Although breast cancer incidence has increased in recent years, largely due to improved diagnostic techniques, greater awareness and the introduction of national screening programmes, mortality rates are declining as result of earlier detection and improved treatment regimes. Despite this, treating advanced disease remains difficult and there is a need to identify new therapeutic targets. Proteins encoded by the q-arm of chromosome 1 are of particular interest as regions of 1q are frequently amplified and over expressed in breast cancer leading to the hypothesis that 1q is important in disease development and progression [1-3]. The frequency at which regions of arm 1q were amplified was investigated and the 1q42.12 locus was found to be amplified in both breast cancer cell lines and primary tumours with a number of genes in or near this region also being over expressed [4]. Of emerging interest is ACBD3, a Golgi protein with multiple functions, only recently linked to breast cancer [5].
{"title":"https://researchopenworld.com/acbd3-its-cellular-interactors-and-its-role-in-breast-cancer/#","authors":"J. Houghton-Gisby, A. Harvey","doi":"10.31038/cst.2020523","DOIUrl":"https://doi.org/10.31038/cst.2020523","url":null,"abstract":"Although breast cancer incidence has increased in recent years, largely due to improved diagnostic techniques, greater awareness and the introduction of national screening programmes, mortality rates are declining as result of earlier detection and improved treatment regimes. Despite this, treating advanced disease remains difficult and there is a need to identify new therapeutic targets. Proteins encoded by the q-arm of chromosome 1 are of particular interest as regions of 1q are frequently amplified and over expressed in breast cancer leading to the hypothesis that 1q is important in disease development and progression [1-3]. The frequency at which regions of arm 1q were amplified was investigated and the 1q42.12 locus was found to be amplified in both breast cancer cell lines and primary tumours with a number of genes in or near this region also being over expressed [4]. Of emerging interest is ACBD3, a Golgi protein with multiple functions, only recently linked to breast cancer [5].","PeriodicalId":72517,"journal":{"name":"Cancer studies and therapeutics","volume":"90 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89879557","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 now becoming a general notion that a hyperactive / dysregulated immune system, with an image that in an autoimmune response, is a significant factor behind the mortality of covid-19 disease [1]. The reaction often arrives late (1-3 weeks after illness) and rapidly in the course of the disease. So far, attempts to find effective drugs have had very limited success. Derivatives of antimalaria drugs and anti-ebola drugs are under review, as is the supply of convalescent plasma from previously infected [1-3]. Autoimmune diseases and also autoimmune reactions in immune checkpoint inhibitors in tumor diseases are often treated with corticosteroids [4]. In severe autoimmune diseases, biological drugs such as TNF blockers, interleukin-1 and 6 inhibitors, and inhibitors of T and B cell surface markers have been used [5]. In very severe autoimmune disease, cytostatic drugs such as methotrexate and cyclophosphamide have been used successfully in, for example, rheumatoid arthritis or vasculitis [6-8]. We now propose that in more severe cases of covid-19 this possibility be tested for the following reasons:
{"title":"https://researchopenworld.com/trials-of-low-dose-cytostatic-drugs-in-severe-covid-19-should-be-considered/#","authors":"H. Olsson, Olof Hjorthorn, I. Bostedt","doi":"10.31038/cst.2020521","DOIUrl":"https://doi.org/10.31038/cst.2020521","url":null,"abstract":"It is now becoming a general notion that a hyperactive / dysregulated immune system, with an image that in an autoimmune response, is a significant factor behind the mortality of covid-19 disease [1]. The reaction often arrives late (1-3 weeks after illness) and rapidly in the course of the disease. So far, attempts to find effective drugs have had very limited success. Derivatives of antimalaria drugs and anti-ebola drugs are under review, as is the supply of convalescent plasma from previously infected [1-3]. Autoimmune diseases and also autoimmune reactions in immune checkpoint inhibitors in tumor diseases are often treated with corticosteroids [4]. In severe autoimmune diseases, biological drugs such as TNF blockers, interleukin-1 and 6 inhibitors, and inhibitors of T and B cell surface markers have been used [5]. In very severe autoimmune disease, cytostatic drugs such as methotrexate and cyclophosphamide have been used successfully in, for example, rheumatoid arthritis or vasculitis [6-8]. We now propose that in more severe cases of covid-19 this possibility be tested for the following reasons:","PeriodicalId":72517,"journal":{"name":"Cancer studies and therapeutics","volume":"160 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80104184","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}
Anger is one of the possible reactions to cancer. There are mutual influences between cancer and psychological status, with repercussions on the immune system. The aim of this study was to analyze differences in the experience, expression and control of anger by gender and to measure the relationship between anger, anxiety, depression, quality of life, and progression of the disease. We have conducted a cross-sectional study assessing 281 cancer patients, using the STAXI-2, HADS and a visual analogue scale to measure Quality of Life. Females reported significantly higher State and Trait Anger scores and lower Anger Control Out scores than males. In the whole sample the anger subscale scores increased with levels of anxiety or depression. In males, high State, Trait and Expression Anger subscale scores resulted associated with low Quality of Life, among females, this relationship seems to be weak. No differences emerged on STAXI-2 scales and subscales between patients in progression of disease. Conclusions: Anxiety, depression and anger seem to be organized into a pattern of a general emotional reaction. Since immunotherapy is the anticancer treatment that increases the body’s natural defenses to fight disease, a balanced immune system has become the main concern. In conclusion, clinicians could gain important insights about their patients by looking at the result of validated self-report patient questionnaires, to identify patients with inadequate expression of emotion or too high levels of emotional reaction in order to improve quality of care and response to treatment.
{"title":"https://researchopenworld.com/the-anger-felt-by-cancer-patients-it-could-be-an-unexpected-obstacle-to-the-treatment-path/#","authors":"M. Eva, S. Claudia, Marchetti Paolo","doi":"10.31038/cst.2020512","DOIUrl":"https://doi.org/10.31038/cst.2020512","url":null,"abstract":"Anger is one of the possible reactions to cancer. There are mutual influences between cancer and psychological status, with repercussions on the immune system. The aim of this study was to analyze differences in the experience, expression and control of anger by gender and to measure the relationship between anger, anxiety, depression, quality of life, and progression of the disease. We have conducted a cross-sectional study assessing 281 cancer patients, using the STAXI-2, HADS and a visual analogue scale to measure Quality of Life. Females reported significantly higher State and Trait Anger scores and lower Anger Control Out scores than males. In the whole sample the anger subscale scores increased with levels of anxiety or depression. In males, high State, Trait and Expression Anger subscale scores resulted associated with low Quality of Life, among females, this relationship seems to be weak. No differences emerged on STAXI-2 scales and subscales between patients in progression of disease. Conclusions: Anxiety, depression and anger seem to be organized into a pattern of a general emotional reaction. Since immunotherapy is the anticancer treatment that increases the body’s natural defenses to fight disease, a balanced immune system has become the main concern. In conclusion, clinicians could gain important insights about their patients by looking at the result of validated self-report patient questionnaires, to identify patients with inadequate expression of emotion or too high levels of emotional reaction in order to improve quality of care and response to treatment.","PeriodicalId":72517,"journal":{"name":"Cancer studies and therapeutics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76285409","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}
Pub Date : 2020-03-01Epub Date: 2020-01-11DOI: 10.31038/cst.2020511
A V Krauze, Mackey Megan, Cooley-Zgela Theresa, Mathen Peter, J H Shih, P J Tofilon, L Rowe, M Gilbert, K Camphausen
Purpose/objectives: Valproic Acid (VPA) is an antiepileptic agent with HDACi (histone deacetylase inhibitor) activity shown to radiosensitize glioblastoma (GBM) cells. We evaluated the addition of VPA to standard radiation therapy (RT) and temozolomide (TMZ) in an open-label, phase II study (NCI-06-C-0112). The intent of the current study was to compare our patient outcomes with modern era standard of care data (RTOG 0525) and general population data (SEER 2006-2013).
Materials/methods: 37 patients with newly diagnosed GBM were treated in a phase II NCI trial with daily VPA (25 mg/kg) in addition to concurrent RT and TMZ (2006 - 2013) and 411 patients with newly diagnosed GBM were treated in the standard TMZ dose arm of RTOG 0525 (2006 - 2008). Using the SEER database, adult patients (age > 15) with diagnostic codes 9440-9443 (third edition (IDC-O-3) diagnosed between 2006 - 2013 were identified and 6083 were included in the analysis. Kaplan-Meier method was used to estimate OS and PFS. The effect of patient characteristics and clinical factors on OS and PFS was analyzed using univariate analysis and a Cox regression model. A landmark analysis was performed to correlate recurrence to OS and conditional probabilities of surviving an additional 12 months at diagnosis, 6, 12, 18, 24 and 30 months were calculated for both the trial data and the SEER data.
Results: Updated median OS in the NCI cohort was 30.9m (22.2- 65.6m), compared to RTOG 0525 18.9m (16.8-20.3m) (p= 0.007) and the SEER cohort of 11m. Median PFS in the NCI cohort was 11.1m (6.6 - 49.6m) compared to RTOG 0525 with a median PFS of 7.5m (6.9-8.2m) (p = 0.004). Younger age, class V RPA and MGMT status were significant for PFS in both the NCI cohort and the RTOG 0525 cohort, in addition KPS was also significant for OS. In comparison to RTOG 0525, the population in the NCI cohort had a more favorable KPS and RPA, and a higher proportion of patients receiving bevacizumab after protocol therapy however with the exception of RPA (V) (8% vs 18%) (0.026), the effects of these factors on PFS and OS were not significantly different between the two cohorts.
Conclusion: Previously reported improvements in PFS and OS with the addition of VPA to concurrent RT and TMZ in the NCI phase II study were confirmed by comparison to both a trial population receiving standard of care (RTOG 0525) and a contemporary SEER cohort. These results provide further justification of a phase III trial of VPA/RT/TMZ.
{"title":"The addition of Valproic acid to concurrent radiation therapy and temozolomide improves patient outcome: a Correlative analysis of RTOG 0525, SEER and a Phase II NCI trial.","authors":"A V Krauze, Mackey Megan, Cooley-Zgela Theresa, Mathen Peter, J H Shih, P J Tofilon, L Rowe, M Gilbert, K Camphausen","doi":"10.31038/cst.2020511","DOIUrl":"10.31038/cst.2020511","url":null,"abstract":"<p><strong>Purpose/objectives: </strong>Valproic Acid (VPA) is an antiepileptic agent with HDACi (histone deacetylase inhibitor) activity shown to radiosensitize glioblastoma (GBM) cells. We evaluated the addition of VPA to standard radiation therapy (RT) and temozolomide (TMZ) in an open-label, phase II study (NCI-06-C-0112). The intent of the current study was to compare our patient outcomes with modern era standard of care data (RTOG 0525) and general population data (SEER 2006-2013).</p><p><strong>Materials/methods: </strong>37 patients with newly diagnosed GBM were treated in a phase II NCI trial with daily VPA (25 mg/kg) in addition to concurrent RT and TMZ (2006 - 2013) and 411 patients with newly diagnosed GBM were treated in the standard TMZ dose arm of RTOG 0525 (2006 - 2008). Using the SEER database, adult patients (age > 15) with diagnostic codes 9440-9443 (third edition (IDC-O-3) diagnosed between 2006 - 2013 were identified and 6083 were included in the analysis. Kaplan-Meier method was used to estimate OS and PFS. The effect of patient characteristics and clinical factors on OS and PFS was analyzed using univariate analysis and a Cox regression model. A landmark analysis was performed to correlate recurrence to OS and conditional probabilities of surviving an additional 12 months at diagnosis, 6, 12, 18, 24 and 30 months were calculated for both the trial data and the SEER data.</p><p><strong>Results: </strong>Updated median OS in the NCI cohort was 30.9m (22.2- 65.6m), compared to RTOG 0525 18.9m (16.8-20.3m) (p= 0.007) and the SEER cohort of 11m. Median PFS in the NCI cohort was 11.1m (6.6 - 49.6m) compared to RTOG 0525 with a median PFS of 7.5m (6.9-8.2m) (p = 0.004). Younger age, class V RPA and MGMT status were significant for PFS in both the NCI cohort and the RTOG 0525 cohort, in addition KPS was also significant for OS. In comparison to RTOG 0525, the population in the NCI cohort had a more favorable KPS and RPA, and a higher proportion of patients receiving bevacizumab after protocol therapy however with the exception of RPA (V) (8% vs 18%) (0.026), the effects of these factors on PFS and OS were not significantly different between the two cohorts.</p><p><strong>Conclusion: </strong>Previously reported improvements in PFS and OS with the addition of VPA to concurrent RT and TMZ in the NCI phase II study were confirmed by comparison to both a trial population receiving standard of care (RTOG 0525) and a contemporary SEER cohort. These results provide further justification of a phase III trial of VPA/RT/TMZ.</p>","PeriodicalId":72517,"journal":{"name":"Cancer studies and therapeutics","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494241/pdf/nihms-1625353.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39497793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fabio Henrique Brasil da Costa, M. Farach-Carson, D. Carson
Heparan sulfate (HS) is a sulfated glycosaminoglycan that is deposited in human tissue matrices at specialized sites [1,2]. HS interacts with diverse extracellular matrix (ECM) components with HS binding sites, including inflammatory cytokines, and heparinbinding growth factors (HBGFs) [3,4]. Within the ECM and in the cell surface glycocalyx, HS-proteoglycans (HSPGs) act as reservoirs for cytokines and HBGFs, and as cofactors for surface receptors where they stabilize active signaling complexes [5–7]. The bioavailability and activity of HBGFs stored on HSPGs are primarily regulated by HS-modifying enzymes that act on HSPGs, such as perlecan, the syndecans and the glypicans [8,9]. Therefore, HSPGs and their enzymic modifiers are crucial for tissue homeostasis, both in normal biology, as in development and wound healing, and in pathological processes such as fibrosis and cancer biology [1,10,11]. To date, studies have identified three key extracellular enzymes that modulate HS function and growth factor signaling: tissue heparanase (HPSE) and the extracellular endosulfatases SULF1 and SULF2. HPSE is an endoglycosidase that cleaves HS chains yielding diffusible HS fragments [12] that often still retain bound growth factors (Fig. 1A). HS-bound growth factors can subsequently bind to surface receptors to form HS-HBGF-receptor ternary complexes (Fig. 1B) [12]. Like HPSE, SULFs are secreted but, for the most part, stay peripherally associated with the cell surface through the interaction with HSPGs in the glycocalyx, primarily syndecans and glypicans [13,14]. Enzymatic activity of SULFs involves selectively removing 6-O-sulfate groups from HS polymers (Figure 1A) [14,15]. Because many HBGFs require 6-O-sulfate for high-affinity binding to HSPGs or surface coreceptors [3,15,16], SULFs release HBGFs in a form free from HS chains. Freed HBGFs can bind subsequently to cognate cell surface receptors to form signaling complexes, or they may rebind to distant unmodified HSPGs that retain 6-O-sulfate. Therefore, both HPSE and SULFs are crucial enzymes that define activation parameters of HS-independent signaling networks in both positive and negative ways that often are context-dependent [17,18].
硫酸乙酰肝素(HS)是一种硫酸化的糖胺聚糖，可沉积在人体组织基质的特定部位[1,2]。HS与多种具有HS结合位点的细胞外基质(ECM)成分相互作用，包括炎症因子和肝素结合生长因子(HBGFs)[3,4]。在ECM和细胞表面糖萼中，hs -蛋白聚糖(HSPGs)作为细胞因子和HBGFs的储存库，并作为表面受体的辅助因子，稳定活性信号复合物[5-7]。储存在HSPGs上的HBGFs的生物利用度和活性主要受作用于HSPGs的hs修饰酶的调控，如perlecan、syndecans和glypicans[8,9]。因此，HSPGs及其酶修饰剂对组织稳态至关重要，无论是在正常生物学中，如发育和伤口愈合，还是在病理过程中，如纤维化和癌症生物学[1,10,11]。到目前为止，研究已经确定了三种调节HS功能和生长因子信号传导的关键细胞外酶:组织肝素酶(HPSE)和细胞外内硫酸酯酶SULF1和sul2。HPSE是一种内糖苷酶，它切割HS链，产生可扩散的HS片段[12]，这些片段通常仍保留结合的生长因子(图1A)。hs结合生长因子随后可与表面受体结合形成hs - hbgf受体三元复合物(图1B)[12]。与HPSE一样，SULFs也会分泌，但在大多数情况下，通过与糖萼中的HSPGs(主要是syndecans和glypicans)相互作用，SULFs与细胞表面保持外周联系[13,14]。硫酸盐的酶活性包括选择性地从HS聚合物中去除6- o -硫酸盐基团(图1A)[14,15]。由于许多HBGFs需要6- o -硫酸盐才能与HSPGs或表面共受体进行高亲和力结合[3,15,16]，因此SULFs以不含HS链的形式释放HBGFs。释放的HBGFs随后可以与同源细胞表面受体结合形成信号复合物，或者它们可能与保留6- o -硫酸盐的远端未修饰的HSPGs重新结合。因此，HPSE和SULFs都是至关重要的酶，它们以积极和消极的方式定义hs独立信号网络的激活参数，这些激活参数通常与上下文相关[17,18]。
{"title":"https://researchopenworld.com/heparan-sulfate-modifying-enzymes-intriguing-players-in-cancer-progression/#","authors":"Fabio Henrique Brasil da Costa, M. Farach-Carson, D. Carson","doi":"10.31038/cst.2020513","DOIUrl":"https://doi.org/10.31038/cst.2020513","url":null,"abstract":"Heparan sulfate (HS) is a sulfated glycosaminoglycan that is deposited in human tissue matrices at specialized sites [1,2]. HS interacts with diverse extracellular matrix (ECM) components with HS binding sites, including inflammatory cytokines, and heparinbinding growth factors (HBGFs) [3,4]. Within the ECM and in the cell surface glycocalyx, HS-proteoglycans (HSPGs) act as reservoirs for cytokines and HBGFs, and as cofactors for surface receptors where they stabilize active signaling complexes [5–7]. The bioavailability and activity of HBGFs stored on HSPGs are primarily regulated by HS-modifying enzymes that act on HSPGs, such as perlecan, the syndecans and the glypicans [8,9]. Therefore, HSPGs and their enzymic modifiers are crucial for tissue homeostasis, both in normal biology, as in development and wound healing, and in pathological processes such as fibrosis and cancer biology [1,10,11]. To date, studies have identified three key extracellular enzymes that modulate HS function and growth factor signaling: tissue heparanase (HPSE) and the extracellular endosulfatases SULF1 and SULF2. HPSE is an endoglycosidase that cleaves HS chains yielding diffusible HS fragments [12] that often still retain bound growth factors (Fig. 1A). HS-bound growth factors can subsequently bind to surface receptors to form HS-HBGF-receptor ternary complexes (Fig. 1B) [12]. Like HPSE, SULFs are secreted but, for the most part, stay peripherally associated with the cell surface through the interaction with HSPGs in the glycocalyx, primarily syndecans and glypicans [13,14]. Enzymatic activity of SULFs involves selectively removing 6-O-sulfate groups from HS polymers (Figure 1A) [14,15]. Because many HBGFs require 6-O-sulfate for high-affinity binding to HSPGs or surface coreceptors [3,15,16], SULFs release HBGFs in a form free from HS chains. Freed HBGFs can bind subsequently to cognate cell surface receptors to form signaling complexes, or they may rebind to distant unmodified HSPGs that retain 6-O-sulfate. Therefore, both HPSE and SULFs are crucial enzymes that define activation parameters of HS-independent signaling networks in both positive and negative ways that often are context-dependent [17,18].","PeriodicalId":72517,"journal":{"name":"Cancer studies and therapeutics","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84159053","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}
Obesity is a risk factor for cancer development and is associated with poor prognosis in multiple tumor types. There is emerging evidence of a strong association between obesity and gastrointestinal cancer. The molecular mechanism underlying gastric cancer invasion and metastasis is still poorly understood. Problem of disseminated tumor cells (DTCs) in gastric cancer remains to be relevant for clinics and less is known concerning this problem for patients with obesity.
{"title":"https://researchopenworld.com/disseminated-tumor-cells-in-bone-marrow-in-gastric-cancer-patients-with-obesity/#","authors":"Bubnovskaya, Merentsev, A. Osinsky","doi":"10.31038/cst.2019452","DOIUrl":"https://doi.org/10.31038/cst.2019452","url":null,"abstract":"Obesity is a risk factor for cancer development and is associated with poor prognosis in multiple tumor types. There is emerging evidence of a strong association between obesity and gastrointestinal cancer. The molecular mechanism underlying gastric cancer invasion and metastasis is still poorly understood. Problem of disseminated tumor cells (DTCs) in gastric cancer remains to be relevant for clinics and less is known concerning this problem for patients with obesity.","PeriodicalId":72517,"journal":{"name":"Cancer studies and therapeutics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83064400","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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