A Marked Synergistic Effect in Antitumor Activity of Salan Titanium(IV) Complexes Bearing Two Differently Substituted Aromatic Rings

2011 ◽  
Vol 133 (42) ◽  
pp. 16812-16814 ◽  
Author(s):  
Hagai Glasner ◽  
Edit Y. Tshuva
Keyword(s):  
Antitumor Activity ◽  
Synergistic Effect ◽  
Aromatic Rings

scholarly journals Co-delivery of doxorubicin, docosahexaenoic acid, and α-tocopherol succinate by nanostructured lipid carriers has a synergistic effect to enhance antitumor activity and reduce toxicity

2020 ◽  
Vol 132 ◽  
pp. 110876
Author(s):  
Eduardo Burgarelli Lages ◽  
Renata Salgado Fernandes ◽  
Juliana de Oliveira Silva ◽  
Ângelo Malachias de Souza ◽  
Geovanni Dantas Cassali ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Docosahexaenoic Acid ◽  
Synergistic Effect ◽  
Nanostructured Lipid Carriers

Targeting the immunosuppressive tumor microenvironment: Synergistic effect of low-dose IL12 in combination with dual immune checkpoint inhibition in a preclinical model of ovarian cancer.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 7-7
Author(s):  
Paul G. Pavicic ◽  
Patricia A. Rayman ◽  
Hussein Al-Sudani ◽  
C. Marcela Diaz-Montero ◽  
Haider Mahdi
Keyword(s):  
Ovarian Cancer ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Antitumor Activity ◽  
Synergistic Effect ◽  
Immune Checkpoint ◽  
Low Dose ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Activated T Cells

7 Background: Epithelial ovarian cancer (OC) is the most lethal gynecologic cancer with ~22,000 women diagnosed annually in the US. The impact of immune checkpoint inhibition (ICI) in the treatment of solid tumors has been significant. However, the response rates for OC are low ranging from 11-15%. It is critical to explore strategies to enhance the efficacy of ICI immunotherapy in OC. Targeting immunosuppressive factors and cells within the tumor microenvironment (TME) represents a feasible approach. The use of IL12 is attractive because induces potent antitumor activity by targeting myeloid cells and lymphocytes. However its clinical application has been hindered by its potential systemic toxicity. Here we explore the use of low dose intraperitoneal IL12 to enhance the antitumor activity of dual ICI in OC. Methods: Mice bearing ID8-VEGF tumors implanted intraperitoneally received either anti-PD1 alone or dual ICI treatment of anti-PD1 plus anti-CTLA4 with or without low dose IL12. Ascites accumulation was used as surrogate for tumor progression and determined by assessing weight increase. Blood and ascites were analyzed by flow cytometry for frequency of PMN-MDSC, M-MDSC, and activated T cells. Results: Low dose IL12 alone induced a significant delay in ascites accumulation when compared to untreated controls or mice treated with PD1 monotherapy or dual ICI. Addition of IL12 to dual ICI resulted in significant tumor regression and extended survival benefit compared to dual ICI alone. A synergistic effect of IL12 was not observed when combined with PD1 monotherapy. Antitumor responses associated with a marked decrease in the frequency of M-MDSC in blood and a decrease in both PMN- and M-MDSC in ascites. Decrease in MDSC associated with elevated levels of activated T cells. Conclusions: Low dose IL12 can induce regression of ID8-VEGF tumors. However, durable responses were only observed when IL12 was added to dual ICI. This suggests that IL12 can induce changes in the TME, particularly on MDSC, that can potentiate the antitumor activity of dual ICI. Our findings also suggest a crucial role of CTLA4 blockade perhaps via Treg targeting.

Antitumor acridines with diaminoalkylo pharmacophoric group

2001 ◽  
Vol 73 (9) ◽  
pp. 1421-1428 ◽  
Author(s):  
Jerzy Konopa
Keyword(s):  
Clinical Trials ◽  
Biological Activity ◽  
Antitumor Activity ◽  
Clinical Evaluation ◽  
Wide Spectrum ◽  
Aromatic Rings ◽  
Transplantable Tumors

The substitution of acridine molecule in positions 1 and/or 4 with diaminoalkylo residue may result in obtaining derivatives displaying antitumor activity. The diaminoalkylo residue can be attached to acridine either directly or indirectly as a carboxamido moiety. In the former case, the presence of appropriate substituent in position para to diaminoalkylo residue is crucial for antitumor activity. Also, heterocyclic aromatic rings condensed with the acridine core can be considered as such substituents. Additional substituents introduced into the acridine core, especially those that may be transformed into quinoid systems, significantly increase antitumor activity of modified analogs. It is, however, of utmost importance that the presence of diaminoalkylo residue is the indispensable prerequisite for biological activity of acridines. Among several groups of synthesized diaminoalkyloacridines, the most potent antineoplastic properties toward a wide spectrum of transplantable tumors are exhibited by acridine-4-carboxamides, imidazo-, triazolo-, and pyrazoloacridinones. Two derivatives belonging to the above groups, acridine-4-carboxamide DACA and imidazoacridinone C-1311, are currently in clinical trials. Other derivatives exhibiting potent antitumor activity, that could be considered as close analogs of diaminolkyloacridines, are pyrazoloacridines, one of which is currently under clinical evaluation.

Comparison of in vitro antitumor activity between SB3 (trastuzumab biosimilar, Ontruzant) and Herceptin combined with an antibody for subdomain II of HER2 in HER2-positive cancer cells.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14001-e14001
Author(s):  
Jae Hee Lee ◽  
Kyungyeol Paek ◽  
Eunji Kim ◽  
Inhee Kim ◽  
Juyeon Jeong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Antitumor Activity ◽  
Synergistic Effect ◽  
Growth Inhibition ◽  
Cancer Cells ◽  
Tyrosine Kinase Receptor ◽  
Inhibition Rate ◽  
Her2 Positive ◽  
Gastric Cancer Cells

e14001 Background: The human epidermal growth factor receptor (HER) family plays a critical role in proliferation and survival of cancer cells. Trastuzumab is a recombinant humanized monoclonal antibody that blocks signaling pathways of HER2 tyrosine kinase receptor via binding to subdomain IV of HER2 extracellular domain. A subdomain II targeting therapeutic antibody (DII antibody, pertuzumab) binds to a different region on the same protein. A combination of the two different antibodies might provide a more effective antitumor activity without binding interference [1] . In this study, we evaluate in vitro antitumor activity of SB3 used in the same manner as Herceptin, in combination with a DII antibody that complements the mechanism of action of trastuzumab. [1] Nahta et al, [CANCER RESEARCH 64, 2343–2346, April 1, 2004]. Methods: Similarity assessment of in vitro antitumor activity between SB3 and Herceptin was performed on HER2-overexpressing breast and gastric cancer cells through analyzing HER2 dimerization, cell proliferation and survival activities, and antibody-dependent cellular cytotoxicity (ADCC) in the presence of a DII antibody. Combination index was calculated to evaluate the synergistic effect. Results: SB3 and Herceptin in combination with a DII antibody, showed similar in vitro inhibition rate for HER2/HER3 heterodimerization. The HER2-overexpressing breast and gastric cancer cells growth inhibition rate was similar whether SB3 or Herceptin was used in combination with a DII antibody. This effect was also shown in apoptosis activity by measuring caspase 3/7 expression. In terms of biological effect via Fc function, cell killing activity was assessed by ADCC assay in the presence of a DII antibody, and non-synergistic effect was shown with both SB3 and Herceptin. Conclusions: This study has concluded that SB3, as a trastuzumab biosimilar, demonstrates highly similar in vitro antitumor activity in experimental conditions when combined with a DII antibody, resulting in enhanced cell growth inhibition and apoptosis activities by inhibiting HER2 dimerization in HER2-positive cancer cells.

scholarly journals Granulin A Synergizes with Cisplatin to Inhibit the Growth of Human Hepatocellular Carcinoma

2018 ◽  
Vol 19 (10) ◽  
pp. 3060 ◽  
Author(s):  
Gan Qiao ◽  
Huanli Xu ◽  
Cong Li ◽  
Xiao Li ◽  
Ammad Farooqi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antitumor Activity ◽  
Synergistic Effect ◽  
Inhibitory Effect ◽  
Inhibitory Rate ◽  
Chemotherapy Drugs ◽  
Combined Use ◽  
Hcc Cells

Cisplatin is one of the most potent chemotherapy drugs widely used for cancer treatment. However, due to resistance and toxicity, the application of cisplatin for the treatment of hepatocellular carcinoma (HCC) is limited. Our previous study has shown that granulin A (GRN A), an anticancer peptide, is able to interact with enolase1 (ENO1) and inhibit the growth of HCC in vitro. In the present study, we studied the synergistic effect of the combination of cisplatin and GRN A for the inhibitory effect on HCC. An 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and Chou-Talalay approaches revealed that the combination of GRN A and cisplatin displayed potent synergistic effect. The colony formation and cell viability of HCC cells were inhibited significantly in cells treated with the combination of cisplatin and GRN A, compared with cells treated with cisplatin or GRN A alone. Overexpression of ENO1 diminished the synergistic effect of GRN A and cisplatin in HCC cells. The combination of the two drugs exhibited a more obvious inhibitory effect on cancer cell apoptosis, as analyzed by the cytometry flow, mitochondrial membrane potential (MMP) and western blot analysis. An in vivo study confirmed that the combined use of the two drugs displayed more potent antitumor activity compared to mice treated with cisplatin and GRN A alone; the inhibitory rate of tumor growth was 65.46% and 68.94%, respectively, in mice treated with GRN A and cisplatin. However, the inhibitory rate increased to 86.63% in mice treated with the combination of the two drugs. This study provides evidence that the combination of GRN A and cisplatin is able to sensitize the liver cancer to cisplatin, and that targeting ENO1 is a promising approach for enhancing the antitumor activity of cisplatin.

Synergistic effect of interleukin-15 and interleukin-12 on antitumor activity in a murine malignant pleurisy model

2000 ◽  
Vol 49 (2) ◽  
pp. 71-77 ◽  
Author(s):  
Keiko Kimura ◽  
Hitoshi Nishimura ◽  
Takeshi Matsuzaki ◽  
Teruo Yokokura ◽  
Yuji Nimura ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Synergistic Effect ◽  
Interleukin 12 ◽  
Interleukin 15 ◽  
Malignant Pleurisy
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