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Papers by Kliment Bozhilov

Research paper thumbnail of ASO Author Reflections: At the Crossroad—Liver Transplantation for Unresectable Colorectal Liver Metastases in the United States

Annals of Surgical Oncology

Research paper thumbnail of Can the Timed Up & Go Test and Montreal Cognitive Assessment predict outcomes in patients waitlisted for renal transplant?

Clinical Transplantation

Frail patients who undergo renal transplantation (RT) have more complications; however, little is... more Frail patients who undergo renal transplantation (RT) have more complications; however, little is known if these patients can sustain the wait to RT. We used the Timed Up and Go Test (TUGT) and Montreal Cognitive Assessment (MoCA) to determine outcomes of RT candidates.

Research paper thumbnail of Combination Immunotherapy of Advanced Lymphoma with Oncolytic Vaccinia Virus and Checkpoint Inhibitor Following Local Tumor Irradiation

Blood

Oncolytic virotherapy is safe and clinically active in solid tumors, however its efficacy in hema... more Oncolytic virotherapy is safe and clinically active in solid tumors, however its efficacy in hematologic malignancies as well as in combination with checkpoint inhibitors and radiation is unexplored.To simulate advanced lymphoma, A20 lymphoma cells were injected subcutaneously on bilateral flanks of BALB/c mice and treatment initiated on day 17 to only the right flank tumor with local irradiation (Irr), intratumoral (i.t.) vaccinia virus (VACV) and i.t. anti-CTLA-4 mAb (Irr-VACV-CTLA4, Figure 1). The Irr-VACV-CTLA4 regimen was the most effective in eradicating or shrinking both treated and untreated tumors and extending survival, followed by the Irr-VACV regimen. Treatment with Irr-VACV-CTLA4, led to initially a mature, activated NK cell (KLRG1+CD27+) infiltrate (day 6 post-treatment) followed by a CD8+T cells infiltrate (day+13) in treated tumors. In contrast, treatment with VACV-CTLA4 led to activated NK-cell accumulation (day +6) followed by a CD8+T-cell infiltrate (day+13) in no...

Research paper thumbnail of Underlying liver disease and advanced stage liver cancer are associated with elevated neutrophil-lymphocyte ratio

Clinical and Molecular Hepatology

Research paper thumbnail of Coatings of Polyethylene Glycol for Suppressing Adhesion between Solid Microspheres and Flat Surfaces

Langmuir, 2012

This article describes the development and the examination of surface coatings that suppress the ... more This article describes the development and the examination of surface coatings that suppress the adhesion between glass surfaces and polymer microspheres. Superparamagnetic doping allowed for exerting magnetic forces on the microbeads. The carboxyl functionalization of the polymer provided the means for coating the beads with polyethylene glycol (PEG) with different molecular weight. Under gravitational force, the microbeads settled on glass surfaces with similar polymer coatings. We examined the efficacy of removing the beads from the glass surfaces by applying a pulling force of ~1.2 pN. The percent beads remaining on the surface after applying the pulling force for approximately 5 s served as an indication of the adhesion propensity. Coating of PEG with molecular weight ranging between 3 and 10 kDa was essential for suppressing the adhesion. For the particular substrates, surface chemistry and aqueous media we used, coatings of 5 kDa manifested optimal suppression of adhesion: that is, only 3% of the microbeads remained on the surface after applying the pulling magnetic force. When either the glass or the beads were not PEGylated, the adhesion between them was substantial. Addition of a noncharged surfactant, TWEEN, above its critical micelle concentrations (CMCs) suppressed the adhesion between noncoated substrates. The extent of this surfactant-induced improvement of the adhesion suppression, however, did not exceed the quality of preventing the adhesion that we attained by PEGylating both substrates. In addition, the use of surfactants did not significantly improve the suppression of bead-surface adhesion when both substrates were PEGylated. These findings suggest that such surfactant additives tend to be redundant and that covalently grafted coatings of PEGs with selected chain lengths provide sufficient suppression of nonspecific interfacial interactions.

Research paper thumbnail of Combination immunotherapy with oncolytic vaccinia virus and checkpoint inhibitor following local tumor irradiation

Journal for ImmunoTherapy of Cancer, 2014

Research paper thumbnail of Prognostic ability of inflammation-based markers in radioembolization for hepatocellular carcinoma

Hepatoma Research, Oct 12, 2020

Aim: Inflammation-based markers, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to... more Aim: Inflammation-based markers, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have recently been used as prognostic indicators in hepatocellular carcinoma (HCC). We aimed to determine whether NLR and PLR may predict response to yttrium-90 transarterial radioembolization (TARE) as primary treatment for HCC.
Methods: We performed a retrospective review of a prospectively collected database of HCC cases (1994-2019) and selected patients who received TARE as primary treatment (n = 42). Laboratory studies were used to calculate NLR and PLR. Response to TARE was determined using the modified response evaluation criteria in solid tumors (mRECIST). Patients were classified as non-responders (stable or progressive disease) or responders (partial or complete response) to treatment based on mRECIST.
Results: Receiver operating characteristic curves identified a pre-treatment NLR cutoff of ≥ 2.83 and a pre-treatment PLR cutoff of ≥ 83 for predicting non-response to treatment. Pre-treatment NLR ≥ 2.83 was the only significant predictor of non-response to TARE in multivariate logistic regression analysis (odds ratio 7.83, P = 0.036). On time to progression analysis, both pre-treatment NLR ≥ 2.83 and pre-treatment PLR ≥ 83 were associated with a higher proportion of tumor progression at 6 months post-treatment (43.6% vs. 10.0%, P = 0.014, log-rank) and (38.6% vs. 0%, P = 0.010, log-rank), respectively.
Conclusion: NLR confers prognostic value and may be superior to PLR in determining response to TARE as primary treatment for HCC. Future studies are necessary to validate these findings in a larger cohort.

Research paper thumbnail of ASO Author Reflections: At the Crossroad—Liver Transplantation for Unresectable Colorectal Liver Metastases in the United States

Annals of Surgical Oncology

Research paper thumbnail of Can the Timed Up & Go Test and Montreal Cognitive Assessment predict outcomes in patients waitlisted for renal transplant?

Clinical Transplantation

Frail patients who undergo renal transplantation (RT) have more complications; however, little is... more Frail patients who undergo renal transplantation (RT) have more complications; however, little is known if these patients can sustain the wait to RT. We used the Timed Up and Go Test (TUGT) and Montreal Cognitive Assessment (MoCA) to determine outcomes of RT candidates.

Research paper thumbnail of Combination Immunotherapy of Advanced Lymphoma with Oncolytic Vaccinia Virus and Checkpoint Inhibitor Following Local Tumor Irradiation

Blood

Oncolytic virotherapy is safe and clinically active in solid tumors, however its efficacy in hema... more Oncolytic virotherapy is safe and clinically active in solid tumors, however its efficacy in hematologic malignancies as well as in combination with checkpoint inhibitors and radiation is unexplored.To simulate advanced lymphoma, A20 lymphoma cells were injected subcutaneously on bilateral flanks of BALB/c mice and treatment initiated on day 17 to only the right flank tumor with local irradiation (Irr), intratumoral (i.t.) vaccinia virus (VACV) and i.t. anti-CTLA-4 mAb (Irr-VACV-CTLA4, Figure 1). The Irr-VACV-CTLA4 regimen was the most effective in eradicating or shrinking both treated and untreated tumors and extending survival, followed by the Irr-VACV regimen. Treatment with Irr-VACV-CTLA4, led to initially a mature, activated NK cell (KLRG1+CD27+) infiltrate (day 6 post-treatment) followed by a CD8+T cells infiltrate (day+13) in treated tumors. In contrast, treatment with VACV-CTLA4 led to activated NK-cell accumulation (day +6) followed by a CD8+T-cell infiltrate (day+13) in no...

Research paper thumbnail of Underlying liver disease and advanced stage liver cancer are associated with elevated neutrophil-lymphocyte ratio

Clinical and Molecular Hepatology

Research paper thumbnail of Coatings of Polyethylene Glycol for Suppressing Adhesion between Solid Microspheres and Flat Surfaces

Langmuir, 2012

This article describes the development and the examination of surface coatings that suppress the ... more This article describes the development and the examination of surface coatings that suppress the adhesion between glass surfaces and polymer microspheres. Superparamagnetic doping allowed for exerting magnetic forces on the microbeads. The carboxyl functionalization of the polymer provided the means for coating the beads with polyethylene glycol (PEG) with different molecular weight. Under gravitational force, the microbeads settled on glass surfaces with similar polymer coatings. We examined the efficacy of removing the beads from the glass surfaces by applying a pulling force of ~1.2 pN. The percent beads remaining on the surface after applying the pulling force for approximately 5 s served as an indication of the adhesion propensity. Coating of PEG with molecular weight ranging between 3 and 10 kDa was essential for suppressing the adhesion. For the particular substrates, surface chemistry and aqueous media we used, coatings of 5 kDa manifested optimal suppression of adhesion: that is, only 3% of the microbeads remained on the surface after applying the pulling magnetic force. When either the glass or the beads were not PEGylated, the adhesion between them was substantial. Addition of a noncharged surfactant, TWEEN, above its critical micelle concentrations (CMCs) suppressed the adhesion between noncoated substrates. The extent of this surfactant-induced improvement of the adhesion suppression, however, did not exceed the quality of preventing the adhesion that we attained by PEGylating both substrates. In addition, the use of surfactants did not significantly improve the suppression of bead-surface adhesion when both substrates were PEGylated. These findings suggest that such surfactant additives tend to be redundant and that covalently grafted coatings of PEGs with selected chain lengths provide sufficient suppression of nonspecific interfacial interactions.

Research paper thumbnail of Combination immunotherapy with oncolytic vaccinia virus and checkpoint inhibitor following local tumor irradiation

Journal for ImmunoTherapy of Cancer, 2014

Research paper thumbnail of Prognostic ability of inflammation-based markers in radioembolization for hepatocellular carcinoma

Hepatoma Research, Oct 12, 2020

Aim: Inflammation-based markers, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to... more Aim: Inflammation-based markers, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), have recently been used as prognostic indicators in hepatocellular carcinoma (HCC). We aimed to determine whether NLR and PLR may predict response to yttrium-90 transarterial radioembolization (TARE) as primary treatment for HCC.
Methods: We performed a retrospective review of a prospectively collected database of HCC cases (1994-2019) and selected patients who received TARE as primary treatment (n = 42). Laboratory studies were used to calculate NLR and PLR. Response to TARE was determined using the modified response evaluation criteria in solid tumors (mRECIST). Patients were classified as non-responders (stable or progressive disease) or responders (partial or complete response) to treatment based on mRECIST.
Results: Receiver operating characteristic curves identified a pre-treatment NLR cutoff of ≥ 2.83 and a pre-treatment PLR cutoff of ≥ 83 for predicting non-response to treatment. Pre-treatment NLR ≥ 2.83 was the only significant predictor of non-response to TARE in multivariate logistic regression analysis (odds ratio 7.83, P = 0.036). On time to progression analysis, both pre-treatment NLR ≥ 2.83 and pre-treatment PLR ≥ 83 were associated with a higher proportion of tumor progression at 6 months post-treatment (43.6% vs. 10.0%, P = 0.014, log-rank) and (38.6% vs. 0%, P = 0.010, log-rank), respectively.
Conclusion: NLR confers prognostic value and may be superior to PLR in determining response to TARE as primary treatment for HCC. Future studies are necessary to validate these findings in a larger cohort.