IN-VITRO CYTOTOXICITY IN OVARIAN-CANCER OF LOW-DOSE CONTINUOUS EXPOSURE TO MICROTUBULE INHIBITORS (PACLITAXEL TAXOTERE) COMBINED WITH CISPLATIN

1995 ◽  
Author(s):  
Y KIYOZUKA ◽  
H NISHIMURA ◽  
A NAKASHIMA ◽  
K IMAMURA ◽  
S OTA ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Low Dose ◽  
In Vitro Cytotoxicity ◽  
Continuous Exposure ◽  
Microtubule Inhibitors

scholarly journals Credentialing and Pharmacologically Targeting PTP4A3 Phosphatase as a Molecular Target for Ovarian Cancer

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 969
Author(s):  
John S. Lazo ◽  
Elizabeth R. Sharlow ◽  
Robert Cornelison ◽  
Duncan J. Hart ◽  
Danielle C. Llaneza ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Migration ◽  
Tyrosine Phosphatase ◽  
In Vitro Cytotoxicity ◽  
Mrna Levels ◽  
High Grade ◽  
Drug Resistant ◽  
Ovca Cell

High grade serous ovarian cancer (OvCa) frequently becomes drug resistant and often recurs. Consequently, new drug targets and therapies are needed. Bioinformatics-based studies uncovered a relationship between high Protein Tyrosine Phosphatase of Regenerating Liver-3 (PRL3 also known as PTP4A3) expression and poor patient survival in both early and late stage OvCa. PTP4A3 mRNA levels were 5–20 fold higher in drug resistant or high grade serous OvCa cell lines compared to nonmalignant cells. JMS-053 is a potent allosteric small molecule PTP4A3 inhibitor and to explore further the role of PTP4A3 in OvCa, we synthesized and interrogated a series of JMS-053-based analogs in OvCa cell line-based phenotypic assays. While the JMS-053 analogs inhibit in vitro PTP4A3 enzyme activity, none were superior to JMS-053 in reducing high grade serous OvCa cell survival. Because PTP4A3 controls cell migration, we interrogated the effect of JMS-053 on this cancer-relevant process. Both JMS-053 and CRISPR/Cas9 PTP4A3 depletion blocked cell migration. The inhibition caused by JMS-053 required the presence of PTP4A3. JMS-053 caused additive or synergistic in vitro cytotoxicity when combined with paclitaxel and reduced in vivo OvCa dissemination. These results indicate the importance of PTP4A3 in OvCa and support further investigations of the lead inhibitor, JMS-053.

scholarly journals Synthesis and Properties of CurNQ for the Theranostic Application in Ovarian Cancer Intervention

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4471
Author(s):  
Lara G. Freidus ◽  
Pradeep Kumar ◽  
Thashree Marimuthu ◽  
Priyamvada Pradeep ◽  
Viness Pillay ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Detection ◽  
Ovarian Cancer Cell ◽  
In Vitro Cytotoxicity ◽  
Cancer Targeting ◽  
The Novel ◽  
Cytotoxicity Assays ◽  
Ovarian Cancer Cell Lines ◽  
Cancer Intervention

Synthesis of a novel theranostic molecule for targeted cancer intervention. A reaction between curcumin and lawsone was carried out to yield the novel curcumin naphthoquinone (CurNQ) molecule (2,2′-((((1E,3Z,6E)-3-hydroxy-5-oxohepta-1,3,6-triene-1,7-diyl) bis(2-methoxy-4,1-phenylene))bis(oxy))bis(naphthalene-1,4-dione). CurNQ’s structure was elucidated and was fully characterized. CurNQ was demonstrated to have pH specific solubility, its saturation solubility increased from 11.15 µM at pH 7.4 to 20.7 µM at pH 6.8. This pH responsivity allows for cancer targeting (Warburg effect). Moreover, CurNQ displayed intrinsic fluorescence, thus enabling imaging and detection applications. In vitro cytotoxicity assays demonstrated the chemotherapeutic properties of CurNQ as CurNQ reduced cell viability to below 50% in OVCAR-5 and SKOV3 ovarian cancer cell lines. CurNQ is a novel theranostic molecule for potential targeted cancer detection and treatment.

In Vitro Cytotoxicity of Low-Dose-Rate Radioimmunotherapy by the Alpha-Emitting Radioimmunoconjugate Thorium-227–DOTA–Rituximab

2009 ◽  
Vol 75 (3) ◽  
pp. 886-895 ◽  
Author(s):  
Jostein Dahle ◽  
Cecilie Krogh ◽  
Katrine B. Melhus ◽  
Jørgen Borrebæk ◽  
Roy H. Larsen ◽  
...  
Keyword(s):  
Dose Rate ◽  
Low Dose ◽  
In Vitro Cytotoxicity ◽  
Low Dose Rate

Doxorubicin weekly low dose administration: in vitro cytotoxicity generated by the typical pharmacokinetic profile

1992 ◽  
Vol 28 (11) ◽  
pp. 1881-1885 ◽  
Author(s):  
G Milano ◽  
E Cassuto-Viguier ◽  
J.L Fischel ◽  
P Formento ◽  
N Renée ◽  
...  
Keyword(s):  
Low Dose ◽  
Pharmacokinetic Profile ◽  
In Vitro Cytotoxicity ◽  
Dose Administration

Low-dose cytarabine for acute myeloid leukaemia and myelodysplastic syndromes: in vivo and in vitro cytotoxicity

1991 ◽  
Vol 27 (7) ◽  
pp. 842-845 ◽  
Author(s):  
Gerrit J. Ossenkoppele ◽  
Pierre W. Wijermans ◽  
J.J.P. Nauta ◽  
Peter C. Huijgens ◽  
Mart M.A.C. Langenhuijsen
Keyword(s):  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
Myelodysplastic Syndromes ◽  
Low Dose ◽  
In Vitro Cytotoxicity ◽  
Low Dose Cytarabine ◽  
Acute Myeloid

Anti-tumor activity of ADH-1 in vitro and in vivo in combination with paclitaxel in ovarian cancer cell lines

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 16050-16050
Author(s):  
M. Gupta ◽  
D. Barnes ◽  
J. Losos ◽  
G. Spehar ◽  
M. Bednarcik ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Combination Therapy ◽  
Tumor Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Xenograft Model ◽  
In Vitro Cytotoxicity ◽  
Anti Tumor Activity

16050 Background: ADH-1 is a novel N-cadherin (Ncad) antagonist. Ncad is a protein present on certain tumor cells and established tumor blood vessels. Its expression on tumor cells increases as they become more aggressive, invasive and metastatic, making it an important target for anti-cancer therapy. ADH-1 was well tolerated in phase I studies and demonstrated evidence of anti-tumor activity in 7 patients whose tumors expressed Ncad. Patient enrollment in two phase II single agent trials concluded at the end of 2006. We report on the anti-tumor activity of ADH-1 in combination with paclitaxel in cancer cell lines in vitro and in the A2780 (Ncad positive) ovarian xenograft model in vivo. Methods: In vitro cytotoxicity of SKOV-3 (ovarian) cells exposed to a fixed ratio of ADH-1 and paclitaxel simultaneously was evaluated by the WST-1 cell proliferation assay. In vivo anti-tumor activity of ADH-1, paclitaxel, and the combination was evaluated in the A2780 xenograft model. ADH-1 100 mg/kg was administered bid IP for 21 days and paclitaxel was administered qod IV for 5 days. Results: In vitro cytotoxicity assays evaluated for combination effects using CalcuSyn software indicated a strong synergistic effect of ADH-1 in combination with paclitaxel (CI <1). In vivo paclitaxel treatment produced a median Time to Endpoint (TTE) (tumor volume >2gm or study end at 60 day) of 32.1 days and 73% Tumor Growth Delay (TGD), compared to control (p=0.028). For the paclitaxel group, there was only one Tumor Free Survivor (TFS) and one transient Complete Responder (CR). ADH-1 produced a TTE of 16.1 and a -13% TGD (p>0.05). The combination of ADH-1 and paclitaxel produced a median TTE of 48.6 days, corresponding to 161% TGD (p<0.0016 compared to untreated controls, p<0.003 for vehicle treated, and p<0.005 compared to paclitaxel alone). The combination therapy generated durable CR in 5 animals, 1 transient CR and 2 PR. The combination therapy had similar toxicity to paclitaxel alone. Conclusions: In this ovarian cancer model, the combination of ADH-1 with paclitaxel produced a synergistic anti-tumor effect. Based in part on these encouraging pre-clinical results, a clinical program of ADH-1 in combination with chemotherapeutic agents has been initiated. No significant financial relationships to disclose.

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