In vitro and in vivo studies of new cationic Zn(II)-benzonaphthoporphyrazines as photosensitizers for PDT

2001 ◽  
Vol 05 (08) ◽  
pp. 645-651 ◽  
Author(s):  
M. PEEVA ◽  
M. SHOPOVA ◽  
U. MICHELSEN ◽  
D. WÖHRLE ◽  
G. PETROV ◽  
...  
Keyword(s):  
Cell Line ◽  
Fluorescence Emission ◽  
In Vivo Studies ◽  
Growth Delay ◽  
Tumour Growth Delay ◽  
Bladder Carcinoma Cell Line ◽  
Maximum Absorption Wavelength ◽  
High Absorption

Four recently synthesized cationic zinc(II)-benzonaphthaporphyrazines 1–4 were studied in vitro and in vivo for their photodynamic therapy (PDT) effectivity. The photophysical measurements showed that in solution and in Cremophor micelles all examined compounds exhibit very high absorption intensity in the spectral range between 680 to 750 nm. The fluorescence emission for 3 and 4 was very well expressed in different media, as well as in cell culture. The dark toxicity examinations on invasive human bladder carcinoma cell line EJ did not show any traces of toxicity. The investigations connected with the detection of their phototoxic capacity on the same cell line demonstrated very promising results especially with photosensitizers 3 and 4. The in vivo studies with these two compounds demonstrating high cell-phototoxic effect were carried out against Lewis lung carcinoma in mice after incorporation in Cremophor micelles. The excitation was done at the respective maximum absorption wavelength for each of the sensitizers at a fluence rate of 380 mW cm-2 and a fluence of 360 J cm-2. The phototherapeutic effect was evaluated through macroscopic observations (tumour growth delay) and by electron microscopy detection. According to these approaches the best effect (including tumour destroyment) was detected after PDT treatment with the cationic tribenzonaphthoporphyrazinato-zinc(II) 3. Typical features of random, but not of programmed, cell death necrosis were observed.

Analysis on Homoeopathic Preparation of Asterias Rubens for Evaluating Anti Breast Cancer Cell Line using Similia Principle

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 805-808
Author(s):  
Ravikumar Raju ◽  
Teja ◽  
Sravanathi P ◽  
Muthu Babu K
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
In Vitro Study ◽  
In Vivo Studies ◽  
Asterias Rubens ◽  
Mcf 7

Breast cancer is the subsequent foremost reason of cancer death in a woman and ranks as the primary foremost reason of death in India. In its conduct, several measures and recommendation are considered. Homoeopathic medicines are one of the part of a corresponding, and another medicine is utilized for the treatment of cancer. The main purpose of the investigation is to evaluate the anticancer action of homoeopathic arrangements of Asterias rubens  on the basis of the similia principle. We directed an in vitro study using MTT assay to control the result of ultra diluted homoeopathic preparation in contradiction of two human breast glandular cancer cell lines(MCF-7 and MDA-MD- 231), frequently used for the breast cancer treatment, by testing the feasibility of breast cancer (MCF-7 and MDA-MD-231) cell line, with various attenuations of Asterias rubens  at 24 hrs. Multiple comparisons between tested reagents at different concentrations confirmed the significance of the said results. At a dilution of 1:25 6CH and 30CH potency shown superior activity on MCF-7 and no such significant changes on MDA-MD-231 at any dilutions As it fails to offer estrogen receptor(ER) Also progesterone receptor (PR) expression, and also HER2 (human epidermal development variable receptor2) so continuously a triple-negative breast cancer it will be a hostility manifestation for breast cancer with restricted medicine choices. However, further potency needs to be tested. These preliminary significant results warrant further in vitro and in vivo studies to estimate the possible of Asterias rubens  a medicine to treat breast cancer.

Rational Combinations Including a Novel Syk Inhibitor, Fostamatinib Disodium (FosD) in Diffuse Large B Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 283-283
Author(s):  
Randall M Rossi ◽  
Valerie Grose ◽  
Polly Pine ◽  
Richard I Fisher ◽  
Craig T. Jordan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cell Viability ◽  
B Cell ◽  
Cell Line ◽  
B Cell Lymphoma ◽  
Cell Receptor ◽  
B Cell Receptor ◽  
In Vivo Studies

Abstract Abstract 283 Certain malignant B-cells rely upon B-cell receptor-mediated survival signals. Spleen tyrosine kinase (Syk) initiates and amplifies the B-cell receptor-mediated signal. We and others have demonstrated that fostamatinib disodium (FosD: a prodrug of R406, a potent and specific inhibitor of Syk) induces apoptosis in lymphoma cell lines and primary tumors. A recent clinical trial has demonstrated significant clinical activity of FosD in relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia, and minimal overlap in toxicities with conventional agents. Given this background, future development in B-cell NHL will include rational combinations of FosD and currently available therapies. Therefore, we conducted in vitro and in vivo studies of rational combinations including FosD, in anticipation of clinical trial development. First, using a human DLBCL cell line of GCB genotype, (OCI-Ly19), we analyzed in vitro the combination of R406 with the following agents: fludarabine, rapamycin, rituximab, bendamustine and bortezomib. Increased cytotoxicity was observed using in vitro culture assays with the addition of fludarabine, rapamycin, or rituximab to R406. Cell viability at 72 hours was 25% with R406 alone, 27% for fludarabine alone, and only 9% for the fludarabine/R406. At 48 hours, cell viability was 49% using R406 alone, 31% using rituximab alone, and 21% for rituximab/R406. At 120 hours using primary lymphoma cells (DLCL27), there were no viable cells treated with the rapamycin/FosD combination, compared with rapamycin alone (7%) or FosD alone (25%) The addition of bortezomib or bendamustine to FosD resulted in only a minimal additive increase in cytotoxicity. Results with all combinations were similar with the OCI-Ly10 human DLBCL line of ABC genotype. We then performed in vivo studies by subcutaneous transplantation of the DLBCL cell line OCI-Ly19, (engineered to express luciferase allowing for real time in vivo imaging) into immune deficient NOD/SCID mice which reproducibly formed tumors. Recipient animals were separated into uniform cohorts when the tumors were less than or equal to 500 mm3 in size. The animals were then simultaneously treated with FosD (n=7; 3 gm/kg ad. lib.; translates into 2-5 micromolar R406 systemically throughout the 24h period) and either bortezomib, (n=6; 0.4 mg/kg weekly IP), or rituximab, (n=13; 3 mg/kg, 2x weekly IP). Analysis of the OCI-Ly19 tumor volumes at day 46 showed a median of 2364 mm3 with bortezomib alone compared with 1823 mm3 with bortezomib and FosD. When FosD was combined with rituximab the most significant cytotoxicity was observed: (p=0.01; median tumor volume of 497 mm3 following the combination) in comparison to either FosD alone (3150 mm3) or rituximab alone (1764 mm3). We conclude that the addition of FosD appears to increase activity against NHL of several drugs, including fludarabine and rapamycin. These agents have significant activity in indolent and mantle cell NHL as well as CLL. Moreover, there is no evidence that FosD impedes rituximab responses in vitro or in vivo; in fact we have suggested possible synergy with the combination of rituximab and FosD. Based upon the documented single agent activity of FosD in humans, and this data, clinical trials are now indicated using these promising combinations in NHL and CLL. Disclosures: Pine: Rigel: Employment. Friedberg:Rigel: Research Funding.

scholarly journals ENHANCED FLUORESCENCE IMAGING WITH DMSO-MEDIATED OPTICAL CLEARING

2010 ◽  
Vol 03 (03) ◽  
pp. 153-158 ◽  
Author(s):  
SANJEEV KARMA ◽  
JAMES HOMAN ◽  
CHARLES STOIANOVICI ◽  
BERNARD CHOI
Keyword(s):  
Fluorescence Emission ◽  
Model Systems ◽  
In Vivo Studies ◽  
In Vivo Model ◽  
Fluorescence Signal ◽  
Optical Clearing ◽  
Treated Site

Recent studies have demonstrated that topical application of glycerol on intact skin does not affect its optical scattering properties. Investigators from our research group recently revisited the use of dimethyl sulfoxide (DMSO) as an agent with optical clearing potential. We address the use of optical clearing to enhance quantitation of subsurface fluorescence emission. We employed both in vitro and in vivo model systems to study the effect of topical DMSO application on fluorescence emission. Our in vitro experiments performed on a tissue-simulating phantom suggest that DMSO-mediated optical clearing enables enhanced characterization of subsurface fluorophores. With topical DMSO application, a marked increase in fluorescence emission was observed. After 30 min, the fluorescence signal at the DMSO-treated site was 9× greater than the contralateral saline-treated site. This ratio increased to 13× at 105 min after agent application. In summary, DMSO is an effective optical clearing agent for improved fluorescence emission quantitation and warrants further study in preclinical in vivo studies. Based on outcomes from previous clinical studies on the toxicity profile of DMSO, we postulate that clinical application of DMSO as an optical clearing agent, can be performed safely, although further study is warranted.

Supremacy of Synergism: A comparison of anticancer activity of Rhizome Extract of Bistorta amplexicualis and gallic acid in Cancer Cell Lines and Primary Cells

2020 ◽  
Vol 01 ◽  
Author(s):  
Salma Batool ◽  
M. Javaid Asad ◽  
Muhammad Arshad ◽  
Rahman Shah Zaib Saleem ◽  
Muhammad Sheeraz Ahmad
Keyword(s):  
Gallic Acid ◽  
Cell Line ◽  
Cancer Cell ◽  
Plant Extract ◽  
Umbilical Vein ◽  
Cancer Cell Line ◽  
In Vivo Studies ◽  
Therapeutic Window

Background: Bistorta amplexicaulis is a seasonal herb with several folkloric uses. The plant extract has been shown to possess various activities including antioxidant, anticancer, anti-bacterial, anti-fungal, cardio-protective, anti-atherosclerosis activities. Objective: The aim of the study was to quantify the activity of the plant extract and relate it to the activity of the isolated compounds, gallic acid. Methods: Extraction of the plant was carried out. Then the activity of the extract was compared with its constituent, gallic acid. Cytotoxic potential of the two against human liver cancer cell line (HepG2), breast cancer cell line (MCF-7) and human umbilical vein endothelial cells (HUVEC) was evaluated through MTS assay. Results: The extract had better activity against HepG2 as compared to gallic acid (IC50 29µg/mL vs 37µg/mL). It also provided a better therapeutic window by having lower toxicity for HUVEC cells than gallic acid (IC50 63µg/mL vs 47µg/mL) suggesting the use of the extract over the purified gallic acid for these cells. We also performed the fluorescence study of the rhizome extract in ethanol (REE), methanol (REM), 80% ethanol (80RE), 80% methanol, (80RM) and acetone (RAC). The highest intensity of fluorescence was found in REE with excitation at 394 nm and emission at 421nm. Conclusion: The comparison of gallic acid with ethanolic rhizome extract of B. amplexicaulis reveals important insights about utilizing the plant extract over purified gallic acid. The ethanolic extract also has the potential to be used as autoflouresent drug during in vitro and in vivo studies.

scholarly journals In vitro and in vivo evaluation of electrochemotherapy with trans-platinum analogue trans-[PtCl2(3-Hmpy)2]

2017 ◽  
Vol 51 (3) ◽  
pp. 295-306 ◽  
Author(s):  
Simona Kranjc ◽  
Maja Cemazar ◽  
Gregor Sersa ◽  
Janez Scancar ◽  
Sabina Grabner
Keyword(s):  
Inductively Coupled Plasma ◽  
Acquired Resistance ◽  
Growth Delay ◽  
Platinum Compound ◽  
In Vivo Evaluation ◽  
Inductively Coupled ◽  
Tumour Growth Delay ◽  
Sarcoma Cells

AbstractBackgroundCisplatin is used in cancer therapy, but its side effects and acquired resistance to cisplatin have led to the synthesis and evaluation of new platinum compounds. Recently, the synthesized platinum compoundtrans-[PtCl2(3-Hmpy)2] (3-Hmpy = 3-hydroxymethylpyridine) (compound2) showed a considerable cytotoxic and antitumour effectiveness. To improve compound2cytotoxicityin vitroand antitumour effectivenessin vivo, electroporation was used as drug delivery approach to increase membrane permeability (electrochemotherapy).Materials and methodsIn vitro, survival of sarcoma cells with different intrinsic sensitivity to cisplatin (TBLCl2 sensitive, TBLCl2Pt resistant and SA-1 moderately sensitive) was determined using a clonogenic assay after treatment with compound2or cisplatin electrochemotherapy.In vivo, the antitumour effectiveness of electrochemotherapy with compound2or cisplatin was evaluated using a tumour growth delay assay. In addition, platinum in the serum, tumours and platinum bound to the DNA in the cells were performed using inductively coupled plasma mass spectrometry.ResultsIn vitro, cell survival after treatment with compound2electrochemotherapy was significantly decreased in all tested sarcoma cells with different intrinsic sensitivity to cisplatin (TBLCl2 sensitive, TBLCl2Pt resistant and SA-1 moderately sensitive). However, this effect was less pronounced compared to cisplatin. Interestingly, the enhancement factor (5-fold) of compound2cytotoxicity was equal in cisplatin-sensitive TBLCl2 and cisplatin-resistant TBLCl2Pt cells.In vivo, the growth delay of subcutaneous tumours after treatment with compound2electrochemotherapy was lower compared to cisplatin. The highest antitumour effectiveness after cisplatin or compound2electrochemotherapy was obtained in TBLCl2 tumours, resulting in 67% and 11% of tumour cures, respectively. Compound2induced significantly smaller loss of animal body weight compared to cisplatin. Furthermore, platinum amounts in tumours after compound2or cisplatin electrochemotherapy were approximately 2-fold higher compared to the drug treatment only, and the same increase of platinum bound to DNA was observed.ConclusionsThe obtained resultsin vitroandin vivosuggest compound2as a potential antitumour agent in electrochemotherapy.

scholarly journals Allyl Isothiocyanate Ameliorates Dextran Sodium Sulfate-Induced Colitis in Mouse by Enhancing Tight Junction and Mucin Expression

2018 ◽  
Vol 19 (7) ◽  
pp. 2025 ◽  
Author(s):  
Min Kim ◽  
Seungho Choi ◽  
Sun Kim ◽  
Yeo Yoon ◽  
Ju-Hee Kang ◽  
...  
Keyword(s):  
Tight Junction ◽  
Cell Line ◽  
Allyl Isothiocyanate ◽  
In Vivo Studies ◽  
Intestinal Barrier Function ◽  
Tight Junction Proteins ◽  
Mucin Expression ◽  
Junction Proteins

Inflammatory bowel disease (IBD) is characterized by chronic or recurrent inflammation of the gastrointestinal tract. Even though the current strategies to treat IBD include anti-inflammatory drugs and immune modulators, these treatments have side-effects. New strategies are, therefore, required to overcome the limitations of the therapies. In this study, we investigated the anti-colitic effects of allyl isothiocyanate (AITC), which is an active ingredient present in Wasabia japonica. The DSS-induced colitis model in the mouse was used to mimic human IBD and we observed that AITC treatment ameliorated the severity of colitis. We further studied the mechanism involved to ameliorate the colitis. To investigate the involvement of AITC on the intestinal barrier function, the effect on the intercellular tight junction was evaluated in the Caco-2 cell line while mucin expression was assessed in the LS174T cell line. AITC positively regulated tight junction proteins and mucin 2 (MUC2) against DSS-induced damage or depletion. Our data of in vivo studies were also consistent with the in vitro results. Furthermore, we observed that MUC2 increased by AITC is dependent on ERK signaling. In conclusion, we propose that AITC can be considered as a new strategy for treating IBD by modulating tight junction proteins and mucin.

Generation of a Conditionally Transformed Murine Embryonic Fibroblast Cell Line Using Doxycycline-Dependent IGF-1R Overexpression

2011 ◽  
Vol 17 (3) ◽  
pp. 339-349
Author(s):  
Ralph Graeser ◽  
Patricia Vrignaud ◽  
Norbert Esser ◽  
Sarah Umber ◽  
Ute Zirrgiebel ◽  
...  
Keyword(s):  
Cell Line ◽  
Expression System ◽  
Tumor Therapy ◽  
In Vivo Studies ◽  
Inhibitory Antibody ◽  
Preclinical Development ◽  
Murine Embryonic Fibroblast ◽  
Cellular Models

The insulin-like growth factor I receptor (IGF1-R) system has long been implicated in cancer and is a promising target for tumor therapy. Besides in vitro screening assays, the discovery of specific inhibitors against IGF-1R requires relevant cellular models, ideally applicable to both in vitro and in vivo studies. With this aim in mind, the authors generated an inducible cell line using the tetracycline-responsive gene expression system to mimic the effects of therapeutic inhibition of the IGF-1R both in vitro and on established tumors in vivo. Inducible overexpression of IGF-1R in murine embryonic fibroblasts was achieved and resulted in the transformation of the cells as verified by their ability to grow in soft agar and in nude mice. Continuous repression of exogenous IGF-1R expression completely prevented outgrowth of the tumors. Furthermore, induced repression of IGF-1R expression in established tumors resulted in regression of the tumors. Interestingly, however, IGF-1R–independent relapse of tumor growth was observed upon prolonged IGF-1R repression. The IGF-1R cell line generated using this approach was successfully employed to test reference small-molecule inhibitors in vitro and an IGF-1R–specific inhibitory antibody, EM164, in vivo. Besides efficacy as a read-out, phospho-AKT could be identified as a pharmacodynamic biomarker, establishing this cell line as a valuable tool for the preclinical development of IGF-1R inhibitors.

scholarly journals In vitro and in vivo evaluation of colon cancer targeted epichlorohydrin crosslinked Portulaca-alginate beads

2018 ◽  
Vol 9 (1) ◽  
pp. 190-199 ◽  
Author(s):  
Geet P. Asnani ◽  
Chandrakant R. Kokare
Keyword(s):  
Colon Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Cancer Cell Line ◽  
Colon Cancer Cell Line ◽  
Colon Cancer Cell ◽  
In Vivo Studies ◽  
Ht 29

AbstractThe aim of this study was to formulate a novel dual crosslinked hydrogel bead using Portulaca mucilage for colon-targeted delivery of 5-fluorouracil (5-FU) and evaluate its safety, specificity and efficacy. The ionotropic gelation technique was employed to prepare the hydrogel beads of Portulaca mucilage. For this, the mucilage was initially crosslinked with alginate and calcium ions. Epichlorohydrin was employed as a crosslinker in the second crosslinking step. The formulation was subjected to in vitro and in vivo studies to evaluate morphology, size, cytotoxicity, and organ distribution. Human HT-29 colon cancer cell-line was used for in vitro assays and in vivo studies were performed in Wistar rats to assess the usefulness and effectiveness of the formulation for colon cancer therapy. Microsphere sizes ranged from 930 to 977μm and possessed a high level of drug encapsulation efficiency (ca. 78% w/w). Compared with 5-FU solution (Tmax = 1.2 h, mean resident time: MRT = 3.3h) the dual crosslinked Portulaca microspheres exhibited sustained drug release after oral administration to rats (Tmax = 16h, MRT = 14h). The relative bioavailability of 5-FU solution and the microspheres were 100 and 93.6% respectively. Tissue distribution studies indicated high concentration of 5-FU in colon. In-vitro anticancer assay demonstrated IC50 value of 11.50 μg/ml against HT-29 colon cancer cell line. The epichlorohydrin cross-linked Portulaca microspheres prepared in this study provided sustained release of 5-FU up to 16h in the colonic region and enhanced the antitumor activity of the neoplastic drug. The formulation is hence an ideal carrier system for colon-targeted drug delivery.

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