Objectives: Recently, it has been shown that a subset population of cancer cells in a tumor, the ... more Objectives: Recently, it has been shown that a subset population of cancer cells in a tumor, the so-called cancer stem cells (CSCs), majorly contributes to chemoresistance and the ability of a tumor to form recurrences and metastases. Since the response to the standard chemotherapeutic drug 5-fluorouracil (5-FU) in patients with colorectal cancer (CRC) leads only to an inadequate response, we aimed to synthesize new hybrid molecules by combining 5-FU with the plant-derived drug thymoquinone (TQ). Methods: The cytotoxic effect of hybrids, the single drugs and the combination was investigated by crystal violet assays. HCT116, HT29 and 5-FU-resistant colorectal tumor cells were used to assess the spheroid forming capability after treatment with different concentrations of the hybrid and the single drugs by staining with the fluorescent stem cell marker CDy1 and Hoechst 3324 after 21 days of incubation. Western Blot analysis for stem cell surface marker CD133 were performed to verify these results. We have analyzed the anticancer effects of the single drugs TQ and 5-FU and the most effective hybrid on deregulation of cancer signaling pathways utilizing the NANOSTRING cancer pathway panel. In addition, we performed a single cell cloning from spheroids to generate monoclonal cell lines with enriched CSC populations. In vivo effects were studied in the chick chorioallantoic membrane (CAM) assay and in mouse xenografts. Results: The 5FU-TQ hybrid has an increased cytotoxic effect towards CRC cells when compared to single drug treatments. The spheroid formation assay revealed the capability of the hybrid to reduce sphere number and size at fairly low concentrations (10, 20 µM), however at 50 µM there was a complete suppression of spheroid growth. NANOSTRING analysis showed that gene expression of main components of the PI3K/AKT signaling pathway was significantly down-regulated after treatment with all drugs but most prominently with the new hybrid. After data processing we found that AKT3, IGF1, COL11A1, FGF10, GNG7, EPO genes were downregulated in hybrid-treated cells, while CDKN1A, BAX, JUN, MDM2, FAS were upregulated. This was verified via Western Blotting for a panel of markers. Next, we investigated the effectiveness of the hybrid to kill clones having an enriched CSC population. Indeed, CD133 protein levels were significantly decreased in hybrid-treated clones. Histological analysis of in vivo CAM grafts showed that HCT116 control cells developed a well vascularized tumor mass whereas HCT116 cells that were treated with the hybrid showed no more vital tumor cells, but extended areas of necrosis, calcification, and desmoplasia. In vivo mouse xenografts verified the potential of this hybrid as an antitumor agent reducing tumor volume significantly. Conclusion: Our findings strongly suggest that the newly synthesized 5-FU-TQ hybrid might become a promising anticancer drug by directly targeting CSCs. Citation Format: Benardina Ndreshkjana, Aysun Capci Karagoz, Volker Klein, Pithi Chanvorachote, Julienne K. Muenzner, Kerstin Huebner, Chuanpit Ninsontia, Sara Steinmann, Abbas Agaimy, Maamoun Fatfat, Hala Gali-Muhtasib, Svetlana B. Tsogoeva, Regine Schneider-Stock. Novel 5-fluorouracil-thymoquinone hybrid kills colon cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1904. doi:10.1158/1538-7445.AM2017-1904
Objectives: The cell cycle regulator p21Waf1/Cip1 belongs to the family of cyclin-dependent kinas... more Objectives: The cell cycle regulator p21Waf1/Cip1 belongs to the family of cyclin-dependent kinase inhibitors (CDKIs). Depending on the cellular condition, p21Waf1/Cip1 can either, inhibit the cell cycle or promote proliferation, prohibit or induce apoptosis and increase or decrease cell differentiation. The contradictory nature of p21Waf1/Cip1 encouraged us to investigate the effects of this CDKI on the expression of chromatin modifying enzymes in colorectal tumor cells. Methods: Three different HCT116 cell lines were used for our studies. HCT116 WT, HCT116 p21-/- and HCT116 p53-/-. The isolated RNA was analyzed via Epigenetic Chromatin Modification Enzymes RT2 Profiler PCR Arrays from Qiagen. Western Blot analysis was performed to verify the results of the PCR arrays. In addition, immunohistochemical staining of different chromatin modifiers was performed on tissue microarrays of colon cancer patients. The protein structure of p21Waf1/Cip1 was generated by computational modelling techniques to investigate possible interactions between p21Waf1/Cip1 and chromatin modifying enzymes. Ex vivo crypt organoids from WT and p21 -/- mice were studied for chromatin signature. Results: The PCR arrays provided us with astonishing results. Compared to the wild type HCT116 cells, we could see a clear deregulation of a high number of different chromatin modifying enzymes in the two knock out cell lines. SETD1B was up-regulated 1,8 times in p21-/- and HDAC1, which is a known interaction partner of p21Waf1/Cip1, was down regulated about 2 times compared to the WT cells. This could also be proven by Western Blot and immunohistochemical analysis. The data was further processed and analyzed using an R package termed as HTqPCR and it was observed that ATF2 was up-regulated, while AURKB, different HDACs, and DNMT3B genes were down-regulated in p21-/- cells compared to the WT cells. The interaction between p21Waf1/Cip1 and HDAC1 could be analyzed on an atomic scale by molecular dynamics simulations. Conclusion: Our data strongly suggests that p21Waf1/Cip1 is very important for chromatin regulation in colon cancer cells and that its loss induces an active histone code. Interestingly most p21-dependent effects were independent of p53. These exciting and new findings have to be further investigated. Citation Format: Pablo Lennert, Katharina Erlenbach-Wuensch, Carsten Kroeger, Sara Steinmann, Kerstin Huebner, Sushmita Paul, Felix Rausch, Arndt Hartmann, Regine Schneider-Stock. p21Waf1/Cip1 dependent chromatin modifications in colorectal tumor cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2194. doi:10.1158/1538-7445.AM2015-2194
Liposarcoma is one of the most common soft tissue sarcomas in adults. Recognized histological sub... more Liposarcoma is one of the most common soft tissue sarcomas in adults. Recognized histological subtypes include well differentiated/dedifferentiated liposarcoma (WD/DDLS), myxoid liposarcoma (MLS) and pleomorphic liposarcoma. Currently, there are no proper subtype-specific treatments due to the genetic, histological and clinical heterogeneity of the liposarcoma subentities. In the past decade, the rising understanding of the various genetic and molecular aberrations in liposarcoma led to the development of novel alternative therapeutic strategies. One such therapy is the inhibition of the heat shock protein 90 (Hsp90) which is overexpressed in liposarcomas. In this study, we dissect the functional role of a novel potent Hsp90 inhibitor NVP-AUY922 (AUY922) in different cell lines of myxoid (MLS402, MLS1765) and undifferentiated (SW872) liposarcomas. We show that compared with 17-AAG treatment, lower concentrations of AUY922 achieve markedly cytotoxic effects on tumor cell viability. Combination treatment of AUY922 (20 nM) with Doxorubicin (300 nM) yielded a further reduction in cell viability in comparison to Doxorubicin alone. In vivo, we document an inhibition of tumor growth after AUY922 treatment. Further analyses revealed that Hsp90-inhibition induces apoptotic cell death and cell cycle arrest. In addition, we report striking perturbations of subtype-specific pattern in Raf/MEK/ERK and PI3K signaling after AUY922 application. In conclusion, our results provide evidence that Hsp90-inhibition by AUY922 may be a promising alternative therapeutic strategy for myxoid liposarcoma patients.
The cytoskeleton-associated serine/threonine kinase death-associated protein kinase (DAPK) has be... more The cytoskeleton-associated serine/threonine kinase death-associated protein kinase (DAPK) has been described as a cancer gene chameleon with functional antagonistic duality in a cell type and context specific manner. The broad range of interaction partners and substrates link DAPK to inflammatory processes especially in the gut. Herein we summarize our knowledge on the role of DAPK in different cell types that play a role under inflammatory conditions in the gut. Besides some promising experimental data suggesting DAPK as an interesting drug target in inflammatory bowel disease there are many open questions regarding direct evidence for a role of DAPK in intestinal inflammation. Contents 1. Introduction 2. DAPK -structure and functional domains 3. Regulation of DAPK 4. DAPK interactome and substrates 5. Molecular Biology of IBD 6. Link of IBD and cancer 7. DAPK regulation and function in different cell types of the intestine 8. Open questions and future challenges
Colorectal cancer (CRC) is one of the leading cancer-related causes of death worldwide. Despite t... more Colorectal cancer (CRC) is one of the leading cancer-related causes of death worldwide. Despite the improvement of surgical and chemotherapeutic treatments, as of yet, the disease has not been overcome due to metastasis to distant organs. Hence, it is of great relevance to understand the mechanisms responsible for metastasis initiation and progression and to identify novel metastatic markers for a higher chance of preventing the metastatic disease. The Death-associated protein kinase 1 (DAPK1), recently, has been shown to be a potential candidate for regulating metastasis in CRC. Hence, the aim of the study was to investigate the impact of DAPK1 protein on CRC aggressiveness. Using CRISPR/Cas9 technology, we generated DAPK1-deficient HCT116 monoclonal cell lines and characterized their knockout phenotype in vitro and in vivo. We show that loss of DAPK1 implemented changes in growth pattern and enhanced tumor budding in vivo in the chorioallantoic membrane (CAM) model. Further, we observed more tumor cell dissemination into chicken embryo organs and increased invasion capacity using rat brain 3D in vitro model. The novel identified DAPK1-loss gene expression signature showed a stroma typical pattern and was associated with a gained ability for remodeling the extracellular matrix. Finally, we suggest the DAPK1-ERK1 signaling axis being involved in metastatic progression of CRC. Our results highlight DAPK1 as an anti-metastatic player in CRC and suggest DAPK1 as a potential predictive biomarker for this cancer type.
The biggest compartment of the musculoskeletal system is the tendons and ligaments. In particular... more The biggest compartment of the musculoskeletal system is the tendons and ligaments. In particular, tendons are dense tissues connecting muscle to bone that are critical for the integrity, function and locomotion of this system. Due to the increasing age of our society and the overall rise in engagement in extreme and overuse sports, there is a growing prevalence of tendinopathies. Despite the recent advances in tendon research and due to difficult early diagnosis, a multitude of risk factors and vague understanding of the underlying biological mechanisms involved in the progression of tendon injuries, the toolbox of treatment strategies remains limited and non-satisfactory. This review is designed to summarize the current knowledge of triggers, trails and end state of tendinopathies.
Cancer stem cells (CSCs) residing in colorectal cancer tissues have tumorigenic capacity and cont... more Cancer stem cells (CSCs) residing in colorectal cancer tissues have tumorigenic capacity and contribute to chemotherapeutic resistance and disease relapse. It is well known that the survival of colorectal CSCs after 5fluorouracil (5-FU)-based therapy leads to cancer recurrence. Thus CSCs represent a promising drug target. Here, we designed and synthesized novel hybrid molecules linking 5-FU with the plant-derived compound thymoquinone (TQ) and tested the potential of individual compounds and their combination to eliminate colorectal CSCs. Both, Combi and SARB hybrid showed augmented cytotoxicity against colorectal cancer cells, but were non-toxic to organoids prepared from healthy murine small intestine. NanoString analysis revealed a unique signature of deregulated gene expression in response to the combination of TQ and 5-FU (Combi) and SARB treatment. Importantly, two principle stem cell regulatory pathways WNT/ß-Catenin and PI3K/AKT were found to be downregulated after Combi and hybrid treatment. Furthermore, both treatments strikingly eliminated CD133+ CSC population, accompanying the depleted self-renewal capacity by eradicating long-term propagated 3D tumor cell spheres at sub-toxic doses. In vivo xenografts on chicken eggs of SARB-treated HCT116 cells showed a prominent nuclear ß-Catenin and E-cadherin staining. This was in line with the reduced transcriptional activity of ß-Catenin and diminished cell adhesion under SARB exposure. In contrast to 5-FU, both, Combi and SARB treatment effectively reduced the angiogenic capacity of the remaining resistant tumor cells. Taken together, combination or hybridization of single compounds target simultaneously a broader spectrum of oncogenic pathways leading to an effective eradication of colorectal cancer cells.
Objectives: Recently, it has been shown that a subset population of cancer cells in a tumor, the ... more Objectives: Recently, it has been shown that a subset population of cancer cells in a tumor, the so-called cancer stem cells (CSCs), majorly contributes to chemoresistance and the ability of a tumor to form recurrences and metastases. Since the response to the standard chemotherapeutic drug 5-fluorouracil (5-FU) in patients with colorectal cancer (CRC) leads only to an inadequate response, we aimed to synthesize new hybrid molecules by combining 5-FU with the plant-derived drug thymoquinone (TQ). Methods: The cytotoxic effect of hybrids, the single drugs and the combination was investigated by crystal violet assays. HCT116, HT29 and 5-FU-resistant colorectal tumor cells were used to assess the spheroid forming capability after treatment with different concentrations of the hybrid and the single drugs by staining with the fluorescent stem cell marker CDy1 and Hoechst 3324 after 21 days of incubation. Western Blot analysis for stem cell surface marker CD133 were performed to verify these results. We have analyzed the anticancer effects of the single drugs TQ and 5-FU and the most effective hybrid on deregulation of cancer signaling pathways utilizing the NANOSTRING cancer pathway panel. In addition, we performed a single cell cloning from spheroids to generate monoclonal cell lines with enriched CSC populations. In vivo effects were studied in the chick chorioallantoic membrane (CAM) assay and in mouse xenografts. Results: The 5FU-TQ hybrid has an increased cytotoxic effect towards CRC cells when compared to single drug treatments. The spheroid formation assay revealed the capability of the hybrid to reduce sphere number and size at fairly low concentrations (10, 20 µM), however at 50 µM there was a complete suppression of spheroid growth. NANOSTRING analysis showed that gene expression of main components of the PI3K/AKT signaling pathway was significantly down-regulated after treatment with all drugs but most prominently with the new hybrid. After data processing we found that AKT3, IGF1, COL11A1, FGF10, GNG7, EPO genes were downregulated in hybrid-treated cells, while CDKN1A, BAX, JUN, MDM2, FAS were upregulated. This was verified via Western Blotting for a panel of markers. Next, we investigated the effectiveness of the hybrid to kill clones having an enriched CSC population. Indeed, CD133 protein levels were significantly decreased in hybrid-treated clones. Histological analysis of in vivo CAM grafts showed that HCT116 control cells developed a well vascularized tumor mass whereas HCT116 cells that were treated with the hybrid showed no more vital tumor cells, but extended areas of necrosis, calcification, and desmoplasia. In vivo mouse xenografts verified the potential of this hybrid as an antitumor agent reducing tumor volume significantly. Conclusion: Our findings strongly suggest that the newly synthesized 5-FU-TQ hybrid might become a promising anticancer drug by directly targeting CSCs. Citation Format: Benardina Ndreshkjana, Aysun Capci Karagoz, Volker Klein, Pithi Chanvorachote, Julienne K. Muenzner, Kerstin Huebner, Chuanpit Ninsontia, Sara Steinmann, Abbas Agaimy, Maamoun Fatfat, Hala Gali-Muhtasib, Svetlana B. Tsogoeva, Regine Schneider-Stock. Novel 5-fluorouracil-thymoquinone hybrid kills colon cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1904. doi:10.1158/1538-7445.AM2017-1904
Objectives: The cell cycle regulator p21Waf1/Cip1 belongs to the family of cyclin-dependent kinas... more Objectives: The cell cycle regulator p21Waf1/Cip1 belongs to the family of cyclin-dependent kinase inhibitors (CDKIs). Depending on the cellular condition, p21Waf1/Cip1 can either, inhibit the cell cycle or promote proliferation, prohibit or induce apoptosis and increase or decrease cell differentiation. The contradictory nature of p21Waf1/Cip1 encouraged us to investigate the effects of this CDKI on the expression of chromatin modifying enzymes in colorectal tumor cells. Methods: Three different HCT116 cell lines were used for our studies. HCT116 WT, HCT116 p21-/- and HCT116 p53-/-. The isolated RNA was analyzed via Epigenetic Chromatin Modification Enzymes RT2 Profiler PCR Arrays from Qiagen. Western Blot analysis was performed to verify the results of the PCR arrays. In addition, immunohistochemical staining of different chromatin modifiers was performed on tissue microarrays of colon cancer patients. The protein structure of p21Waf1/Cip1 was generated by computational modelling techniques to investigate possible interactions between p21Waf1/Cip1 and chromatin modifying enzymes. Ex vivo crypt organoids from WT and p21 -/- mice were studied for chromatin signature. Results: The PCR arrays provided us with astonishing results. Compared to the wild type HCT116 cells, we could see a clear deregulation of a high number of different chromatin modifying enzymes in the two knock out cell lines. SETD1B was up-regulated 1,8 times in p21-/- and HDAC1, which is a known interaction partner of p21Waf1/Cip1, was down regulated about 2 times compared to the WT cells. This could also be proven by Western Blot and immunohistochemical analysis. The data was further processed and analyzed using an R package termed as HTqPCR and it was observed that ATF2 was up-regulated, while AURKB, different HDACs, and DNMT3B genes were down-regulated in p21-/- cells compared to the WT cells. The interaction between p21Waf1/Cip1 and HDAC1 could be analyzed on an atomic scale by molecular dynamics simulations. Conclusion: Our data strongly suggests that p21Waf1/Cip1 is very important for chromatin regulation in colon cancer cells and that its loss induces an active histone code. Interestingly most p21-dependent effects were independent of p53. These exciting and new findings have to be further investigated. Citation Format: Pablo Lennert, Katharina Erlenbach-Wuensch, Carsten Kroeger, Sara Steinmann, Kerstin Huebner, Sushmita Paul, Felix Rausch, Arndt Hartmann, Regine Schneider-Stock. p21Waf1/Cip1 dependent chromatin modifications in colorectal tumor cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2194. doi:10.1158/1538-7445.AM2015-2194
Liposarcoma is one of the most common soft tissue sarcomas in adults. Recognized histological sub... more Liposarcoma is one of the most common soft tissue sarcomas in adults. Recognized histological subtypes include well differentiated/dedifferentiated liposarcoma (WD/DDLS), myxoid liposarcoma (MLS) and pleomorphic liposarcoma. Currently, there are no proper subtype-specific treatments due to the genetic, histological and clinical heterogeneity of the liposarcoma subentities. In the past decade, the rising understanding of the various genetic and molecular aberrations in liposarcoma led to the development of novel alternative therapeutic strategies. One such therapy is the inhibition of the heat shock protein 90 (Hsp90) which is overexpressed in liposarcomas. In this study, we dissect the functional role of a novel potent Hsp90 inhibitor NVP-AUY922 (AUY922) in different cell lines of myxoid (MLS402, MLS1765) and undifferentiated (SW872) liposarcomas. We show that compared with 17-AAG treatment, lower concentrations of AUY922 achieve markedly cytotoxic effects on tumor cell viability. Combination treatment of AUY922 (20 nM) with Doxorubicin (300 nM) yielded a further reduction in cell viability in comparison to Doxorubicin alone. In vivo, we document an inhibition of tumor growth after AUY922 treatment. Further analyses revealed that Hsp90-inhibition induces apoptotic cell death and cell cycle arrest. In addition, we report striking perturbations of subtype-specific pattern in Raf/MEK/ERK and PI3K signaling after AUY922 application. In conclusion, our results provide evidence that Hsp90-inhibition by AUY922 may be a promising alternative therapeutic strategy for myxoid liposarcoma patients.
The cytoskeleton-associated serine/threonine kinase death-associated protein kinase (DAPK) has be... more The cytoskeleton-associated serine/threonine kinase death-associated protein kinase (DAPK) has been described as a cancer gene chameleon with functional antagonistic duality in a cell type and context specific manner. The broad range of interaction partners and substrates link DAPK to inflammatory processes especially in the gut. Herein we summarize our knowledge on the role of DAPK in different cell types that play a role under inflammatory conditions in the gut. Besides some promising experimental data suggesting DAPK as an interesting drug target in inflammatory bowel disease there are many open questions regarding direct evidence for a role of DAPK in intestinal inflammation. Contents 1. Introduction 2. DAPK -structure and functional domains 3. Regulation of DAPK 4. DAPK interactome and substrates 5. Molecular Biology of IBD 6. Link of IBD and cancer 7. DAPK regulation and function in different cell types of the intestine 8. Open questions and future challenges
Colorectal cancer (CRC) is one of the leading cancer-related causes of death worldwide. Despite t... more Colorectal cancer (CRC) is one of the leading cancer-related causes of death worldwide. Despite the improvement of surgical and chemotherapeutic treatments, as of yet, the disease has not been overcome due to metastasis to distant organs. Hence, it is of great relevance to understand the mechanisms responsible for metastasis initiation and progression and to identify novel metastatic markers for a higher chance of preventing the metastatic disease. The Death-associated protein kinase 1 (DAPK1), recently, has been shown to be a potential candidate for regulating metastasis in CRC. Hence, the aim of the study was to investigate the impact of DAPK1 protein on CRC aggressiveness. Using CRISPR/Cas9 technology, we generated DAPK1-deficient HCT116 monoclonal cell lines and characterized their knockout phenotype in vitro and in vivo. We show that loss of DAPK1 implemented changes in growth pattern and enhanced tumor budding in vivo in the chorioallantoic membrane (CAM) model. Further, we observed more tumor cell dissemination into chicken embryo organs and increased invasion capacity using rat brain 3D in vitro model. The novel identified DAPK1-loss gene expression signature showed a stroma typical pattern and was associated with a gained ability for remodeling the extracellular matrix. Finally, we suggest the DAPK1-ERK1 signaling axis being involved in metastatic progression of CRC. Our results highlight DAPK1 as an anti-metastatic player in CRC and suggest DAPK1 as a potential predictive biomarker for this cancer type.
The biggest compartment of the musculoskeletal system is the tendons and ligaments. In particular... more The biggest compartment of the musculoskeletal system is the tendons and ligaments. In particular, tendons are dense tissues connecting muscle to bone that are critical for the integrity, function and locomotion of this system. Due to the increasing age of our society and the overall rise in engagement in extreme and overuse sports, there is a growing prevalence of tendinopathies. Despite the recent advances in tendon research and due to difficult early diagnosis, a multitude of risk factors and vague understanding of the underlying biological mechanisms involved in the progression of tendon injuries, the toolbox of treatment strategies remains limited and non-satisfactory. This review is designed to summarize the current knowledge of triggers, trails and end state of tendinopathies.
Cancer stem cells (CSCs) residing in colorectal cancer tissues have tumorigenic capacity and cont... more Cancer stem cells (CSCs) residing in colorectal cancer tissues have tumorigenic capacity and contribute to chemotherapeutic resistance and disease relapse. It is well known that the survival of colorectal CSCs after 5fluorouracil (5-FU)-based therapy leads to cancer recurrence. Thus CSCs represent a promising drug target. Here, we designed and synthesized novel hybrid molecules linking 5-FU with the plant-derived compound thymoquinone (TQ) and tested the potential of individual compounds and their combination to eliminate colorectal CSCs. Both, Combi and SARB hybrid showed augmented cytotoxicity against colorectal cancer cells, but were non-toxic to organoids prepared from healthy murine small intestine. NanoString analysis revealed a unique signature of deregulated gene expression in response to the combination of TQ and 5-FU (Combi) and SARB treatment. Importantly, two principle stem cell regulatory pathways WNT/ß-Catenin and PI3K/AKT were found to be downregulated after Combi and hybrid treatment. Furthermore, both treatments strikingly eliminated CD133+ CSC population, accompanying the depleted self-renewal capacity by eradicating long-term propagated 3D tumor cell spheres at sub-toxic doses. In vivo xenografts on chicken eggs of SARB-treated HCT116 cells showed a prominent nuclear ß-Catenin and E-cadherin staining. This was in line with the reduced transcriptional activity of ß-Catenin and diminished cell adhesion under SARB exposure. In contrast to 5-FU, both, Combi and SARB treatment effectively reduced the angiogenic capacity of the remaining resistant tumor cells. Taken together, combination or hybridization of single compounds target simultaneously a broader spectrum of oncogenic pathways leading to an effective eradication of colorectal cancer cells.
Uploads
Papers by Sara Steinmann