R M Hoffman

..These SOI models are uniquely useful for innovative drug discovery and mechanism studies and serve as a bridge linking preclinical and clinical drug development...

..The implications of this technology for discovery of new visible targets at the cellular level for treatment of cancer are discussed...

..This model will be useful for understanding the mechanism of angiogenesis of pancreatic cancer liver metastasis and for the discovery of effective new inhibitors of this process...

..More effective drugs for brain cancer and brain metastasis can be screened and can be identified with this technology...

..The results of the present study suggest effective future clinical strategies of bacterial treatment of cancer...

..These results suggest that fluorescence-guided surgery has significant potential for brain cancer treatment...

..AIIB2 treatment also increased survival of mice with orthotopically growing 143B-RFP...

..These results suggest that the expression of fluorescent proteins in cancer cells can enhance photodynamic therapy (PDT) using UVC and possibly with other wavelengths of light as well...

..Because the barriers to efficacy of standard therapy of cancer appear to be opportunities for bacterial cancer therapy, the future of bacterial therapy of cancer appears bright...

..This non-invasive imageable tumorgraft model will be valuable to screen for effective treatment options for individual patients with pancreatic cancer, as well as for the discovery of improved agents for this treatment-resistant disease...

..Take home message: SOI mouse models of cancer reproduce the features of clinical cancer...

..The results of this study suggest that p.o. administration was the most safe to the host and the i.v. route was most effective for tumor targeting with S. typhimurium A1-R...

..The future goal, based on these studies, is the culture of CTCs from cancer patients' peripheral blood for chemosensitivity testing, for improved individualized therapy...

..This technology has furthered our understanding of the spread of cancer at the subcellular level. Fluorescent proteins thereby provide the basis for the new field of in vivo cell biology...

..0001) and 4.18 in the CTC plus semi-solid ECM group (p<0.0001). The results demonstrate that reduction of CTC metastatic potential is possible, in this case with an ECM produced by human foreskin fibroblasts in culture...

..The new imageable model of patient pancreatic cancer metastasis provides unique opportunities to identify current and novel antimetastatic therapeutics for individual patients...

..Salmonella typhimurium shows much promise for this paradigm...

..Such imaging possibilities can provide new visual targets for novel drug therapy. Fluorescent proteins thus enable both micro as well as macro imaging technology and thereby provide the basis for the new field of in vivo cell biology...

..The results in this report, demonstrating the anti-metastatic efficacy of S. typhimurium A1-R in immunocompetent mice, indicate the clinical potential of bacterial therapy of cancer...

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..Exploitation of the tumor-killing capability of Salmonella has great promise for a new paradigm of cancer therapy...

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..Thus, fluorescent proteins expressed in vivo offer very high resolution and sensitivity for real-time imaging of angiogenesis...

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..Fluorescent proteins thus enable both macro and micro imaging technology and thereby provide the basis for the new field of in vivo cell biology...

..It is the brightest known protein with emission at wavelengths longer than 620 nm. This new protein offers the potential for noninvasive whole-body imaging of numerous cellular and molecular processes in live animals...

..The double transfection and selection procedures described here take 6-8 weeks. Cancer cell trafficking, deformation, extravasation, mitosis and cell death can be imaged with clarity...

..The transplanted mice regain the ability to walk normally. Thus, hair follicle stem cells provide an effective, accessible, autologous source of stem cells for treatment of peripheral nerve injury...

..Further developments in subcellular imaging in live animals is expected to result in a new 'in vivo cell biology' that will provide visible targets for cancer and other diseases...

..These results suggest that amino acid auxotrophic virulent bacteria, which selectively infect and attack viable tumor tissue, are a promising approach to cancer therapy...

..The 'color-coded' tumor-host models enable imaging and therefore a deeper understanding of the host cells involved and their function in tumor progression. Approximately 4-8 weeks are needed for these procedures...

..These multicolored proteins have allowed the color-coding of cancer cells growing in vivo with distinction of different cell types, including host from tumor, with single-cell resolution...

..Fluorescent protein-based imaging technology can be used for whole-body imaging of fluorescent cells on essentially all organs. The timeline for these experiments varies from 2 days to 2 months...

..This imaging technology affords a powerful approach to visualizing the infection process, determining the tissue specificity of infection, the spatial migration of the infectious agents and the response to antimicrobial agents...

..Visualization of many aspects of cancer initiation and progression in vivo should be possible with fluorescent proteins...

..The simple fluorescence method of determining clonality of metastases described here can allow large-scale clonal analysis in numerous types of metastatic models...

..The results of the current study demonstrate the broad clinical potential for rMETase and PEG-rMETase for cancer treatment...

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..These unique SOI models have been used for innovative drug discovery and mechanism studies and serve as a bridge linking pre-clinical and clinical research and drug development...

..The GFP-transfected tumor cells enabled a fundamental advance in the visualization of tumor growth and metastasis in real time in vivo...

..The results with the GFP-transfected tumor cells, combined with the use of SOI, demonstrate a fundamental advance to visualize and study cancer metastasis and the role of angiogenesis and other factors in the metastatic process...

..The results of this study show that differentially labeling cells with spectrally-distinct fluorescent protein can allow subcellular-resolution imaging of cell-cell interactions between host and cancer cells...

..GFP technology has also been used for real-time imaging and quantification of angiogenesis...

..These fluorescent models can be used to study the early events of angiogenesis and to quantitatively determine efficacy of antiangiogenesis compounds...

..Most importantly, we review and hypothesize how the developing therapeutic recombination methioninase (rMETase) can be utilized to cure or prevent all of these diseases...

..In each organ, single disseminated cells tended to die earlier than aggregated cells. The results of this study suggest that the early steps of metastasis are different in the lung, liver and muscle...

..rAdMET/SeMET prodrug gene therapy is therefore a promising novel strategy effective against bcl-2 overexpression, which has blocked other gene therapy strategies...

..The multi-colored models described in this report provide new opportunities to study the cellular interactions in the live primary and metastatic TME...

..The approach described here is a significant improvement over previous bacterial tumor-therapy strategies that require combination with toxic chemotherapy...

..The tumor doubling-time was increased to approximately 10 days with the combination therapy of Ad-MET + SeMET + DOX as opposed to 2-3 days in all other treatment groups...

..In this study, we measured antitumour efficacy of the Salmonella typhimurium A1-R tumour-targeting bacterium strain, administered systemically or intrathecally, to spinal cord cancer in orthotopic mouse models...

..These powerful and clinically relevant angiogenesis mouse models can be used for real-time in vivo evaluation of agents inhibiting or promoting tumor angiogenesis in physiological microenvironments...

..These results suggest that this model is useful for the imaging of the angiogenesis of human as well as rodent tumors and visualization of the efficacy of angiogenetic inhibitors...

..The simultaneous real-time dual-color imaging of metastatic colonies described in this report gives rise to the possibility of color-coded imaging of clones of cancer cells carrying various forms of gene of interest...

..The metastatic pattern in the model thus reflected clinical metastatic breast cancer and provides a powerful model for drug discovery for this disease...

..We demonstrate in this report, using powerful color-coded fluorescent imageable tumor-host models, the onset of angiogenesis of these sarcomas and its inhibition...

..The dual-color cells thus are a useful tool for visualizing living-cell dynamics in vivo as well as in vitro. Drugs that could specifically perturb these processes can now be readily screened in real time in vivo...

..PTHrP and OPG may be useful as tumor biomarkers for PCa that has metastasized to bone. This novel human PCa model can be used to study the clinical potential of diagnostic and therapeutic modalities in the skeletal progression of PCas...

..Adenoviral MET-gene/SeMET treatment also inhibited tumor growth in rodents and significantly prolonged their survival. Recombinant adenovirus-encoding MET gene-SeMET treatment thereby offers a new paradigm for cancer gene therapy...

..The results showed that CPT-11 is an effective inhibitor of angiogenesis and provided strong implications for wider clinical application of CPT-11 for colon cancer...

..The approach described here, where bacterial monotherapy effectively treats metastatic prostate tumors, is a significant improvement over previous bacterial tumor-therapy strategies that require combination with toxic chemotherapy...

..The GFP mouse model should greatly expand our knowledge of human tumor-host interaction...

..The results have important implications for the clinical application of gemcitabine in this disease...

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..This imageable model should lead to many new insights of in vivo cancer cell biology and to novel drug discovery...

..The expression of the unique protein, nestin, in both neural stem cells and hair follicle stem cells suggests their possible relation...

..This imaging technology will enable further understanding of the critical steps of metastasis and provide visible targets for antimetastasis drug development...

..Dual-color fluorescence imaging visualizes the tumor-host interaction by whole-body imaging and at the cellular level in fresh tissues, dramatically expanding previous studies in fixed and stained preparations...

..This imaging technology affords a powerful approach to visualizing the infection process, determining the tissue specificity of infection, and the spatial migration of the infectious agents...

..Cancer of the spinal cord is highly malignant and often leads to paralysis and death. A realistic mouse model would be an important benefit for the better understanding and treatment of spinal cord glioma...

..The results of this study indicate that IHC therapy for resection of HCC should be investigated clinically...

..No adverse effects were observed. This new strategy demonstrates the clinical potential of targeting and curing cancer metastasis with engineered bacteria without the need of toxic chemotherapy...

..This new technology makes it possible to observe real-time monitoring of cancer-cell dynamics of metastasis in the lung and to identify potential metastatic stem cells...

..This result is in marked contrast to bacteria previously tried for cancer therapy that were confined to necrotic areas of the tumor, which may account, in part, for the strain's unique antitumor efficacy...

..Despite ongoing interest in this area of research, the real-time behavior of cancer cells trafficking in the lymphatic system is poorly understood due to lack of appropriate tools to image this process...

..This procedure enabled external imaging at the micrometastasis level. Real-time evaluation of spontaneous lung metastasis in the same animals should allow drug evaluation and mechanistic studies not previously possible...

..The use of the dual-color cancer cells differentially labeled in the cytoplasm and nucleus and associated fluorescent imaging provide a powerful tool to understand the mechanism of cancer cell migration and deformation in small vessels...

..The data in this report suggest that adenoviral-GFP labeling tumors in patients can enable fluorescence-guided surgical navigation...

..We have termed these cells hair follicle pluripotent stem (hfPS) cells. These results suggest that hfPS cells provide an important accessible, autologous source of adult stem cells with potential for use in regenerative medicine...

..The GFP imaging technology presented in this report will facilitate studies of modulators of pancreatic cancer growth, including inhibition by potential chemotherapeutic agents...

..These results suggest a novel tumor-host interaction that enables efficient formation of liver metastasis via intrasplenic injection...

..Fluorescence color coding of cancer cells enables visualization of the interaction of cancer cells and can be used to distinguish cancer cells of any genotype or phenotype...

..Most follicles produced GFP-fluorescent growing hair shafts. This technique has produced efficient genetic modification of the hair shaft...

..Thus methioninase is a highly effective antitumor agent with a new tumor-selective mode of action with minimal toxicity, demonstrating potential clinical effectiveness against solid tumors...

..Such a combination has been found to increase the cytotoxic effect of the drug to tumor cells...

..These fluorescent models are therefore powerful and reliable tools with which to investigate metastatic human pancreatic cancer and novel therapeutic strategies directed against it...

..The data reported here support future experiments utilizing methionine depletion as a target for tumor-selective cell cycle-dependent therapy...

..Doxorubicin inhibited the nascent tumor angiogenesis as well as tumor growth in the ND-GFP mice transplanted with B16F10-RFP. This model is useful for direct visualization of tumor angiogenesis and evaluation of angiogenic inhibitors...

..After 7 days of treatment, the pancreatic cancer had regressed without the need of chemotherapy or any other treatment. This new strategy demonstrates the clinical potential of bacterial targeting for pancreatic cancer...

..These observations suggest that the inter-hair-follicle blood-vessel network contributes to skin transplant survival and wound healing...

..Pressure also deformed the shed emboli, increasing their maximum major axis. Imaging lymphatic trafficking of cancer cells can reveal critical steps of lymph node metastasis...

..The dual-color cells described here thus enable the sub-cellular dynamics of cancer cell trafficking to be imaged in the living animal...

..Possible future technical developments are suggested by the image, through a lower-abdominal skin-flap, of an invasive prostate tumor expressing both red and green fluorescent proteins in separate colonies...

..Our results suggest the potential of this therapeutic paradigm against pancreatic cancer in the adjuvant and maintenance settings...

..These results suggest that a cyclophosphamide-sensitive host cellular system attacked the HCT-116-GFP-RFP cells but could not effectively kill the MMT-GFP-RFP cells...

..PROPOSED COMMERCIAL APPLICATIONS: Liposomal 4-MA will be developed as a topical selectively targeted therapeutic for acne for which they should be a very market. ..

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..Human hair- follicle bulge cells will be further characterized and developed for therapeutic potential for nerve regeneration in Phase III. ..

..These models have significant commercial potential for discovery and development of stroma-targeted and anti-angiogenesis drugs. ..

..Future human trials of the tumor-killing bacteria can be held after the Phase I and Phase II grant periods are completed. ..

..In addition, Salmonella amino acid tumor-targeting auxotroph strains will be modified to secrete cytokines to enhance the bacterial killing of the tumor with stimulation of host antitumor immune reactions in Phase II. ..

..Phase II results will lead to an IND for MEGC-PEG-rMETase for end stage renal disease patients and other patients with intractable hyperhomocysteinemia and high cardiovascular disease mortality. ..

..Reporters with spectral properties that can be used for whole-body imaging of tumors in the lung and their metastases will be candidates for further development for numerous applications of multi-color imaging. ..

..The tHCY enzymatic kits for these applications will be ready for commercial launch at this point. PROPOSED COMMERCIAL APPLICATION: Not Available ..