In Vivo and in Vitro Growth of SCLC Cells Derived from Biopsies

In order to increase the availability of SCLC cells derived from biopsies, in vivo and in vitro growth methods were investigated. The cells grown in both conditions were periodically monitored for reactivity with 2 monoclonal antibodies (MAbs): MLuC1 directed against SCLC cells and IM1 which recognizes the class II antigen on activated lymphocytes and macrophages. About 50 % of the 28 analyzed SCLC specimens were found to proliferate in one or both systems. The in vitro-grown cells exhibited the same heterogeneity found in the original cell suspensions and moreover, in some cases only normal cells were recovered after several in vitro passages. From the subcutaneous transplanted tumors a large number of MLuC1-positive tumor cells could easily be recovered, thus indicating the validity of the in vivo methodology. The MBr1 MAb, directed against an epithelial antigen, was found to react with about 50 % of the 26 tested tumors, mainly those which demonstrated in vivo and/or in vitro growth capacity. These data suggest that only some tumors, presumably with peculiar biological characteristics, can efficiently grow in these artificial systems.

Download Full-text

Effect of in Vivo Oxidized Cellulose on in Vitro Growth of Human Respiratory Mucosa and Sub-mucosa During Endoscopic Skull Base Approaches

Journal of Neurological Surgery Part B Skull Base ◽

10.1055/s-0036-1579850 ◽

2016 ◽

Vol 77 (S 01) ◽

Author(s):

Ezequiel Goldschmidt ◽

Jorge Rasmussen ◽

Joseph Chabot ◽

Monica Loressi ◽

Marcelo Ielpi ◽

...

Keyword(s):

Skull Base ◽

Oxidized Cellulose ◽

In Vitro Growth ◽

Respiratory Mucosa

Download Full-text

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

Nuklearmedizin ◽

10.1055/s-0038-1624353 ◽

1987 ◽

Vol 26 (01) ◽

pp. 1-6 ◽

Cited By ~ 2

Author(s):

S. Selvaraj ◽

M. R. Suresh ◽

G. McLean ◽

D. Willans ◽

C. Turner ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Tumor Cell ◽

T Antigen ◽

Human Carcinomas ◽

Animal Tumor ◽

Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

Download Full-text

Cytotoxicity Studies of Curcumin Loaded-Cockle Shell-Derived Calcium Carbonate Nanoparticles

Nanoscience &Nanotechnology-Asia ◽

10.2174/2210681209666191128155819 ◽

2019 ◽

Vol 09 ◽

Cited By ~ 1

Author(s):

Maryam Muhammad Mailafiya ◽

Mohamad Aris Mohd Moklas ◽

Kabeer Abubakar ◽

Abubakar Danmaigoro ◽

Samaila Musa Chiroma ◽

...

Keyword(s):

Calcium Carbonate ◽

Safety Margin ◽

Bone Diseases ◽

In Vivo Studies ◽

Normal Cells ◽

Cytotoxicity Studies ◽

Standard Techniques ◽

Cockle Shell

Background: Cockle shell-derived calcium carbonate nanoparticles (CSCaCO3NP) are natural biogenic inorganic material that is used in drug delivery mainly as a bone-remodeling agent as well as a delivery agent for various therapeutics against bone diseases. Curcumin possess wide safety margin and yet puzzled with the problem of poor bioavailability due to insolubility. Propounding in vitro and in vivo studies on toxicity assessments of newly synthesized nanoparticles are ongoing to overcome some crucial challenges regarding their safety administration. Nanotoxicology has paved ways for concise test protocols to monitor sequential events with regards to possible toxicity of newly synthesized nanomaterials. The development of nanoparticle with no or less toxic effect has gained tremendous attentions. Objective: This study aimed at evaluating the in vitro cytotoxic effect of curcumin-loaded cockle shell-derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) and assessing its biocompatibility on normal cells using standard techniques of WST’s assay. Method: Standard techniques of WST’s assay was used for the evaluation of the biocompatibility and cytotoxicity. Result: The result showed that CSCaCO3NP and Cur-CSCaCO3NP possess minimal toxicity and high biocompatibility on normal cells even at higher dose of 500 µg/ml and 40 µg/ml respectively. Conclusion: CSCaCO3NP can be termed an excellent non-toxic nanocarrier for curcumin delivery. Hence, curcumin loaded cockle shell derived calcium carbonate nanoparticles (Cur-CSCaCO3NP) could further be assessed for various in vivo and in vitro therapeutic applications against various bone related ailments.

Download Full-text

In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP)

Scientific Reports ◽

10.1038/s41598-021-84622-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Merricka C. Livingstone ◽

Alexis A. Bitzer ◽

Alish Giri ◽

Kun Luo ◽

Rajeshwer S. Sankhala ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Monoclonal Antibodies ◽

Disease Burden ◽

Vaccine Candidate ◽

Specific Binding ◽

Circumsporozoite Protein ◽

Target Epitope ◽

Selection Of

AbstractPlasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NPNA)n repeat region. We compared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mAb 317 that specifically binds the (NPNA)n epitope, had the highest affinity and it elicited the best sterile protection in mice. The most potent inhibitor of sporozoite invasion in vitro was mAb CIS43 which shows dual-specific binding to the junctional sequence and (NPNA)n. In vivo mouse protection was associated with the mAb reactivity to the NANPx6 peptide, the in vitro inhibition of sporozoite invasion activity, and kinetic parameters measured using intact mAbs or their Fab fragments. Buried surface area between mAb and its target epitope was also associated with in vivo protection. Association and disconnects between in vitro and in vivo readouts has important implications for the design and down-selection of the next generation of CSP based interventions.

Download Full-text

Design, Synthesis, Molecular Modeling and Antitumor Evaluation of Novel Indolyl-Pyrimidine Derivatives with EGFR Inhibitory Activity

Molecules ◽

10.3390/molecules26071838 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1838

Author(s):

Naglaa M. Ahmed ◽

Mahmoud M. Youns ◽

Moustafa K. Soltan ◽

Ahmed M. Said

Keyword(s):

Molecular Modeling ◽

Antitumor Activity ◽

Cell Lines ◽

Cancer Cell ◽

Antiproliferative Activity ◽

Antitumor Agents ◽

Cancer Cell Lines ◽

Normal Cells

Scaffolds hybridization is a well-known drug design strategy for antitumor agents. Herein, series of novel indolyl-pyrimidine hybrids were synthesized and evaluated in vitro and in vivo for their antitumor activity. The in vitro antiproliferative activity of all compounds was obtained against MCF-7, HepG2, and HCT-116 cancer cell lines, as well as against WI38 normal cells using the resazurin assay. Compounds 1–4 showed broad spectrum cytotoxic activity against all these cancer cell lines compared to normal cells. Compound 4g showed potent antiproliferative activity against these cell lines (IC50 = 5.1, 5.02, and 6.6 μM, respectively) comparable to the standard treatment (5-FU and erlotinib). In addition, the most promising group of compounds was further evaluated for their in vivo antitumor efficacy against EAC tumor bearing mice. Notably, compound 4g showed the most potent in vivo antitumor activity. The most active compounds were evaluated for their EGFR inhibitory (range 53–79 %) activity. Compound 4g was found to be the most active compound against EGFR (IC50 = 0.25 µM) showing equipotency as the reference treatment (erlotinib). Molecular modeling study was performed on compound 4g revealed a proper binding of this compound inside the EGFR active site comparable to erlotinib. The data suggest that compound 4g could be used as a potential anticancer agent.

Download Full-text

Possible Future Monoclonal Antibody (mAb)-Based Therapy against Arbovirus Infections

BioMed Research International ◽

10.1155/2013/838491 ◽

2013 ◽

Vol 2013 ◽

pp. 1-21 ◽

Cited By ~ 12

Author(s):

Giuseppe Sautto ◽

Nicasio Mancini ◽

Giacomo Gorini ◽

Massimo Clementi ◽

Roberto Burioni

Keyword(s):

Monoclonal Antibody ◽

Monoclonal Antibodies ◽

Side Effects ◽

Antiviral Activity ◽

The Other ◽

Viral Escape ◽

Passive Immunotherapy ◽

Medical Need

More than 150 arboviruses belonging to different families are known to infect humans, causing endemic infections as well as epidemic outbreaks. Effective vaccines to limit the occurrence of some of these infections have been licensed, while for the others several new immunogens are under development mostly for their improvements concerning safety and effectiveness profiles. On the other hand, specific and effective antiviral drugs are not yet available, posing an urgent medical need in particular for emergency cases. Neutralizing monoclonal antibodies (mAbs) have been demonstrated to be effective in the treatment of several infectious diseases as well as in preliminaryin vitroandin vivomodels of arbovirus-related infections. Given their specific antiviral activity as well-tolerated molecules with limited side effects, mAbs could represent a new therapeutic approach for the development of an effective treatment, as well as useful tools in the study of the host-virus interplay and in the development of more effective immunogens. However, before their use as candidate therapeutics, possible hurdles (e.g., Ab-dependent enhancement of infection, occurrence of viral escape variants) must be carefully evaluated. In this review are described the main arboviruses infecting humans and candidate mAbs to be possibly used in a future passive immunotherapy.

Download Full-text

Novel Clostridium difficile Anti-Toxin (TcdA and TcdB) Humanized Monoclonal Antibodies Demonstrate In Vitro Neutralization across a Broad Spectrum of Clinical Strains and In Vivo Potency in a Hamster Spore Challenge Model

PLoS ONE ◽

10.1371/journal.pone.0157970 ◽

2016 ◽

Vol 11 (6) ◽

pp. e0157970 ◽

Cited By ~ 13

Author(s):

Hongyu Qiu ◽

Robyn Cassan ◽

Darrell Johnstone ◽

Xiaobing Han ◽

Antony George Joyee ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Clostridium Difficile ◽

Broad Spectrum ◽

Clinical Strains ◽

Humanized Monoclonal Antibodies

Download Full-text

Monoclonal antibodies specific to a Ca2+-bound form of lipocortin I distinguish its Ca2+-dependent phospholipid-binding ability from its ability to inhibit phospholipase A2

Biochemical Journal ◽

10.1042/bj2690709 ◽

1990 ◽

Vol 269 (3) ◽

pp. 709-715 ◽

Cited By ~ 11

Author(s):

H Hayashi ◽

M K Owada ◽

S Sonobe ◽

K Domae ◽

T Yamanouchi ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Phospholipase A2 ◽

Inhibitory Activity ◽

Biological Effects ◽

Free Form ◽

E Coli ◽

Phospholipid Binding ◽

Ef Hand

Lipocortin I, a Ca2(+)-and phospholipid-binding protein without EF-hand structures, has many biological effects in vitro. Its actual role in vivo, however is unknown. We obtained and characterized five monoclonal antibodies to lipocortin I. Two of these monoclonal antibodies (L2 and L4-MAbs) reacted with the Ca(+)-bound form of lipocortin I, but not with the Ca2(+)-free form, both in vivo and in vitro. Lipocortin I required greater than or equal to 10 microM-Ca2+ to bind the two antibodies, and this Ca2+ requirement was not affected by phosphatidylserine. L2-MAb abolished the phospholipase A2 inhibitory activity of lipocortin I and inhibited its binding to Escherichia coli membranes and to phosphatidylserine in vitro. L4-MAb abolished the phospholipase A2 inhibitory activity of lipocortin I, but did not affect its binding to E. coli membranes or to phosphatidylserine. These findings indicated that the inhibition of phospholipase A2 by lipocortin I was not simply due to removal or capping of the substrates in E. coli membranes. Furthermore, an immunofluorescence study using L2-MAb showed the actual existence of Ca2(+)-bound form of lipocortin I in vivo.

Download Full-text