scholarly journals Combinatorial Treatment of Tinzaparin and Chemotherapy Can Induce a Significant Antitumor Effect in Pancreatic Cancer

2021 ◽  
Vol 22 (13) ◽  
pp. 7053
Author(s):  
Panagiotis Sarantis ◽  
Alexandros Bokas ◽  
Adriana Papadimitropoulou ◽  
Evangelos Koustas ◽  
Stamatios Theocharis ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Low Molecular Weight ◽  
Proliferative Potential ◽  
Therapeutic Approaches ◽  
In Vivo Evaluation ◽  
Tumor Reduction ◽  
Triple Regimen ◽  
Therapeutic Compounds

Pancreatic Cancer (PC) is recognized as a highly thrombogenic tumor; thus, low-molecular-weight heparin (LMWH) such as tinzaparin is routinely used for PC patients. On the basis of combinatorial therapy approaches to treat highly malignant and refractory cancers such as PC, we hypothesized that tinzaparin can augment the effectiveness of traditional chemotherapeutic drugs and induce efficient antitumor activity. PANC-1 and MIAPaCa-2 were incubated alone or in combination with tinzaparin, nab-paclitaxel and gemcitabine. In vivo evaluation of these compounds was performed in a NOD/SCID mouse using a model injected with PANC-1. Tinzaparin enhances the anti-tumor effects of nab-paclitaxel and gemcitabine in mtKRAS PC cell lines via apoptosis in in vitro experiments. The triple combination power acts through the induction of apoptosis, reduction of the proliferative potential and angiogenesis; hence, contributing to a decrease in tumor volume observed in vivo. The triple regimen provided an extra 24.3% tumor reduction compared to the double combination (gemcitabine plus nab-paclitaxel). Combinatorial strategies can create novel therapeutic approaches for the treatment of patients with PC, achieving a better clinical outcome and prolonged survival. Further prospective randomized research is needed and the investigation of various concentrations of tinzaparin above 150 UI/Kg, would potentially provide a valuable synergistic effect to the conventional therapeutic compounds.

scholarly journals Combinatorial Treatment of Tinzaparin and Chemotherapy can Induce a Significant Antitumor Effectin Pancreatic Cancer

2021 ◽  
Author(s):  
Panagiotis Sarantis ◽  
Alexandros Bokas ◽  
Adriana Papadimitropoulou ◽  
Evangelos Koustas ◽  
Stamatios Theocharis ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Volume ◽  
Low Molecular Weight ◽  
Proliferative Potential ◽  
Therapeutic Approaches ◽  
Tumor Reduction ◽  
Induction Of Apoptosis ◽  
Therapeutic Compounds

Abstract Background: Pancreatic Cancer (PC) is recognized as a highly thrombogenic tumor, with over 20% of patients suffering from venous thromboembolism during the disease. Thus, low-molecular-weight heparin (LMWH) such as Tinzaparin is routinely used for PC patients. On the basis of combinatorial therapy approach to treating highly malignant and refractory cancers such as PC, we hypothesized that Tinzaparin can augment the effectiveness of traditional chemotheurapeutic drugs and induce efficient antitumor activity.Methods: PANC-1 and MIAPaCa-2 were incubated alone or in combination with Tinzaparin, Nab-paclitaxel and gemcitabine. In vivo evaluation of these compounds was performed at NOD/SCID mouse using a model injected with PANC-1.Results: Tinzaparin enhances the anti-tumor effect of Nab-paclitaxel and gemcitabine in mtKRAS PC cell lines via apoptosis at in vitro experiments. The triple combination acts through induction of apoptosis, reduction of the proliferative potential and angiogenesis hence contributing to a decrease in tumor volume observed in vivo. Tumor reduction observed in mice receiving the triple combinational chemotherapy, was 74.5% compared to the control. The triple regime provided an extra 8.2% and 24.3% tumor reduction compared to the control and the double combination (gemcitambine plus Nab-paclitaxel) respectively.Conclusions: Combinatorial strategy can create novel therapeutic approaches for the treatment of patients with Pancreatic Cancer, achieving a better clinical outcome and prolonged survival. Further prospective randomized research is recommended and the investigation of various concentrations of Tinzaparin above of 150 UI/Kg, would potentially provide a valuable synergistic effect to the conventional therapeutic compounds.

scholarly journals Preparation, Characterization, and in Vitro/in Vivo Evaluation of Paclitaxel-Bound Albumin-Encapsulated Liposomes for the Treatment of Pancreatic Cancer

ACS Omega ◽  
2019 ◽  
Vol 4 (5) ◽  
pp. 8693-8700 ◽  
Author(s):  
Yuko Okamoto ◽  
Kazuaki Taguchi ◽  
Mina Sakuragi ◽  
Shuhei Imoto ◽  
Keishi Yamasaki ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
In Vivo Evaluation

In Vivo Evaluation Of The Antithrombotic Effects Of Some Polysaccharides Of Ultra Low Molecular Weight

1981 ◽  
Author(s):  
J Fareed ◽  
H L Messmore ◽  
J Choay ◽  
C Lormeau ◽  
M Petitou ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Serine Proteases ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Thrombin Time ◽  
Prothrombin Complex Concentrates ◽  
In Vivo Evaluation ◽  
Activated Prothrombin Complex Concentrates

Ultra low molecular weight saccharide fragments (ULMFs) have been obtained from porcine mucosal heparin (PMH) by extraction (e-ULMF) and by bacterial heparinase depolymerization (h-ULMF-8) processes. Both fragments showed a strong anti Xa activity (>2000 u/mg units, Yin and Wessler, J. Lab. Clin. Med. 81, 298, 1973) and possess relatively weak potencies in the US Pharmacoepial (<40 USP u/mg) and other conventional coagulant assays (activated and non activated partial thromboplastin time, thrombin time and whole blood activated recalcification times). Since ULMFs showed a strong anti Xa activity, we evaluated their antithrombotic actions in a modified stasis-thrombosis model (Wessler et. al. J. App. Phys. 14, 943, 1959) challenging the animals with various thrombogenic stimuli; activated and non activated prothrombin complex concentrates, factor Xa concentrates and human serum. h-ULMF-8 at dosage <0.125 mg/kg (<250 Anti Xa u/kg) IV and <1.0 mg/kg (>2000 anti Xa u/kg) SC completely protected the thrombogenic effects of various thrombogenic agents, whereas PMH at these dosages failed to produce any protection in pre and post treatment regiments. Similar studies with e-ULMF showed protection, however, the antithrombotic responses varied among animals. In vitro supplementation of heparin fragments at 5 times the concentration which protected animals against the thrombogenic effects of activated prothrombin complex concentrates failed to produce any elevation of prothrombin time, partial thromboplastin times, thrombin time and other coagulant assays. Our studies suggest that ULMFs are potent antithrombotic agents and may exert their effects involving multiple sites and primarily inhibiting the Xa and the non-thrombin serine proteases formed during activated states.

In vitro and in vivo evaluation of the anti-inflammatory effects of Arzanol from Helichrysum italicum

Planta Medica ◽  
2010 ◽  
Vol 76 (12) ◽  
Author(s):  
J Bauer ◽  
F Dehm ◽  
A Koeberle ◽  
F Pollastro ◽  
G Appendino ◽  
...  
Keyword(s):  
In Vivo Evaluation ◽  
Anti Inflammatory

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

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