Quote:
>> My niece's son, aged 4 has just been diagnosed with Rhabdomyosarcoma of the
>> Bile duct and has had hiss gall bladder and bile duct removed. However,
>> there are still traces in the liver.
>> He's scheduled for chemo next week.
This article speaks to the finding of higher than normal levels of
serum ferritin in those with this disease.
Serum ferritin is the marker of iron levels in the body.
Iron is KNOWN to 'feed' cancer .
Studies have shown the body has an upper LIMIT to the amount of
iron it can SAFELY hold .
Up until a year ago researchers had suspected this but had
always thought the transferrin had to be 100% full before the
iron became a 'problem'.
Problem being defined as not being held tightly away by the body.
They have found the iron becomes 'unsafe' or free when the transferrin
is only 35% full.
This is a compilation of articles which speak to this problem.
The NIH is funding studies as we speak to find suitable chelators..
iron binders ..which enter the body and remove this iron.
Subject: rhabdomyosarcoma
Scand J Haematol 1977 Aug;19(2):153-8
Elevated serum ferritin in children with malignancies.
Siimes MA, Wang WC, Dallman PR
Serum ferritin (SF) is elevated in {*filter*}s with malignancies, chronic
inflammatory disease, liver disease and iron overload. The purpose of
this study was to determine whether the concentration of SF in
children with a variety of malignancies correlated with the activity
of their disease. Patients with acute lymphoblastic leukaemia (ALL) at
initial diagnosis (n = 11) and relapse (n = 15) had a mean SF of 238
and 338 ng/ml, respectively, compared to the normal mean of 31 ng/ml
and range of 7 to 140 ng/ml in children. In 30 patients with ALL in
remission the mean SF was 109 ng/ml, less than the values in patients
with active disease and greater than the normal mean (P less than
0.001). The concentration of SF was also increased in a group of 77
patients with a variety of solid tumors. The 28 cases with active
disease had a mean SF of 242 ng/ml, significantly higher (P less than
0.001) that the value of 84 ng/ml in 49 patients with no evidence of
residual tumor. The differences in SF concentration did reflect the
activity of disease in the groups as a whole but it remains uncertain
whether the assay will prove useful in following the response to
treatment of patients with certain types of tumor.
PMID: 197590, UI: 77258754
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Subject: transferrin saturation/35%/iron
J Hepatol 2000 May;32(5):727-33
Determination of non-transferrin-bound iron in genetic hemochromatosis using a
new HPLC-based method.
Loreal O, Gosriwatana I, Guyader D, Porter J, Brissot P, Hider RC
INSERM U522, CHR Pontchaillou, Rennes, France.
[Medline record in process]
BACKGROUND/AIMS: Non-transferrin-bound iron may play a major
pathogenic role in iron overload diseases due to its high hepatic
uptake and potential damaging effect.
The aim of this study was to
evaluate the relevance of measuring serum non-transferrin-bound iron
levels in genetic hemochromatosis using a new high performance liquid
chromatography-based method.
METHODS: This method includes a
presaturation step of transferrin with cobalt(II) in order to avoid
secondary deplacement of non-transferrin-bound iron toward transferrin
during the assay.
Six genetic hemochromatotic patients were followed
serially during venesection treatment.
RESULTS/CONCLUSIONS:
The results indicate:
(i) that this new method permits detection of
non-transferrin-bound iron when transferrin is not fully saturated,
(ii) that non-transferrin-bound iron levels persist almost until the
completion of treatment,
(iii) that non-transferrin-bound iron levels
are well correlated with transferrin saturation for a given patient,
and
(iv) that despite some individual variations, a transferrin
saturation value lower than 35% usually corresponds to the
disappearance of non-transferrin-bound iron.
PMID: 10845658, UI: 20302281
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Subject: cancer/kaposi
J Invest Dermatol 2000 Nov;115(5):893-900
Iron chelators inhibit the growth and induce the apoptosis of Kaposi's sarcoma
cells and of their putative endothelial precursors.
Simonart T, Degraef C, Andrei G, Mosselmans R, Hermans P, Van Vooren JP,
Noel JC, Boelaert JR, Snoeck R, Heenen M
Department of Dermatology, Erasme University Hospital, Brussels,
Iron is suspected to be involved in the induction and/or progression
of various human tumors. More particularly, iron may be involved in
the pathogenesis of Kaposi's sarcoma, a tumor of probable vascular
origin. This study was designed to investigate the effect of iron
deprivation on Kaposi's sarcoma. The effects of iron chelators and
iron deprivation associated with serum withdrawal were investigated on
Kaposi's sarcoma-derived spindle cells, on a transformed Kaposi's
sarcoma cell line (Kaposi's sarcoma Y-1) and on endothelial cells,
which are the probable progenitors of Kaposi's sarcoma cells.
Desferrioxamine and deferiprone, two chemically unrelated iron
chelators, induced a time- and concentration-dependent inhibition of
endothelial and Kaposi's sarcoma cell growth. The inhibition of cell
growth was associated with a decrease in Ki-67 and in both stable and
total proliferating cell nuclear antigen expression. Inhibition of the
progression through the G1-phase of the cell cycle was further
evidenced by decreased expression of cyclin D1 and of p34
cyclin-dependent kinase 4. Terminal deoxynucleotidyl
transferase-mediated desoxyuridinetriphosphate nick end labeling
assay, flow cytometry with annexin-V-fluorescein and morphologic
analysis indicated that iron chelation also induced a time- and
concentration-dependent apoptosis. This apoptotic effect was prevented
by the addition of exogenous iron. Induction of iron deprivation in
the culture medium by serum withdrawal led to similar cell cycle
effects, which, however, could only be partly reverted by the addition
of exogenous iron. In conclusion, these results show that iron
deprivation inhibits the growth and induces the apoptosis of Kaposi's
sarcoma cells and of their putative endothelial precursors. This
suggests that iron chelators may represent a potential therapeutic
approach for the treatment of Kaposi's sarcoma.
PMID: 11069629, UI: 20532598
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Subject: chelator / cancer
Carcinogenesis 2001 Oct;22(10):1607-14
p53-independent apoptosis mediated by tachpyridine, an anti-cancer iron
chelator.
Abeysinghe RD, Greene BT, Haynes R, Willingham MC, Turner J, Planalp RP,
Brechbiel MW, Torti FM, Torti SV
Department of Biochemistry, Wake Forest University School of Medicine,
Winston-Salem, NC, USA.
[Medline record in process]
Iron is involved in essential biochemical reactions ranging from
respiration to DNA synthesis. Consequently, iron deprivation has been
proposed as a strategy for inhibition of tumor cell growth. We
recently described a novel iron chelator, tachypyridine
[N,N',N"-tris(2-pyridylmethyl)-cis,cis-1,3,5-triaminocyclohexane], and
demonstrated that it not only inhibited growth of cultured tumor
cells, but was actively cytotoxic. Here we explore the mechanisms
underlying tachpyridine cytotoxicity. Using several criteria,
including time-lapse video microscopy, DNA staining and TUNEL assays,
tachpyridine was shown to specifically induce apoptotic cell death.
Further, unlike numerous cytotoxic chemotherapeutic {*filter*} which induce
apoptosis by activating p53-dependent pathways, tachpyridine-mediated
cell death did not require p53 activation. Although immunoblotting
revealed rapid accumulation of p53 following treatment with
tachpyridine, p21(WAF1) was not induced. Further, neither cytotoxicity
nor apoptosis required p53. p53 null human lung cancer H1299 cells
transfected with an ecdysone-inducible p53 exhibited equivalent
sensitivity to tachpyridine in the presence and absence of p53,
demonstrating the lack of requirement for p53 in an isogenic cell
system. Further, time-lapse video microscopy and TUNEL assays
demonstrated that both p53 null and p53 wild-type cells underwent
apoptotic cell death in response to tachpyridine. In addition, in 55
human cancer cell lines the mean GI(50) of tachpyridine in cells with
mutant p53 was virtually identical to the GI(50) in cells with
wild-type p53. These results demonstrate that tachpyridine initiates
an apoptotic mode of cell death that does not require functional p53.
Since over 50% of human tumors contain a functionally defective p53
that reduces sensitivity to commonly used chemotherapeutic agents,
such as etoposide and cisplatin, the ability of tachpyridine to induce
apoptosis independently of p53 may offer an advantage in anti-tumor
therapy.
PMID: 11576999, UI: 21460375
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