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Old 04-30-2008, 12:19 PM   #4
hutchibk
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I believe that studies are showing that it simply ISN'T true that glutamine potentially could promote tumor growth...

Here's what I found: (from March 2007)

http://theoncologist.alphamedpress.o.../full/12/3/312


Excerpts:

"...Glutamine is a gluconeogenic nonessential amino acid that is<sup> </sup>stored primarily in skeletal muscle and liver [14], and is often<sup> </sup>depleted in stress states, such as malignancy [16]. It serves<sup> </sup>as the primary carrier of nitrogen and is the main energy source<sup> </sup>for rapidly proliferating cells. Rapid proliferation of a tumor<sup> </sup>may deplete glutamine stores and subsequently lead to cancer-related<sup> </sup>cachexia [17]. Studies have indicated that glutamine supplementation<sup> </sup>is well tolerated and potentially effective in preventing side<sup> </sup>effects for patients receiving high-dose chemotherapy and bone<sup> </sup>marrow transplantation [25]. Supplementation with glutamine<sup> </sup>can also protect against doxorubicin-induced cardiac toxicity<sup> </sup>[26] and prevents atrophy of the intestinal mucosa in patients<sup> </sup>receiving total parenteral nutrition [27]. Preliminary animal<sup> </sup>studies suggest that glutamine may prevent neurotoxicity caused<sup> </sup>by vincristine, cisplatin, as well as paclitaxel [28, 29]. Clinically,<sup> </sup>paclitaxel-induced myalgias and arthralgias have been successfully<sup> </sup>reduced by glutamine in breast cancer patients [30]. Glutamine<sup> </sup>supplements may also reduce the severity of peripheral neuropathy<sup> </sup>in metastatic breast cancer patients receiving high-dose paclitaxel<sup> </sup>and hematopoietic stem cell transplantation [18]. Interestingly,<sup> </sup>a byproduct of glutamine metabolism has been identified that<sup> </sup>protects advanced CRC patients from oxaliplatin-induced neuropathy<sup> </sup>[13].<sup> </sup>

In the current study, supplementation with glutamine significantly<sup> </sup>reduced the incidence and severity of peripheral neuropathy<sup> </sup>as well as the need for dose reduction of oxaliplatin in these<sup> </sup>patients (Tables 1 and 3). These properties may increase the<sup> </sup>therapeutic index of oxaliplatin. The potential role of glutamine<sup> </sup>as a neuroprotectant may be better understood in the context<sup> </sup>of the current hypothesis explaining chemotherapy-induced neuropathy.<sup> </sup>A study of circulating nerve growth factor (NGF) levels in cancer<sup> </sup>patients treated with neurotoxic chemotherapeutic agents found<sup> </sup>that peripheral neuropathy worsened as serum levels of NGF declined<sup> </sup>[31]. Moreover, the administration of NGF prevents paclitaxel-induced<sup> </sup>neuropathy in mice [32]. Because glutamine is known to upregulate<sup> </sup>NGF mRNA in an animal model [33], glutamine supplements may<sup> </sup>prevent chemotherapy-induced neuropathy via upregulating the<sup> </sup>NGF level. On the other hand, it has also been hypothesized<sup> </sup>that high systemic levels of glutamine may downregulate the<sup> </sup>conversion of glutamine to an excitatory neuropeptide, glutamate,<sup> </sup>which may also account for the reduced symptoms observed in<sup> </sup>patients receiving glutamine [34]...."<sup> </sup>
<sup>

</sup>"...A major concern is that glutamine supplements might protect<sup> </sup>tumor cells from the cytotoxic effects of chemotherapy. However,<sup> </sup>in the current study, no between-group difference was found<sup> </sup>in the response to chemotherapy (52.4% versus 47.8%; p = .90)<sup> </sup>or survival (p = .79; log-rank test). Although in vitro evidence<sup> </sup>of the dependence of tumor growth on glutamine has deterred<sup> </sup>its application in cancer patients [36], several studies have<sup> </sup>failed to show that supplemental glutamine stimulates tumor<sup> </sup>growth [37, 38]. In fact, accumulating in vivo evidence suggests<sup> </sup>that glutamine may actually decrease tumor growth, possibly<sup> </sup>by upregulating the immune system [37, 39]. The net outcome<sup> </sup>may improve the therapeutic index of oxaliplatin. The overall<sup> </sup>lymphocyte response (i.e., entry into the cell cycle and proliferation)<sup> </sup>has been directly correlated with glutamine concentration of<sup> </sup>the culture medium [40]. In a breast cancer xenograft model,<sup> </sup>the supplemental glutamine group had higher natural killer cell<sup> </sup>activity and nearly one half the tumor volume, compared with<sup> </sup>the placebo group [41]..."
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Brenda

NOV 2012 - 9 yr anniversary
JULY 2012 - 7 yr anniversary stage IV (of 50...)

Nov'03~ dX stage 2B
Dec'03~
Rt side mastectomy, Her2+, ER/PR+, 10 nodes out, one node positive
Jan'04~
Taxotere/Adria/Cytoxan x 6, NED, no Rads, Tamox. 1 year, Arimadex 3 mo., NED 14 mo.
Sept'05~
micro mets lungs/chest nodes/underarm node, Switched to Aromasin, T/C/H x 7, NED 6 months - Herceptin only
Aug'06~
micro mets chest nodes, & bone spot @ C3 neck, Added Taxol to Herceptin
Feb'07~ Genetic testing, BRCA 1&2 neg

Apr'07~
MRI - two 9mm brain mets & 5 punctates, new left chest met, & small increase of bone spot C3 neck, Stopped Aromasin
May'07~
Started Tykerb/Xeloda, no WBR for now
June'07~
MRI - stable brain mets, no new mets, 9mm spots less enhanced, CA15.3 down 45.5 to 9.3 in 10 wks, Ty/Xel working magic!
Aug'07~
MRI - brain mets shrunk half, NO NEW BRAIN METS!!, TMs stable @ 9.2
Oct'07~
PET/CT & MRI show NED
Apr'08~
scans still show NED in the head, small bone spot on right iliac crest (rear pelvic bone)
Sept'08~
MRI shows activity in brain mets, completed 5 fractions/5 consecutive days of IMRT to zap the pesky buggers
Oct'08~
dropped Xeloda, switched to tri-weekly Herceptin in combo with Tykerb, extend to tri-monthly Zometa infusion
Dec'08~
Brain MRI- 4 spots reduced to punctate size, large spot shrunk by 3mm, CT of torso clear/pelvis spot stable
June'09~
new 3-4mm left cerrebellar spot zapped with IMRT targeted rads
Sept'09~
new 6mm & 1 cm spots in pituitary/optic chiasm area. Rx= 25 days of 3D conformal fractionated targeted IMRT to the tumors.
Oct'09~
25 days of low dose 3D conformal fractionated targeted IMRT to the bone mets spot on rt. iliac crest that have been watching for 2 years. Added daily Aromasin back into treatment regimen.
Apr'10~ Brain MRI clear! But, see new small spot on adrenal gland. Change from Aromasin back to Tamoxifen.
June'10~ Tumor markers (CA15.3) dropped from 37 to 23 after one month on Tamoxifen. Continue to monitor adrenal gland spot. Remain on Tykerb/Herceptin/Tamoxifen.
Nov'10~ Radiate positive mediastinal node that was pressing on recurrent laryngeal nerve, causing paralyzed larynx and a funny voice.
Jan'11~ MRI shows possible activity or perhaps just scar tissue/necrotic increase on 3 previously treated brain spots and a pituitary spot. 5 days of IMRT on 4 spots.
Feb'11~ Enrolled in T-DM1 EAP in Denver, first treatment March 25, 2011.
Mar'11~ Finally started T-DM1 EAP in Denver at Rocky Mountain Cancer Center/Rose on Mar. 25... hallelujah.

"I would rather be anecdotally alive than statistically dead."

Last edited by hutchibk; 04-30-2008 at 12:21 PM..
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