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Papers by Daniel Panca

Research paper thumbnail of Identification of Histone H1 as a Cognate Antigen of the Ulcerative Colitis-associated Marker Antibody pANCA

Journal of Autoimmunity, 2000

Perinuclear anti-neutrophil cytoplasmic antibody (pANCA) 4 is a predominant serum marker of ulcer... more Perinuclear anti-neutrophil cytoplasmic antibody (pANCA) 4 is a predominant serum marker of ulcerative colitis (UC), and a familial trait associated with disease susceptibility and disease associated MHC haplotypes. This study characterizes the pANCA antigen defined by representative UC-pANCA human monoclonal antibodies, Fab 5-3 and 5-2. Western blot analysis probed with Fab 5-3 revealed specific binding to a nuclear protein doublet (apparent MW=32-33 kDa) expressed in several cell types. Purification and tryptic peptide sequencing identified the protein as histone H1, and this specificity was confirmed by Fab 5-3 binding to purified H1. Rabbit anti-histone H1 immunostaining and Western blot analysis confirmed that the pANCA epitope is preferentially immunoaccessible in polymorphonuclear neutrophils (PMN). The epitope was localized to the COOH-terminal region by site-specific proteolysis, and recombinant deletants further localized binding activity for both Fab 5-2 and 5-3 to two non-overlapping segments (AA 69-171 and 172-226) associated with a recurring PKKAK motif. Serum IgG binding was detectable to these segments, but was not significantly correlated with pANCA titer or disease status. These findings indicate that histone H1 bears a recurring COOH-terminal epitope recognized by monoclonal ulcerative colitis-associated pANCA marker antibodies, but this epitope is not a predominant specificity of serum pANCA.

Research paper thumbnail of Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn's disease

American Journal of Gastroenterology, 2002

Research paper thumbnail of Nanotechnology-based combination therapy improves treatment response in cancer models

Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5%. Photodynam... more Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5%. Photodynamic therapy (PDT) has shown promising results in treating PanCa. Mechanism-based combinations with PDT have enhanced treatment outcome. Agents tested with PDT include Avastin, an antibody against vascular endothelial growth factor (VEGF) which is approved for treating various cancers. Simultaneous delivery of drugs in nano-constructs could improve the treatment response of mechanism based combination therapies. Here, we investigate the effect of neutralizing VEGF using nanotechnology for the delivery of Avastin in combination with PDT. For this we used a construct called "nanocells" in which the photosensitizer was trapped inside polymer nanoparticles and these, with Avastin, were then encapsulated inside liposomes. In vitro, nanocells containing Avastin (NCA) significantly enhanced cytotoxicity in PanCa cells. NCA based PDT also significantly improved treatment response in mice that were orthotopically implanted with PanCa. Avastin delivered extracellularly in combination with PDT did not show any improvement. Here we propose a new paradigm for Avastin-based therapy by combining intracellular delivery of the antibody and PDT using nanotechnology for treating PanCa.

Research paper thumbnail of Are anti-saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (PANCA) useful in indeterminate colitis? A prospective follow-up study

Gastroenterology, 2000

Patients with IBD undergo numerous diagnostic examinations of the 01tract during the course of th... more Patients with IBD undergo numerous diagnostic examinations of the 01tract during the course of their chronic disease. Conventional colonoscopy and enteroclysis for assessment of the colon and the small intestine are the methods of choice. A less invasive method for visualizing the colon and detecting polyps seems to be MR-based virtual colonoscopy. For the small bowel we have shown that oral MR enteroclysis is an adequate diagnostic tool. Purpose: To perform 3D-MR examinations with virtual endoscopy of the small intestine and colon in patients with IBD. Methods We performed MR enteroclysis using Tl shortening oral contrast in 30 consecutive patients with IBD after conventional enteroclysis. Gd-DTPA was given iv to assess inflammation of the bowel. Fat suppressed breathhold 3D-MR acquisitions were done before and after iv application. In 10 patients, who underwent conventional colonoscopy we performed virtual colonoscopy the same day. Patients were filled rectally with 2 liters water spiked with Gd-DTPA and 3D-Tl weighted MRI was acquired. Using a graphical workstation (02, Silicon Graphics) we performed VE of the bowel applying volume rendering technique. Feasibility and quality of VE were assessed. Results In 9% of all patients VE of the small bowel was not feasible because of motion artifacts or inadequate bowel filling. In 57% fair VE results were achieved but approximately 1/5 of the small intestine were not visualized due to incomplete contrast or local bowel movement. In 34% at least one series resulted in a VE with excellent quality revealing typical fold patterns of the small intestine. Pathologic conditions such as stenoses or fistulae were depicted impressively. In 9/10 patients good quality virtual colonoscopy was achieved. Even the granularity of the mucosa and pseudopolyps in a patient with ulcerative colitis could be clearly delineated. Conclusion MR-based VE of the small intestine and colon is feasible in most cases. Further developments in MR-scanning and high performance 3D-computing will improve the quality of this recently introduced modality. This minimal invasive examination without radiation can be a useful complementary tool to conventional endoscopy and may open up valuable diagnostic opportunities in IBD especially in a joint approach of Radiology and Gastroenterology. It's practical value needs to be assessed in larger prospective studies.

Research paper thumbnail of Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role

Gut, 1998

Background-Perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) are a well recognised ma... more Background-Perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) are a well recognised marker for ulcerative colitis. Antibodies to oligomannosidic epitopes of the yeast Saccharomyces cerevisiae (ASCA) are a new marker associated with Crohn's disease. Aims-To assess the value of detecting pANCA and/or ASCA for the diagnosis of ulcerative colitis and Crohn's disease. Methods-Serum samples were obtained from 100 patients with Crohn's disease, 101 patients with ulcerative colitis, 27 patients with other miscellaneous diarrhoeal illnesses, and 163 healthy controls. Determination of pANCA and ASCA was performed using the standardised indirect immunofluorescence technique and an ELISA, respectively. Results-The combination of a positive pANCA test and a negative ASCA test yielded a sensitivity, specificity, and positive predictive value of 57%, 97%, and 92.5% respectively for ulcerative colitis. The combination of a positive ASCA test and a negative pANCA test yielded a sensitivity, specificity, and positive predictive value of 49%, 97%, and 96% respectively for Crohn's disease. Among patients with miscellaneous non-inflammatory bowel disorders, three were ASCA positive and two were pANCA positive. One control was ASCA positive. The presence of ASCA in patients with Crohn's disease was associated with small bowel involvement. Conclusion-ASCA and pANCA are strongly associated with Crohn's disease and ulcerative colitis, respectively. Combination of both tests could help the diagnosis of inflammatory bowel disease. (Gut 1998;42:788-791)

Research paper thumbnail of MAKALAH METODOLOGI PENELITIAN HUKUM

Research paper thumbnail of Identification of Histone H1 as a Cognate Antigen of the Ulcerative Colitis-associated Marker Antibody pANCA

Journal of Autoimmunity, 2000

Perinuclear anti-neutrophil cytoplasmic antibody (pANCA) 4 is a predominant serum marker of ulcer... more Perinuclear anti-neutrophil cytoplasmic antibody (pANCA) 4 is a predominant serum marker of ulcerative colitis (UC), and a familial trait associated with disease susceptibility and disease associated MHC haplotypes. This study characterizes the pANCA antigen defined by representative UC-pANCA human monoclonal antibodies, Fab 5-3 and 5-2. Western blot analysis probed with Fab 5-3 revealed specific binding to a nuclear protein doublet (apparent MW=32-33 kDa) expressed in several cell types. Purification and tryptic peptide sequencing identified the protein as histone H1, and this specificity was confirmed by Fab 5-3 binding to purified H1. Rabbit anti-histone H1 immunostaining and Western blot analysis confirmed that the pANCA epitope is preferentially immunoaccessible in polymorphonuclear neutrophils (PMN). The epitope was localized to the COOH-terminal region by site-specific proteolysis, and recombinant deletants further localized binding activity for both Fab 5-2 and 5-3 to two non-overlapping segments (AA 69-171 and 172-226) associated with a recurring PKKAK motif. Serum IgG binding was detectable to these segments, but was not significantly correlated with pANCA titer or disease status. These findings indicate that histone H1 bears a recurring COOH-terminal epitope recognized by monoclonal ulcerative colitis-associated pANCA marker antibodies, but this epitope is not a predominant specificity of serum pANCA.

Research paper thumbnail of Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn's disease

American Journal of Gastroenterology, 2002

Research paper thumbnail of Nanotechnology-based combination therapy improves treatment response in cancer models

Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5%. Photodynam... more Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5%. Photodynamic therapy (PDT) has shown promising results in treating PanCa. Mechanism-based combinations with PDT have enhanced treatment outcome. Agents tested with PDT include Avastin, an antibody against vascular endothelial growth factor (VEGF) which is approved for treating various cancers. Simultaneous delivery of drugs in nano-constructs could improve the treatment response of mechanism based combination therapies. Here, we investigate the effect of neutralizing VEGF using nanotechnology for the delivery of Avastin in combination with PDT. For this we used a construct called "nanocells" in which the photosensitizer was trapped inside polymer nanoparticles and these, with Avastin, were then encapsulated inside liposomes. In vitro, nanocells containing Avastin (NCA) significantly enhanced cytotoxicity in PanCa cells. NCA based PDT also significantly improved treatment response in mice that were orthotopically implanted with PanCa. Avastin delivered extracellularly in combination with PDT did not show any improvement. Here we propose a new paradigm for Avastin-based therapy by combining intracellular delivery of the antibody and PDT using nanotechnology for treating PanCa.

Research paper thumbnail of Are anti-saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (PANCA) useful in indeterminate colitis? A prospective follow-up study

Gastroenterology, 2000

Patients with IBD undergo numerous diagnostic examinations of the 01tract during the course of th... more Patients with IBD undergo numerous diagnostic examinations of the 01tract during the course of their chronic disease. Conventional colonoscopy and enteroclysis for assessment of the colon and the small intestine are the methods of choice. A less invasive method for visualizing the colon and detecting polyps seems to be MR-based virtual colonoscopy. For the small bowel we have shown that oral MR enteroclysis is an adequate diagnostic tool. Purpose: To perform 3D-MR examinations with virtual endoscopy of the small intestine and colon in patients with IBD. Methods We performed MR enteroclysis using Tl shortening oral contrast in 30 consecutive patients with IBD after conventional enteroclysis. Gd-DTPA was given iv to assess inflammation of the bowel. Fat suppressed breathhold 3D-MR acquisitions were done before and after iv application. In 10 patients, who underwent conventional colonoscopy we performed virtual colonoscopy the same day. Patients were filled rectally with 2 liters water spiked with Gd-DTPA and 3D-Tl weighted MRI was acquired. Using a graphical workstation (02, Silicon Graphics) we performed VE of the bowel applying volume rendering technique. Feasibility and quality of VE were assessed. Results In 9% of all patients VE of the small bowel was not feasible because of motion artifacts or inadequate bowel filling. In 57% fair VE results were achieved but approximately 1/5 of the small intestine were not visualized due to incomplete contrast or local bowel movement. In 34% at least one series resulted in a VE with excellent quality revealing typical fold patterns of the small intestine. Pathologic conditions such as stenoses or fistulae were depicted impressively. In 9/10 patients good quality virtual colonoscopy was achieved. Even the granularity of the mucosa and pseudopolyps in a patient with ulcerative colitis could be clearly delineated. Conclusion MR-based VE of the small intestine and colon is feasible in most cases. Further developments in MR-scanning and high performance 3D-computing will improve the quality of this recently introduced modality. This minimal invasive examination without radiation can be a useful complementary tool to conventional endoscopy and may open up valuable diagnostic opportunities in IBD especially in a joint approach of Radiology and Gastroenterology. It's practical value needs to be assessed in larger prospective studies.

Research paper thumbnail of Anti-Saccharomyces cerevisiae mannan antibodies combined with antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease: prevalence and diagnostic role

Gut, 1998

Background-Perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) are a well recognised ma... more Background-Perinuclear antineutrophil cytoplasmic autoantibodies (pANCA) are a well recognised marker for ulcerative colitis. Antibodies to oligomannosidic epitopes of the yeast Saccharomyces cerevisiae (ASCA) are a new marker associated with Crohn's disease. Aims-To assess the value of detecting pANCA and/or ASCA for the diagnosis of ulcerative colitis and Crohn's disease. Methods-Serum samples were obtained from 100 patients with Crohn's disease, 101 patients with ulcerative colitis, 27 patients with other miscellaneous diarrhoeal illnesses, and 163 healthy controls. Determination of pANCA and ASCA was performed using the standardised indirect immunofluorescence technique and an ELISA, respectively. Results-The combination of a positive pANCA test and a negative ASCA test yielded a sensitivity, specificity, and positive predictive value of 57%, 97%, and 92.5% respectively for ulcerative colitis. The combination of a positive ASCA test and a negative pANCA test yielded a sensitivity, specificity, and positive predictive value of 49%, 97%, and 96% respectively for Crohn's disease. Among patients with miscellaneous non-inflammatory bowel disorders, three were ASCA positive and two were pANCA positive. One control was ASCA positive. The presence of ASCA in patients with Crohn's disease was associated with small bowel involvement. Conclusion-ASCA and pANCA are strongly associated with Crohn's disease and ulcerative colitis, respectively. Combination of both tests could help the diagnosis of inflammatory bowel disease. (Gut 1998;42:788-791)

Research paper thumbnail of MAKALAH METODOLOGI PENELITIAN HUKUM