| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Tumor Biology |
Departments of Endocrinology [C. S., E. R. B., J. C. M.], Nuclear Medicine [M. K. O.], and Urology [D. J. T., C. Y. F. Y.], Mayo Clinic, Rochester, Minnesota 55905
 |
ABSTRACT |
|---|
 Top ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
|
INTRODUCTION |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
A novel form of gene therapy, using NIS gene transfer to induce iodide accumulation activity in prostate cancer cells by expression of functionally active NIS, would therefore extend the utility of radioiodine therapy to the treatment of prostate cancer. To minimize extratumoral toxicity, a tissue-specific promoter, such as the PSA3 promoter, may be used to provide selective, prostate-specific NIS gene expression (7, 8, 9) . The PSA promoter has been extensively characterized in recent years and has been shown to be responsible for prostate-specific and androgen-regulated expression of PSA, a serine protease of 237 amino acids, that is mainly expressed within the epithelial lining and acini of the prostate gland (10, 11, 12, 13) .
We reported recently the induction of tissue-specific,
androgen-dependent iodide uptake activity in prostate cancer cells
in vitro by PSA promoter-directed NIS gene
delivery (14)
. The androgen-sensitive human prostatic
adenocarcinoma cell line LNCaP was stably transfected with an
expression vector in which full-length NIS cDNA had been
coupled to a 6-kb PSA promoter fragment (14
, 15)
. The
stably transfected LNCaP cell line NP-1 showed perchlorate-sensitive,
androgen-dependent iodide uptake activity, whereas no iodide uptake
activity was detected in LNCaP cells transfected with the control
vectors. The magnitude of iodide uptake in NP-1 cells concentrating
125I 
50-fold was highly encouraging and
suggested that a therapeutic effect of accumulated radioiodine
(14)
could be achieved. Although these in vitro
data suggested the feasibility of the concept of NIS gene
transfer as a first step toward radioiodine therapy of prostate cancer,
its utility required direct demonstration. Therefore, the aim of our
current study was to investigate radioiodine accumulation in
NIS-transfected LNCaP cell xenografts in vivo and
to examine the therapeutic effectiveness of 131I
in vitro and in vivo for prostate cancer cells.
|
MATERIALS AND METHODS |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Establishment of Stable Transfected LNCaP Cell Lines.
Stable transfection of LNCaP cells was performed as described
previously (14)
. In brief, the androgen-sensitive human
prostatic adenocarcinoma cell line LNCaP was transfected with
NIS/PSA-pEGFP-1 and the control vectors
NIS-pEGFP-1 and PSA-pEGFP-1, respectively, using
LipofectAMINE Plus Reagent (Life Technologies, Inc., Gaithersburg, MD).
Selection was performed with geneticin, and surviving clones were
isolated and subjected to screening for androgen-dependent iodide
uptake activity. NP-1, the clone with the highest androgen-dependent
iodide uptake activity, was chosen for the following studies, as well
as the stably transfected (PSA-pEGFP-1) control cell line P-1
(14)
.
In Vitro Clonogenic Assay.
LNCaP cells stably transfected with the expression vector (NP-1) or the
control vector (P-1) were incubated for 7 h with 0.8 mCi
Na131I in HBSS supplemented with 10
µM NaI and 10 mM HEPES at pH 7.3. After
incubation with radioiodine, cells were trypsinized and plated in
quadruplicates at cell densities of 1000, 2000, 3000, 5000, and 7000
cells/well in 12-well plates. Four weeks later, after colony
development, cells were fixed with methanol and stained with crystal
violet, and colonies containing >50 cells were counted. Parallel
experiments were performed for each cell line using HBSS without
131I, and all values were adjusted for plating
efficiency. The percentage of survival represents the percentage of
cell colonies after 131I treatment compared with
mock treatment with HBSS. Results are expressed as mean ± SE of quadruplicates. Statistical significance was tested using
Student’s t test.
Establishment of LNCaP Cell Xenotransplants.
Xenotransplants derived from NP-1 (right flank) and P-1 (left flank)
were established in male BALB/c nu/nu mice (Harlan Sprague
Dawley, Indianapolis, IN) by s.c. injection of 1 x 106 cells suspended in 0.25 ml of RPMI 1640 and
0.25 ml of Matrigel Basement Membrane Matrix (Becton Dickinson,
Bedford, MA). Nude mice were maintained in our facility under specific
pathogen-free conditions with access to mouse chow and water ad
libitum. All experiments were performed in accordance with the
Institutional Animal Care and Use Committee guidelines of the
Mayo Clinic (Rochester, MN).
Western Blot Analysis.
Membrane proteins were prepared from LNCaP cell xenografts as described
previously (14)
and subjected to electrophoresis on a
4–12% Bis-Tris-HCl buffered polyacrylamide gel. After transfer of
proteins to nitrocellulose membranes by electroblotting, membranes were
preincubated in 5% low fat dried milk in TBS-T (20 mM
Tris, 137 mM NaCl, and 0.1% Tween 20). Western blot
analysis was performed using a mouse monoclonal antibody directed
against amino acid residues 468–643 of human NIS (dilution 1:3000;
Ref. 16
) as described previously (14)
.
Immunohistochemistry.
Immunohistochemical staining of frozen tissue sections derived from
LNCaP cell xenografts was performed using the Vectastain Elite ABC kit
(Vector Laboratories, Burlingame, CA). After fixation of tissue
sections in cold acetone, inhibition of endogenous peroxidase activity,
and blocking of nonspecific binding with blocking serum for 30 min,
slides were incubated with the mouse monoclonal hNIS antibody at a
dilution of 1:1600 (16)
for 90 min. Tissue sections were
incubated with biotin-conjugated antimouse-immunoglobulin for 30 min at
room temperature, followed by incubation with preformed avidin and
biotinylated horseradish peroxidase macromolecular complex.
Diaminobenzidine was used as the chromogen (bluish-black precipitate).
Parallel control slides were examined with the primary and secondary
antibodies replaced in turn by PBS and isotype matched nonimmune IgGs.
Iodide Uptake Studies in Vivo.
Eight to 12 weeks after s.c. injection of transfected LNCaP cells, when
tumors had reached 10 mm in diameter, mice were switched to a
low-iodine diet and received T4 supplementation (5 mg/l) in their
drinking water for 2 weeks to maximize radioiodine uptake in the
tumor and reduce uptake by the thyroid gland. After i.p. injection
of 500 µCi 123I, radioiodine imaging was
performed using a gamma camera (Helix system; Elscint, Inc., Haifa,
Israel). Regions of uptake have been quantified and expressed as a
fraction of the total amount of the applied radioiodine. Iodide
retention time within the tumor was determined by serial scanning after
radioiodine injection, and dosimetric calculations were performed.
Radioiodine Therapy Study in Vivo.
Xenografts of NP-1 and P-1 cells were established in four groups
of mice (five mice in each group) as described above. One group of mice
(group 1) was administered 3 mCi 131I by a single
i.p. injection after 8–10 weeks of tumor growth (late tumors), and
another group of mice (group 2) was administered 3 mCi of
131I after 4–6 weeks of tumor growth (early
tumors). The other two groups of five mice were administered saline by
i.p. injections and were used as controls. Tumors were measured before
administration of radioiodine and weekly thereafter. Tumor volume was
estimated using the formula: tumor volume = length x width x height x 0.52 (17)
. All mice were followed for a total of 6
weeks. Tumor volumes of NP-1 tumors in the therapy groups were compared
with tumor volumes of P-1 tumors in the therapy groups and tumor
volumes of NP-1 and P-1 tumors in the control groups. Statistical
significance was tested using Student’s t test (for
unpaired samples: when examining between treated and untreated mice;
and for paired samples: when examining tumors within the same
mouse).
|
RESULTS |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
20% of the P-1 cells were
killed by exposure to 131I, 75% of NP-1 cells
were killed (Fig. 1)
. These data indicate that a sufficiently high dose of radiation was
achieved in NIS-transfected LNCaP cells to result in cell
killing at a dose that spared control LNCaP cells that are not able to
trap iodine.
|
10 mm in diameter, 500 µCi
123I were injected i.p. (n = 6), and radioiodine uptake by the tumors was monitored and
quantified by imaging with a gamma camera. In contrast to the control
P-1 tumors, which showed no in vivo uptake of radioiodine,
NP-1 tumors accumulated 25–30% of the total radioiodine dose
administered (Fig. 2)
. The maximum radioiodine uptake with an average of 27.5% occurred
around 15–20 h after 123I injection. The average
biological half-life of accumulated radioiodine in LNCaP cell
xenotransplants was 45 h with a minimum of 30 h and a maximum
of 61.5 h (Fig. 3)
.
|
|
350 rads after an i.p. application of a 1 mCi dose
of 131I (37 MBq). In comparison, the average
absorbed dose to stomach was 138 rads/mCi 131I
and approximately 450 rads/mCi 131I to the
thyroid gland.
Western Blot Analysis.
Using a mouse monoclonal hNIS-specific antibody, Western blot analysis
of membrane proteins derived from NP-1 cell xenografts revealed a band
of a molecular weight of Mr
90,000 [consistent with previously reported NIS protein
(16)
], which was not detected in P-1 cell xenografts
(data not shown).
Immunohistochemical Staining.
Immunostaining of frozen tissue sections derived from LNCaP cell
xenografts using a mouse monoclonal hNIS antibody revealed marked cell
membrane-associated hNIS-specific immunoreactivity in LNCaP cells in
NP-1 cell xenografts (Fig. 4A)
. In contrast, LNCaP cells in P-1 cell xenografts did not
show hNIS-specific immunoreactivity (Fig. 4B)
. Control
slides stained with primary and secondary antibodies replaced in turn
by PBS and isotype-matched nonimmune mouse immunoglobulin were
consistently negative (Fig. 4C)
.
|
, the NP-1 and P-1 tumors in the control groups (saline injection) as
well as P-1 tumors in the therapy groups continued their growth
unabated throughout the observation period. In contrast, NP-1 tumors in
therapy group 1 (late tumors; mean tumor volume, 177 ± 72 mm3
) demonstrated dramatic reduction in tumor
volumes. All five tumors demonstrated >50% reduction in volume, and
two of five tumors became undetectable, indicating complete response
(mean tumor volume reduction, 95 ± 3%;
P < 0.01; Fig. 5A
). Therapy group
2 (early tumors; mean tumor volume, 43 ± 25
mm3
) showed an even more prominent
(P < 0.05) therapeutic response in that 60%
of the NP-1 tumors demonstrated complete response (mean tumor volume
reduction, 99 ± 0.6%; P < 0.01; Fig. 5B
). None of the mice demonstrated adverse
effects of the radioiodine therapy.
|
|
DISCUSSION |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
Cloning and characterization of the hNIS gene offers the possibility of NIS gene transfer into nonthyroidal tumor cells, thereby inducing radioiodine accumulation and making imaging and treatment of nonthyroidal tumors with radioiodine possible (3 , 4 , 6) . This could offer a highly effective therapy that is remarkably free of adverse affects, except for transient and usually mild sialadenitis and depression of bone marrow activity (2 , 18) . Because thyroidal NIS expression is exquisitely thyroid-stimulating hormone sensitive (19 , 20) , pretreating the patients with thyroid hormone would suppress thyroid-stimulating hormone levels and thyroidal 131I uptake and thereby prevent hypothyroidism. Even if thyroidal radioiodine uptake would cause hypothyroidism, patients could be easily and inexpensively managed by thyroid hormone replacement therapy.
Recently, expression of functionally active NIS was reported in human glioma cells using adenovirus-mediated gene delivery (21) . Shimura et al. (22) reported transfection of malignantly transformed rat thyroid cells (FRTL-5 cells), which normally do not concentrate iodide, with a rat NIS cDNA expression vector. The resulting rat NIS-expressing FRTL-5 cell line accumulated 125I in vitro and in vivo (22) . Furthermore, Mandell et al. (23) demonstrated in vitro and in vivo iodide accumulation in several cancer cell lines, including melanoma, liver, colon carcinoma, and ovarian carcinoma cell lines, after transfection with the rat NIS gene. These data demonstrate the potential of NIS gene transfer to induce iodide accumulation activity in tumor cells, although the therapeutic efficacy of accumulated 131I remains to be investigated.
The purpose of the present study was to evaluate the efficacy of
prostate-specific NIS gene transfer as a novel form of gene
therapy in which tissue-specific radioiodine accumulation is induced in
prostate cancer cells. To maximize intratumoral cytotoxicity and
minimize extratumoral side effects, we used a prostate tissue-specific
promoter to target the NIS gene selectively to prostate
cancer cells. With the PSA gene being strictly regulated in
a tissue-specific and androgen-dependent manner, the PSA promoter,
which has been extensively characterized in recent years
(10, 11, 12, 13)
, provides an efficient means for prostate
cell-specific, androgen-regulated gene delivery (7, 8, 9)
.
Recently, using the PSA promoter, antisense gene delivery targeting DNA
polymerase-
and topoisomerase II was shown to inhibit cell growth
specifically in human prostate cancer cells. In contrast, no
cytotoxicity was observed in five control nonprostatic cell lines
(24)
.
In our experiments, we stably transfected the human prostatic adenocarcinoma cell line LNCaP with an expression vector containing full-length NIS cDNA coupled to a 6-kb promoter fragment that has been shown recently to mimic, in transgenic mice, the prostate-specific and androgen-regulated expression of the endogenous PSA gene in humans (15) . Prostate cell-specific, androgen-regulated iodide uptake activity was demonstrated in LNCaP cell lines stably expressing NIS under the control of the PSA promoter in vitro (14) . In the current study, the amount of accumulated 131I has been shown to be sufficiently high to selectively kill NIS-transfected LNCaP cells in an in vitro clonogenic assay. These results are highly significant for transfected prostate cancer cells growing in a monolayer, considering that a great proportion of the ß-energy emitted from accumulated 131I is deposited outside from the monolayer. Radioiodine accumulation has further been confirmed in vivo in NIS-transfected LNCaP cell xenografts that accumulated 25–30% of the total administered radioiodine with a biological half-life of 45 h. NIS protein expression was confirmed by Western blot analysis and immunohistochemistry. Considering a tumor mass of 1 g, a tumor dose of 350 rad/mCi 131I has been calculated, which is comparable with therapeutic doses achieved in thyroid metastases during radioiodine therapy with a 100–150 mCi 131I therapy dose (25) . According to the dosimetry studies, a single therapeutic 131I dose of 3 mCi was administered and shown to elicit a dramatic therapeutic response in NIS-transfected LNCaP cell xenografts with an average volume reduction of >90% and complete tumor regression in up to 60% of the tumors.
In conclusion, a therapeutic effect of 131I has been demonstrated in prostate cancer cells after induction of tissue-specific iodide uptake activity by PSA promoter-directed NIS expression in vitro and in vivo. This study clearly demonstrates the potential of NIS to serve as a novel therapeutic gene in the therapy of nonthyroidal cancers, in particular metastatic prostate cancer.
|
ACKNOWLEDGMENTS |
|---|
|
FOOTNOTES |
|---|
1 This study was supported in part by Grant Sp
581/1-1 (to C. S.) from the German Research Council (Deutsche
Forschungsgemeinschaft, Bonn, Germany), by NIH Grants DK 41995 and CA
70892 (to D. J. T. and C. Y. F. Y.), by a CaPCURE research award
(to J. C. M.), and by the Mayo Foundation. 
2 To whom requests for reprints should be
addressed, at Division of Endocrinology, Mayo Clinic, Guggenheim 625,
200 First Street SW, Rochester, MN 55905. Phone: (507) 284-2324; Fax:
(507) 284-4521; E-mail: spitzweg.christine{at}mayo.edu
3 The abbreviations used are: PSA,
prostate-specific antigen; hNIS, human sodium iodide symporter.
Received 4/21/00. Accepted 9/20/00.
|
REFERENCES |
|---|
|
TopABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
|---|
and topoisomerase II in prostate cancer. Anticancer Res., 16: 1805-1812, 1996.[Medline]
This article has been cited by other articles:
|
|
 |
|
  K. Klutz, V. Russ, M. J. Willhauck, N. Wunderlich, C. Zach, F. J. Gildehaus, B. Goke, E. Wagner, M. Ogris, and C. Spitzweg Targeted Radioiodine Therapy of Neuroblastoma Tumors following Systemic Nonviral Delivery of the Sodium Iodide Symporter Gene Clin. Cancer Res., October 1, 2009; 15(19): 6079 - 6086. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Carlson, K. L. Classic, E. M. Hadac, D. Dingli, C. E. Bender, B. J. Kemp, and S. J. Russell Quantitative Molecular Imaging of Viral Therapy for Pancreatic Cancer Using an Engineered Measles Virus Expressing the Sodium-Iodide Symporter Reporter Gene Am. J. Roentgenol., January 1, 2009; 192(1): 279 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hingorani, C. L. White, S. Zaidi, A. Merron, I. Peerlinck, M. E. Gore, C. M. Nutting, H. S. Pandha, A. A. Melcher, R. G. Vile, et al. Radiation-Mediated Up-Regulation of Gene Expression from Replication-Defective Adenoviral Vectors: Implications for Sodium Iodide Symporter Gene Therapy Clin. Cancer Res., August 1, 2008; 14(15): 4915 - 4924. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. H. Jeon, Y. Choi, S. O. Yoon, C. W. Kim, and J.-K. Chung Synergistic tumoricidal effect of combined hMUC1 vaccination and hNIS radioiodine gene therapy Mol. Cancer Ther., July 1, 2008; 7(7): 2252 - 2260. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Willhauck, B.-R. Sharif Samani, F.-J. Gildehaus, I. Wolf, R. Senekowitsch-Schmidtke, H.-J. Stark, B. Goke, J. C. Morris, and C. Spitzweg Application of 188Rhenium as an Alternative Radionuclide for Treatment of Prostate Cancer after Tumor-Specific Sodium Iodide Symporter Gene Expression J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4451 - 4458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Goel, S. K. Carlson, K. L. Classic, S. Greiner, S. Naik, A. T. Power, J. C. Bell, and S. J. Russell Radioiodide imaging and radiovirotherapy of multiple myeloma using VSV({Delta}51)-NIS, an attenuated vesicular stomatitis virus encoding the sodium iodide symporter gene Blood, October 1, 2007; 110(7): 2342 - 2350. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. I. Kim, J. H. Kang, J.-K. Chung, Y. J. Lee, J. M. Jeong, D. S. Lee, and M. C. Lee Doxorubicin Enhances the Expression of Transgene Under Control of the CMV Promoter in Anaplastic Thyroid Carcinoma Cells J. Nucl. Med., September 1, 2007; 48(9): 1553 - 1561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Riesco-Eizaguirre and P. Santisteban A perspective view of sodium iodide symporter research and its clinical implications. Eur. J. Endocrinol., October 1, 2006; 155(4): 495 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T Kogai, K Taki, and G A Brent Enhancement of sodium/iodide symporter expression in thyroid and breast cancer. Endocr. Relat. Cancer, September 1, 2006; 13(3): 797 - 826. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Elisei, A. Vivaldi, R. Ciampi, P. Faviana, F. Basolo, F. Santini, C. Traino, F. Pacini, and A. Pinchera Treatment with Drugs Able to Reduce Iodine Efflux Significantly Increases the Intracellular Retention Time in Thyroid Cancer Cells Stably Transfected with Sodium Iodide Symporter Complementary Deoxyribonucleic Acid J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2389 - 2395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Chen, A. Altmann, W. Mier, H. Eskerski, K. Leotta, L. Guo, R. Zhu, and U. Haberkorn Radioiodine Therapy of Hepatoma Using Targeted Transfer of the Human Sodium/Iodide Symporter Gene J. Nucl. Med., May 1, 2006; 47(5): 854 - 862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Petrich, L. Quintanilla-Martinez, Z. Korkmaz, E. Samson, H. J. Helmeke, G. J. Meyer, W. H. Knapp, and E. Potter Effective Cancer Therapy with the {alpha}-Particle Emitter [211At]Astatine in a Mouse Model of Genetically Modified Sodium/Iodide Symporter-Expressing Tumors Clin. Cancer Res., February 15, 2006; 12(4): 1342 - 1348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Unterholzner, M. J. Willhauck, N. Cengic, M. Schutz, B. Goke, J. C. Morris, and C. Spitzweg Dexamethasone Stimulation of Retinoic Acid-Induced Sodium Iodide Symporter Expression and Cytotoxicity of 131-I in Breast Cancer Cells J. Clin. Endocrinol. Metab., January 1, 2006; 91(1): 69 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhang, Y.-Y. Liu, and S. M. Jhiang Cell Surface Targeting Accounts for the Difference in Iodide Uptake Activity between Human Na+/I- Symporter and Rat Na+/I- Symporter J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6131 - 6140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Cengic, C. H. Baker, M. Schutz, B. Goke, J. C. Morris, and C. Spitzweg A Novel Therapeutic Strategy for Medullary Thyroid Cancer Based on Radioiodine Therapy following Tissue-Specific Sodium Iodide Symporter Gene Expression J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4457 - 4464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Dwyer, E. R. Bergert, M. K. O'Connor, S. J. Gendler, and J. C. Morris In vivo Radioiodide Imaging and Treatment of Breast Cancer Xenografts after MUC1-Driven Expression of the Sodium Iodide Symporter Clin. Cancer Res., February 15, 2005; 11(4): 1483 - 1489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. I. Kim, J.-K. Chung, J. H. Kang, Y. J. Lee, J. H. Shin, H. J. Oh, J. M. Jeong, D. S. Lee, and M. C. Lee Visualization of Endogenous p53-Mediated Transcription In vivo Using Sodium Iodide Symporter Clin. Cancer Res., January 1, 2005; 11(1): 123 - 128. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Faivre, J. Clerc, R. Gerolami, J. Herve, M. Longuet, B. Liu, J. Roux, F. Moal, M. Perricaudet, and C. Brechot Long-Term Radioiodine Retention and Regression of Liver Cancer after Sodium Iodide Symporter Gene Transfer in Wistar Rats Cancer Res., November 1, 2004; 64(21): 8045 - 8051. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Mitrofanova, R. Unfer, N. Vahanian, W. Daniels, E. Roberson, T. Seregina, P. Seth, and C. Link Jr. Rat Sodium Iodide Symporter for Radioiodide Therapy of Cancer Clin. Cancer Res., October 15, 2004; 10(20): 6969 - 6976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Dentice, C. Luongo, A. Elefante, R. Romino, R. Ambrosio, M. Vitale, G. Rossi, G. Fenzi, and D. Salvatore Transcription Factor Nkx-2.5 Induces Sodium/Iodide Symporter Gene Expression and Participates in Retinoic Acid- and Lactation-Induced Transcription in Mammary Cells Mol. Cell. Biol., September 15, 2004; 24(18): 7863 - 7877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Kang, J.-K. Chung, Y. J. Lee, J. H. Shin, J. M. Jeong, D. S. Lee, and M. C. Lee Establishment of a Human Hepatocellular Carcinoma Cell Line Highly Expressing Sodium Iodide Symporter for Radionuclide Gene Therapy J. Nucl. Med., September 1, 2004; 45(9): 1571 - 1576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. L. Wapnir, M. Goris, A. Yudd, O. Dohan, D. Adelman, K. Nowels, and N. Carrasco The Na+/I- Symporter Mediates Iodide Uptake in Breast Cancer Metastases and Can Be Selectively Down-Regulated in the Thyroid Clin. Cancer Res., July 1, 2004; 10(13): 4294 - 4302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Haberkorn, P. Beuter, W. Kubler, H. Eskerski, M. Eisenhut, R. Kinscherf, S. Zitzmann, L. G. Strauss, A. Dimitrakopoulou-Strauss, and A. Altmann Iodide Kinetics and Dosimetry In Vivo After Transfer of the Human Sodium Iodide Symporter Gene in Rat Thyroid Carcinoma Cells J. Nucl. Med., May 1, 2004; 45(5): 827 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. V. Scholz, N. Cengic, B. Goke, J. C. Morris, and C. Spitzweg Dexamethasone Enhances the Cytotoxic Effect of Radioiodine Therapy in Prostate Cancer Cells Expressing the Sodium Iodide Symporter J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1108 - 1116. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Barzon, M. Boscaro, and G. Palu Endocrine Aspects of Cancer Gene Therapy Endocr. Rev., February 1, 2004; 25(1): 1 - 44. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kogai, Y. Kanamoto, L. H. Che, K. Taki, F. Moatamed, J. J. Schultz, and G. A. Brent Systemic Retinoic Acid Treatment Induces Sodium/Iodide Symporter Expression and Radioiodide Uptake in Mouse Breast Cancer Models Cancer Res., January 1, 2004; 64(1): 415 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kakinuma, E. R. Bergert, C. Spitzweg, J. C. Cheville, M. M. Lieber, and J. C. Morris Probasin Promoter (ARR2PB)-Driven, Prostate-Specific Expression of the Human Sodium Iodide Symporter (h-NIS) for Targeted Radioiodine Therapy of Prostate Cancer Cancer Res., November 15, 2003; 63(22): 7840 - 7844. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Carlin, G. Akabani, and M. R. Zalutsky In Vitro Cytotoxicity of 211At-Astatide and 131I-Iodide to Glioma Tumor Cells Expressing the Sodium/Iodide Symporter J. Nucl. Med., November 1, 2003; 44(11): 1827 - 1838. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Spitzweg, I. V. Scholz, E. R. Bergert, D. J. Tindall, C. Y. F. Young, B. Goke, and J. C. Morris Retinoic Acid-Induced Stimulation of Sodium Iodide Symporter Expression and Cytotoxicity of Radioiodine in Prostate Cancer Cells Endocrinology, August 1, 2003; 144(8): 3423 - 3432. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Dingli, R. M. Diaz, E. R. Bergert, M. K. O'Connor, J. C. Morris, and S. J. Russell Genetically targeted radiotherapy for multiple myeloma Blood, July 15, 2003; 102(2): 489 - 496. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Braga-Basaria and M. D. Ringel Beyond Radioiodine: A Review of Potential New Therapeutic Approaches for Thyroid Cancer J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 1947 - 1960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. L. Wapnir, M. van de Rijn, K. Nowels, P. S. Amenta, K. Walton, K. Montgomery, R. S. Greco, O. Dohan, and N. Carrasco Immunohistochemical Profile of the Sodium/Iodide Symporter in Thyroid, Breast, and Other Carcinomas Using High Density Tissue Microarrays and Conventional Sections J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1880 - 1888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-K. Chung Sodium Iodide Symporter: Its Role in Nuclear Medicine J. Nucl. Med., September 1, 2002; 43(9): 1188 - 1200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. A. Smit, J. P. Schroder-van der Elst, M. Karperien, I. Que, M. Stokkel, D. van der Heide, and J. A. Romijn Iodide Kinetics and Experimental 131I Therapy in a Xenotransplanted Human Sodium-Iodide Symporter-Transfected Human Follicular Thyroid Carcinoma Cell Line J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1247 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Spitzweg, K. J. Harrington, L. A. Pinke, R. G. Vile, and J. C. Morris The Sodium Iodide Symporter and Its Potential Role in Cancer Therapy J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3327 - 3335. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
) and P-1 (
, 
) xenografts in
nude mice after injection of 3 mCi of 131I (