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Vikas Kundra

Publications and source records attributed to Vikas Kundra.

11 recordsLinked to original sources
PubMed2007

In vivo imaging of prostate cancer involving bone in a mouse model.

BACKGROUND: We compared the abilities of clinically relevant imaging modalities to quantify prostate cancer involving bone in a mouse model. Such non-invasive methods are needed pre-clinically to understand tumor biology and to evaluate therapy. METHODS: Human prostate cancer cells (MDA PCa 2b) or vehicle were injected into the right or left femur of SCID mice (n = 8). Radiography, computed tomography, and magnetic resonance imaging were performed 5 and 8 weeks later (n = 7). Bone scintigraphy (n = 6) was also performed at week 8. Imaging findings were compared with histology and correlated with contemporaneous serum prostate-specific antigen levels. RESULTS: Among the modalities evaluated, only MR imaging delineated prostate tumors involving bone. Tumor volume assessed by MR imaging correlated with PSA levels (R(2) = 0.87, P < 0.001). MR imaging of tumors corresponded with histology. Imaging of mineralized bone by CT corresponded with histology. CONCLUSION: In a mouse model, prostate tumors involving bone can be quantified using MR imaging.

Animals↗
PubMed2006

The 3p21.3 tumor suppressor NPRL2 plays an important role in cisplatin-induced resistance in human non-small-cell lung cancer cells.

NPRL2 is one of the novel candidate tumor suppressor genes identified in the human chromosome 3p21.3 region. The NPRL2 has shown potent tumor suppression activity in vitro and in vivo and has been suggested to be involved in DNA mismatch repair, cell cycle checkpoint signaling, and regulation of the apoptotic pathway. In this study, we analyzed the endogenous expression of the NPRL2 protein and the cellular response to cisplatin in 40 non-small-cell lung cancer cell lines and found that expression of NPRL2 was significantly and reciprocally correlated to cisplatin sensitivity, with a Spearman correlation coefficient of -0.677 (P < 0.00001). Exogenously introduced expression of NPRL2 by N-[1-(2,3-dioleoyloxyl)propyl]-NNN-trimethylammoniummethyl sulfate:cholesterol nanoparticle-mediated gene transfer significantly resensitized the response to cisplatin, yielding a 40% greater inhibition of tumor cell viability and resulting in a 2- to 3-fold increase in induction of apoptosis by activation of multiple caspases in NPRL2-transfected cells compared with untransfected cells at an equal dose of cisplatin. Furthermore, a systemic treatment with a combination of NPRL2 nanoparticles and cisplatin in a human H322 lung cancer orthotopic mouse model significantly enhanced the therapeutic efficacy of cisplatin and overcame cisplatin-induced resistance (P < 0.005). These findings implicate the potential of NPRL2 as a biomarker for predicting cisplatin response in lung cancer patients and as a molecular therapeutic agent for enhancing response and resensitizing nonresponders to cisplatin treatment.

Animals↗
PubMed2006

Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma.

Stress can alter immunological, neurochemical and endocrinological functions, but its role in cancer progression is not well understood. Here, we show that chronic behavioral stress results in higher levels of tissue catecholamines, greater tumor burden and more invasive growth of ovarian carcinoma cells in an orthotopic mouse model. These effects are mediated primarily through activation of the tumor cell cyclic AMP (cAMP)-protein kinase A (PKA) signaling pathway by the beta(2) adrenergic receptor (encoded by ADRB2). Tumors in stressed animals showed markedly increased vascularization and enhanced expression of VEGF, MMP2 and MMP9, and we found that angiogenic processes mediated the effects of stress on tumor growth in vivo. These data identify beta-adrenergic activation of the cAMP-PKA signaling pathway as a major mechanism by which behavioral stress can enhance tumor angiogenesis in vivo and thereby promote malignant cell growth. These data also suggest that blocking ADRB-mediated angiogenesis could have therapeutic implications for the management of ovarian cancer.

Animals↗
PubMed2006

Validation of an anti-sphingosine-1-phosphate antibody as a potential therapeutic in reducing growth, invasion, and angiogenesis in multiple tumor lineages.

S1P has been proposed to contribute to cancer progression by regulating tumor proliferation, invasion, and angiogenesis. We developed a biospecific monoclonal antibody to S1P to investigate its role in tumorigenesis. The anti-S1P mAb substantially reduced tumor progression and in some cases eliminated measurable tumors in murine xenograft and allograft models. Tumor growth inhibition was attributed to antiangiogenic and antitumorigenic effects of the antibody. The anti-S1P mAb blocked EC migration and resulting capillary formation, inhibited blood vessel formation induced by VEGF and bFGF, and arrested tumor-associated angiogenesis. The anti-S1P mAb also neutralized S1P-induced proliferation, release of proangiogenic cytokines, and the ability of S1P to protect tumor cells from apoptosis in several tumor cell lines, validating S1P as a target for therapy.

Animals↗
PubMed2005

Telomerase activity predicts malignancy in percutaneous image-guided needle biopsy specimens of the abdomen and pelvis.

PURPOSE: To determine prospectively if assessment of telomerase activity in percutaneous needle biopsy specimens improves sensitivity and specificity in the diagnosis of abdominal and pelvic malignancy. MATERIALS AND METHODS: The study was approved by the institutional review board, and written informed consent was obtained from all patients. A prospective double-blinded design was used to assess telomerase activity in abdominal and pelvic biopsy specimens from 99 patients (64 men, 35 women; age range, 22-87 years). After the clinical sample was retrieved, a study specimen from an extra needle pass was divided and independently analyzed for cytologic characteristics and telomerase activity. The final diagnosis was based on chart review at a minimum 1-year follow-up. Statistical analyses included sensitivity, specificity, and accuracy of cytologic examination and/or telomerase activity in predicting malignancy. RESULTS: Data from study specimens indicated that the sensitivity, specificity, and accuracy of telomerase activity (n=99) in predicting malignancy were 55%, 79%, and 60%, respectively. For cytologic examination (n=86), the sensitivity, specificity, and accuracy in predicting malignancy were 74%, 94%, and 78%, respectively. Combining the two tests (n=86) and classifying a positive reading with either test as malignant improved sensitivity (83%) (P <.05) without altering specificity (76%). In 20 patients who had clinical sample reports that were classified as indeterminate, telomerase activity (n=20) yielded a higher sensitivity (62%) (P <.05) and similar specificity (86%) compared with cytologic examination (n=15), which yielded a sensitivity of 11% and a specificity of 83%. CONCLUSION: In percutaneous biopsy specimens of the abdomen and pelvis, the combination of cytologic examination and telomerase activity yielded an increased sensitivity in predicting malignancy. In addition, assessing telomerase activity can help identify cancer even when cytologic results are indeterminate.

Abdominal Neoplasms↗
PubMed2005

Exogenous gene expression in tumors: noninvasive quantification with functional and anatomic imaging in a mouse model.

PURPOSE: To assess whether a combination of functional (planar imaging and single photon emission computed tomography [SPECT]) and anatomic (magnetic resonance [MR] imaging) imaging techniques can be used to noninvasively quantify tumor expression of a somatostatin receptor type 2A (SSTR2A) gene chimera in vivo. MATERIALS AND METHODS: All animal experiments were approved by the institutional animal care and use committee. Expression of the SSTR2A gene chimera was quantified in vitro, in vivo, and ex vivo. The epitope tag of the fusion protein was detected through an antibody, and the receptor portion was detected by using the Food and Drug Administration-approved radiopharmaceutical indium 111 octreotide. Six mice were injected with cells transfected with vector and with two clonal cell lines that each expressed different amounts of the gene chimera. With a dedicated small-animal gamma camera, planar imaging and SPECT were used for quantification of radiopharmaceutical uptake in vivo; 4.7-T MR imaging was used to derive tumor weight. After imaging, excised tumors were evaluated for uptake and weight. For statistical analysis, linear regression analysis, Wilcoxon rank sum test, and Kruskal-Wallis test were employed. RESULTS: Different expression levels of the chimeric gene were confirmed in vitro. Radiopharmaceutical uptake assessed in excised tumors and that derived from in vivo planar (r = 0.94, P < .05, n = 18) or SPECT (r = 0.90, P < .05, n = 18) images correlated. Weight of excised tumors and that derived from MR images (r = 0.98, P < .05, n = 18) correlated. MR images also allowed morphologic assessment. The biodistribution parameter of percentage of injected dose per gram of excised tumors correlated with the same measure derived from a combination of planar (r = 0.90, P < .05, n = 18) or SPECT (r = 0.87, P < .05, n = 18) images and MR images. CONCLUSION: A combination of noninvasive functional and anatomic imaging can be used in vivo to quantify gene transfer in tumors.

Animals↗
PubMed2004

Testicular cancer.

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Diagnosis, Differential↗
PubMed2003

Impact of multislice CT on imaging of acute abdominal disease.

The increased speed, greater coverage, and thinner slices of MSCT are exciting developments in radiology, and these feature should only improve with newer generation multislice scanners. The impact of this technology on abdominal imaging has just begun.

Abdomen, Acute↗
PubMed2002

Noninvasive monitoring of somatostatin receptor type 2 chimeric gene transfer.

UNLABELLED: Noninvasive monitoring of gene transfer will benefit basic research and patient care. Most gene-transfer imaging systems do not directly detect the gene of interest, and most do not exploit radiopharmaceuticals that have Food and Drug Administration approval for total-body use. (111)In-Octreotide is used clinically to locate tumors overexpressing primarily somatostatin receptor type 2 (SSTR2). We report the in vitro and in vivo detection of SSTR2 chimeric gene transfer with this radiopharmaceutical. METHODS: Full-length SSTR2A was ligated into a vector downstream of a 5' Igkappa leader sequence and the hemagglutinin A (HA) sequence. The vector plus insert was then introduced into HT1080 cells. Igkappa and HA domain functions were confirmed by immunologic methods. Receptor binding was studied in transfected cells incubated with (111)In-octreotide with and without somatostatin-28. Mice bearing tumors produced by transfected cells were injected with (111)In-octreotide for biodistribution and imaging studies. RESULTS: Cell-membrane localization by the amino-terminal Igkappa domain was confirmed by immunofluorescence. The HA domain was identified by enzyme-linked immunosorbent assay, immunofluorescence, and Western blotting analysis with anti-HA antibodies. (111)In-Octreotide detected the SSTR2 portion of the fusion protein in vitro (receptor-binding assay) and in vivo (biodistribution studies and gamma-camera imaging). In addition, in vitro studies using either the anti-HA antibody or (111)In-octreotide correlated with biodistribution and imaging studies when cell clones expressing different levels of the fusion protein were tested. This approach may be feasible clinically because we were able to discern chimeric gene transfer in tumor-bearing animals with (111)In-octreotide at doses similar to those already used in humans. CONCLUSION: With this method it may be possible to monitor transfer of a gene of interest directly and noninvasively.

Animals↗