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      1. Author :
        Neal, Robert E, 2nd; Singh, Ravi; Hatcher, Heather C; Kock, Nancy D; Torti, Suzy V; Davalos, Rafael V
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Breast cancer research and treatment
      6. Products :
      7. Volume :
        123
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Bioware; Cell Line, Tumor; Electrochemotherapy; Electrodes; Female; Humans; Mammary Neoplasms, Experimental; MDA-MB-231-D3H1 cells; Mice; Mice, Nude; Needles; Xenograft Model Antitumor Assays
      12. Abstract :
        Irreversible electroporation (IRE) is a therapeutic technology for the ablation of soft tissues using electrodes to deliver intense but short electric pulses across a cell membrane, creating nanopores that lead to cell death. This phenomenon only affects the cell membrane, leaving the extracellular matrix and sensitive structures intact, making it a promising technique for the treatment many types of tumors. In this paper, we present the first in vivo study to achieve tumor regression using a translatable, clinically relevant single needle electrode for treatment administration. Numerical models of the electric field distribution for the protocol used suggest that a 1000 V/cm field threshold is sufficient to treat a tumor, and that the electric field distribution will slightly decrease if the same protocol were used on a tumor deep seated within a human breast. Tumor regression was observed in 5 out of 7 MDA-MB231 human mammary tumors orthotopically implanted in female Nu/Nu mice, with continued growth in controls.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20191380
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8988
      1. Author :
        Ghali, Shadi; Bhatt, Kirit A; Dempsey, Marlese P; Jones, Deidre M; Singh, Sunil; Aarabi, Shahram; Arabi, Shahram; Butler, Peter E; Gallo, Robert L; Gurtner, Geoffrey C
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Plastic and reconstructive surgery
      6. Products :
      7. Volume :
        123
      8. Issue :
        4
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Bioware; Cathelicidins; Chronic Disease; Drug Carriers; Genetic Engineering; Male; Rats; Rats, Inbred F344; Surgical Flaps; Wound Infection; Xen29
      12. Abstract :
        BACKGROUND The success of antimicrobial therapy has been impaired by the emergence of resistant bacterial strains. Antimicrobial peptides are ubiquitous proteins that are part of the innate immune system and are successful against such antibiotic-resistant microorganisms. The authors have previously demonstrated the feasibility of protein delivery via microvascular free flap gene therapy and here they examine this approach for recalcitrant infections. METHODS The authors investigated the production of the human cathelicidin antimicrobial peptide-LL37, delivered by ex vivo transduction of the rodent superficial inferior epigastric free flap with Ad/CMV-LL37. The vascular permeabilizing agent vascular endothelial growth factor (VEGF) was co-administered during ex vivo transduction with adenoviral vectors in an attempt to augment transduction efficiency. A rodent model of chronic wound/foreign body infection seeded with bioluminescent Staphylococcus aureus was used to assess the biological efficacy of delivering therapeutic antimicrobial genes using this technology. RESULTS The authors were successful in demonstrating significant LL37 expression, which persisted for 14 days after ex vivo transduction with Ad/CMV-LL37. Transduction efficiency was significantly improved with the co-administration of 5 micrograms of VEGF during transduction without significantly increasing systemic dissemination of adenovirus or systemic toxicity. They were able to demonstrate in the rodent model of chronic wound/foreign body infections a significant reduction in bacterial loads from infected catheters following transduction with Ad/CMV-LL37 and increased bacterial clearance. CONCLUSION This study demonstrates for the first time that microbicidal gene therapy via microvascular free flaps is able to clear chronic infections such as occurs with osteomyelitis resulting from trauma or an infected foreign body [corrected]
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19337084
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        9040
      1. Author :
        Qingbei Zhang; Meng Yang; Jikun Shen; Lynnette M. Geerhold; Robert M Hoffman; H. Rosie Xing
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        International Journal of Cancer
      6. Products :
      7. Volume :
        126
      8. Issue :
        11
      9. Page Numbers :
        N/A
      10. Research Area :
        Cancer
      11. Keywords :
        metastasis; hemotogenous spread; prostate cancer; GFP; in vivo imaging
      12. Abstract :
        Metastasis is primarily responsible for the morbidity and mortality of cancer. Improved therapeutic outcomes and prognosis depend on improved understanding of mechanisms regulating the establishment of early metastasis. In this study, use of green fluorescent protein (GFP)-expressing PC-3 orthotopic model of human prostate cancer and two complementary fluorescence in vivo imaging systems (Olympus OV100 and VisEn FMT) allowed for the first time real-time characterization of cancer cell-endothelium interactions during spontaneous metastatic colonization of the liver and lung in live mice. We observed that prior to the detection of extra-vascular metastases, GFP-expressing PC-3 cancer cells resided initially inside the blood vessels of the liver and the lung, where they proliferated and expressed Ki-67 and exhibited matrix metalloprotenases (MMP) activity. Thus, the intravascular cancer cells produced their own microenvironment, where they could continue to proliferate. Extravasation occurred earlier in the lung than in the liver. Our results demonstrate that the intravascular microenvironment is a critical staging area for the development of metastasis that later can invade the parenchyma. Intravascular tumor cells may represent a therapeutic target to inhibit the development of extravascular metastases. Therefore, this imageable model of intravascular metastasis may be used for evaluation of novel anti-metastatic agents.
      13. URL :
        http://onlinelibrary.wiley.com/doi/10.1002/ijc.24979/abstract
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4493
      1. Author :
        Sharma, Praveen K; Singh, Rajesh; Novakovic, Kristian R; Eaton, John W; Grizzle, William E; Singh, Shailesh
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        International journal of cancer. Journal international du cancer
      6. Products :
      7. Volume :
        127
      8. Issue :
        9
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Animals; Antineoplastic Agents; Apoptosis; Bioware; Caspase 3; Cell Line, Tumor; Chemokines, CC; Disease Progression; Enzyme Activation; Etoposide; Humans; Male; Mice; Mice, Nude; PC-3M-luc; Phosphatidylinositol 3-Kinases; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Receptors, CCR; Signal Transduction
      12. Abstract :
        Despite recent advances in treatment and management of prostate cancer (PCa), it remains the second leading cause of cancer-related deaths among men in the US. Chemotherapy is one of the treatment alternatives for hormone refractory metastatic PCa. However, current chemotherapeutic regimens provide palliative benefit but relatively modest survival advantage primarily due to chemo-resistance and upregulated antiapoptotic machineries in PCa cells. Therefore, blocking the mechanisms responsible for suppression of apoptosis might improve current chemotherapeutic regimens. In this study, we show that CC chemokine receptor-9 (CCR9) and its natural ligand CCL25 interaction upregulates antiapoptotic proteins (i.e., PI3K, AKT, ERK1/2 and GSK-3beta) and downregulate activation of caspase-3 in PCa cells. Significant downregulation of these CCR9-mediated antiapoptotic proteins in the presence of a PI3K inhibitor (wortmannin), further suggests that the antiapoptotic action of CCR9 is primarily regulated through PI3K. Furthermore, the cytotoxic effect of etoposide was significantly inhibited in the presence of CCL25, and this inhibitory effect of CCL25 was abrogated when CCR9-CCL25 interaction was blocked using anti-CCR9 monoclonal antibodies. In conformation to these in vitro studies, significant reduction in tumor burden was found in mice receiving CCL25 neutralizing antibodies and etoposide together as compared to both as a single agent. These results suggest that the CCR9-CCL25 axis mediates PI3K/AKT-dependent antiapoptotic signals in PCa cells and could be a possible reason for low apoptosis and modest chemotherapeutic response. Therefore, targeting CCR9-CCL25 axis with cytotoxic agents may provide better therapeutic outcomes than using cytotoxic agents alone.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20127861
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8945
      1. Author :
        Mieog, J. S.; Hutteman, M.; van der Vorst, J. R.; Kuppen, P. J.; Que, I.; Dijkstra, J.; Kaijzel, E. L.; Prins, F.; Lowik, C. W.; Smit, V. T.; van de Velde, C. J.; Vahrmeijer, A. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Breast Cancer Res Treat
      6. Products :
      7. Volume :
        128
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        ProSense, IVIS, Animals; Breast Neoplasms/pathology/*surgery; Cell Line, Tumor; Disease Models, Animal; Female; *Microscopy, Fluorescence; Rats; *Surgery, Computer-Assisted; Transplantation, Isogeneic; Xenograft Model Antitumor Assays
      12. Abstract :
        Tumor involvement of resection margins is found in a large proportion of patients who undergo breast-conserving surgery. Near-infrared (NIR) fluorescence imaging is an experimental technique to visualize cancer cells during surgery. To determine the accuracy of real-time NIR fluorescence imaging in obtaining tumor-free resection margins, a protease-activatable NIR fluorescence probe and an intraoperative camera system were used in the EMR86 orthotopic syngeneic breast cancer rat model. Influence of concentration, timing and number of tumor cells were tested in the MCR86 rat breast cancer cell line. These variables were significantly associated with NIR fluorescence probe activation. Dosing and tumor size were also significantly associated with fluorescence intensity in the EMR86 rat model, whereas time of imaging was not. Real-time NIR fluorescence guidance of tumor resection resulted in a complete resection of 17 out of 17 tumors with minimal excision of normal healthy tissue (mean minimum and a mean maximum tumor-free margin of 0.2 +/- 0.2 mm and 1.3 +/- 0.6 mm, respectively). Moreover, the technique enabled identification of remnant tumor tissue in the surgical cavity. Histological analysis revealed that the NIR fluorescence signal was highest at the invasive tumor border and in the stromal compartment of the tumor. In conclusion, NIR fluorescence detection of breast tumor margins was successful in a rat model. This study suggests that clinical introduction of intraoperative NIR fluorescence imaging has the potential to increase the number of complete tumor resections in breast cancer patients undergoing breast-conserving surgery.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/20821347
      14. Call Number :
        PKI @ kd.modi @ 4
      15. Serial :
        10429
      1. Author :
        Barman, T. K.; Rao, M.; Bhati, A.; Kishore, K.; Shukla, G.; Kumar, M.; Mathur, T.; Pandya, M.; Upadhyay, D. J.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2011
      5. Publication :
        Indian J Med Res
      6. Products :
      7. Volume :
        134
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen10, Xen 10, Streptococcus pnuemoniae Xen10, IVIS,
      12. Abstract :
        Background & objectives: In vivo imaging system has contributed significantly to the understanding of bacterial infection and efficacy of drugs in animal model. We report five rapid, reproducible, and non invasive murine pulmonary infection, skin and soft tissue infection, sepsis, and meningitis models using Xenogen bioluminescent strains and specialized in vivo imaging system (IVIS). Methods: The progression of bacterial infection in different target organs was evaluated by the photon intensity and target organ bacterial counts. Genetically engineered bioluminescent bacterial strains viz. Staphylococcus aureus Xen 8.1, 29 and 31; Streptococcus pneumoniae Xen 9 and 10 and Pseudomonas aeruginosa Xen-5 were used to induce different target organs infection and were validated with commercially available antibiotics. Results: The lower limit of detection of colony forming unit (cfu) was 1.7-log10 whereas the lower limit of detection of relative light unit (RLU) was 4.2-log10 . Recovery of live bacteria from different target organs showed that the bioluminescent signal correlated to the live bacterial count. Interpretation & conclusions: This study demonstrated the real time monitoring and non-invasive analysis of progression of infection and pharmacological efficacy of drugs. These models may be useful for pre-clinical discovery of new antibiotics.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22199109
      14. Call Number :
        PKI @ kd.modi @ 3
      15. Serial :
        10399
      1. Author :
        Sehrawat, A.; Arlotti, J. A.; Murakami, A.; Singh, S. V.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        Breast Cancer Res Treat
      6. Products :
      7. Volume :
        136
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        MDA-MB-231-D3H1, MDA-MB-231-luc-D3H1, IVIS, Bioware, Breast Cancer
      12. Abstract :
        The present study was undertaken to determine the anticancer efficacy of zerumbone (ZER), a sesquiterpene from subtropical ginger, against human breast cancer cells in vitro and in vivo. ZER treatment caused a dose-dependent decrease in viability of MCF-7 and MDA-MB-231 human breast cancer cells in association with G(2)/M phase cell cycle arrest and apoptosis induction. ZER-mediated cell cycle arrest was associated with downregulation of cyclin B1, cyclin-dependent kinase 1, Cdc25C, and Cdc25B. Even though ZER treatment caused stabilization of p53 and induction of PUMA, these proteins were dispensable for ZER-induced cell cycle arrest and/or apoptosis. Exposure of MDA-MB-231 and MCF-7 cells to ZER resulted in downregulation of Bcl-2 but its ectopic expression failed to confer protection against ZER-induced apoptosis. On the other hand, the SV40 immortalized mouse embryonic fibroblasts derived from Bax and Bak double knockout mice were significantly more resistant to ZER-induced apoptosis. ZER-treated MDA-MB-231 and MCF-7 cells exhibited a robust activation of both Bax and Bak. In vivo growth of orthotopic MDA-MB-231 xenografts was significantly retarded by ZER administration in association with apoptosis induction and suppression of cell proliferation (Ki-67 expression). These results indicate that ZER causes G(2)/M phase cell cycle arrest and Bax/Bak-mediated apoptosis in human breast cancer cells, and retards growth of MDA-MB-231 xenografts in vivo.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/23053663
      14. Call Number :
        PKI @ kd.modi @ 5
      15. Serial :
        10518
      1. Author :
        Ignat M, Aprahamian M, Lindner V, Altmeyer A, Perretta S, Dallemagne B, Mutter D and Marescaux J
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Gastroenterology
      6. Products :
      7. Volume :
        137
      8. Issue :
        5
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        ProSense; AngioSense; AngioSpark; in vivo imaging; pancreatic cancer
      12. Abstract :
        BACKGROUND & AIMS: Surgical management of pancreatic cancer depends on tumor resectability and staging. This study evaluated a new in vivo technique, fiberoptic confocal fluorescence microscopy (FCFM), for detection and staging of pancreatic tumors in rats.

        METHODS: FCFM was used with a protease-activated fluorescent marker (ProSense; VisEn Medical Inc, Woburn, MA) for in vivo imaging of solid organs (1.8-microm resolution) in a rat model of pancreatic ductal adenocarcinoma. A preliminary study described the FCFM rendering of normal and pathologic tissues. Subsequently, 2 double-blind studies compared FCFM to standard histology in (1) detection of tumors in rat models of cancer and controls and (2) detection of nodal involvement (splenic, celiac, mesenteric, and colic) 4, 5, and 6 weeks after tumor induction vs controls.

        RESULTS: Tumor cells displayed a fluorescent ductal pattern compared with non-fluorescent normal pancreas or normal follicular pattern of lymph nodes (LNs). FCFM detected all the pancreatic tumors (1.7-mm mean diameter) and identified 23 LNs that contained metastases of 99 LNs examined. Standard histologic analyses resulted in 1 false-negative result in tumor detection and 2 false negatives in LN detection, whereas FCFM produced no false-negative results. Additional serial sectioning confirmed all tumors and 16 metastatic LNs; FCFM had a negative predictive value of 100% and a positive predictive value of 69.6%.

        CONCLUSIONS: Real-time “virtual biopsy” using FCFM detects tumors and LN metastases with 100% sensitivity and 92.2% specificity in rats, making it a reliable technique for detection and staging of pancreatic cancer.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19632230
      14. Call Number :
        PKI @ sarah.piper @
      15. Serial :
        4540
      1. Author :
        Subbarayan, P. R.; Sarkar, M.; Nagaraja Rao, S.; Philip, S.; Kumar, P.; Altman, N.; Reis, I.; Ahmed, M.; Ardalan, B.; Lokeshwar, B. L.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2012
      5. Publication :
        J Ethnopharmacol
      6. Products :
      7. Volume :
        142
      8. Issue :
        N/A
      9. Page Numbers :
        523-30
      10. Research Area :
        N/A
      11. Keywords :
        BxPC-3, BxPC-3-luc2, IVIS, Achyranthes; Animals; Antineoplastic Agents, Phytogenic/pharmacology/*therapeutic use; Apoptosis/*drug effects; Caspase 3/genetics/metabolism; Gene Expression/drug effects; Humans; Injections, Intraperitoneal; Medicine, Ayurvedic; Mice; Mice, Nude; Pancreatic Neoplasms/*drug therapy/genetics/metabolism; Phosphorylation; *Phytotherapy; Plant Extracts/pharmacology/*therapeutic use; Plant Leaves; Proto-Oncogene Proteins c-akt/metabolism; RNA, Messenger/metabolism; Xenograft Model Antitumor Assays
      12. Abstract :
        ETHNOPHARMACOLOGICAL RELEVANCE: Achyranthes aspera (Family Amaranthacea) is used for cancer therapy by ayurvedic medical practitioners in India. However, due to the non formal nature of its use, there are no systematic studies validating its medicinal properties. Thus, it's utility as an anti cancer agent remains anecdotal. Earlier, we demonstrated A. aspera to exhibit time and dose-dependent preferential cytotoxicity to cultured human pancreatic cancer cells. In this report we validate in vivo anti tumor properties of A. aspera. MATERIALS AND METHODS: The in vivo anti tumor activity of leaf extract (LE) was tested by intraperitoneal (IP) injections into athymic mice harboring human pancreatic tumor subcutaneous xenograft. Toxicity was monitored by recording changes in behavioral, histological, hematological and body weight parameters. RESULTS: Dosing LE to athymic mice by I.P. injection for 32 days showed no adverse reactions in treated mice. Compared to the control set, IP administration of LE to tumor bearing mice significantly reduced both tumor weight and volume. Gene expression analysis using Real time PCR methods revealed that LE significantly induced caspase-3 mRNA (p<0.001) and suppressed expression of the pro survival kinase Akt-1 (p<0.05). TUNEL assay and immunohistochemistry confirmed apoptosis induction by activation of caspase-3 and inhibiting Akt phosphorylation in treated sets. These results are in agreement with RT PCR data. CONCLUSION: Taken together, these data suggest A. aspera to have potent anti cancer property.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/22640722
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10484