oh and Derry's much awaited cool new sniper-rifle finally arrived, not sure what he's gonna snipe but he sure is happy ...
Scott & Sunny
Wednesday, June 24, 2009
Tuesday, June 23, 2009
I'm almost too scared to say it but Scott is starting to feel better.
He hasnt thrown up in 2 weeks and his panicky charge to the bathroom is almost a thing of the past. He is also eating fairly well, still gluggling back too much Sunny D (which I should really stop buying but, according to Scott, it helps the medicines go down - lol), but apart from that he's doing good. The neuropathy in his ankles and feet is still an issue but he isnt complaining about it as much.
Last night we went to knock a few balls around and without thinking HE RAN a few steps. Scott hasnt run anywhere in over 2 years. Pretty cool huh?
He hasnt thrown up in 2 weeks and his panicky charge to the bathroom is almost a thing of the past. He is also eating fairly well, still gluggling back too much Sunny D (which I should really stop buying but, according to Scott, it helps the medicines go down - lol), but apart from that he's doing good. The neuropathy in his ankles and feet is still an issue but he isnt complaining about it as much.
Last night we went to knock a few balls around and without thinking HE RAN a few steps. Scott hasnt run anywhere in over 2 years. Pretty cool huh?
Sunday, June 21, 2009
Friday, June 19, 2009
ScienceDaily (June 19, 2009) — Despite great strides in treating childhood leukemia, a form of the disease called T-cell acute lymphoblastic leukemia (T-ALL) poses special challenges because of the high risk of leukemic cells invading the brain and spinal cord of children who relapse.
Now, a new study in the June 18, 2009, issue of the journal Nature by scientists at NYU School of Medicine reveals the molecular agents behind this devastating infiltration of the central nervous system. The finding may lead to new drugs that block these agents and thus lower the risk of relapse.
T-ALL, a blood-borne cancer in which the bone marrow makes too many lymphocytes, or white blood cells, strikes several hundred children and adolescents in the U.S. annually. While greater than 90% percent go into remission through a combination of chemotherapy and radiation, up to one third of this group end up relapsing. These patients are at particular risk for tumor cells to invade the brain and spinal cord, and to prevent this all patients receive chemotherapy injections into the central nervous system and in some cases cranial irradiation—approaches that cause dangerous side effects, including secondary tumors and potentially permanent cognitive and developmental deficits.
“In general, T-cell acute lymphoblastic leukemia is treatable with chemotherapy and radiation,” said Ioannis Aifantis, PhD, associate professor of pathology and co-director of the Cancer Stem Cell Program at the NYU Cancer Institute, who led the new study. “But you have a very high rate of relapse. And after the relapse, it is not treatable because the cancer occurs in tricky places like the central nervous system,” said Dr. Aifantis, who is also an Early Career Scientist at the Howard Hughes Medical Institute.
“We are very proud of this research and very excited about the potential implications for new therapeutic approaches to prevent or reduce the spread of leukemic cells into the central nervous system,” said Vivian S. Lee MD, PhD, MBA, the vice dean for science, senior vice president and chief scientific officer of NYU Langone Medical Center.
In the new study, Dr. Aifantis and his colleagues found that a key protein receptor embedded on the outer surface of leukemic cells is responsible for infiltrating the brain and spinal cord. “What we have found is that leukemic cells over-express this receptor.” said Dr. Aifantis, “If you knock out this receptor, these cells will not go to the brain under any circumstances.”
Previous research had strongly implicated a famous gene regulator called Notch1 in the progression of T-ALL. The Notch1 gene (a mutated version gives fruit flies notched wings) is an oncogene, or cancer-causing gene, in humans. Certain kinds of mutations in this gene have been found in nearly half of all T-ALL patients, and current estimates suggest that the gene’s regulatory influence might be implicated in nearly 90 percent of all T-ALL cases.
For their new study, Dr. Aifantis and his colleagues first introduced overactive forms of Notch1 into mice. As a result, the mice developed leukemia and the leukemic cells efficiently infiltrated the inner layers of the membrane covering the brain. “What happens is that the leukemic cells get into the cerebrospinal fluidthat protects our brain and spine, where they fill up the space and they can affect brain function, either by secreting chemicals and toxic factors or even by simple pressure,” Dr. Aifantis said.
His team then examined an array of other mouse genes to identify candidates that might fall under the regulatory spell of Notch1 to promote the brain and spinal cord infiltration. The screen revealed a promising gene for a protein named CCR7, which is embedded on the surface of lymphocytes. This chemokine receptor, as it’s known, normally senses and responds to small chemical attractants called chemokines, which act like recruitment signals for lymphocytes to converge on a specific site during the body’s response to infection or injury. In leukemia, however, these lymphocytes proliferate abnormally.
CCR7 was already known as a key player in normal lymphocyte migration and as a binding partner of two chemokines named CCL19 and CCL21. Previous studies had implicated these protein interactions in the metastasis of other tumors such as melanomas and breast cancers. Dr. Aifantis’s team also discovered that the gene for CCR7 was overactive in four of five T-ALL cell lines derived from human patients, bolstering suspicions that it played a central role in the disease. Conversely, a mutation that knocked out Notch1 also led to dramatically reduced CCR7 levels.
To characterize CCR7’s potential role in T-ALL, the researchers used two sets of mice: one in which the receptor was turned on, and a second in which it was turned off. When the team delivered an identical number of human-derived leukemic cells to both sets of mice, those with the CCR7 chemokine receptor turned off lived almost twice as long. Using bioluminescent imaging, the researchers quickly understood why: animals with the active CCR7 receptor had many more tumors. Tellingly, the T-ALL cells had infiltrated the brain and spinal cord of those mice.
Further experiments suggested that when healthy mice received leukemic cells in which the gene for CCR7 had been turned off, the cells could not migrate to the brain even though they reached other body tissues. As a result, the mice survived significantly longer than counterparts with an active copy of the gene. On the other hand, introducing a normal version of the same gene to mice otherwise lacking it was enough to recruit leukemic cells to the brain and spine.
“We wanted to determine whether CCR7 by itself was sufficient for entry into the central nervous system and that’s what this experiment shows,” Dr. Aifantis said. “By changing one specific gene, you now have your function back.”
Finally, the researchers identified the small protein that acted as the “come hither” signal for the CCR7 protein receptors. One candidate, CCL21, was undetectable in leukemic mice. But a second, CCL19, appeared in tiny veins of the brain near the infiltrating tumor cells. When the researchers introduced leukemic cells carrying a gene for CCR7 to mice that naturally lacked the CCL19 chemokine, the mice survived longer, suggesting that their increased life spans might be due to a disrupted interaction of the two proteins. The leukemic cells had no trouble infiltrating other tissue like the lymph nodes, but were completely incapable of infiltrating the brains of CCL19-deficient mice, the researchers report.
“Perhaps there are antibodies or small molecules that can block the interaction between these two proteins or reduce their interactions,” Dr. Aifantis said, “and hopefully that could be used as a type of prophylactic treatment to prevent a relapse in the central nervous system among patients who have already been treated for leukemia.” Such a treatment, he said, could prove a good alternative to the intensive and often poorly tolerated radiation and chemotherapy now used to try to block such a relapse.
The study was led by Dr. Silvia Buonamici, a post-doctoral fellow in the laboratory of Dr. Aifantis in the Department of Pathology and the NYU Cancer Institute, and in the Helen L. and Martin S. Kimmel Stem Cell Center at NYU Langone Medical Center. Other study investigators are; Thomas Trimarchi, Maria Grazia Ruocco, Linsey Reavie, Severine Cathelin, Yevgeniy Lukyanov, Jen-Chieh Tseng, Filiz Sen, Mengling Li, Elizabeth Newcomb, Jiri Zavadil, Daniel Meruelo, Sherif Ibrahim, David Zagzag, and Michael L. Dustin from NYU Langone Medical Center; Brenton G. Mar, Apostolos Klinakis, and Argiris Efstratiadis from Columbia University Medical Center; Eric Gehrie and Jonathan S. Bromberg from Mount Sinai School of Medicine; and Martin Lipp from the Max Delbrück Center for Molecular Medicine in Berlin.
The study was supported by grants from the National Institutes of Health, the American Cancer Society, the Dana Foundation, The Chemotherapy Foundation, the Alex’s Lemonade Stand Foundation, the Lauri Strauss Leukemia foundation, the G&P Foundation, an NYU School of Medicine Molecular Oncology and Immunology training grant, the American Society of Hematology, the Juvenile Diabetes Research Foundation, the National Cancer Institute, a gift from the Berrie Foundation, and a fellowship from the Jane Coffin Childs Memorial Fund for Medical Research.
Now, a new study in the June 18, 2009, issue of the journal Nature by scientists at NYU School of Medicine reveals the molecular agents behind this devastating infiltration of the central nervous system. The finding may lead to new drugs that block these agents and thus lower the risk of relapse.
T-ALL, a blood-borne cancer in which the bone marrow makes too many lymphocytes, or white blood cells, strikes several hundred children and adolescents in the U.S. annually. While greater than 90% percent go into remission through a combination of chemotherapy and radiation, up to one third of this group end up relapsing. These patients are at particular risk for tumor cells to invade the brain and spinal cord, and to prevent this all patients receive chemotherapy injections into the central nervous system and in some cases cranial irradiation—approaches that cause dangerous side effects, including secondary tumors and potentially permanent cognitive and developmental deficits.
“In general, T-cell acute lymphoblastic leukemia is treatable with chemotherapy and radiation,” said Ioannis Aifantis, PhD, associate professor of pathology and co-director of the Cancer Stem Cell Program at the NYU Cancer Institute, who led the new study. “But you have a very high rate of relapse. And after the relapse, it is not treatable because the cancer occurs in tricky places like the central nervous system,” said Dr. Aifantis, who is also an Early Career Scientist at the Howard Hughes Medical Institute.
“We are very proud of this research and very excited about the potential implications for new therapeutic approaches to prevent or reduce the spread of leukemic cells into the central nervous system,” said Vivian S. Lee MD, PhD, MBA, the vice dean for science, senior vice president and chief scientific officer of NYU Langone Medical Center.
In the new study, Dr. Aifantis and his colleagues found that a key protein receptor embedded on the outer surface of leukemic cells is responsible for infiltrating the brain and spinal cord. “What we have found is that leukemic cells over-express this receptor.” said Dr. Aifantis, “If you knock out this receptor, these cells will not go to the brain under any circumstances.”
Previous research had strongly implicated a famous gene regulator called Notch1 in the progression of T-ALL. The Notch1 gene (a mutated version gives fruit flies notched wings) is an oncogene, or cancer-causing gene, in humans. Certain kinds of mutations in this gene have been found in nearly half of all T-ALL patients, and current estimates suggest that the gene’s regulatory influence might be implicated in nearly 90 percent of all T-ALL cases.
For their new study, Dr. Aifantis and his colleagues first introduced overactive forms of Notch1 into mice. As a result, the mice developed leukemia and the leukemic cells efficiently infiltrated the inner layers of the membrane covering the brain. “What happens is that the leukemic cells get into the cerebrospinal fluidthat protects our brain and spine, where they fill up the space and they can affect brain function, either by secreting chemicals and toxic factors or even by simple pressure,” Dr. Aifantis said.
His team then examined an array of other mouse genes to identify candidates that might fall under the regulatory spell of Notch1 to promote the brain and spinal cord infiltration. The screen revealed a promising gene for a protein named CCR7, which is embedded on the surface of lymphocytes. This chemokine receptor, as it’s known, normally senses and responds to small chemical attractants called chemokines, which act like recruitment signals for lymphocytes to converge on a specific site during the body’s response to infection or injury. In leukemia, however, these lymphocytes proliferate abnormally.
CCR7 was already known as a key player in normal lymphocyte migration and as a binding partner of two chemokines named CCL19 and CCL21. Previous studies had implicated these protein interactions in the metastasis of other tumors such as melanomas and breast cancers. Dr. Aifantis’s team also discovered that the gene for CCR7 was overactive in four of five T-ALL cell lines derived from human patients, bolstering suspicions that it played a central role in the disease. Conversely, a mutation that knocked out Notch1 also led to dramatically reduced CCR7 levels.
To characterize CCR7’s potential role in T-ALL, the researchers used two sets of mice: one in which the receptor was turned on, and a second in which it was turned off. When the team delivered an identical number of human-derived leukemic cells to both sets of mice, those with the CCR7 chemokine receptor turned off lived almost twice as long. Using bioluminescent imaging, the researchers quickly understood why: animals with the active CCR7 receptor had many more tumors. Tellingly, the T-ALL cells had infiltrated the brain and spinal cord of those mice.
Further experiments suggested that when healthy mice received leukemic cells in which the gene for CCR7 had been turned off, the cells could not migrate to the brain even though they reached other body tissues. As a result, the mice survived significantly longer than counterparts with an active copy of the gene. On the other hand, introducing a normal version of the same gene to mice otherwise lacking it was enough to recruit leukemic cells to the brain and spine.
“We wanted to determine whether CCR7 by itself was sufficient for entry into the central nervous system and that’s what this experiment shows,” Dr. Aifantis said. “By changing one specific gene, you now have your function back.”
Finally, the researchers identified the small protein that acted as the “come hither” signal for the CCR7 protein receptors. One candidate, CCL21, was undetectable in leukemic mice. But a second, CCL19, appeared in tiny veins of the brain near the infiltrating tumor cells. When the researchers introduced leukemic cells carrying a gene for CCR7 to mice that naturally lacked the CCL19 chemokine, the mice survived longer, suggesting that their increased life spans might be due to a disrupted interaction of the two proteins. The leukemic cells had no trouble infiltrating other tissue like the lymph nodes, but were completely incapable of infiltrating the brains of CCL19-deficient mice, the researchers report.
“Perhaps there are antibodies or small molecules that can block the interaction between these two proteins or reduce their interactions,” Dr. Aifantis said, “and hopefully that could be used as a type of prophylactic treatment to prevent a relapse in the central nervous system among patients who have already been treated for leukemia.” Such a treatment, he said, could prove a good alternative to the intensive and often poorly tolerated radiation and chemotherapy now used to try to block such a relapse.
The study was led by Dr. Silvia Buonamici, a post-doctoral fellow in the laboratory of Dr. Aifantis in the Department of Pathology and the NYU Cancer Institute, and in the Helen L. and Martin S. Kimmel Stem Cell Center at NYU Langone Medical Center. Other study investigators are; Thomas Trimarchi, Maria Grazia Ruocco, Linsey Reavie, Severine Cathelin, Yevgeniy Lukyanov, Jen-Chieh Tseng, Filiz Sen, Mengling Li, Elizabeth Newcomb, Jiri Zavadil, Daniel Meruelo, Sherif Ibrahim, David Zagzag, and Michael L. Dustin from NYU Langone Medical Center; Brenton G. Mar, Apostolos Klinakis, and Argiris Efstratiadis from Columbia University Medical Center; Eric Gehrie and Jonathan S. Bromberg from Mount Sinai School of Medicine; and Martin Lipp from the Max Delbrück Center for Molecular Medicine in Berlin.
The study was supported by grants from the National Institutes of Health, the American Cancer Society, the Dana Foundation, The Chemotherapy Foundation, the Alex’s Lemonade Stand Foundation, the Lauri Strauss Leukemia foundation, the G&P Foundation, an NYU School of Medicine Molecular Oncology and Immunology training grant, the American Society of Hematology, the Juvenile Diabetes Research Foundation, the National Cancer Institute, a gift from the Berrie Foundation, and a fellowship from the Jane Coffin Childs Memorial Fund for Medical Research.
Thursday, June 18, 2009
Wednesday, June 17, 2009
Thursday, June 11, 2009
So another clinic day dawned, Scott and I shared a bottle of Pepto, downed some good pills and went forth unto the dragons den. I hate clinic.
However, we have been reprieved once more and all is well - ish! Woooooooohooooooooooooo!
His counts werent great, platelets - 260, wbc 4.4 and hgb 10.8. No unclassifieds! :) I was really surprised his hemoglobin was so crap since he has decent colour in his cheeks but his nutrition levels were also abysmal so it would seem the two are possibly linked. If he's not vomiting he's fasting (because he's too scared to eat) so maybe the lack of iron and protein are now showing up in the bloodwork.
His physical went fine, bp a little high but I think it was just nerves. No swollen lymph nodes or balls (yup he always gets a thorough groping down there because thats one of leukemia's favourite hiding places!!!!). Spleen also normal (again a hiding place).
Scott has been referred to a GI specialist, so hopefully we can get an appointment soon and nothing too sinister will be found. The possibilities of either crohns or colitis were mentioned today which are obviously not the most pleasant of conditions for Scott to have to deal with, anyhow we'll just have to see what the doc says and go from there.
Well thats it for now, Im so tired and my nerves are shot.
Thanks for checking in y'all.
However, we have been reprieved once more and all is well - ish! Woooooooohooooooooooooo!
His counts werent great, platelets - 260, wbc 4.4 and hgb 10.8. No unclassifieds! :) I was really surprised his hemoglobin was so crap since he has decent colour in his cheeks but his nutrition levels were also abysmal so it would seem the two are possibly linked. If he's not vomiting he's fasting (because he's too scared to eat) so maybe the lack of iron and protein are now showing up in the bloodwork.
His physical went fine, bp a little high but I think it was just nerves. No swollen lymph nodes or balls (yup he always gets a thorough groping down there because thats one of leukemia's favourite hiding places!!!!). Spleen also normal (again a hiding place).
Scott has been referred to a GI specialist, so hopefully we can get an appointment soon and nothing too sinister will be found. The possibilities of either crohns or colitis were mentioned today which are obviously not the most pleasant of conditions for Scott to have to deal with, anyhow we'll just have to see what the doc says and go from there.
Well thats it for now, Im so tired and my nerves are shot.
Thanks for checking in y'all.
Tuesday, June 9, 2009
On a brighter note
Yesterday Derry, Scott and I received congratulatory letters from the United States Citizenship and Immigration Centre stating that we have jumped through all the necessary hoops and were now Legal Permanent Residents of the USA.
It has been an hilarious experience, and now, just for fun, maybe we should do the whole process again but in reverse. All in favour of our deep-South David becoming a minion of her Majesty the Queen, say "aye".
As for Scotty boy, well he's an enigma for sure. One day he's duracelling up and down the pool, devouring everything in site, spouting forth weird and wonderful facts (we call him 'Oracle', he wasn't that way prior to the cranial radiation, something mystical happened in that human microwave!!!!) and chattering non-stop. The next, he's doing the dying swan routine.
He has his monthly appointment on Thursday and will also have his port flushed and a breathing treatment. Hopefully counts will look good and we can all exhale.
It has been an hilarious experience, and now, just for fun, maybe we should do the whole process again but in reverse. All in favour of our deep-South David becoming a minion of her Majesty the Queen, say "aye".
As for Scotty boy, well he's an enigma for sure. One day he's duracelling up and down the pool, devouring everything in site, spouting forth weird and wonderful facts (we call him 'Oracle', he wasn't that way prior to the cranial radiation, something mystical happened in that human microwave!!!!) and chattering non-stop. The next, he's doing the dying swan routine.
He has his monthly appointment on Thursday and will also have his port flushed and a breathing treatment. Hopefully counts will look good and we can all exhale.
Monday, June 8, 2009
Its been one year since Callum left us. Scott talks about him all the time, sometimes he's broken-hearted and other times he laughs and giggles at his 'highlander' daddy. Derry never mentions him. This morning Scott was reminiscing and coming out with some of his favourite doric phrases. "Awa and bile yer heed maither" (be off with you mum, and boil your head), "Ken fit like" (you know what I mean) and "Foos yer doos" (how are you doing).
Kevin is still very ill from the stroke he suffered a few weeks after Callum died. He's out of hospital but still needs full time care. He cant talk except to say, "aye". He seems to live in a world of confusion with no signs of recovery. I get so choked up when I think about Kev, we were incredibly close.
I still cant believe that I'll never again be able to pick them up, dust them off or put their world's to rights. More importantly, I'll never again hear Callum's interpretation of why the Giza monuments were built or what he thought of Margaret Thatcher and the Poll Tax. LOL.
Saturday, June 6, 2009
Friday, June 5, 2009
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