humidified atmosphere with 5% CO2. All cell culture reagents were from PAA (Pasching, Austria).
Drugs and drug treatment
Nelfinavir (Viracept®) was generously provided by Pfizer. Nelfinavir was dissolved in ethanol and kept at -20°C as a 100 mg/ml stock solution. Tamoxifen (Sigma, Munich, Germany) was dissolved in dimethylsulfoxide at a concentration of 100 mg/ml. In control experiments, equal amounts of dimethylsulfoxide or ethanol were added.
Cell proliferation analysis
A total of 2 × 104 cells per well were seeded in quadruplicate in 24-well cell culture plates and were incubated with nelfinavir for up to 4 days. The number of viable, trypan blue-excluding cells was determined by a haemocytometer.
MTT assay
For the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay analysis, 20 μl MTT (Sigma) stock solution (5 mg/ml PBS) was added to viable cells in 200 μl cell culture medium for 1 hour under cell culture conditions. The water-insoluble precipitate was dissolved in 100 μl dimethylsulfoxide and analysed by an ELISA reader at 595 nm.
Annexin binding assay
FITC-labelled annexin V (Biocat, Heidelberg, Germany) was applied to viable cells as recommended by the supplier in combination with propidium iodide, and was analysed by FACScan with an FL-1 setting (propidium iodide) at 575 nm and an FL-2 setting (FITC) at 530 nm. FACScan analysis was performed using a Becton Dickinson FACScan analyser (Becton Dickinson, Heidelberg, Germany).
Western blot analysis
Cell extracts of cancer cells cultured in cell culture plates were prepared with radio-immunoprecipitation buffer (50 mM Tris, pH 8.0, 150 mM NaCl, 1% NP40, 0.5% doxycholine, 0.1% SDS) and 20 μg protein (BioRad Bradford Assay; BioRad, Munich, Germany) were subjected to SDS-PAGE. Proteins were transferred to polyvinylidene fluoride membranes in a BioRad Mini Protean II Cell (BioRad) at 1 mA/cm2 membrane in 10% methanol, 192 mM glycine, 25 mM Tris, pH 8.2. Membranes were blocked with 4% nonfat milk powder in PBS-0.05% Tween for 4 hours. Primary antibodies were applied in blocking buffer and incubated at room temperature overnight.
Antibodies against poly(ADP-ribose) polymerase, phospho-ERK1/2 (pp44/pp42), AKT, phospho-AKT, mcl-1, IκB, and autophagy marker light chain 3B were all purchased from Cell Signaling Technology (NEB, Frankfurt, Germany). Antibodies against BiP (H-129), activating transcription factor 3 (C-19) and β-actin (C4) were from SantaCruz Biotech (Heidelberg, Germany). Secondary, alkaline phosphatase-coupled antibodies against the corresponding primary antibodies were from Dianova (Hamburg, Germany). Alkaline phosphatase detection was performed either by the chromogenic BCIP/NBT assay (Promega, Mannheim, Germany) or by the chemiluminescent alkaline phosphatase detection assay (Millipore, Schwalbach, Germany), and the results were analysed and documented using a BioRad QuantityOne Image Analyzer and documentation software (BioRad).
Determination of intracellular glutathione levels
To detect intracellular glutathione levels, cells were seeded in 96-well cell culture dishes and allowed to grow for 24 hours under cell culture conditions. Cells were then incubated with the cytotoxic drugs for up to 5 hours. Intracellular glutathione levels were quantified using the bioluminescent Promega GSH-Glo™ glutathione assay (Promega), essentially as recommended by the supplier. In brief, adherent cells were directly dissolved in 100 μl GSH-Glo™ lysis and reaction buffer. After addition of 100 μl GSH-Glo™ Luciferin detection reagent, luminescence was detected using a MicroLumat LB 96P bioluminometer (EG&G Berthold, Bad Wildbad, Germany).
Determination of proteasomal activity
For the determination of cellular proteasome activity, cells were seeded in 96-well cell culture dishes, allowed to grow for 24 hours under cell culture conditions, and then incubated with cytotoxic drugs for up to 5 hours. Proteasomal activity was analysed using the bioluminescent Promega Proteasome-Glo™ assay (Promega) as recommended by the supplier. Adherent cells were directly dissolved in 50 μl Proteasome-Glo™ lysis and reagent buffer, containing Suc-LLVY-aminoluciferin as a substrate. Leukaemia cells were collected by centrifugation before lysis. Bioluminescence was detected using a MicroLumat LB 96P bioluminometer (EG&G Berthold).
Statistical analysis
All experiments, except western blots and FACScan analysis, were performed in quadruplicate. The results were evaluated using the nonparametric Wilcoxon sum test and the Mann-Whitney U rank-sum test where applicable (PASW version 17.0; SPSS Inc., Chigaco, IL, USA). Values were plotted as the mean ± standard deviation, and significance was assumed at P < 0.05 using the two-tailed test. Significant relations are indicated in the figures and the statistical test used is mentioned in the corresponding figure legend.
Ethical aspects
All experiments were performed on established cancer cell lines. No ethical approval or informed consent was thus needed.
Nelfinavir reduces cell proliferation of breast cancer cells and is able to induce apoptosis in breast cancer cells when applied at higher concentrations
Tamoxifen enhances the cytotoxic effect of nelfinavir
The mean plasma concentration of nelfinavir in HIV-infected persons taking oral doses of nelfinavir was determined to be 2.2 μg/ml, reaching maximal plasma concentrations of up to 4 μg/ml [23, 24]. These concentrations can achieve only a partial reduction of breast cancer cell proliferation (Figure 1), and are not efficient in inducing apoptosis in breast cancer cells. The plasma concentration of nelfinavir, however, can be significantly increased by administering higher oral doses of nelfinavir or by intravenous application of nelfinavir [25]. Still, a possible combination strategy of nelfinavir with other chemotherapeutic drugs that would allow a reduction of single drug concentrations would be advantageous.
Quantitative analysis of apoptotic and necrotic cells after tamoxifen and nelfinavir treatment
Cell line | LL (%) | UL (%) | UR (%) | LR (%) |
Control | 98.78 | 0.44 | 0.77 | 0.03 |
TAM 6 μg/ml | 92.71 | 4.42 | 2.71 | 0.17 |
NFV 6 μg/ml | 95.50 | 2.17 | 2.31 | 0.03 |
Control | 88.04 | 3.10 | 7.52 | 1.33 |
TAM 6 μg/ml | 83.05 | 7.16 | 6.89 | 2.90 |
NFV 6 μg/ml | 92.80 | 2.46 | 3.80 | 0.95 |
Nelfinavir exerts pleiotropic proapoptotic and anti-apoptotic effects in breast cancer cells
In all four cell lines, no change in the expression of the proteasome-regulated NF-κB inhibitor IκB could be observed, suggesting no influence of nelfinavir on the proteasome activity in breast cancer cells. We have previously described an upregulation of the anti-apoptotic mcl-1 protein by nelfinavir in ovarian cancer cells [26], but this could only be observed in one (MDA-MB-435) of the four tested breast cancer cell lines. Nelfinavir has further been described as reducing AKT phosphorylation, resulting in enhanced radiosensitivity [11, 16] - which could be of special importance for breast cancer treatment, for which radiotherapy can be applied. We observed no inhibition of AKT signalling in MCF7 and T47 D cells by nelfinavir, however, and we even observed a markedly enhanced AKT phosphorylation level in nelfinavir-treated MDA-MB-453 and MDA-MB-435 cells (Figure 4).
Tamoxifen enhances the pleiotropic effects of nelfinavir in breast cancer cells
Nelfinavir reduces glutathione levels in breast cancer cells
The intracellular glutathione levels might vary not only because of external drug applications, but likewise due to differences in cell growth, nutrient concentrations (especially that of cysteine), and the redox state within the cells or of the surrounding medium. These factors can vary under cell culture conditions. Exogenously applied glutathione or cysteine derivatives such as N-acetyl-cysteine can enhance or replenish intracellular glutathione levels or support the antioxidative effect of glutathione. To analyse the involvement of glutathione depletion on nelfinavir-induced apoptosis, intracellular glutathione contents were replenished by the addition of externally applied glutathione or N-acetyl-cysteine. Figure 6c demonstrates that the addition of glutathione, and even more so the addition of N-acetyl-cysteine, can attenuate the cytotoxic effect of nelfinavir on breast cancer cells. In the absence of external glutathione or N-acetyl-cysteine, only 5% of the MCF7 cells and 12% of the MDA-MB-435 cells survived the application of 15 μg/ml nelfinavir (Figure 6c). Although the addition of 5 mM glutathione was not without negative effects on the cell viability of MCF7 cells (Figure 6c), the presence of external glutathione enhanced the remaining cell viability of MCF7 cells to 15% and to 17% in the case of MDA-MB-435 cells (Figure 6c). In the presence of 5 mM N-acetyl-cysteine, 18% of the MCF7 cells remained viable, and up to 34% of the MDA-MB-435 cells survived the addition of nelfinavir (Figure 6c).
Nelfinavir has no effect on the chymotrypsin-like proteasome activity of breast cancer cells
Some previous studies have indicated the inhibition of proteasomal activity by HIV protease inhibitors, including nelfinavir [26, 28]. The fact that nelfinavir has no influence on expression of the proteasome-regulated NF-κB inhibitor IκB (Figure 4), however, indirectly suggests that nelfinavir has no effect on the proteasomal activity of breast cancer cells.
The HIV protease inhibitor nelfinavir is a prospective new anti-cancer drug, as shown by several in vitro as well as in vivo studies [8–13]. The concentrations of nelfinavir needed to induce cell death of cancer cells are higher than those applied for HIV-infected individuals for HIV suppression, but this may be achieved by the application of higher oral or intravenous doses of nelfinavir [25]. Still, the prospects of nelfinavir as an anti-cancer drug will rely less on its efficacy as a single drug and more on its ability to cooperate with or sensitise to other chemotherapeutic drugs or cancer treatment options. For example, we have recently demonstrated that nelfinavir cooperates with the multiple kinase inhibitor sorafenib to induce apoptosis in various cancer cell types [26, 29], and enhances TNF-related apoptosis inducing ligand sensitivity in ovarian cancer cells [30].
The present results show that the cytotoxic effects of nelfinavir on breast cancer cells can be enhanced by combination with tamoxifen, thus allowing the effective concentration of nelfinavir to be reduced. Tamoxifen, although originally designed and applied as a selective oestrogen receptor modulator, also represents a drug with several described pleiotropic anti-tumoral effects [6, 7] - and two recent and independent studies observed that tamoxifen is able to induce the endoplasmic reticulum stress reaction [31, 32], thus explaining the synergistic effect of nelfinavir and tamoxifen on the induction of endoplasmic reticulum stress. The nelfinavir-boosting effect of tamoxifen was obviously independent of its ability to induce oxidative stress [6]. Instead, we observed that nelfinavir itself reduced cellular glutathione levels, indicating the occurrence of oxidative stress after nelfinavir treatment. Induction of oxidative stress occurs within a few hours as an early effect of nelfinavir treatment and has so far been neglected as an additional mechanism of the pleiotropic anti-cancer effects of nelfinavir. The observation that the effect of nelfinavir can be attenuated by the addition of antioxidants (glutathione or N-acetyl-cysteine) could have an impact on the efficacy of nelfinavir in cancer cells, as well as on the nelfinavir-induced adverse effects occurring in HIV-infected persons.
Nelfinavir has been reported to exert a radiosensitising effect by inhibiting proteasome activity and AKT signalling [16]. Inhibition of proteasomal activity or AKT signalling in breast cancer cells, however, was not observed in the present study. In contrast, nelfinavir markedly enhanced AKT phosphorylation in some breast cancer cell lines (MDA-MB-453 cells and MDA-MB-435 cells). This observation is not surprising, however, since we previously demonstrated activation of the cell-protective ERK1/2 signalling pathway by nelfinavir [26]. The endoplasmic stress reaction is primarily a cell-protective mechanism, aiming to rescue cells from transient stress-induced cell damage [21, 33]. Longer exposure to cell stress mechanisms or a cellular inability to cope with the stress-induced cell damage then finally induces a switch from cell protection to autophagy and apoptosis [21, 33]. Endoplasmic reticulum stress has repeatedly been shown to induce activation of both ERK1/2 and AKT signalling [34–37]. Several studies, however, have likewise shown that AKT activation, which can occur directly at the endoplasmic reticulum [38], primarily represents a short-term effect, and prolonged exposure of cells to endoplasmic reticulum stress indeed induces AKT inactivation [38, 39]. In fact, we observed a reduced AKT phosphorylation when breast cancer cells were treated with nelfinavir for more than 48 hours (data not shown), although this indicates downregulation of AKT phosphorylation as a secondary event. The present data therefore do not exclude the potential use of nelfinavir as a radiosensitiser even for breast cancer patients, but a potential negative interaction between these two treatment options, especially shortly after nelfinavir application, should be kept in mind.
In addition to the data on AKT signalling, the present data revealed some other differences to previous studies performed by us and other workers on different cancer cell types. For example, upregulation of the anti-apoptotic mcl-1 protein by nelfinavir - as we observed in ovarian cancer cells [26] and leukaemia cells [29] - could only be observed in a single breast cancer cell line (MDA-MB-435 cells), and only at high concentrations of nelfinavir (Figure 4). Further, we could not demonstrate proteasome inhibition by nelfinavir in breast cancer cells.
Although nelfinavir induced cell death in all four breast cancer cell lines tested, the data presented further indicate that the cell lines respond quite differently to nelfinavir, especially regarding the effect on cell stress, autophagy, and apoptosis. This variation might be due to the different hormone receptor status of the cells, but likewise may be due to the different malignancies of the tumours from which these cell lines have been derived. We therefore tried to include various types of breast cancer cell lines in the present study, ranging from hormone receptor-positive breast cancer cells of a high differentiation grade (T47 D cells) to highly de-differentiated hormone receptor-negative breast cancer cells (MDA-MB-435 cells). Interestingly, especially when low doses of nelfinavir were applied, the de-differentiated hormone receptor-negative breast cancer cell lines (MDA-MB-453 and MDA-MB-435 cells) appeared to react even better to nelfinavir than the T47 D and MCF7 cells (Figure 1).
We observed that the combination of tamoxifen and nelfinavir was able to induce cell death in oestrogen receptor-positive as well as in oestrogen receptor-negative breast cancer cell lines. This indicates that both oestrogen receptor-positive as well as oestrogen receptor-negative breast cancer patients could benefit from a combination of these two drugs.
Since both nelfinavir and tamoxifen have to be used at concentrations higher than those used to inhibit the HIV protease in HIV-infected persons or the oestrogen receptor in hormone receptor-positive breast cancer patients, however, care has to be taken that no unexpected adverse effects occur - especially when both drugs, although displaying moderate and tolerable adverse effects as single agents, are combined. Further, the observed reduction in glutathione levels by nelfinavir might cause an unexpected drug sensitisation in other tissues.
Clinical studies on breast cancer patients testing the described combination of nelfinavir and tamoxifen are thus of high interest in order to assess both efficacy and safety of this drug combination.
The present study demonstrates the efficacy of nelfinavir in breast cancer cells as a single agent, and a possible combination treatment with tamoxifen. Both nelfinavir and tamoxifen are already-approved drugs with known pharmacokinetics, and they generally exhibit relative mild and well tolerable adverse effects even after long-term application. Since the concentrations of both drugs have to be increased for an efficient cancer therapy, and a combination of these two drugs has not yet been tested in humans, however, it is important to first test the safety and tolerability of this combination in phase I studies.
activating transcription factor 3
- BiP:
binding protein
enzyme-linked immunosorbent assay
extracellular signal-regulated kinase: FACS: fluorescence-activated cell sorting
fluorescein isothiocyanate
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide
nuclear factor
phosphate-buffered saline
tumour necrosis factor.
The authors are greatly indebted to Marianne Vogel, Reinhild Joswig, and Petra Burger for their excellent and highly motivated technical assistance. The generous supply of nelfinavir by Pfizer (Groton, CT, USA) is gratefully appreciated. This work was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft DFG BR 3641/1-1 and DFG BR 3641/3-1).
Authors' Affiliations
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Resource Name & Link to Resource: | Année Philologique |
Description: | Bibliography, with brief abstracts, for classical studies. Indexes articles from 1,500 periodicals as well as relevant articles from collections and conferences. Also lists related new books. Covers material in French, English, German, Italian and Spanish. See journal abbreviations in the Tables of Contents of Journals of Interest to Classicists (TOCS-IN), which publishes indexing a bit more quickly than L'Année Philologique. |
Resource Type(s): | All Relevant Database(s), Key Database(s) |
Access information: | Resource is available on-campus or off-campus via EZProxy; Click the resource name to access it or here for off-campus instructions. |
Fulltext: | This resource does not provide direct access to fulltext content. |
Vendor Name: | Société Internationale de Bibliographie Classique (Annee Philologique) |
Research Guides: | Classical Studies, German Studies, History, Philosophy & Religion |
Coverage: | 1924 - most recent |
Update Frequency: | annually |
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GHOSTS IN THE BACKYARD! hi my name is Ann, and this is the most remarkable picture I have ever taken . it was Christmas 1994 and my daughter had just gotten a Polaroid camera . we have a very active house in the country and at this time the dogs were going nuts out back. I grabbed the camera and the first photo I took displayed this image. you can actually make out the old clothing and veil . the little girl seems to be pointing down to the ground. thanks for looking!
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Related Sections: | Bloomington | Monroe County |
Indiana University Golf Course - Par 3 Course
State Road 46 BypassBloomington, IN 47405
Phone: (812)855-7543Fax: (812)855-8125
This facility has both an eighteen hole regulation course and a nine hole executive course. The Championship Course was built on rolling terrain. The main hazards on this course are its mature trees. The fairways vary from narrow to open, and the greens are undulating and medium-sized. The Par 3 Course is wide open and has one par 4.
Holes: 9 | Greens: Bent Grass | Fairways: Winter Rye |
Greens Fees: | $20 or Less |
Course Type: | public |
Dress Code: | No tank tops or cutoffs |
Season: | Feb 1 to Dec 31 |
Guest Policy: |
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Besides being a popular and successful team, Barca has become a symbol of Catalan nationalism, inspiring the motto "Mas que un club", or "more than a club".
Joan Gamper, a football enthusiast from Switzerland, founded FC Barcelona on November 29, 1899. The successful team quickly amassed a dedicated Catalan fan base.
Fans of FC Barcelona are known as culés, the Catalan word for 'ass'. This nickname originated in the twenties from Barca fans who sat in the highest row of the stadium with their culés visible to passerbys.
Under Franco, the Catalan language and symbols were banned and the team was forced to change their name to Club de Futbol Barcelona in 1939. The Catalan flag was also removed from the club shield. Despite this, the stadium remained one of the only places during Franco's regime where Catalan could be spoken and their flags could be displayed freely.
The two most successful Spanish football teams, FC Barcelona and Real Madrid are also fierce competitors. The rivalry stems from Franco's dictatorship; Barca represented an opposition to Franco while Real Madrid was a symbol of nationalism and was favored by the regime and Franco.
With Franco in attendance, the club beat Real Madrid 1-0 at the Copa del Generalísimo final in 1968. The club's coach at the time, Salvador Artigas, was a Republican pilot during the Spanish Civil War.
Barca's stadium, Camp Nou, was built in 1957. With a capacity of 98,000, Camp Nou is the largest stadium in Europe and the third largest stadium in the world.
In 1974, the club changed their name back to Futbol Club Barcelona.
Since it was founded, Barca has refused to advertise corporate sponsors on their uniforms. However, on July 14th, 2006, the club announced an agreement with UNICEF that included, for the first time in Barca's history, the organization's logo on their shirts. As part of the five year agreement, the club donates €1.5 million a year to Unicef.
Club president Joan Laporta, a self-proclaimed nationalist, requires all foreign Barca's players to learn Catalan.
In 2007, Laporta dedicated a portion of the ticket sales from the FC Barcelona v Real Madrid match to Federacio Llull, an organization that promotes the spread of the Catalan language. Jose Luis Rodriguez Zapatero, the Prime Minister of Spain since 2004, supports FC Barcelona.
Paul Symonds deals with Barcelona boat charters and Barcelona stag weekends.
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Studying Blood Samples in Young Patients With Cytopenia After a Donor Stem Cell Transplant
Recruitment status was: Recruiting
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RATIONALE: Studying samples of blood from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer.
PURPOSE: This research study is looking at blood samples in young patients with cytopenia after undergoing a donor stem cell transplant.
Condition | Intervention |
Leukemia Myelodysplastic Syndromes |
Genetic: polymerase chain reaction Other: flow cytometry Other: laboratory biomarker analysis Procedure: allogeneic hematopoietic stem cell transplantation |
Study Type: | Observational |
Official Title: | Serial Analysis of Chimerism in Patients With Refractory Cytopenia (RC) Transplanted With Reduced Intensity Conditioning (RIC) |
- Number of patients with complete chimerism as measured by standard short tandem nucleotide polymorphism PCR in whole blood and the different cell populations
- Number of patients with complete chimerism as measured by single nucleotide polymorphisms PCR in the different cell populations
- Number of patients with mixed chimerism and full hematological recovery at day 100
- Number of patients with mixed chimerism and acute or chronic graft-versus-host disease
Estimated Enrollment: | 125 |
Study Start Date: | April 2007 |
Estimated Primary Completion Date: | March 2013 (Final data collection date for primary outcome measure) |
- To study hematopoietic chimerism in whole blood and different cell populations (i.e., CD14, CD15, CD 56, CD3, and CD19) as well as in dendritic cells and regulatory T cells after allogeneic hematopoietic stem cell transplantation with reduced intensity conditioning in patients with refractory cytopenia.
- To compare the results of chimerism obtained with standard short tandem nucleotide polymorphism PCR (sensitivity 1%) with those obtained with single nucleotide polymorphisms PCR (sensitivity 0.1- 0.01%).
- To evaluate the relationship between mixed chimerism and hematological engraftment, overall survival, and event-free survival.
- To study the impact of mixed chimerism in plasmacytoid dendritic and regulatory T cells on the incidence of acute and chronic graft-versus-host-disease.
OUTLINE: This is a multicenter study.
Peripheral blood is collected from patients and donors prior to hematopoietic stem cell transplantation (HSCT). Patients also undergo blood sample collection on days 30, 60, 100, and 180 after transplantation. Peripheral blood cells are enriched and separated into lineage-specific subpopulations (i.e., CD3, CD14, CD15, CD19, and CD56) which are then divided equally for either DNA isolation via PCR or for flow cytometry. DNA concentrations in pre-HSCT donor and patient samples and in post-HSCT subpopulation samples are determined using quantitative real-time PCR. Samples are also analyzed for quantification of chimerism and detection of genetic markers via short tandem repeats- and sequence nucleotide polymorphism-based chimerism analyses.
Ages Eligible for Study: | up to 17 Years (Child) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Diagnosed with refractory cytopenia
- Hypocellular bone marrow and normal karyotype
Underwent stem cell transplantation (SCT) from an HLA identical (8/8) sibling, an HLA identical (10/10) relative, or an HLA identical or single allelic disparate unrelated donor
- Received a preparative regimen including either thiotepa or fludarabine phosphate
- Concurrently enrolled on EWOG-MDS-2006
- Not specified
- See Disease Characteristics
Please refer to this study by its ClinicalTrials.gov identifier: NCT00898118
Austria | |
St. Anna Children's Hospital | Recruiting |
Vienna, Austria, A-1090 | |
Contact: Contact Person 43-1-401-700 firstname.lastname@example.com | |
Belgium | |
Ghent University | Recruiting |
Ghent, Belgium, B-9000 | |
Contact: Contact Person 32-9240-3875 email@example.com | |
Czech Republic | |
University Hospital Motol | Recruiting |
Prague, Czech Republic, 150 06 | |
Contact: Contact Person 42-022-443-6401 email@example.com | |
Denmark | |
Aarhus Universitetshospital - Aarhus Sygehus | Recruiting |
Aarhus, Denmark, DK-8000 | |
Contact: Contact Person 45-8949-6841 firstname.lastname@example.com | |
Germany | |
European Working Group of MDS in Childhood | Recruiting |
Freiburg, Germany, 79106 | |
Contact: Contact 49-761-270-4617 firstname.lastname@example.com | |
Universitaetskinderklinik - Universitaetsklinikum Freiburg | Recruiting |
Freiburg, Germany, D-79106 | |
Contact: Contact Person 49-761-270-4506 firstname.lastname@example.com | |
Italy | |
IRCCS "Casa Sollievo della Sofferenza" | Recruiting |
South Giovanni Rotondo, Italy, 71013 | |
Contact: Contact person 39-038-250-1251 firstname.lastname@example.com | |
Netherlands | |
Erasmus MC - Sophia Children's Hospital | Recruiting |
Rotterdam, Netherlands, 3015 GJ | |
Contact: Contact Person 31-104-636-691 email@example.com | |
Poland | |
Akademia Medyczna im. Piastow Slaskich | Recruiting |
Wroclaw, Poland, 50-367 | |
Contact: Contact Person 48-71-328-2040 email@example.com | |
Switzerland | |
University Children's Hospital | Recruiting |
Zurich, Switzerland, CH-8032 | |
Contact: Contact Person 41-44-266-7723 firstname.lastname@example.com |
Principal Investigator: | Peter Bader, MD | European Working Group of MDS in Childhood |
ClinicalTrials.gov Identifier: | NCT00898118 History of Changes |
Other Study ID Numbers: |
EWOG-MDS-SCT RC RIC-06 CDR0000587523 ( Registry Identifier: PDQ (Physician Data Query) ) EU-20808 |
Study First Received: | May 9, 2009 |
Last Updated: | August 9, 2013 |
Keywords provided by National Cancer Institute (NCI):
refractory cytopenia with multilineage dysplasia childhood myelodysplastic syndromes previously treated myelodysplastic syndromes secondary myelodysplastic syndromes |
Additional relevant MeSH terms:
Syndrome Myelodysplastic Syndromes Preleukemia Disease Pathologic Processes |
Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Neoplasms |
ClinicalTrials.gov processed this record on March 24, 2017


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Shop Japan. We ship worldwide, bringing Japan directly to you.
◆ compliance can launder at home also, also do not lose color, is a very good bargain g Teijin materials used. So to match what your wearing of various note colors we offer. Adopting to the tip of your kimono, choosing your favorite color free?.
* After your order, will be outsourced, so delivery times Approximately 1-2 days It takes. Also, join the gold after Cancellations and returns Will have to refuse. Please be forewarned.
PayPal OK
Start Date:01/03/2017 00:00 JST End Date:31/05/2017 23:59 JST
This product cannot be shipped to United States from the store.
Please contact the store for further information.


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From Iron Chariots Wiki
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'''Matthew''' can refer to: | '''Matthew''' can refer to: | ||
− | * [[Matthew the evangelist]], one of [[ | + | * '''[[Matthew the evangelist]]''', one of the [[apostle]]s of [[Jesus]]. |
− | * The [[Book of Matthew]], one of the four [[gospel]]s. | + | * The '''[[Book of Matthew]]''', one of the four [[gospel]]s of the [[New Testament]]. |
Latest revision as of 18:13, 26 February 2007
This is a disambiguation page: a list of articles associated with the same title. If an internal link referred you to this page, you may wish to change the link to point directly to the intended article.
Matthew can refer to:
- Matthew the evangelist, one of the apostles of Jesus.
- The Book of Matthew, one of the four gospels of the New Testament.


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Made in Brooklyn: MCMC Fragrances
One of the best things about living in Brooklyn is all of the seriously talented and creative people who live and work here. I decided to start a series of studio visits with some of these inspiring folk. They each have such interesting and beautiful work spaces, so we did a little photo shoot in their studios. I was even lucky enough to get them to model a bag or two.
The first of the series is perfumer, Anne McClain's studio, of MCMC Fragrances. Anne studied her craft in Grasse, France and now works out of my old studio space in Greenpoint. Her perfumes are beautifully complex, yet have notes of very recognizable scents. Anne mixes all of her scents in small batches by hand, and each is inspired by a memory from her past. She calls them "The Stories Collection".
Anne gave me a sample pack when I first met her and I must say that Hunter is my favorite. Here is the story on Hunter:
When I was younger I had a friend named Harrison, who I liked to call Hunter. He lent me the book Ishmael, and played guitar, and taught me about loving the environment. Years later, memories of our long friendship and his adventures building maple sugar cabins in Vermont inspired the fragrance Hunter. With tobacco absolute, organic Bourbon vanilla and fir balsam, this fragrance is best when worn with a flannel shirt.
Anne is modeling the Portland and the Dekalb. Her jewelry is by Odette NY. Photos by Romain Sarda.
6 Responses
I love this shannon! And love these photos!
Thanks! Romain did a good job, no?!
ohhh – so lovely! And Hunter is my favorite scent too.
Looking forward to the other studio visits in your series Shannon!
xoxxx k-
I need to come out to SF soon to visit YOU! xo
this is amazing! do you know what dress Anne is wearing? I think it's gorgeous and would love to get the same!
I'm not sure – you could always email her – I'm sure she'd be happy to tell you! email@example.com