Rainer Heuchel - Academia.edu (original) (raw)

Papers by Rainer Heuchel

Research paper thumbnail of Pancreatic heterospecies heterospheroids in cancer/stroma crosstalk investigation

Pancreatology, Jun 1, 2019

Research paper thumbnail of Detection methods for circulating tumor cells in the blood of patients with pancreatic cancer in a pre-operative setting

Pancreatology, Jun 1, 2019

database. The meta-analysis of the relation of marginal length on survival was performed with the... more database. The meta-analysis of the relation of marginal length on survival was performed with the inverse variance method in RevMan. Results: There were five studies (902 patients) reporting median survival (MS) for RM 0 mm resection (12.6-23.4), seven studies (1167 patients) reporting MS for RM <1 mm, two studies (259 patients) reporting MS for RM <1.5 mm and three studies (319 patients) reporting MS for RM <2 mm. A total of five studies comprising 1275 patients reported multivariate hazard rations for RM 1 mm vs. RM <1 mm. A RM over 1 mm reduced risk for death compared with patients with RM < 1 mm (HR 1.32 and 95% confidence interval from 1.03 to 1.68, p¼0.03). Three studies reported multivariate HRs for RM 1 mm (929 patients) vs. RM 0 mm (701 patients). The HRs ranged from 0.73-1.31. Two studies reported multivariate HRs for RM >2 mm (63 patients) vs. <2 mm (296 patients). The HRs ranged from 1.2-2.66. Conclusion: RM 1 mm or more leads to longer survival than RM <1 mm. However, not enough evidence exists to analyse benefits of wider RMs.

Research paper thumbnail of Bio-functionalized recombinant spider silk modified microdevice for capture and release of circulating tumor cells from pancreatic cancer patients

Effective isolation and purification of circulating tumor cells from whole blood provides importa... more Effective isolation and purification of circulating tumor cells from whole blood provides important capability for clinical application and biological research. Here, we demonstrate a single step s ...

Research paper thumbnail of Microfluidic based circulating tumor cell isolation and release from whole blood of pancreatic cancer patients using bio-functionalized recombinant spider silk

A bio-functionalized microsystem was developed for the capture and release of cancer cells from w... more A bio-functionalized microsystem was developed for the capture and release of cancer cells from whole blood. Effective isolation and purification of circulating tumor cells from whole blood provide ...

Research paper thumbnail of PO-278 Assessment of the influence of stellate cells on primary pancreatic cancer cell growth and drug resistance in a spheroid model: MET inhibitors to the rescue

Research paper thumbnail of Overcoming diagnostic issues in precision treatment of pancreatic cancer

Expert review of precision medicine and drug development, May 4, 2018

Research paper thumbnail of A novel pancreatic tumour and stellate cell 3D co-culture spheroid model

Research paper thumbnail of Investigation of tumor/stroma crosstalk in pancreatic heterospecies heterospheroids

Pancreatology, Nov 1, 2020

Research paper thumbnail of Therapy with Cell Encapsulation for Substitution of Organ Function and Tumor Treatment (Adv. Eng. Mater. 8/2009)

Advanced Engineering Materials, Aug 1, 2009

Research paper thumbnail of Targeting myeloid suppressive cells revives cytotoxic anti-tumor responses in pancreatic cancer

Research paper thumbnail of Variant Profiling of Candidate Genes in Pancreatic Ductal Adenocarcinoma

Clinical Chemistry, Nov 1, 2015

Research paper thumbnail of Pancreatic Ductal Adenocarcinoma: Preclinical in vitro and ex vivo Models

Frontiers in Cell and Developmental Biology, Oct 22, 2021

Research paper thumbnail of Cerulein-induced pancreatic fibrosis is modulated by Smad7, the major negative regulator of transforming growth factor-β signaling

Biochimica Et Biophysica Acta: Molecular Basis Of Disease, Sep 1, 2016

Research paper thumbnail of A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients With Pancreatic Cancer

Journal of Immunotherapy, May 1, 2017

We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) ... more We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT. Both TAAs were highly expressed in the original tumor tissue suggesting that HSCT promoted a clinically relevant, long-lasting cellular immune response. In contrast to untreated controls, who succumbed to progressive disease, both patients are tumor-free 9 years after diagnosis. Radical surgery combined with HSCT may cure pancreatic adenocarcinoma and change the cellular immune repertoire capable of responding to clinically and biologically relevant TAAs.

Research paper thumbnail of Human Cell Encapsulation in Gel Microbeads with Cosynthesized Concentric Nanoporous Solid Shells

Advanced Functional Materials, Apr 10, 2018

Research paper thumbnail of Immunohistochemical pattern of liver metastases and paired sample analysis in patients with metastatic pancreatic cancer: Pronounced CDX2 expression and loss of SMAD4 indicate poor survival

Pancreatology, Jun 1, 2019

Software was used to identify skeletal muscle (sliceOmatic, Tomovision). Sarcopenia was defined a... more Software was used to identify skeletal muscle (sliceOmatic, Tomovision). Sarcopenia was defined as SMI<41(female) and <53 cm 2 /m 2 (male). Body mass index (BMI), performance status, demographic data were also compared between patients that went on to receive chemotherapy and those who did not. Results: EUS-Bconfirmed PDAC in 85 eligible patients during the study (median age 70;41e84 years). A total of 61/85(71%) of patients received at least one dose of chemotherapy. Sarcopenia was present in 57/85 (57.6%). Patients who did not take up chemotherapy had a lower SMI (40.5 vs 45.2 cm 2 /m 2 ,p¼0.04) and a poorer mean performance status (1.25 vs 0.7, p¼0.002). There was no difference in BMI (26.8 vs 24.6 p¼0.10) in patients that did and did not take up chemotherapy. In those having chemotherapy, survival was higher in non-sarcopenic patients compared to sarcopenic patients (11.8 vs 7.7 months, p¼0.04). Survival was similar in sarcopenic patients having chemotherapy and non-sarcopenic patients who did not have chemotherapy (7.7 vs 7.4 months p¼0.5). Patients with performance status 2 and sarcopenia were much less likely to receive chemotherapy compared to those with performance status 0-1 without sarcopenia (83.9% vs 37.5%, p¼0.02). Conclusion: Patients with PDAC and a performance status of 2 and low SMI were significant less likely to take up chemotherapy and had poorer survival. SMI measurement could act as part of a decision tool to assess suitability of patients to triage patients for rapid EUS-B, or clinical assessment prior to considering chemotherapy.

Research paper thumbnail of Pathophysiology of pancreatic cancer

Research paper thumbnail of Abstract 4244: The role of hypoxia on the tumor-stromal interaction in pancreatic ductal adenocarcinoma

INTRODUCTION: Pancreatic cancer is characterized by extraordinary fibrosis and pancreatic stellat... more INTRODUCTION: Pancreatic cancer is characterized by extraordinary fibrosis and pancreatic stellate cells (PSCs) are the major player in synthesizing extracellular matrix (ECM) upon activation. The interaction/communication between PSCs and pancreatic ductal adenocarcinoma (PDAC) cells is essential for inducing stroma/ECM production, pancreatic cancer progression and general therapy resistance. Compared to traditional 2D cell culture, cells in a three-dimensional context demonstrate different behavior and functions as reflected by building up a microenvironment that more closely mimics the one observed in the native tissue. This feature is especially critical for testing drug efficiency as cellular response to drugs is profoundly affected by environmental cues. AIMS &amp; METHODS: Our aim was to build up a more reliable and predictive drug screening system. To this end we set up and compared 2D and 3D cell cultures containing either human PSC and PDAC cells alone or in combination. RESULTS: Among PDAC cells, panc-1 cells are the most commonly used which are also able to form spheres in vitro. We generated mono-spheres from panc-1 cells and compared them to conventional 2D culture. The efficiency of different drugs on viability of cells in panc-1 sphere resulted to be much lower than on viability in 2D cultures. Cells in 3D compared to the 2D culture show higher gene expression for ECM proteins as collagen and fibronectin, for growth factors as PDGF and VEGF, as well as for protein like Cox2, Glut1. We co-cultured panc-1 and PSCs, allowing them to interact and form hetero-spheres in which PSCs localized in the cortical area and were identified e.g. by expression of asma, a marker for PSCs activation. These avascular mini-tumors were further characterized at different levels. CONCLUSION: 3D cultures are more resistant to chemotherapy compared to their 2D counterpart offering a more predictive platform for drug screening before proceeding to more expensive in vivo models and clinical trials. The avascular mini-tumors can be considered as an alternative in vitro cell model for studying pancreatic cancer development and fibrosis from a more complete perspective. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4244. doi:1538-7445.AM2012-4244

Research paper thumbnail of Detection of hypoxic areas in a syngeneic, orthotopic model of pancreatic ductal adenocarcinoma in mouse by in vivo imaging using photoacoustics

Pancreatology, May 1, 2013

and/or IgG4 positive were 20 of 26 patients. Of the AIP type 1 patients, 13 had other-organ invol... more and/or IgG4 positive were 20 of 26 patients. Of the AIP type 1 patients, 13 had other-organ involvement, of which the immune-associated cholangitis (IAC) was the most frequent (n ¼ 9). 21/26 patients were classified AIP type 1 (median age: 61 years), whereas 5/26 were classified AIP type 2 (median age: 67 years). 17/26 patients received steroids, 10 patients were only followed, 2 patients were resected. Of the 17 patients who received steroids, 11 relapsed requiring retreatment with steroids or azathioprine/cyclosporine. Conclusion: The great majority of the Swedish AIP patients are of AIP type 1 with frequent other-organ involvement, most with immune-associated cholangitis. They exhibited a high rate of relapse necessitating retreatment.

Research paper thumbnail of Therapy with Cell Encapsulation for Substitution of Organ Function and Tumor Treatment

Advanced Engineering Materials, Aug 1, 2009

Research paper thumbnail of Pancreatic heterospecies heterospheroids in cancer/stroma crosstalk investigation

Pancreatology, Jun 1, 2019

Research paper thumbnail of Detection methods for circulating tumor cells in the blood of patients with pancreatic cancer in a pre-operative setting

Pancreatology, Jun 1, 2019

database. The meta-analysis of the relation of marginal length on survival was performed with the... more database. The meta-analysis of the relation of marginal length on survival was performed with the inverse variance method in RevMan. Results: There were five studies (902 patients) reporting median survival (MS) for RM 0 mm resection (12.6-23.4), seven studies (1167 patients) reporting MS for RM <1 mm, two studies (259 patients) reporting MS for RM <1.5 mm and three studies (319 patients) reporting MS for RM <2 mm. A total of five studies comprising 1275 patients reported multivariate hazard rations for RM 1 mm vs. RM <1 mm. A RM over 1 mm reduced risk for death compared with patients with RM < 1 mm (HR 1.32 and 95% confidence interval from 1.03 to 1.68, p¼0.03). Three studies reported multivariate HRs for RM 1 mm (929 patients) vs. RM 0 mm (701 patients). The HRs ranged from 0.73-1.31. Two studies reported multivariate HRs for RM >2 mm (63 patients) vs. <2 mm (296 patients). The HRs ranged from 1.2-2.66. Conclusion: RM 1 mm or more leads to longer survival than RM <1 mm. However, not enough evidence exists to analyse benefits of wider RMs.

Research paper thumbnail of Bio-functionalized recombinant spider silk modified microdevice for capture and release of circulating tumor cells from pancreatic cancer patients

Effective isolation and purification of circulating tumor cells from whole blood provides importa... more Effective isolation and purification of circulating tumor cells from whole blood provides important capability for clinical application and biological research. Here, we demonstrate a single step s ...

Research paper thumbnail of Microfluidic based circulating tumor cell isolation and release from whole blood of pancreatic cancer patients using bio-functionalized recombinant spider silk

A bio-functionalized microsystem was developed for the capture and release of cancer cells from w... more A bio-functionalized microsystem was developed for the capture and release of cancer cells from whole blood. Effective isolation and purification of circulating tumor cells from whole blood provide ...

Research paper thumbnail of PO-278 Assessment of the influence of stellate cells on primary pancreatic cancer cell growth and drug resistance in a spheroid model: MET inhibitors to the rescue

Research paper thumbnail of Overcoming diagnostic issues in precision treatment of pancreatic cancer

Expert review of precision medicine and drug development, May 4, 2018

Research paper thumbnail of A novel pancreatic tumour and stellate cell 3D co-culture spheroid model

Research paper thumbnail of Investigation of tumor/stroma crosstalk in pancreatic heterospecies heterospheroids

Pancreatology, Nov 1, 2020

Research paper thumbnail of Therapy with Cell Encapsulation for Substitution of Organ Function and Tumor Treatment (Adv. Eng. Mater. 8/2009)

Advanced Engineering Materials, Aug 1, 2009

Research paper thumbnail of Targeting myeloid suppressive cells revives cytotoxic anti-tumor responses in pancreatic cancer

Research paper thumbnail of Variant Profiling of Candidate Genes in Pancreatic Ductal Adenocarcinoma

Clinical Chemistry, Nov 1, 2015

Research paper thumbnail of Pancreatic Ductal Adenocarcinoma: Preclinical in vitro and ex vivo Models

Frontiers in Cell and Developmental Biology, Oct 22, 2021

Research paper thumbnail of Cerulein-induced pancreatic fibrosis is modulated by Smad7, the major negative regulator of transforming growth factor-β signaling

Biochimica Et Biophysica Acta: Molecular Basis Of Disease, Sep 1, 2016

Research paper thumbnail of A Preliminary Report: Radical Surgery and Stem Cell Transplantation for the Treatment of Patients With Pancreatic Cancer

Journal of Immunotherapy, May 1, 2017

We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) ... more We examined the immunologic effects of allogeneic hematopoietic stem cell transplantation (HSCT) in the treatment of pancreatic ductal adenocarcinoma, a deadly disease with a median survival of 24 months for resected tumors and a 5-year survival rate of 6%. After adjuvant chemotherapy, 2 patients with resected pancreatic ductal adenocarcinoma underwent HSCT with HLA-identical sibling donors. Comparable patients who underwent radical surgery, but did not have a donor, served as controls (n=6). Both patients developed humoral and cellular (ie, HLA-A*01:01-restricted) immune responses directed against 2 novel tumor-associated antigens (TAAs), INO80E and UCLH3 after HSCT. Both TAAs were highly expressed in the original tumor tissue suggesting that HSCT promoted a clinically relevant, long-lasting cellular immune response. In contrast to untreated controls, who succumbed to progressive disease, both patients are tumor-free 9 years after diagnosis. Radical surgery combined with HSCT may cure pancreatic adenocarcinoma and change the cellular immune repertoire capable of responding to clinically and biologically relevant TAAs.

Research paper thumbnail of Human Cell Encapsulation in Gel Microbeads with Cosynthesized Concentric Nanoporous Solid Shells

Advanced Functional Materials, Apr 10, 2018

Research paper thumbnail of Immunohistochemical pattern of liver metastases and paired sample analysis in patients with metastatic pancreatic cancer: Pronounced CDX2 expression and loss of SMAD4 indicate poor survival

Pancreatology, Jun 1, 2019

Software was used to identify skeletal muscle (sliceOmatic, Tomovision). Sarcopenia was defined a... more Software was used to identify skeletal muscle (sliceOmatic, Tomovision). Sarcopenia was defined as SMI<41(female) and <53 cm 2 /m 2 (male). Body mass index (BMI), performance status, demographic data were also compared between patients that went on to receive chemotherapy and those who did not. Results: EUS-Bconfirmed PDAC in 85 eligible patients during the study (median age 70;41e84 years). A total of 61/85(71%) of patients received at least one dose of chemotherapy. Sarcopenia was present in 57/85 (57.6%). Patients who did not take up chemotherapy had a lower SMI (40.5 vs 45.2 cm 2 /m 2 ,p¼0.04) and a poorer mean performance status (1.25 vs 0.7, p¼0.002). There was no difference in BMI (26.8 vs 24.6 p¼0.10) in patients that did and did not take up chemotherapy. In those having chemotherapy, survival was higher in non-sarcopenic patients compared to sarcopenic patients (11.8 vs 7.7 months, p¼0.04). Survival was similar in sarcopenic patients having chemotherapy and non-sarcopenic patients who did not have chemotherapy (7.7 vs 7.4 months p¼0.5). Patients with performance status 2 and sarcopenia were much less likely to receive chemotherapy compared to those with performance status 0-1 without sarcopenia (83.9% vs 37.5%, p¼0.02). Conclusion: Patients with PDAC and a performance status of 2 and low SMI were significant less likely to take up chemotherapy and had poorer survival. SMI measurement could act as part of a decision tool to assess suitability of patients to triage patients for rapid EUS-B, or clinical assessment prior to considering chemotherapy.

Research paper thumbnail of Pathophysiology of pancreatic cancer

Research paper thumbnail of Abstract 4244: The role of hypoxia on the tumor-stromal interaction in pancreatic ductal adenocarcinoma

INTRODUCTION: Pancreatic cancer is characterized by extraordinary fibrosis and pancreatic stellat... more INTRODUCTION: Pancreatic cancer is characterized by extraordinary fibrosis and pancreatic stellate cells (PSCs) are the major player in synthesizing extracellular matrix (ECM) upon activation. The interaction/communication between PSCs and pancreatic ductal adenocarcinoma (PDAC) cells is essential for inducing stroma/ECM production, pancreatic cancer progression and general therapy resistance. Compared to traditional 2D cell culture, cells in a three-dimensional context demonstrate different behavior and functions as reflected by building up a microenvironment that more closely mimics the one observed in the native tissue. This feature is especially critical for testing drug efficiency as cellular response to drugs is profoundly affected by environmental cues. AIMS &amp; METHODS: Our aim was to build up a more reliable and predictive drug screening system. To this end we set up and compared 2D and 3D cell cultures containing either human PSC and PDAC cells alone or in combination. RESULTS: Among PDAC cells, panc-1 cells are the most commonly used which are also able to form spheres in vitro. We generated mono-spheres from panc-1 cells and compared them to conventional 2D culture. The efficiency of different drugs on viability of cells in panc-1 sphere resulted to be much lower than on viability in 2D cultures. Cells in 3D compared to the 2D culture show higher gene expression for ECM proteins as collagen and fibronectin, for growth factors as PDGF and VEGF, as well as for protein like Cox2, Glut1. We co-cultured panc-1 and PSCs, allowing them to interact and form hetero-spheres in which PSCs localized in the cortical area and were identified e.g. by expression of asma, a marker for PSCs activation. These avascular mini-tumors were further characterized at different levels. CONCLUSION: 3D cultures are more resistant to chemotherapy compared to their 2D counterpart offering a more predictive platform for drug screening before proceeding to more expensive in vivo models and clinical trials. The avascular mini-tumors can be considered as an alternative in vitro cell model for studying pancreatic cancer development and fibrosis from a more complete perspective. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4244. doi:1538-7445.AM2012-4244

Research paper thumbnail of Detection of hypoxic areas in a syngeneic, orthotopic model of pancreatic ductal adenocarcinoma in mouse by in vivo imaging using photoacoustics

Pancreatology, May 1, 2013

and/or IgG4 positive were 20 of 26 patients. Of the AIP type 1 patients, 13 had other-organ invol... more and/or IgG4 positive were 20 of 26 patients. Of the AIP type 1 patients, 13 had other-organ involvement, of which the immune-associated cholangitis (IAC) was the most frequent (n ¼ 9). 21/26 patients were classified AIP type 1 (median age: 61 years), whereas 5/26 were classified AIP type 2 (median age: 67 years). 17/26 patients received steroids, 10 patients were only followed, 2 patients were resected. Of the 17 patients who received steroids, 11 relapsed requiring retreatment with steroids or azathioprine/cyclosporine. Conclusion: The great majority of the Swedish AIP patients are of AIP type 1 with frequent other-organ involvement, most with immune-associated cholangitis. They exhibited a high rate of relapse necessitating retreatment.

Research paper thumbnail of Therapy with Cell Encapsulation for Substitution of Organ Function and Tumor Treatment

Advanced Engineering Materials, Aug 1, 2009