Panagiotis Koliou | Royal Surrey County Hospital NHS Foundation Trust (original) (raw)

Papers by Panagiotis Koliou

International journal of molecular sciences, Feb 23, 2024

ΕΙΣΑΓΩΓΗ: Ο αυξητικός παράγοντας του ενδοθηλίου (VEGF-A) είναι ένας ισχυρός ρυθμιστής της αγγειογ... more ΕΙΣΑΓΩΓΗ: Ο αυξητικός παράγοντας του ενδοθηλίου (VEGF-A) είναι ένας ισχυρός ρυθμιστής της αγγειογένεσης και επιπλέον πιθανά έχει προγνωστική αξία σε ασθενείς με καρκίνο του παχέος εντέρου. Στους ασθενείς αυτούς, οι μικρού μοριακού βάρους ηπαρίνες (LMWH), ενδείκνυνται για την περιεγχειρητική θρομβοπροφύλαξη.ΣΚΟΠΟΣ ΤΗΣ ΜΕΛΕΤΗΣ: Στόχος της μελέτης ήταν η εκτίμηση της επίδρασης διαφορετικών δόσεων και διαφορετικής χρονικής διάρκειας χορήγησης της τινζαπαρίνης, στα περιεγχειρητικά επίπεδα του VEGF-Α, σε ασθενείς με καρκίνο του παχέος εντέρου που υποβλήθηκαν σε θεραπευτική εκτομή (R0). ΥΛΙΚΟ & ΜΕΘΟΔΟΙ: Στη μελέτη τυχαιοποιήθηκαν 76 ασθενείς, από τους οποίους τελικά, τα αποτελέσματα αναλύθηκαν σε 59, που αποτέλεσαν τον πληθυσμό των 4 ομάδων μελέτης. Στις ομάδες I και II, οι ασθενείς έλαβαν περιεγχειρητική θρομβοπροφύλαξη με τινζαπαρίνη, 3.500 IU, μια φορά την ημέρα, για 10 και 30 ημέρες, αντίστοιχα. Στις ομάδες III και IV, οι ασθενείς έλαβαν 4.500 IU τινζαπαρίνης, για αντίστοιχες χρονικές ...

Annals of Oncology, 2020

outcomes among patients with metastatic urothelial cancer (mUC) in the real-world setting. Method... more outcomes among patients with metastatic urothelial cancer (mUC) in the real-world setting. Methods: This was a retrospective analysis of Truven Health MarketScanÒ Commercial, Medicare Supplemental, and Coordination of Benefits (Medicare) databases. Patients with a primary diagnosis of mUC, 18 years old, received ICI for any line of treatment between 1/1/2016-6/30/2019, and continuously enrolled in the database from 6 months prior to 1 month following the metastatic date were analyzed. AD was identified at any time prior to ICI therapy initiation. Time to treatment discontinuation was used as a proxy to quantify ICI treatment outcomes. Results: Of the 455 eligible patients, 71 (16%) had a prior AD. Among those with AD, the most common was type 1 diabetes (25%), followed by rheumatoid arthritis (10%) and pernicious anemia (10%), while 28% had a history of two or more ADs. Patients with vs. without prior AD were older (mean age 70.4 vs. 66.5; p<0.001) and had a higher co-morbidity burden. There was a shorter median unadjusted time to ICI treatment discontinuation among patients with a prior AD (6.82 months; 95% CI¼3.93-29.02) vs. without (8.13 months; 95% CI¼6.49-12.50), but findings were not statistically significant (p¼0.27). Adjusting for age, sex, comorbidity, and line of therapy, there was no significant difference in time to ICI treatment discontinuation between patients with vs. without prior AD (HR¼1.29; 95%CI¼0.87-1.90). Conclusions: There was a shorter time to treatment discontinuation in patients with vs. without prior AD, but findings were not statistically significant. Broader inclusion of patients with mUC reflective of real-world populations in ICI clinical studies will better define tolerance and efficacy of novel therapies for urothelial cancer. Legal entity responsible for the study: Genentech.

IEEE Journal of Biomedical and Health Informatics, 2014

Cancer-tumor growth is a complex process depending on several biological factors, such as the che... more Cancer-tumor growth is a complex process depending on several biological factors, such as the chemical microenvironment of the tumor, the cellular metabolic profile and its proliferation rate. Several mathematical models have been developed for identifying the interactions between tumor cells and tissue microenvironment, since they play an important role in tumor formation and progression. Towards this direction we propose a new continuum model of avascular glioma-tumor growth, which incorporates a new factor, namely the glycolytic potential of cancer cells, to express the interactions of three different tumor-cell populations (proliferative, hypoxic and necrotic) with their tissue microenvironment. The glycolytic potential engages three vital nutrients, i.e. oxygen, glucose and lactate, which provide cells with the necessary energy for their survival and proliferation. Extensive simulations are performed for different evolution times and various proliferation rates, in order to investigate how the tumor growth is affected. According to medical experts, the experimental observations indicate that the model predicts quite satisfactorily the overall tumor growth as well as the expansion of each region separately. Following extensive evaluation, the proposed model may provide an essential tool for patient-specific tumor simulation and reliable prediction of glioma spatio-temporal expansion.

BACKGROUND: The vascular endothelial growth factor (VEGF-A) is a potent regulator of angiogenesis... more BACKGROUND: The vascular endothelial growth factor (VEGF-A) is a potent regulator of angiogenesis and most likely has a prognostic value in patients with colon cancer. In these patients, low molecular weight heparins (LMWH), are indicated for the perioperative thromoboprophylaxis.AIM OF THE STUDY: The main goal of the study was to evaluate the impact of the usage of different doses (3.500 IU vs. 4.500 IU) and/or different time periods (10 vs. 30 days) of a specific LMWH (tinzaparin), for perioperative thromboprophylaxis, upon the perioperative levels of serum VEGF, in colon cancer patients who underwent planned to have curative tumor resection (R0). MATERIALS & METHODS: 76 consecutive colon cancer patients were initially randomized and the results of 59, who conducted the four study groups, were finally analyzed. In groups I and II, the patients received 3.500 IU of tinzaparin once per day for 10 and 30 days accordingly. In groups III and IV, the patients received 4.500 IU of tinzaparin once per day for the same time-periods. Blood samples for the evaluation of serum VEGF levels and the activities of protein C, Antithrombin III (ATIII) and coagulation factor VIII (FVIII) were obtained at the following days: pre-op, 10th and 30th post-op day. Genetic analysis for thrombophilic gene mutations were performed by PCR. Statistical analysis of the results was done using repeated measurements in mixed desing ANOVA (SPSS v21, Inc. Chicago, Ill).RESULTS: With regard to the main study groups (group I to IV), all patients showed a constant increase in VEGF-A levels at the 10th post-op day, compared to the pre-op day. This increase was statistically significant in groups I, II and IV (p=0.008, p=0.017, p=0.000 accordingly). Patients of groups I and II (short duration thromboprophylaxis) showed increased serum VEGF-A levels at 30th post-op day, compared to that of patients with extended duration thromboprophylaxis (groups II and IV - p=0.000). This result was mainly due to the effect of group IV in which the serum VEGF levels at the 30th post-op day were comparable to the pre-op levels. Additionally, the higher dose of tinzaparin administered for the extended period, was the most effective in regulating the coagulation cascade. This regulation was achieved through a better regulation of fluctuation of the activity levels of proteins C, ATIII, FVIII.CONCLUSIONS: In colon cancer patients the perioperative thromboprophylaxis with LMWH 4.500 IU for 30 days results in regulation of the variations of serum VEGF levels during the post operative period. At the 30th post-op day these levels are similar to that preoperatively. Simultaneously this thromboprophylaxis scheme regulates more effectively the coagulation cascade proteins.ΕΙΣΑΓΩΓΗ: Ο αυξητικός παράγοντας του ενδοθηλίου (VEGF-A) είναι ένας ισχυρός ρυθμιστής της αγγειογένεσης και επιπλέον πιθανά έχει προγνωστική αξία σε ασθενείς με καρκίνο του παχέος εντέρου. Στους ασθενείς αυτούς, οι μικρού μοριακού βάρους ηπαρίνες (LMWH), ενδείκνυνται για την περιεγχειρητική θρομβοπροφύλαξη.ΣΚΟΠΟΣ ΤΗΣ ΜΕΛΕΤΗΣ: Στόχος της μελέτης ήταν η εκτίμηση της επίδρασης διαφορετικών δόσεων και διαφορετικής χρονικής διάρκειας χορήγησης της τινζαπαρίνης, στα περιεγχειρητικά επίπεδα του VEGF-Α, σε ασθενείς με καρκίνο του παχέος εντέρου που υποβλήθηκαν σε θεραπευτική εκτομή (R0). ΥΛΙΚΟ & ΜΕΘΟΔΟΙ: Στη μελέτη τυχαιοποιήθηκαν 76 ασθενείς, από τους οποίους τελικά, τα αποτελέσματα αναλύθηκαν σε 59, που αποτέλεσαν τον πληθυσμό των 4 ομάδων μελέτης. Στις ομάδες I και II, οι ασθενείς έλαβαν περιεγχειρητική θρομβοπροφύλαξη με τινζαπαρίνη, 3.500 IU, μια φορά την ημέρα, για 10 και 30 ημέρες, αντίστοιχα. Στις ομάδες III και IV, οι ασθενείς έλαβαν 4.500 IU τινζαπαρίνης, για αντίστοιχες χρονικές περιόδους. Αιμοληψίες, για εκτίμηση των επιπέδων VEGF και ενεργότητας της πρωτεΐνης C, αντιθρομβίνης III (ATIII) και του παράγοντα VIII, ελήφθησαν στις κάτωθι ημέρες: προεγχειρητικά (pre-op), τη 10η μετεγχειρητική ημέρα (10th post-op day) και την 30η μετεγχειρητική ημέρα (30th post-op day). Γενετική ανάλυση για γονιδιακές μεταλλάξεις σχετιζόμενες με θρομβοφιλία έγιναν με PCR. Η στατιστική ανάλυση των αποτελεσμάτων, έγινε με επαναλαμβανόμενες μετρήσεις μικτού σχεδιασμού ANOVA (SPSS v21, Inc, Chicago, Ill).ΑΠΟΤΕΛΕΣΜΑΤΑ: Oι ασθενείς όλων των ομάδων έδειξαν αύξηση των επιπέδων VEGF την 10th post-op day, σε σχέση με την pre-op day. Η αύξηση αυτή ήταν στατιστικά σημαντική στις ομάδες I, II και IV (p=0.008, p=0.017 και p=0.000, αντίστοιχα). Οι ασθενείς των ομάδων I και IIΙ (βραχεία διάρκεια θρομβοπροφύλαξης) είχαν, κατά την 30th post-op day, υψηλότερα επίπεδα VEGF, σε σχέση με τα αντίστοιχα των ασθενών με μακράς διάρκειας θρομβοπροφύλαξη, δηλαδή των ομάδων II και IV (p=0.000). Το αποτέλεσμα αυτό οφείλονταν κυρίως στα επίπεδα της ομάδας IV, οι ασθενείς της οποίας ήταν οι μόνοι των οποίων τα επίπεδα VEGF κατά την 30η post-op day, δεν διέφεραν από αυτά της pre-op day. Επιπλέον, η υψηλή δόση τινζαπαρίνης, για μακρά διάρκεια χορήγησης,…

European Journal of Medical Case Reports, 2021

Forum of Clinical Oncology, 2021

The field of ovarian cancer has been revolutionized with the use of poly (ADP-ribose) polymerase ... more The field of ovarian cancer has been revolutionized with the use of poly (ADP-ribose) polymerase (PARP) inhibitors, which present greater inhibition effect in epithelial subtype due to high rates of homologous recombination deficiency. PARP inhibition exploits this cancer pitfall by disrupting DNA repair, leading to genomic instability and apoptosis. Three PARP inhibitors (olaparib, niraparib, and rucaparib) are now approved for use in women with epithelial ovarian cancer, while others are under development. Among women with BRCA1/2 mutations, maintenance PARP therapy has led to a nearly fourfold prolongation of PFS, while those without BRCA1/2 mutations experience an approximately twofold increase in PFS. Differences in trial design, patient selection and primary analysis population affect the conclusions on PARP inhibitors. Limited OS data have been published and there is also limited experience regarding long-term safety. With regard to toxicity profile, there are no differences ...

Cancer Management and Research, 2018

Eribulin mesylate is a synthetic derivative of halichondrin B isolated from a marine sponge. Its ... more Eribulin mesylate is a synthetic derivative of halichondrin B isolated from a marine sponge. Its mechanism of action is through microtubule inhibition, which is different from that of taxanes. Eribulin has been approved for the treatment of metastatic breast cancer and more recently for non-operable or metastatic liposarcoma in patients who have received prior anthracycline chemotherapy. The major side effects of eribulin are bone marrow suppression including neutropenia, leukopenia, anemia, and fatigue/weakness, which can be well managed. In this article, we reviewed evidence from the latest published data on eribulin and its use in the treatment of soft tissue sarcomas. We explored the drug's mechanism of action, pharmacodynamics, pharmacokinetics, and metabolism. Lastly, we reviewed all preclinical studies as well as clinical trials that investigated eribulin.

Medical & biological engineering & computing, 2018

Glioma brain tumors exhibit considerably aggressive behavior leading to high mortality rates. Mat... more Glioma brain tumors exhibit considerably aggressive behavior leading to high mortality rates. Mathematical modeling of tumor growth aims to explore the interactions between glioma cells and tissue microenvironment, which affect tumor evolution. Leveraging this concept, we present a three-dimensional model of glioma spatio-temporal evolution based on existing continuum approaches, yet incorporating novel factors of the phenomenon. The proposed model involves the interactions between different tumor cell phenotypes and their microenvironment, investigating how tumor growth is affected by complex biological exchanges. It focuses on the separate and combined effect of vital nutrients and cellular wastes on tumor expansion, leading to the formation of cell populations with different metabolic, proliferative, and diffusive profiles. Several simulations were performed on a virtual and a real glioma, using combinations of proliferation and diffusion rates for different evolution times. The ...

Journal of Cancer, 2017

Background/Purpose: In colon cancer (CC) patients preoperative (pre-op) levels of VEGF-A165 (VEGF... more Background/Purpose: In colon cancer (CC) patients preoperative (pre-op) levels of VEGF-A165 (VEGF) is a strong predictor for disease recurrence. Elevated postoperative (post-op) VEGF levels could have undesirable effects by enhancing tumor growth and metastasis formation. It has been suggested that thromboprophylaxis with a Low Molecular Weight Heparin (LMWH) in surgical cancer patients, further to thromboembolic protection, may exert some anti-neoplastic properties, as well. The aim of our study was to assess the potential impact of the LMWH Tinzaparin (Innohep®-Leo Pharma, Copenhagen, Denmark), given at different doses and for different perioperative (peri-op) periods, upon the post-op variability of serum VEGF levels in surgical CC patients. Methods: A total of 54 consecutive CC patients who underwent a curative resection were randomized in four groups according to their peri-op thromboprophylaxis scheme, which was based on administrating Tinzaparin in different doses and at different periods, as follows: group I: 3,500 IU for 10 days, group II: 3,500 IU for 30 days, group III: 4,500 IU for 10 days and group IV: 4,500 IU for 30 days. Serum VEGF concentrations were evaluated on the pre-op day (Day 0) and on the 10 th and 30 th post-op days (Day 10 and Day 30, respectively). For statistical analyses the mixed design ANOVA was used. P < 0.05 was considered significant. Results: On Day 0, VEGF didn't differ between groups I, II, III and IV (p>0.05, for every comparison). On Day 10, VEGF was increased in all groups. Between Day 10 and Day 30, VEGF remained stable in groups I (p=0.031) and II (p=1.000) and increased significantly in group III (p=0.005). On the contrary, VEGF decreased significantly in group IV (p<0.001). The most remarkable finding was observed when we compared VEGF between Day 0 and Day 30: while in groups I, II and III, VEGF remained significantly higher compared to Day 0 (p<0.001, p=0.041 and p<0.001, respectively), on the contrary, in group IV (extended-duration with the highest dose of 4,500 IU of tinzaparin) it was comparable to Day 0 (p=1.000). Conclusions: In surgical CC patients only the recommended thromboprophylaxis scheme with the highest prophylactic dose of Tinzaparin (4,500 IU) for extended-duration (30 days) normalizes VEGF levels at the end of the first post-op month by reducing them to the pre-op levels.

Thrombosis Research

Introduction: Patients with glioblastoma multiforme (GBM) are at high risk of venous thromboembol... more Introduction: Patients with glioblastoma multiforme (GBM) are at high risk of venous thromboembolism (VTE). Although clinical factors such as immobility, paresis and hypovolemia contribute to this risk, they do not correlate with occurrence of VTE. Indeed, biological factors may be more significant than clinical factors in predicting post-operative thrombosis. Tissue factor (TF), the initiator of coagulation in vivo, is expressed in all gliomas, and correlates with tumor grade. TF is normally expressed extravascularly, but has recently been shown to be present in blood. Whether blood-borne TF is functionally active remains unclear. We report the presence of active TF in cell-free plasma of a 38 year old male patient with GBM. Methods: Pre-and post-operative (day 3) blood samples were collected. Whole blood coagulation analysis was performed by thromboelastography (TEG). Platelet activation was determined by measuring platelet surface P-selectin and monocyte-platelet conjugates. Plasma microparticles (MP) were isolated by high-speed centrifugation of cell-free plasma. Procoagulant activities of MP and particle-free supernatant (SN) were measured by thrombin generation assay. Results: Pre-op TEG revealed a hypercoagulable state as evidenced by a shortened clot time (6.8 mins, normal: 9-27mins), and elevated clot rate and strength values. Post-operatively, the clot time normalized (10 mins), indicating the reduction of a plasmatic procoagulant trigger. Other TEG parameters remained elevated. Platelet counts were normal in both samples, although platelet activation decreased by >50% postoperatively. TF-dependent procoagulant activity was detected in MP (but not in SN). Consistent with the TEG clot times, this TF activity was reduced postoperatively, but remained higher than that of control plasma. Conclusion: In this report we have shown TF activity in the plasma of a patient with GBM. The post-op reduction of this circulating, MP-associated TF activity suggests that the observed hypercoagulability could be at least partially due to TF shed from the tumor.

Theoretical Biology and Medical Modelling, 2013

IEEE Journal of Biomedical and Health Informatics, 2014

Cancer-tumor growth is a complex process depending on several biological factors, such as the che... more Cancer-tumor growth is a complex process depending on several biological factors, such as the chemical microenvironment of the tumor, the cellular metabolic profile and its proliferation rate. Several mathematical models have been developed for identifying the interactions between tumor cells and tissue microenvironment, since they play an important role in tumor formation and progression. Towards this direction we propose a new continuum model of avascular glioma-tumor growth, which incorporates a new factor, namely the glycolytic potential of cancer cells, to express the interactions of three different tumor-cell populations (proliferative, hypoxic and necrotic) with their tissue microenvironment. The glycolytic potential engages three vital nutrients, i.e. oxygen, glucose and lactate, which provide cells with the necessary energy for their survival and proliferation. Extensive simulations are performed for different evolution times and various proliferation rates, in order to investigate how the tumor growth is affected. According to medical experts, the experimental observations indicate that the model predicts quite satisfactorily the overall tumor growth as well as the expansion of each region separately. Following extensive evaluation, the proposed model may provide an essential tool for patient-specific tumor simulation and reliable prediction of glioma spatio-temporal expansion.

International journal of molecular sciences, Feb 23, 2024

ΕΙΣΑΓΩΓΗ: Ο αυξητικός παράγοντας του ενδοθηλίου (VEGF-A) είναι ένας ισχυρός ρυθμιστής της αγγειογ... more ΕΙΣΑΓΩΓΗ: Ο αυξητικός παράγοντας του ενδοθηλίου (VEGF-A) είναι ένας ισχυρός ρυθμιστής της αγγειογένεσης και επιπλέον πιθανά έχει προγνωστική αξία σε ασθενείς με καρκίνο του παχέος εντέρου. Στους ασθενείς αυτούς, οι μικρού μοριακού βάρους ηπαρίνες (LMWH), ενδείκνυνται για την περιεγχειρητική θρομβοπροφύλαξη.ΣΚΟΠΟΣ ΤΗΣ ΜΕΛΕΤΗΣ: Στόχος της μελέτης ήταν η εκτίμηση της επίδρασης διαφορετικών δόσεων και διαφορετικής χρονικής διάρκειας χορήγησης της τινζαπαρίνης, στα περιεγχειρητικά επίπεδα του VEGF-Α, σε ασθενείς με καρκίνο του παχέος εντέρου που υποβλήθηκαν σε θεραπευτική εκτομή (R0). ΥΛΙΚΟ & ΜΕΘΟΔΟΙ: Στη μελέτη τυχαιοποιήθηκαν 76 ασθενείς, από τους οποίους τελικά, τα αποτελέσματα αναλύθηκαν σε 59, που αποτέλεσαν τον πληθυσμό των 4 ομάδων μελέτης. Στις ομάδες I και II, οι ασθενείς έλαβαν περιεγχειρητική θρομβοπροφύλαξη με τινζαπαρίνη, 3.500 IU, μια φορά την ημέρα, για 10 και 30 ημέρες, αντίστοιχα. Στις ομάδες III και IV, οι ασθενείς έλαβαν 4.500 IU τινζαπαρίνης, για αντίστοιχες χρονικές ...

Annals of Oncology, 2020

outcomes among patients with metastatic urothelial cancer (mUC) in the real-world setting. Method... more outcomes among patients with metastatic urothelial cancer (mUC) in the real-world setting. Methods: This was a retrospective analysis of Truven Health MarketScanÒ Commercial, Medicare Supplemental, and Coordination of Benefits (Medicare) databases. Patients with a primary diagnosis of mUC, 18 years old, received ICI for any line of treatment between 1/1/2016-6/30/2019, and continuously enrolled in the database from 6 months prior to 1 month following the metastatic date were analyzed. AD was identified at any time prior to ICI therapy initiation. Time to treatment discontinuation was used as a proxy to quantify ICI treatment outcomes. Results: Of the 455 eligible patients, 71 (16%) had a prior AD. Among those with AD, the most common was type 1 diabetes (25%), followed by rheumatoid arthritis (10%) and pernicious anemia (10%), while 28% had a history of two or more ADs. Patients with vs. without prior AD were older (mean age 70.4 vs. 66.5; p<0.001) and had a higher co-morbidity burden. There was a shorter median unadjusted time to ICI treatment discontinuation among patients with a prior AD (6.82 months; 95% CI¼3.93-29.02) vs. without (8.13 months; 95% CI¼6.49-12.50), but findings were not statistically significant (p¼0.27). Adjusting for age, sex, comorbidity, and line of therapy, there was no significant difference in time to ICI treatment discontinuation between patients with vs. without prior AD (HR¼1.29; 95%CI¼0.87-1.90). Conclusions: There was a shorter time to treatment discontinuation in patients with vs. without prior AD, but findings were not statistically significant. Broader inclusion of patients with mUC reflective of real-world populations in ICI clinical studies will better define tolerance and efficacy of novel therapies for urothelial cancer. Legal entity responsible for the study: Genentech.

IEEE Journal of Biomedical and Health Informatics, 2014

Cancer-tumor growth is a complex process depending on several biological factors, such as the che... more Cancer-tumor growth is a complex process depending on several biological factors, such as the chemical microenvironment of the tumor, the cellular metabolic profile and its proliferation rate. Several mathematical models have been developed for identifying the interactions between tumor cells and tissue microenvironment, since they play an important role in tumor formation and progression. Towards this direction we propose a new continuum model of avascular glioma-tumor growth, which incorporates a new factor, namely the glycolytic potential of cancer cells, to express the interactions of three different tumor-cell populations (proliferative, hypoxic and necrotic) with their tissue microenvironment. The glycolytic potential engages three vital nutrients, i.e. oxygen, glucose and lactate, which provide cells with the necessary energy for their survival and proliferation. Extensive simulations are performed for different evolution times and various proliferation rates, in order to investigate how the tumor growth is affected. According to medical experts, the experimental observations indicate that the model predicts quite satisfactorily the overall tumor growth as well as the expansion of each region separately. Following extensive evaluation, the proposed model may provide an essential tool for patient-specific tumor simulation and reliable prediction of glioma spatio-temporal expansion.

BACKGROUND: The vascular endothelial growth factor (VEGF-A) is a potent regulator of angiogenesis... more BACKGROUND: The vascular endothelial growth factor (VEGF-A) is a potent regulator of angiogenesis and most likely has a prognostic value in patients with colon cancer. In these patients, low molecular weight heparins (LMWH), are indicated for the perioperative thromoboprophylaxis.AIM OF THE STUDY: The main goal of the study was to evaluate the impact of the usage of different doses (3.500 IU vs. 4.500 IU) and/or different time periods (10 vs. 30 days) of a specific LMWH (tinzaparin), for perioperative thromboprophylaxis, upon the perioperative levels of serum VEGF, in colon cancer patients who underwent planned to have curative tumor resection (R0). MATERIALS & METHODS: 76 consecutive colon cancer patients were initially randomized and the results of 59, who conducted the four study groups, were finally analyzed. In groups I and II, the patients received 3.500 IU of tinzaparin once per day for 10 and 30 days accordingly. In groups III and IV, the patients received 4.500 IU of tinzaparin once per day for the same time-periods. Blood samples for the evaluation of serum VEGF levels and the activities of protein C, Antithrombin III (ATIII) and coagulation factor VIII (FVIII) were obtained at the following days: pre-op, 10th and 30th post-op day. Genetic analysis for thrombophilic gene mutations were performed by PCR. Statistical analysis of the results was done using repeated measurements in mixed desing ANOVA (SPSS v21, Inc. Chicago, Ill).RESULTS: With regard to the main study groups (group I to IV), all patients showed a constant increase in VEGF-A levels at the 10th post-op day, compared to the pre-op day. This increase was statistically significant in groups I, II and IV (p=0.008, p=0.017, p=0.000 accordingly). Patients of groups I and II (short duration thromboprophylaxis) showed increased serum VEGF-A levels at 30th post-op day, compared to that of patients with extended duration thromboprophylaxis (groups II and IV - p=0.000). This result was mainly due to the effect of group IV in which the serum VEGF levels at the 30th post-op day were comparable to the pre-op levels. Additionally, the higher dose of tinzaparin administered for the extended period, was the most effective in regulating the coagulation cascade. This regulation was achieved through a better regulation of fluctuation of the activity levels of proteins C, ATIII, FVIII.CONCLUSIONS: In colon cancer patients the perioperative thromboprophylaxis with LMWH 4.500 IU for 30 days results in regulation of the variations of serum VEGF levels during the post operative period. At the 30th post-op day these levels are similar to that preoperatively. Simultaneously this thromboprophylaxis scheme regulates more effectively the coagulation cascade proteins.ΕΙΣΑΓΩΓΗ: Ο αυξητικός παράγοντας του ενδοθηλίου (VEGF-A) είναι ένας ισχυρός ρυθμιστής της αγγειογένεσης και επιπλέον πιθανά έχει προγνωστική αξία σε ασθενείς με καρκίνο του παχέος εντέρου. Στους ασθενείς αυτούς, οι μικρού μοριακού βάρους ηπαρίνες (LMWH), ενδείκνυνται για την περιεγχειρητική θρομβοπροφύλαξη.ΣΚΟΠΟΣ ΤΗΣ ΜΕΛΕΤΗΣ: Στόχος της μελέτης ήταν η εκτίμηση της επίδρασης διαφορετικών δόσεων και διαφορετικής χρονικής διάρκειας χορήγησης της τινζαπαρίνης, στα περιεγχειρητικά επίπεδα του VEGF-Α, σε ασθενείς με καρκίνο του παχέος εντέρου που υποβλήθηκαν σε θεραπευτική εκτομή (R0). ΥΛΙΚΟ & ΜΕΘΟΔΟΙ: Στη μελέτη τυχαιοποιήθηκαν 76 ασθενείς, από τους οποίους τελικά, τα αποτελέσματα αναλύθηκαν σε 59, που αποτέλεσαν τον πληθυσμό των 4 ομάδων μελέτης. Στις ομάδες I και II, οι ασθενείς έλαβαν περιεγχειρητική θρομβοπροφύλαξη με τινζαπαρίνη, 3.500 IU, μια φορά την ημέρα, για 10 και 30 ημέρες, αντίστοιχα. Στις ομάδες III και IV, οι ασθενείς έλαβαν 4.500 IU τινζαπαρίνης, για αντίστοιχες χρονικές περιόδους. Αιμοληψίες, για εκτίμηση των επιπέδων VEGF και ενεργότητας της πρωτεΐνης C, αντιθρομβίνης III (ATIII) και του παράγοντα VIII, ελήφθησαν στις κάτωθι ημέρες: προεγχειρητικά (pre-op), τη 10η μετεγχειρητική ημέρα (10th post-op day) και την 30η μετεγχειρητική ημέρα (30th post-op day). Γενετική ανάλυση για γονιδιακές μεταλλάξεις σχετιζόμενες με θρομβοφιλία έγιναν με PCR. Η στατιστική ανάλυση των αποτελεσμάτων, έγινε με επαναλαμβανόμενες μετρήσεις μικτού σχεδιασμού ANOVA (SPSS v21, Inc, Chicago, Ill).ΑΠΟΤΕΛΕΣΜΑΤΑ: Oι ασθενείς όλων των ομάδων έδειξαν αύξηση των επιπέδων VEGF την 10th post-op day, σε σχέση με την pre-op day. Η αύξηση αυτή ήταν στατιστικά σημαντική στις ομάδες I, II και IV (p=0.008, p=0.017 και p=0.000, αντίστοιχα). Οι ασθενείς των ομάδων I και IIΙ (βραχεία διάρκεια θρομβοπροφύλαξης) είχαν, κατά την 30th post-op day, υψηλότερα επίπεδα VEGF, σε σχέση με τα αντίστοιχα των ασθενών με μακράς διάρκειας θρομβοπροφύλαξη, δηλαδή των ομάδων II και IV (p=0.000). Το αποτέλεσμα αυτό οφείλονταν κυρίως στα επίπεδα της ομάδας IV, οι ασθενείς της οποίας ήταν οι μόνοι των οποίων τα επίπεδα VEGF κατά την 30η post-op day, δεν διέφεραν από αυτά της pre-op day. Επιπλέον, η υψηλή δόση τινζαπαρίνης, για μακρά διάρκεια χορήγησης,…

European Journal of Medical Case Reports, 2021

Forum of Clinical Oncology, 2021

The field of ovarian cancer has been revolutionized with the use of poly (ADP-ribose) polymerase ... more The field of ovarian cancer has been revolutionized with the use of poly (ADP-ribose) polymerase (PARP) inhibitors, which present greater inhibition effect in epithelial subtype due to high rates of homologous recombination deficiency. PARP inhibition exploits this cancer pitfall by disrupting DNA repair, leading to genomic instability and apoptosis. Three PARP inhibitors (olaparib, niraparib, and rucaparib) are now approved for use in women with epithelial ovarian cancer, while others are under development. Among women with BRCA1/2 mutations, maintenance PARP therapy has led to a nearly fourfold prolongation of PFS, while those without BRCA1/2 mutations experience an approximately twofold increase in PFS. Differences in trial design, patient selection and primary analysis population affect the conclusions on PARP inhibitors. Limited OS data have been published and there is also limited experience regarding long-term safety. With regard to toxicity profile, there are no differences ...

Cancer Management and Research, 2018

Eribulin mesylate is a synthetic derivative of halichondrin B isolated from a marine sponge. Its ... more Eribulin mesylate is a synthetic derivative of halichondrin B isolated from a marine sponge. Its mechanism of action is through microtubule inhibition, which is different from that of taxanes. Eribulin has been approved for the treatment of metastatic breast cancer and more recently for non-operable or metastatic liposarcoma in patients who have received prior anthracycline chemotherapy. The major side effects of eribulin are bone marrow suppression including neutropenia, leukopenia, anemia, and fatigue/weakness, which can be well managed. In this article, we reviewed evidence from the latest published data on eribulin and its use in the treatment of soft tissue sarcomas. We explored the drug's mechanism of action, pharmacodynamics, pharmacokinetics, and metabolism. Lastly, we reviewed all preclinical studies as well as clinical trials that investigated eribulin.

Medical & biological engineering & computing, 2018

Glioma brain tumors exhibit considerably aggressive behavior leading to high mortality rates. Mat... more Glioma brain tumors exhibit considerably aggressive behavior leading to high mortality rates. Mathematical modeling of tumor growth aims to explore the interactions between glioma cells and tissue microenvironment, which affect tumor evolution. Leveraging this concept, we present a three-dimensional model of glioma spatio-temporal evolution based on existing continuum approaches, yet incorporating novel factors of the phenomenon. The proposed model involves the interactions between different tumor cell phenotypes and their microenvironment, investigating how tumor growth is affected by complex biological exchanges. It focuses on the separate and combined effect of vital nutrients and cellular wastes on tumor expansion, leading to the formation of cell populations with different metabolic, proliferative, and diffusive profiles. Several simulations were performed on a virtual and a real glioma, using combinations of proliferation and diffusion rates for different evolution times. The ...

Journal of Cancer, 2017

Background/Purpose: In colon cancer (CC) patients preoperative (pre-op) levels of VEGF-A165 (VEGF... more Background/Purpose: In colon cancer (CC) patients preoperative (pre-op) levels of VEGF-A165 (VEGF) is a strong predictor for disease recurrence. Elevated postoperative (post-op) VEGF levels could have undesirable effects by enhancing tumor growth and metastasis formation. It has been suggested that thromboprophylaxis with a Low Molecular Weight Heparin (LMWH) in surgical cancer patients, further to thromboembolic protection, may exert some anti-neoplastic properties, as well. The aim of our study was to assess the potential impact of the LMWH Tinzaparin (Innohep®-Leo Pharma, Copenhagen, Denmark), given at different doses and for different perioperative (peri-op) periods, upon the post-op variability of serum VEGF levels in surgical CC patients. Methods: A total of 54 consecutive CC patients who underwent a curative resection were randomized in four groups according to their peri-op thromboprophylaxis scheme, which was based on administrating Tinzaparin in different doses and at different periods, as follows: group I: 3,500 IU for 10 days, group II: 3,500 IU for 30 days, group III: 4,500 IU for 10 days and group IV: 4,500 IU for 30 days. Serum VEGF concentrations were evaluated on the pre-op day (Day 0) and on the 10 th and 30 th post-op days (Day 10 and Day 30, respectively). For statistical analyses the mixed design ANOVA was used. P < 0.05 was considered significant. Results: On Day 0, VEGF didn't differ between groups I, II, III and IV (p>0.05, for every comparison). On Day 10, VEGF was increased in all groups. Between Day 10 and Day 30, VEGF remained stable in groups I (p=0.031) and II (p=1.000) and increased significantly in group III (p=0.005). On the contrary, VEGF decreased significantly in group IV (p<0.001). The most remarkable finding was observed when we compared VEGF between Day 0 and Day 30: while in groups I, II and III, VEGF remained significantly higher compared to Day 0 (p<0.001, p=0.041 and p<0.001, respectively), on the contrary, in group IV (extended-duration with the highest dose of 4,500 IU of tinzaparin) it was comparable to Day 0 (p=1.000). Conclusions: In surgical CC patients only the recommended thromboprophylaxis scheme with the highest prophylactic dose of Tinzaparin (4,500 IU) for extended-duration (30 days) normalizes VEGF levels at the end of the first post-op month by reducing them to the pre-op levels.

Thrombosis Research

Introduction: Patients with glioblastoma multiforme (GBM) are at high risk of venous thromboembol... more Introduction: Patients with glioblastoma multiforme (GBM) are at high risk of venous thromboembolism (VTE). Although clinical factors such as immobility, paresis and hypovolemia contribute to this risk, they do not correlate with occurrence of VTE. Indeed, biological factors may be more significant than clinical factors in predicting post-operative thrombosis. Tissue factor (TF), the initiator of coagulation in vivo, is expressed in all gliomas, and correlates with tumor grade. TF is normally expressed extravascularly, but has recently been shown to be present in blood. Whether blood-borne TF is functionally active remains unclear. We report the presence of active TF in cell-free plasma of a 38 year old male patient with GBM. Methods: Pre-and post-operative (day 3) blood samples were collected. Whole blood coagulation analysis was performed by thromboelastography (TEG). Platelet activation was determined by measuring platelet surface P-selectin and monocyte-platelet conjugates. Plasma microparticles (MP) were isolated by high-speed centrifugation of cell-free plasma. Procoagulant activities of MP and particle-free supernatant (SN) were measured by thrombin generation assay. Results: Pre-op TEG revealed a hypercoagulable state as evidenced by a shortened clot time (6.8 mins, normal: 9-27mins), and elevated clot rate and strength values. Post-operatively, the clot time normalized (10 mins), indicating the reduction of a plasmatic procoagulant trigger. Other TEG parameters remained elevated. Platelet counts were normal in both samples, although platelet activation decreased by >50% postoperatively. TF-dependent procoagulant activity was detected in MP (but not in SN). Consistent with the TEG clot times, this TF activity was reduced postoperatively, but remained higher than that of control plasma. Conclusion: In this report we have shown TF activity in the plasma of a patient with GBM. The post-op reduction of this circulating, MP-associated TF activity suggests that the observed hypercoagulability could be at least partially due to TF shed from the tumor.

Theoretical Biology and Medical Modelling, 2013

IEEE Journal of Biomedical and Health Informatics, 2014

Cancer-tumor growth is a complex process depending on several biological factors, such as the che... more Cancer-tumor growth is a complex process depending on several biological factors, such as the chemical microenvironment of the tumor, the cellular metabolic profile and its proliferation rate. Several mathematical models have been developed for identifying the interactions between tumor cells and tissue microenvironment, since they play an important role in tumor formation and progression. Towards this direction we propose a new continuum model of avascular glioma-tumor growth, which incorporates a new factor, namely the glycolytic potential of cancer cells, to express the interactions of three different tumor-cell populations (proliferative, hypoxic and necrotic) with their tissue microenvironment. The glycolytic potential engages three vital nutrients, i.e. oxygen, glucose and lactate, which provide cells with the necessary energy for their survival and proliferation. Extensive simulations are performed for different evolution times and various proliferation rates, in order to investigate how the tumor growth is affected. According to medical experts, the experimental observations indicate that the model predicts quite satisfactorily the overall tumor growth as well as the expansion of each region separately. Following extensive evaluation, the proposed model may provide an essential tool for patient-specific tumor simulation and reliable prediction of glioma spatio-temporal expansion.