Angiogenesis, the growth of new blood vessels from the existing vasculature, and is maintained in adult tissues by the balanced presence of both angiogenic inducers and inhibitors in the tissue milieu. When inducers predominate, vascular endothelial cells (VECs) become activated and in this activated VECs, distinct cell signaling pathways are initiated providing the specificity of anti-angiogenic therapies to the tumor vasculature. VEC apoptosis has been well documented in regressing vessels, and it has been shown that, in addition to activating the VECs, some inducers such as vascular endothelial growth factor also up-regulate Fas expression, thus sensitizing the cell to apoptotic stimuli. Endogenous angiogenesis inhibitors, such as thrombospondin-1(TSP-1) and pigment epithelium-derived factor (PEDF), stimulate signaling cascades within the VECs and also induce the expression of Fas ligand in activated VECs. Therefore, when inhibitors predominate, the apoptotic cascade is initiated ,thus anti-angiogenic therapies can target the inducer supply or directly target the VECs. Although clinical studies suggest that anti-angiogenic therapies may prove to be most effective when used in combination with traditional therapies
{"title":"Evaluate the response of Apoptosis, Angiogenesis and Cancer Therapies","authors":"Chathura Gayan","doi":"10.31579/2640-1053/022","DOIUrl":"https://doi.org/10.31579/2640-1053/022","url":null,"abstract":"Angiogenesis, the growth of new blood vessels from the existing vasculature, and is maintained in adult tissues by the balanced presence of both angiogenic inducers and inhibitors in the tissue milieu. When inducers predominate, vascular endothelial cells (VECs) become activated and in this activated VECs, distinct cell signaling pathways are initiated providing the specificity of anti-angiogenic therapies to the tumor vasculature. VEC apoptosis has been well documented in regressing vessels, and it has been shown that, in addition to activating the VECs, some inducers such as vascular endothelial growth factor also up-regulate Fas expression, thus sensitizing the cell to apoptotic stimuli. Endogenous angiogenesis inhibitors, such as thrombospondin-1(TSP-1) and pigment epithelium-derived factor (PEDF), stimulate signaling cascades within the VECs and also induce the expression of Fas ligand in activated VECs. Therefore, when inhibitors predominate, the apoptotic cascade is initiated ,thus anti-angiogenic therapies can target the inducer supply or directly target the VECs. Although clinical studies suggest that anti-angiogenic therapies may prove to be most effective when used in combination with traditional therapies","PeriodicalId":93018,"journal":{"name":"Journal of cancer research and cellular therapeutics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70017858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It is well established that tumors are unable to grow beyond a certain size (1-2 mm) unless they acquire their own blood supply via angiogenesis. Also, angiogenesis helps tumors to invade adjacent tissues and metastasize to distant sites [1]. Therefore, it has been postulated that interfering with the blood supply using anti-angiogenic therapies will destroy the tumor [2]. However, there is an emerging alternative concept that depriving the tumor of its blood supply interferes with the delivery of chemotherapeutic agents to the tumor and creates an unfavorable hypoxic environment that compromises the action of radiotherapy [3]. This concept was supported by the modest responses to anti-angiogenic therapies in clinical trials and the lack of any impact on patient’s survival when antiangiogenic drugs are administered as single agents [4]. Although, Hurwitz et al. [5] have shown that combining the antiangiogenic drug, bevacizumab with chemotherapy significantly improved survival among metastatic colorectal cancer patients. Still, other studies demonstrated reductions in tumor concentrations of chemotherapy or effectiveness of radiotherapy when antiangiogenic drugs were co-administered [6-8]. Even when antiangiogenic drugs yielded significant effects on the growth of some tumors such as renal cell carcinoma, cervical cancer, and ovarian cancer, they failed to demonstrate significant improvements in patients’ survival [9,10]. Furthermore, complete resistance to antiangiogenic therapies has been reported for prostate and pancreatic adenocarcinoma and melanoma that might be attributed to the redundant involvement of several angiogenic factors that are difficult to be targeted by a single anti-angiogenic agent in some tumors [11-13]. To explain this inconsistency, further research is needed for better understanding of the underlying cellular and molecular mechanisms of tumor vascularization and its interaction with cancer therapies in different tumor beds.
{"title":"Thermal tumor ablation therapy:Implications in Radio and Chemo-sensitization","authors":"Deepak P. Kumar","doi":"10.31579/2640-1053/002","DOIUrl":"https://doi.org/10.31579/2640-1053/002","url":null,"abstract":"It is well established that tumors are unable to grow beyond a certain size (1-2 mm) unless they acquire their own blood supply via angiogenesis. Also, angiogenesis helps tumors to invade adjacent tissues and metastasize to distant sites [1]. Therefore, it has been postulated that interfering with the blood supply using anti-angiogenic therapies will destroy the tumor [2]. However, there is an emerging alternative concept that depriving the tumor of its blood supply interferes with the delivery of chemotherapeutic agents to the tumor and creates an unfavorable hypoxic environment that compromises the action of radiotherapy [3]. This concept was supported by the modest responses to anti-angiogenic therapies in clinical trials and the lack of any impact on patient’s survival when antiangiogenic drugs are administered as single agents [4]. Although, Hurwitz et al. [5] have shown that combining the antiangiogenic drug, bevacizumab with chemotherapy significantly improved survival among metastatic colorectal cancer patients. Still, other studies demonstrated reductions in tumor concentrations of chemotherapy or effectiveness of radiotherapy when antiangiogenic drugs were co-administered [6-8]. Even when antiangiogenic drugs yielded significant effects on the growth of some tumors such as renal cell carcinoma, cervical cancer, and ovarian cancer, they failed to demonstrate significant improvements in patients’ survival [9,10]. Furthermore, complete resistance to antiangiogenic therapies has been reported for prostate and pancreatic adenocarcinoma and melanoma that might be attributed to the redundant involvement of several angiogenic factors that are difficult to be targeted by a single anti-angiogenic agent in some tumors [11-13]. To explain this inconsistency, further research is needed for better understanding of the underlying cellular and molecular mechanisms of tumor vascularization and its interaction with cancer therapies in different tumor beds.","PeriodicalId":93018,"journal":{"name":"Journal of cancer research and cellular therapeutics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42619398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The introduction of three-dimensional (3D) tumor cultures has revolutionized anticancer drug research as these cultures allow for the study of drug resistance mechanisms that cannot be explored in traditional two dimensional (2D) monolayer cultures. Discoveries in the 3D tumor culture field suggest that individualized drug sensitivity testing of solid tumor specimens through the establishment and use of 3D tumor cell cultures following tissue collection will become a routine service offered by modern tissue repositories as they expand from their traditional research role to active participation in personalized medicine. Unfortunately, most information related to 3D tumor cultures comes from studies using established tumor cell lines rather than primary tumor cultures. However, accumulation of genetic aberrations in cancer cell lines occurs with increasing number of passages severely limiting their usefulness for personalized medicine. There is only very limited information available concerning technologies and standard operating procedures for the efficient and routine isolation and processing of primary tumor cells for the establishment of 3D tumor cultures from solid tumor specimens. The purpose of this work was to review experimental data from the literature that may provide relevant information concerning the isolation and processing of primary tumor cells for the establishment of 3D tumor cultures. Information reviewed here may help bio repositories in the development and standardization of technologies and standard operating procedures related to the use of 3D tumor cultures.
{"title":"Potentiation of Bio Repositories In Personalized Medicine: Tumor Cells Establishment","authors":"Cheng Li","doi":"10.31579/2640-1053/003","DOIUrl":"https://doi.org/10.31579/2640-1053/003","url":null,"abstract":"The introduction of three-dimensional (3D) tumor cultures has revolutionized anticancer drug research as these cultures allow for the study of drug resistance mechanisms that cannot be explored in traditional two dimensional (2D) monolayer cultures. Discoveries in the 3D tumor culture field suggest that individualized drug sensitivity testing of solid tumor specimens through the establishment and use of 3D tumor cell cultures following tissue collection will become a routine service offered by modern tissue repositories as they expand from their traditional research role to active participation in personalized medicine. Unfortunately, most information related to 3D tumor cultures comes from studies using established tumor cell lines rather than primary tumor cultures. However, accumulation of genetic aberrations in cancer cell lines occurs with increasing number of passages severely limiting their usefulness for personalized medicine. There is only very limited information available concerning technologies and standard operating procedures for the efficient and routine isolation and processing of primary tumor cells for the establishment of 3D tumor cultures from solid tumor specimens. The purpose of this work was to review experimental data from the literature that may provide relevant information concerning the isolation and processing of primary tumor cells for the establishment of 3D tumor cultures. Information reviewed here may help bio repositories in the development and standardization of technologies and standard operating procedures related to the use of 3D tumor cultures.","PeriodicalId":93018,"journal":{"name":"Journal of cancer research and cellular therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45795878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Focused Resonance Nano-permeabilization (FORN) (US Patent 9,616, 245 B2-Apr 11th 2017) enables the 'targeted' delivery of chemo-therapeutic molecules using a safe, non-invasive, whole-body therapeutic device. The prototype device houses a gantry with specialized, near field, radio-frequency (RF) antennae and guns to deliver instantaneous, magnetic resonance. Drug focusing and delivery was enabled using FORN in a patient with advanced, loco-regionally recurrent, metastatic, nasopharyngeal carcinoma (NPC). Nonionizing, safe, extraneous-source radio-frequencies (RF) were delivered in the presence of an instantaneous magnetic field, to create temporary drug molecular weight-specific nanopores in the cell membrane of target lesions, concurrently with systemic chemotherapy. The high frequency RF is timed and delivered to regions of interest (ROIs) to span peak plasma concentrations of infused chemotherapeutic drugs over multiple treatment cycles. FORN-enabled chemotherapy-related adverse event evaluation and tumor response based on PERCIST 1.0 reflected improved clinical, anatomical and metabolic outcomes and significantly reduced myelosuppression in the patient who received 6+1 Cycles of combination chemotherapy, over an extended period of time. Functional Assessment of Cancer Treatment-Head & Neck (FACT-H&N) / Quality of Life (QoL) and Karnofsky Performance Status (KPS) reflected overall patient well-being. Recurrent, loco-regional disease, nodal, hepatic and skeletal metastases showed dramatic response on PET-CT follow up. Concurrent chemo-radiotherapy (CCRT) as a treatment paradigm is the standard of practice in locally advanced nasopharyngeal carcinoma (NPC).
{"title":"The quality Targeting of Cancer Chemotherapy Using Non-Invasive Focused Resonance Nano-Permeabilization","authors":"Saritha Garrepalli","doi":"10.31579/2640-1053/006","DOIUrl":"https://doi.org/10.31579/2640-1053/006","url":null,"abstract":"Focused Resonance Nano-permeabilization (FORN) (US Patent 9,616, 245 B2-Apr 11th 2017) enables the 'targeted' delivery of chemo-therapeutic molecules using a safe, non-invasive, whole-body therapeutic device. The prototype device houses a gantry with specialized, near field, radio-frequency (RF) antennae and guns to deliver instantaneous, magnetic resonance. Drug focusing and delivery was enabled using FORN in a patient with advanced, loco-regionally recurrent, metastatic, nasopharyngeal carcinoma (NPC). Nonionizing, safe, extraneous-source radio-frequencies (RF) were delivered in the presence of an instantaneous magnetic field, to create temporary drug molecular weight-specific nanopores in the cell membrane of target lesions, concurrently with systemic chemotherapy. The high frequency RF is timed and delivered to regions of interest (ROIs) to span peak plasma concentrations of infused chemotherapeutic drugs over multiple treatment cycles. FORN-enabled chemotherapy-related adverse event evaluation and tumor response based on PERCIST 1.0 reflected improved clinical, anatomical and metabolic outcomes and significantly reduced myelosuppression in the patient who received 6+1 Cycles of combination chemotherapy, over an extended period of time. Functional Assessment of Cancer Treatment-Head & Neck (FACT-H&N) / Quality of Life (QoL) and Karnofsky Performance Status (KPS) reflected overall patient well-being. Recurrent, loco-regional disease, nodal, hepatic and skeletal metastases showed dramatic response on PET-CT follow up. Concurrent chemo-radiotherapy (CCRT) as a treatment paradigm is the standard of practice in locally advanced nasopharyngeal carcinoma (NPC).","PeriodicalId":93018,"journal":{"name":"Journal of cancer research and cellular therapeutics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70017802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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