Petr Pancoska
University of Pittsburgh, UPMC, Faculty Member
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nanotechnology, microarrays and molecular computers using Eulerian graphs
A primary goal of current clinical cancer research is the identification of prognostic tumor subtypes. It is increasingly clear that tumor growth depends on both internal tumor factors, and factors that are external to the tumor, such as... more
A primary goal of current clinical cancer research is the identification of prognostic tumor subtypes. It is increasingly clear that tumor growth depends on both internal tumor factors, and factors that are external to the tumor, such as microenvironment. We recently showed that parameter values alone are less important than the patterns of all patient parameters together for the identification of prognostic subtypes and have identified a network phenotyping strategy method to quantitatively describe the dependency of the tumor on the environment, to characterize hepatocellular carcinoma (HCC) subtypes. We have also shown that information about tumor mass together with patterns of other prognostic factors is related to survival. We now use a different patient cohort to validate this prognostic approach. A main finding is our identification of a common time of total disease duration (TDD) for every HCC patient. Clinical prognosis at the time of baseline patient evaluation is then calculable as the difference between TDD and the time from disease onset to diagnosis (Tonset). We show that the total pattern of all parameter values and the differences in the relationships between this pattern and a reference pattern that, together with the tumor mass, best reflects the patient's prognosis at baseline. Our approach led us to identify 15 different composite HCC subtypes. Our results highlight the nearly identical TDD in all patients, which must therefore be a characteristic of the HCC disease, as opposed to the variable quantity of Tonset, which is impacted by multiple macro- and micro-environmental factors.
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The analytical methods for characterizing DNA sequence-dependent thermodynamic stability have been reviewed. A set of n-n sequence stability parameters is presented. Examples in which these values are used to calculate the thermodynamic... more
The analytical methods for characterizing DNA sequence-dependent thermodynamic stability have been reviewed. A set of n-n sequence stability parameters is presented. Examples in which these values are used to calculate the thermodynamic stability of short duplex DNA oligomers are presented. The problem of determining sets of isothermal sequences is addressed by representing DNA sequences as graphs. Representing DNA sequences by a graph descriptor with special mathematical properties minimizes the computational difficulty of determining the number of DNA sequences with identical predicted thermodynamic stability. This is achieved by replacement of a whole set of sequences by a single representative. Applications of this concept were demonstrated for sequences assembled from individual bases and sequences assembled from oligomeric blocks.
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Clinical phenotypes of small and large hepatocellular carcinomas (HCCs) are not well characterized. To evaluate the characteristics of small HCCs diagnosed by screening. A cohort of 430 small HCCs that were diagnosed through screening,... more
Clinical phenotypes of small and large hepatocellular carcinomas (HCCs) are not well characterized. To evaluate the characteristics of small HCCs diagnosed by screening. A cohort of 430 small HCCs that were diagnosed through screening, were dichotomized according to a size of ≤ 3 cm or >3 cm maximum tumor diameter and compared for radiological and blood-test parameters. There were 330 males and 100 females. A higher percent of females had smaller tumors. The majority of patients had single tumors, but 15% of those with larger tumors had portal vein thrombosis (PVT) compared to 5% of those with smaller tumors. Significant differences between the tumor-size groups included alpha-fetoprotein (AFP) values and platelet counts, with thrombocytopenia and elevated bilirubin levels being associated with smaller tumors. In comparing PVT-positive and PVT-negative patients, AFP levels and platelet counts were also significantly different between the 2 groups. A mean multinomial multiple logistic regression model was developed for maximum tumor diameter plus PVT. The finding of larger tumors being associated with normal platelets and bilirubin levels in comparison to smaller tumors having thrombocytopenia reveals 2 different patterns of HCC presentation.
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Hepatocellular carcinoma (HCC) size at diagnosis is important in management. Without screening programs, tumor size at diagnosis is heterogeneous. To examine the clinical parameters related to tumor size. Using prospectively collected... more
Hepatocellular carcinoma (HCC) size at diagnosis is important in management. Without screening programs, tumor size at diagnosis is heterogeneous. To examine the clinical parameters related to tumor size. Using prospectively collected data from a 1,100-patient biopsy-proven HCC cohort presenting in the absence of screening, tumor sizes were ordered and trichotomized and the resulting terciles were compared for tumor and blood parameters. The terciles were significantly different with respect to portal hypertension and thrombocytopenia, which were present in a higher percent of tercile I patients with smaller tumors. Tercile III patients with larger HCCs had the highest serum α-fetoprotein (AFP), γ-glutamyl transpeptidase (GGTP), and alkaline phosphatase (ALKP) levels and the most portal vein (PV) thrombosis. Subclassification of tercile I patients by AFP showed that patients with high serum AFP had increased numbers of tumor nodules, more PV thrombosis, higher bilirubin, ALKP, and GGTP levels, and shorter survival. Smaller-tumor tercile I patients had more advanced portal hypertension with thrombocytopenia than did larger-tumor patients. Tercile I patients with higher AFP levels had more frequent PV thrombosis and worse survival than those with lower AFP levels. Elevated serum GGTP and ALKP levels appear to be associated with a more aggressive HCC phenotype. These differing patterns suggest more than one HCC pathway.
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p53 induces apoptosis by target gene regulation and transcription-independent signaling. However, a mechanism for the latter was unknown. We recently reported that a fraction of induced p53 translocates to the mitochondria of apoptosing... more
p53 induces apoptosis by target gene regulation and transcription-independent signaling. However, a mechanism for the latter was unknown. We recently reported that a fraction of induced p53 translocates to the mitochondria of apoptosing tumor cells. Targeting p53 to mitochondria is sufficient to launch apoptosis. Here, we provide evidence that p53 translocation to the mitochondria occurs in vivo in irradiated thymocytes. Further, we show that the p53 protein can directly induce permeabilization of the outer mitochondrial membrane by forming complexes with the protective BclXL and Bcl2 proteins, resulting in cytochrome c release. p53 binds to BclXL via its DNA binding domain. We probe the significance of mitochondrial p53 and show that tumor-derived transactivation-deficient mutants of p53 concomitantly lose the ability to interact with BclXL and promote cytochrome c release. This opens the possibility that mutations might represent "double-hits" by abrogating the transcriptional and mitochondrial apoptotic activity of p53.
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Heteromorphic hybrid duplex DNA complexes are duplex states, other than perfectly matched duplexes, that can form when single strands comprising several different perfectly matched duplexes are simultaneously present in solution. Such... more
Heteromorphic hybrid duplex DNA complexes are duplex states, other than perfectly matched duplexes, that can form when single strands comprising several different perfectly matched duplexes are simultaneously present in solution. Such cross-hybridization "side reactions" are of particular nuisance in multiplex reaction schemes, where many strands are designed to hybridize in parallel fashion with only their corresponding perfect complement strand. Relative to the perfect match duplexes, the sequence dependent features of these heteromorphic duplex states and their thermodynamic stability are an important consideration for multiplex hybridization reaction design. We have measured absorbance versus temperature melting curves and performed differential scanning calorimetry measurements on various mixtures of eight different 24 base single strands. When perfect complementary pairs of strands are mixed in single reactions, four perfectly matched duplexes form. When mixtures of strands that are not perfectly matched are prepared and analyzed, melting transitions for cross-hybridization are observed along with significant hyperchromicity changes. This is indicative of a melting hybrid, heteromorphic duplex states formed from two nonperfectly matched strands. In addition, when both the perfectly matched and noncomplementary strands are mixed together (in multiplex hybridization reactions) at molar ratios of 1:1, 3:1, and 1:3, evidence of perfect duplex and heteromorphic duplex complexes is found in all cases. A new analytical tool for considering heterogeneous, duplex complexes in multiplex hybridization mixtures is presented and employed to interpret the acquired melting data.
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Research Interests: Chemical Engineering, Inorganic Chemistry, Laser Spectroscopy, Raman Spectroscopy, Vibrational Spectroscopy, and 15 moreElectromagnetic Radiation, Metal Complexes, Nitrogen, Chemical Analysis, Oscillations, Structural Change, Oxygen Transport, Infrared, Surface Properties, Water soluble polymers, Raman Scattering, Raman Spectra, Energy Levels, Organic Compound, and Organic Acid
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... 1989, Vol. 54, Issue 8, pp. 22712275 [Abstract]; Jan Hlaváček and Ivo Frič The effect of non-coded amino acids on the degradation of oxytocin analogs with α-chymotrypsin 1989, Vol. 54, Issue 8, pp. 22612270 [Abstract]; Karel ...
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Community-Based Participatory Research (CBPR) has been advocated to translate advances in health care sciences to the community. We describe a novel approach applied to obesity management and diabetes prevention. This takes advantage of a... more
Community-Based Participatory Research (CBPR) has been advocated to translate advances in health care sciences to the community. We describe a novel approach applied to obesity management and diabetes prevention. This takes advantage of a network of science clubs organized by the Health Sciences and Technology Academy (HSTA) for extracurricular activity of disadvantaged high school students in rural Appalachia. Physician scientists and educators provided an intensive summer course on CBPR, ethics, and study design on obesity management and diabetes prevention. Ethical certification for CBPR investigation was obtained for 210 students and 18 mentors for a study on the prevalence of obesity and Type II diabetes within their community. Over a 6-month period, 989 had a collection of complete analyzable data, of which 103 had diabetes. The proportion with obesity (BMI > or = 30) was over 50%. The frequency of diabetes was related to increasing BMI. When BMI > or = 40, the frequency approached 50%, and exhibited a clear familial distribution. We conclude that trained adolescents can effectively conduct CBPR, and obesity and diabetes are more prevalent than previously reported in this community. This experience provides encouragement to conduct future studies to infl uence weight management from high-risk populations in this medically disadvantaged community.
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... 14 August 1987 FLUORESCENCE PROPERTIES OF TETRAPHENYLPORPHYRINPOLYPEPTIDE COMPLEXES AS MODEL PHOTOSYNTHETIC SYSTEMS Petr PANCOSKA3, Marie URBANOVA8, Boris N ... J. Hála, V. Kapsa, P. Pan o ka, I. Pelant, L. Skála and L. Sou kova In: J... more
... 14 August 1987 FLUORESCENCE PROPERTIES OF TETRAPHENYLPORPHYRINPOLYPEPTIDE COMPLEXES AS MODEL PHOTOSYNTHETIC SYSTEMS Petr PANCOSKA3, Marie URBANOVA8, Boris N ... J. Hála, V. Kapsa, P. Pan o ka, I. Pelant, L. Skála and L. Sou kova In: J ...
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ACS; Journals; C&EN; CAS. ACS Publications. Journals A–Z Books|Authors & Reviewers|Librarians|ACS Members|About Us|e-Alerts|Help. Quick Search. Advanced Search. Biochemistry All Journals/Website. Biochemistry. ...
Research Interests: Biochemistry, Mathematics, Membranes, Methods, Computers, and 23 moreSharks, Insulin, Circular Dichroism, Pancreas, Animals, Horses, Proteins, Cetacea, Cattle, Myoglobin, Secondary Structure, Myocardium, Spectrum analysis, Staphylococcus, SYNAPTOSOMES, Protein Conformation, Egg White, Bovine Serum Albumin, Infrared Rays, Biochemistry and cell biology, Chymotrypsin, Ribonucleases, and Methemoglobin
ABSTRACT
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Vibrational circular dichroism (VCD) studies are reported for two unrelated recombinant growth factor proteins: epidermal growth factor and basic fibroblast growth factor (bFGF). NMR, electronic CD, and bFGF X-ray studies indicate that... more
Vibrational circular dichroism (VCD) studies are reported for two unrelated recombinant growth factor proteins: epidermal growth factor and basic fibroblast growth factor (bFGF). NMR, electronic CD, and bFGF X-ray studies indicate that these two proteins are primarily composed of beta-sheet and loop secondary structure elements with no detectable alpha-helices. Two reports on solution conformation of these proteins using FTIR absorption spectroscopy with subsequent resolution enhancement confirmed the presence of a large fraction of a beta-sheet conformation but in addition indicated the presence of large absorption bands in the 1650-1656 cm-1 region, which are typically assigned to alpha-helices. The VCD spectra of both proteins have band shapes that strongly resemble those of other high beta-sheet fraction proteins, such as the trypsin family of proteins. Quantitative analysis of the VCD spectra also indicates that these proteins are predominantly in beta-sheet and extended ("other") conformations with very little alpha-helix fraction. These results agree with the CD interpretation and affirm that the FTIR peaks in the region 1650-1656 cm-1 can be assigned to loops. This study provides an example of the limitations of using FTIR frequencies alone for examination of protein secondary structure.
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... PETR PANCOSKA, VIT JANOTA, and TIMOTHY A. KEIDERLING* Department of Chemistry, University of lllinois at Chicago, (M/C 111), 845 W. Taylor St ... The success of the con-version of VCD spectra into ECD for a given protein was... more
... PETR PANCOSKA, VIT JANOTA, and TIMOTHY A. KEIDERLING* Department of Chemistry, University of lllinois at Chicago, (M/C 111), 845 W. Taylor St ... The success of the con-version of VCD spectra into ECD for a given protein was characterized by the difference between the ...
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We previously showed that for hepatocellular cancer (HCC) prognostication, disease parameters need to be considered within a total personal clinical context. This requires preserving the coherence of data values, observed simultaneously... more
We previously showed that for hepatocellular cancer (HCC) prognostication, disease parameters need to be considered within a total personal clinical context. This requires preserving the coherence of data values, observed simultaneously for each patient during baseline diagnostic evaluation. Application of the Network Phenotyping Strategy (NPS) provided quantitative descriptors of these patient coherences. Combination of these descriptors with Fisher information about the patient tumor mass and the histogram of the tumor masses in the whole cohort permitted estimation of the time from disease onset until clinical diagnosis (tbaseline). We found faster growth of smaller tumors having total masses<70 (80% of cohort) which involved about three times more interacting cellular processes than were observed for slower growing larger tumors (20% of cohort) with total masses>70. Combining the clinical survival and tbaseline normalized all HCC patients to a common 1,045 days of mean tot...
Research Interests: Humans, Female, Male, Hepatocellular Carcinoma, Aged, and 4 moreMiddle Aged, Theoretical Models, Adult, and Prognosis
We used a database of 4139 Taiwanese HCC patients to take a new approach (Network Phenotyping Strategy) to HCC subset identification. Individual parameters for liver function tests, complete blood count, portal vein thrombosis, AFP levels... more
We used a database of 4139 Taiwanese HCC patients to take a new approach (Network Phenotyping Strategy) to HCC subset identification. Individual parameters for liver function tests, complete blood count, portal vein thrombosis, AFP levels and clinical demographics of age, gender, hepatitis or alcohol consumption, were considered within the whole context of complete relationships, being networked with all other parameter levels in the entire cohort. We identified 4 multi-parameter patterns for one tumor phenotype of patients and a separate 5 multi-parameter patterns to characterize another tumor phenotype of patterns. The 2 subgroups were quite different in their clinical profiles. The means of the tumor mass distributions in these phenotype subgroups were significantly different, one being associated with larger (L) and the other with smaller (S) tumor masses. These significant differences were seen systematically throughout the tumor mass distributions. Essential and common clinica...
A large dataset of patients with biopsy-proven and unresectable HCC who were prospectively followed from diagnosis till death, was examined for the prognostic significance of serum GGTP levels. Their survival-ordered baseline clinical... more
A large dataset of patients with biopsy-proven and unresectable HCC who were prospectively followed from diagnosis till death, was examined for the prognostic significance of serum GGTP levels. Their survival-ordered baseline clinical parameter data was examined. Two cohorts of patients with both low AFP and bilirubin levels were identified, who had serum GGTP levels with an increasing trend with increasing AFP levels. The survival of these patients also decreased as their GGTP levels trended up, as did their tumor masses. By contrast, in patients with elevated serum AFP levels, the GGTP trends were less informative, although patients with the highest AFP levels had a worse prognosis if their GGTP levels were simultaneously elevated. The results suggest that following trends in serum GGTP levels, in the context of specific ranges of AFP and bilirubin levels, might be useful in diagnosis of small HCCs.
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A large cohort of unresectable and untransplantable biopsy-proven HCC patients was rank-ordered for survival. Non-random clustering by age was noted, with 3 sub-cohorts of younger patients with survival in the range of 90-360 days. One... more
A large cohort of unresectable and untransplantable biopsy-proven HCC patients was rank-ordered for survival. Non-random clustering by age was noted, with 3 sub-cohorts of younger patients with survival in the range of 90-360 days. One sub-cohort had a predominance of females. Tumor numbers were well monitored by serum AFP, but tumor mass was better monitored by serum GGTP. In contrast to the older patients, the probability of hepatitis appeared to have a major impact on their survival and these patients tended to have larger numbers of smaller tumors, consistent with the idea of a hepatitis-mediated carcinogenic field defect.
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Objective: Non-syndromic cleft-lip-with/out-cleft-palate(CL/P) is one of the most common craniofacial anomalies worldwide. Demonstrated to be a heterogeneous trait, substantial work has been done in the past several years to further... more
Objective: Non-syndromic cleft-lip-with/out-cleft-palate(CL/P) is one of the most common craniofacial anomalies worldwide. Demonstrated to be a heterogeneous trait, substantial work has been done in the past several years to further characterize CL/P by exploring sub-clinical and extended phenotypes. Prior studies exploring genes associated with increased risk of CL/P have utilized this phenotypic information through three approaches: creating potentially homogenous data subsets for categorical phenotype values, recoding affection status based on cumulative phenotypic information, or analyzing each phenotype individually. Here, multiple phenotypes (predictors) are regressed against individual SNP genotypes (outcome), where a series of scenarios also explore approaches to incorporate family data in the analyses. Method: The regression analyses were conducted using the software program Multiphen. Individuals from 66 families in the Pittsburgh Study were included based on the following...