Even though nodular fasciitis (NF) is benign and self-limited nature, the presentations of clinical, ultrasonographic, and pathological features have been described as mimicking sarcoma. Erickson-Johnson et al. suggested that ubiquitin-specific protease 6 (USP6) transcriptional upregulation may be the driving force behind the high proliferative activity and growth of NF. When the lesion showed the proliferative findings of the margin on both ultrasonography (US) and pathology, accompanied by clinically rapid growth, self-limited and/or regress course, NF could be strongly suggested as previously described. In this article, the author reviews the current knowledge of NF as USP6-associated neoplasia and also describes the therapeutic strategy in NF. In addition to the presentations of clinical, ulrtrasonographic, and pathological appearances of NF, the evaluation of percentage of USP6 break-apart FISH signals reflecting lifetime and mitotic counts in NF may be a potential procedure for accurate diagnosis in particularly young NF. It is putative that the inhibition of USP6-related genes might be the potential therapeutic strategies for the extremely rare malignant nodular fasciitis.
{"title":"Nodular fasciitis: USP6-associated neoplasia through multiple pathways","authors":"K. Fujioka","doi":"10.31579/2640-1053/100","DOIUrl":"https://doi.org/10.31579/2640-1053/100","url":null,"abstract":"Even though nodular fasciitis (NF) is benign and self-limited nature, the presentations of clinical, ultrasonographic, and pathological features have been described as mimicking sarcoma. Erickson-Johnson et al. suggested that ubiquitin-specific protease 6 (USP6) transcriptional upregulation may be the driving force behind the high proliferative activity and growth of NF. When the lesion showed the proliferative findings of the margin on both ultrasonography (US) and pathology, accompanied by clinically rapid growth, self-limited and/or regress course, NF could be strongly suggested as previously described. In this article, the author reviews the current knowledge of NF as USP6-associated neoplasia and also describes the therapeutic strategy in NF. In addition to the presentations of clinical, ulrtrasonographic, and pathological appearances of NF, the evaluation of percentage of USP6 break-apart FISH signals reflecting lifetime and mitotic counts in NF may be a potential procedure for accurate diagnosis in particularly young NF. It is putative that the inhibition of USP6-related genes might be the potential therapeutic strategies for the extremely rare malignant nodular fasciitis.","PeriodicalId":93018,"journal":{"name":"Journal of cancer research and cellular therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43692429","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}
Gehan R. Abdel-Hamid, Lobna A. Abdel-Aziz, Mona G. Anany
Background: Zingerone is one of the active components of ginger that possesses multiple biological activities and anti-inflammatory properties against either radiation effect or cisplatin toxicity. Purpose: to examine the protective effect of zingerone against gamma radiation (IR) or cisplatin-induced immunotoxicity. Material and Methods: 48 rats were divided into six groups as follows: (group-1); normal control group received distilled water; (group-2); rats received Zingerone orally at a dose of 25 mg/kg b.wt. Once / day for 14 consecutive days (Zing.). (group-3); Rats were given a single injection of Cisplatin at a dose of 7.5 mg/kg b.wt. intraperitoneally (Cispl.). (group-4); Rats exposed to a single dose of 6 Gy whole-body gamma irradiation using 137Cesium source in a Gamma cell 40 (Rad.). (group-5); rats received same dose of Zingerone then they were exposed to gamma radiation as in group 4 (Zing+Rad.). (group-6); rats received Zingerone followed by single injection of Cisplatin at the dose of 7.5 mg/kg b.wt. Intraperitoneally (Zing+Cisp.). Results: Exhibited a significant increase in expression of NF-κB, IL-10, caspase-3, and gene expression of TNF-α as well as oxidative stress biomarkers (MDA and NO) levels accompanied with a reduced level of SOD in either whole body-irradiated or cisplatin-received group. Conversely, pro-inflammatory cytokines levels were significantly decreased with an improvement of oxidative stress in groups that received zingerone. Conclusion: It could be concluded that zingerone exerts its antioxidative activity and immunomodulatory effects through inhibition of pro-inflammatory mediators induced by whole body-gamma irradiation or cisplatin administration at two time interval early and late stage of radiation exposure (after 2 h and one week).Therefore, further studies are required to elucidate the molecular signaling pathway concerning zingerone.
{"title":"Zingerone Alleviate Toxicity Induced by Cisplatin or Gamma Radiation in Rats by Modulating Pro-Inflammatory Mediators","authors":"Gehan R. Abdel-Hamid, Lobna A. Abdel-Aziz, Mona G. Anany","doi":"10.31579/2640-1053/101","DOIUrl":"https://doi.org/10.31579/2640-1053/101","url":null,"abstract":"Background: Zingerone is one of the active components of ginger that possesses multiple biological activities and anti-inflammatory properties against either radiation effect or cisplatin toxicity. Purpose: to examine the protective effect of zingerone against gamma radiation (IR) or cisplatin-induced immunotoxicity. Material and Methods: 48 rats were divided into six groups as follows: (group-1); normal control group received distilled water; (group-2); rats received Zingerone orally at a dose of 25 mg/kg b.wt. Once / day for 14 consecutive days (Zing.). (group-3); Rats were given a single injection of Cisplatin at a dose of 7.5 mg/kg b.wt. intraperitoneally (Cispl.). (group-4); Rats exposed to a single dose of 6 Gy whole-body gamma irradiation using 137Cesium source in a Gamma cell 40 (Rad.). (group-5); rats received same dose of Zingerone then they were exposed to gamma radiation as in group 4 (Zing+Rad.). (group-6); rats received Zingerone followed by single injection of Cisplatin at the dose of 7.5 mg/kg b.wt. Intraperitoneally (Zing+Cisp.). Results: Exhibited a significant increase in expression of NF-κB, IL-10, caspase-3, and gene expression of TNF-α as well as oxidative stress biomarkers (MDA and NO) levels accompanied with a reduced level of SOD in either whole body-irradiated or cisplatin-received group. Conversely, pro-inflammatory cytokines levels were significantly decreased with an improvement of oxidative stress in groups that received zingerone. Conclusion: It could be concluded that zingerone exerts its antioxidative activity and immunomodulatory effects through inhibition of pro-inflammatory mediators induced by whole body-gamma irradiation or cisplatin administration at two time interval early and late stage of radiation exposure (after 2 h and one week).Therefore, further studies are required to elucidate the molecular signaling pathway concerning zingerone.","PeriodicalId":93018,"journal":{"name":"Journal of cancer research and cellular therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43917309","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 incidence and prevalence of lip and oral cavity cancer has increased over the last decade, worldwide and in India. It ranks at 1st position in males in india, all ages, in 2020. Lips are essential organ of the body which carries dynamic role in facial expression, speech, sensuality, deglutition. Resection of central, large, lower lip cancer creates a more than 2/3rd large defect. Covering of this defect with maintenance of oral competency is a difficult task for a treating surgeon. Number of techniques are described for covering of large lower lip defects. Out of these techniques, karapandzic flap is a successful, accepted, simple, easy to learn reconstructive procedure with good cosmetic results. It is a modification of Gillie’s fan flap and it involves unilateral or bilateral full-thickness circumoral advancement-rotation flaps. The feature which distinguishes it from other techniques is preservation of neuro-vascular integrity, symmetry and oral competency. We are reporting a case of an elderly gentleman with large, central, lower lip cancer who underwent oncological resection with reconstruction by karapandzic flap technique.
{"title":"Karapandzic Flap for Functional & Cosmetic Reconstruction of Lower Lip Cancer with Review of Literature","authors":"Sachin S Kadam, S. Phadke, Tejaswini Kadam","doi":"10.31579/2640-1053/099","DOIUrl":"https://doi.org/10.31579/2640-1053/099","url":null,"abstract":"The incidence and prevalence of lip and oral cavity cancer has increased over the last decade, worldwide and in India. It ranks at 1st position in males in india, all ages, in 2020. Lips are essential organ of the body which carries dynamic role in facial expression, speech, sensuality, deglutition. Resection of central, large, lower lip cancer creates a more than 2/3rd large defect. Covering of this defect with maintenance of oral competency is a difficult task for a treating surgeon. Number of techniques are described for covering of large lower lip defects. Out of these techniques, karapandzic flap is a successful, accepted, simple, easy to learn reconstructive procedure with good cosmetic results. It is a modification of Gillie’s fan flap and it involves unilateral or bilateral full-thickness circumoral advancement-rotation flaps. The feature which distinguishes it from other techniques is preservation of neuro-vascular integrity, symmetry and oral competency. We are reporting a case of an elderly gentleman with large, central, lower lip cancer who underwent oncological resection with reconstruction by karapandzic flap technique.","PeriodicalId":93018,"journal":{"name":"Journal of cancer research and cellular therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48819985","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}
Recent investigation successfully identified a pre leukemic ETV6/RUNX1-positive clone in the healthy twin of a patient diagnosed with ETV6/RUNXI-positive acute lymphoblastic leukemia (ALL) and also some studies with ETV6/RUNX1 knock in mice showed that the expression of the fusion gene is not sufficient for the invivo induction of ALL. Taken together, these data indicate that ETV6/RUNX1-positive leukemia is .generated through a multi-step mechanism, and that accumulation of additional genetic changes is necessary for the development of overt leukemia. Hence, to understand fully the genetic evolution of this disorder, identification of the complete spectrum of genetic changes that accompany the ETV6/RUNX1 fusion gene is necessary. Moreover, critical patho genetic insights may be gained from studying the correlation pattern of the different copy number changes.
{"title":"ETV6/RUNX1 fusion gene and its active role","authors":"A. Rahnemoon","doi":"10.31579/2640-1053/091","DOIUrl":"https://doi.org/10.31579/2640-1053/091","url":null,"abstract":"Recent investigation successfully identified a pre leukemic ETV6/RUNX1-positive clone in the healthy twin of a patient diagnosed with ETV6/RUNXI-positive acute lymphoblastic leukemia (ALL) and also some studies with ETV6/RUNX1 knock in mice showed that the expression of the fusion gene is not sufficient for the invivo induction of ALL. Taken together, these data indicate that ETV6/RUNX1-positive leukemia is .generated through a multi-step mechanism, and that accumulation of additional genetic changes is necessary for the development of overt leukemia. Hence, to understand fully the genetic evolution of this disorder, identification of the complete spectrum of genetic changes that accompany the ETV6/RUNX1 fusion gene is necessary. Moreover, critical patho genetic insights may be gained from studying the correlation pattern of the different copy number changes.","PeriodicalId":93018,"journal":{"name":"Journal of cancer research and cellular therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43273607","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}
J. Ravicz, S. Chawla, Christopher W. Szeto, M. Morse, F. Hall, E. Gordon
Background: Metastatic cancer is associated with an invariably fatal outcome. However, DeltaRex-G, a tumor-targeted retrovector encoding a gene-edited dominant-negative CCNG1 inhibitor gene, has induced long term (>10 years) survival of patients with chemo-resistant metastatic pancreatic adenocarcinoma, malignant peripheral nerve sheath tumor, osteosarcoma, B-cell lymphoma, and breast carcinoma. Objective: To evaluate the level of CCNG1 expression in tumors as a potential biomarker for CCNG1 (Cyclin G1-blocking) inhibitor therapy. Methods: CCNG1 RNA expression levels that were previously measured as part of whole genome molecular profiling of tumors (TCGA, N=9161), adjacent “tissues” (TCGA, N=678) and GTEx normal tissues (N=7187) across 22 organ sites were analyzed. Differential expression of CCNG1 and Ki-67 in primary (N= 9161) vs metastatic (N= 393) tumors were also compared in primary (N=103) vs. metastatic (N=367) skin cancers (i.e., melanoma). Statistical Analysis: To detect systematically differential expression of CCNG1 and Ki-67 expression between populations (e.g. tumor vs. normal), unpaired Student's t-tests were performed. Results: Enhanced CCNG1 RNA and Cyclin G1 protein expression were noted in tumors compared to normal analogous counterparts, and CCNG1 expression correlated significantly with that of Ki-67. Moreover, CCNG1 expression tended to be higher than that of Ki-67 in metastatic vs primary tumors. Conclusions: Taken together with the emerging Cyclin G1 / Cdk / Myc / Mdm2 / p53 Axis governing Cancer Stem Cell Competence, this supportive data indicates: (1) CCNG1 expression is frequently enhanced in tumors when compared to their normal analogous counterparts, (2) CCNG1 and Ki-67 expressions are higher in metastatic vs primary tumors, (3) CCNG1 expression is significantly correlated with that of Ki-67, and (4) CCNG1 may actually be a stronger prognostic marker of stem cell competence, chemo-refractoriness, and EMT/metastasis than Ki-67. Phase 2 studies are planned to identify patients most likely to respond favorably to CCNG1 inhibitor therapy.
{"title":"CCNG1 oncogene: a novel biomarker for cancer therapy /gene therapy","authors":"J. Ravicz, S. Chawla, Christopher W. Szeto, M. Morse, F. Hall, E. Gordon","doi":"10.31579/2640-1053/090","DOIUrl":"https://doi.org/10.31579/2640-1053/090","url":null,"abstract":"Background: Metastatic cancer is associated with an invariably fatal outcome. However, DeltaRex-G, a tumor-targeted retrovector encoding a gene-edited dominant-negative CCNG1 inhibitor gene, has induced long term (>10 years) survival of patients with chemo-resistant metastatic pancreatic adenocarcinoma, malignant peripheral nerve sheath tumor, osteosarcoma, B-cell lymphoma, and breast carcinoma. Objective: To evaluate the level of CCNG1 expression in tumors as a potential biomarker for CCNG1 (Cyclin G1-blocking) inhibitor therapy. Methods: CCNG1 RNA expression levels that were previously measured as part of whole genome molecular profiling of tumors (TCGA, N=9161), adjacent “tissues” (TCGA, N=678) and GTEx normal tissues (N=7187) across 22 organ sites were analyzed. Differential expression of CCNG1 and Ki-67 in primary (N= 9161) vs metastatic (N= 393) tumors were also compared in primary (N=103) vs. metastatic (N=367) skin cancers (i.e., melanoma). Statistical Analysis: To detect systematically differential expression of CCNG1 and Ki-67 expression between populations (e.g. tumor vs. normal), unpaired Student's t-tests were performed. Results: Enhanced CCNG1 RNA and Cyclin G1 protein expression were noted in tumors compared to normal analogous counterparts, and CCNG1 expression correlated significantly with that of Ki-67. Moreover, CCNG1 expression tended to be higher than that of Ki-67 in metastatic vs primary tumors. Conclusions: Taken together with the emerging Cyclin G1 / Cdk / Myc / Mdm2 / p53 Axis governing Cancer Stem Cell Competence, this supportive data indicates: (1) CCNG1 expression is frequently enhanced in tumors when compared to their normal analogous counterparts, (2) CCNG1 and Ki-67 expressions are higher in metastatic vs primary tumors, (3) CCNG1 expression is significantly correlated with that of Ki-67, and (4) CCNG1 may actually be a stronger prognostic marker of stem cell competence, chemo-refractoriness, and EMT/metastasis than Ki-67. Phase 2 studies are planned to identify patients most likely to respond favorably to CCNG1 inhibitor therapy.","PeriodicalId":93018,"journal":{"name":"Journal of cancer research and cellular therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45786272","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}
A. Chandio, A. Rai, Mehak Chandio, Asirvatham Rhody, Katherine Brown
Background: Older surgical patients remain at increased risk of adverse postoperative outcome when undergoing both elective and emergency surgery. The needs of the older surgical patient are often substantially different from those of younger patients. As a surgeons we have dilemmas in appropriately treating elderly patients. Specifically, those with cancer have been shown to receive inappropriate care, being either undertreated or overtreated based on their chronological age rather than their degree of frailty. Aim:To evaluate outcome of patients diagnosed with colorectal cancer in patients aged 80 years and over. Methods:Retrospective study of all patients 80 years and above managed with colorectal cancer at the Luton and Dunstable University Hospital UK from January 2015 through December 2019 Results: In the study period 278 patients were diagnosed with colorectal cancer, Male 143 Female 135 ratio 1:1.05. Age range from 80 to 101years. 54.31% patients underwent surgical intervention. 15.10% had complications after surgery. 36.69% patients deemed unsuitable for resection surgery were treated with best supportive care palliatively. 57.19% patients were in ASAIII, 24.10% ASAII and 12.23% ASAIV. 46.40% patients died during the study period. Conclusion:Age on its own would not be taken as for less aggressive therapy; Careful assessment of the patient taking into consideration comorbidities, functional status and patient wishes are essential in decision making and choosing appropriate management plan. Curative surgery for colorectal carcinoma in the geriatric patients are well tolerated. Management of comorbidities preceding surgery may impact postoperative outcome.
{"title":"Outcome of Colorectal cancer in Geriatric Patient","authors":"A. Chandio, A. Rai, Mehak Chandio, Asirvatham Rhody, Katherine Brown","doi":"10.31579/2640-1053/094","DOIUrl":"https://doi.org/10.31579/2640-1053/094","url":null,"abstract":"Background: Older surgical patients remain at increased risk of adverse postoperative outcome when undergoing both elective and emergency surgery. The needs of the older surgical patient are often substantially different from those of younger patients. As a surgeons we have dilemmas in appropriately treating elderly patients. Specifically, those with cancer have been shown to receive inappropriate care, being either undertreated or overtreated based on their chronological age rather than their degree of frailty. Aim:To evaluate outcome of patients diagnosed with colorectal cancer in patients aged 80 years and over. Methods:Retrospective study of all patients 80 years and above managed with colorectal cancer at the Luton and Dunstable University Hospital UK from January 2015 through December 2019 Results: In the study period 278 patients were diagnosed with colorectal cancer, Male 143 Female 135 ratio 1:1.05. Age range from 80 to 101years. 54.31% patients underwent surgical intervention. 15.10% had complications after surgery. 36.69% patients deemed unsuitable for resection surgery were treated with best supportive care palliatively. 57.19% patients were in ASAIII, 24.10% ASAII and 12.23% ASAIV. 46.40% patients died during the study period. Conclusion:Age on its own would not be taken as for less aggressive therapy; Careful assessment of the patient taking into consideration comorbidities, functional status and patient wishes are essential in decision making and choosing appropriate management plan. Curative surgery for colorectal carcinoma in the geriatric patients are well tolerated. Management of comorbidities preceding surgery may impact postoperative outcome.","PeriodicalId":93018,"journal":{"name":"Journal of cancer research and cellular therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42584366","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}
Afua A. Yorke, Gary C. McDonald, D. Solis, T. Guerrero
Purpose: Expert selected landmark points on clinical image pairs to provide a basis for rigid registration validation. Using combinatorial rigid registration optimization (CORRO) provide a statistically characterized reference data set for image registration of the pelvis by estimating optimal registration. Materials ad Methods: Landmarks for each CT/CBCT image pair for 58 cases were identified. From the landmark pairs, combination subsets of k-number of landmark pairs were generated without repeat, forming k-set for k=4, 8, and 12. A rigid registration between the image pairs was computed for each k-combination set (2,000-8,000,000). The mean and standard deviation of the registration were used as final registration for each image pair. Joint entropy was used to validate the output results. Results: An average of 154 (range: 91-212) landmark pairs were selected for each CT/CBCT image pair. The mean standard deviation of the registration output decreased as the k-size increased for all cases. In general, the joint entropy evaluated was found to be lower than results from commercially available software. Of all 58 cases 58.3% of the k=4, 15% of k=8 and 18.3% of k=12 resulted in the better registration using CORRO as compared to 8.3% from a commercial registration software. The minimum joint entropy was determined for one case and found to exist at the estimated registration mean in agreement with the CORRO algorithm. Conclusion: The results demonstrate that CORRO works even in the extreme case of the pelvic anatomy where the CBCT suffers from reduced quality due to increased noise levels. The estimated optimal registration using CORRO was found to be better than commercially available software for all k-sets tested. Additionally, the k-set of 4 resulted in overall best outcomes when compared to k=8 and 12, which is anticipated because k=8 and 12 are more likely to have combinations that affected the accuracy of the registration.
{"title":"Quality Assurance of Image Registration Using Combinatorial Rigid Registration Optimization (CORRO)","authors":"Afua A. Yorke, Gary C. McDonald, D. Solis, T. Guerrero","doi":"10.31579/2640-1053/076","DOIUrl":"https://doi.org/10.31579/2640-1053/076","url":null,"abstract":"Purpose: Expert selected landmark points on clinical image pairs to provide a basis for rigid registration validation. Using combinatorial rigid registration optimization (CORRO) provide a statistically characterized reference data set for image registration of the pelvis by estimating optimal registration. Materials ad Methods: Landmarks for each CT/CBCT image pair for 58 cases were identified. From the landmark pairs, combination subsets of k-number of landmark pairs were generated without repeat, forming k-set for k=4, 8, and 12. A rigid registration between the image pairs was computed for each k-combination set (2,000-8,000,000). The mean and standard deviation of the registration were used as final registration for each image pair. Joint entropy was used to validate the output results. Results: An average of 154 (range: 91-212) landmark pairs were selected for each CT/CBCT image pair. The mean standard deviation of the registration output decreased as the k-size increased for all cases. In general, the joint entropy evaluated was found to be lower than results from commercially available software. Of all 58 cases 58.3% of the k=4, 15% of k=8 and 18.3% of k=12 resulted in the better registration using CORRO as compared to 8.3% from a commercial registration software. The minimum joint entropy was determined for one case and found to exist at the estimated registration mean in agreement with the CORRO algorithm. Conclusion: The results demonstrate that CORRO works even in the extreme case of the pelvic anatomy where the CBCT suffers from reduced quality due to increased noise levels. The estimated optimal registration using CORRO was found to be better than commercially available software for all k-sets tested. Additionally, the k-set of 4 resulted in overall best outcomes when compared to k=8 and 12, which is anticipated because k=8 and 12 are more likely to have combinations that affected the accuracy of the registration.","PeriodicalId":93018,"journal":{"name":"Journal of cancer research and cellular therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41745704","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}
Erlinda M. Gordon, Seiya Liu, Sant P. Chawla, Frederick L. Hall
Background and Rationale: Although PTX is widely used as a single chemotherapeutic agent and in various combination regimens, its clinical utility is hindered by acquired drug resistance and serious dose-limiting side effects that result from the ungoverned biodistribution of the taxane. Hypothesis: Conceptually, the precision, validity, and efficiency of paclitaxel delivery to tumor compartments might be substantially improved by “actively targeting” the exposed collagenous (XC-) proteins presented within the tumor microenvironment (TME)—XC-proteins physically exposed by the pathologic biochemical processes of tumor invasion, reactive stroma formation, and neo-angiogenesis. Objective: An adaptive bioengineering approach aims to apply pathotropic tumor-targeting functionality to paclitaxel (PTX), a powerful cytotoxic taxane which exhibits anti-tubulin / anti-mitotic / anti-cancer activities against a broad range of solid tumors. Materials and Methods: Synthetic peptide XC-targeting probes (< 40 aa) and polypeptide aptamers (40 to 53 aa), 85 - 99% purity, were prepared by 9-fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis, purified by high performance liquid chromatography (HPLC), and verified by mass spectrometry and amino acid analysis, and the XC-targeting probes were FITC-labeled. Analysis of fluorescence in XC-binding assays was visualized with an Ultra Bright Blue Light trans-illuminator equipped with an amber filter; photo-documentation was provided by a Leica V-Lux 1 digital camera; and comparative fluorescence was quantified using a Quantus benchtop fluorimeter (Promega). The tumor-targeting properties of Taxol-Tropins were tested in vitro by Taxol-aptamer binding assays and collagen-agarose binding assays and the bioactivities of PTX bound non-covalently toTaxol-Tropin aptamers were tested on XC-agarose beads. Further, the tumor targeting property of the Taxol-Tropin aptamers was tested in vivo in a murine model of metastatic cancer. Results: Here we report on the first actively targeted delivery of paclitaxel utilizing bifunctional polypeptide targeting onco-aptamers, called Taxol-Tropins, which: (i) bind PTX upon simple mixing with suitably high affinities and; (ii) bind exposed XC-proteins, thereby promoting enhanced partitioning and drug delivery into the TME. The bifunctional peptide sequence-optimized Taxol-Tropins bound tightly non-covalently to PTX and also exhibited high affinity and selectivity for XC-agarose beads in vitro. Importantly, the cytotoxic bioactivity of the Taxol-Tropin-bound-PTX molecule was well preserved in cellulo, as was demonstrated by cytocidal activity observed in MDA-MB-231 breast cancer cell cultures. Tumor-targeted PTX delivery by Taxol-Tropin onco-aptamers in vivo was modeled by subcutaneous xenografts of human pancreatic cancer in nude mice: where intense fluorescence of the PTX probe was observed in tumors of mice injected with the Taxol-Tropin-bound-PTX within minutes after intravenous
{"title":"Polypeptidic Taxol-Tropins: Targeting paclitaxel to the tumor microenvironment","authors":"Erlinda M. Gordon, Seiya Liu, Sant P. Chawla, Frederick L. Hall","doi":"10.31579/2640-1053/089","DOIUrl":"https://doi.org/10.31579/2640-1053/089","url":null,"abstract":"Background and Rationale: Although PTX is widely used as a single chemotherapeutic agent and in various combination regimens, its clinical utility is hindered by acquired drug resistance and serious dose-limiting side effects that result from the ungoverned biodistribution of the taxane. Hypothesis: Conceptually, the precision, validity, and efficiency of paclitaxel delivery to tumor compartments might be substantially improved by “actively targeting” the exposed collagenous (XC-) proteins presented within the tumor microenvironment (TME)—XC-proteins physically exposed by the pathologic biochemical processes of tumor invasion, reactive stroma formation, and neo-angiogenesis. Objective: An adaptive bioengineering approach aims to apply pathotropic tumor-targeting functionality to paclitaxel (PTX), a powerful cytotoxic taxane which exhibits anti-tubulin / anti-mitotic / anti-cancer activities against a broad range of solid tumors. Materials and Methods: Synthetic peptide XC-targeting probes (< 40 aa) and polypeptide aptamers (40 to 53 aa), 85 - 99% purity, were prepared by 9-fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis, purified by high performance liquid chromatography (HPLC), and verified by mass spectrometry and amino acid analysis, and the XC-targeting probes were FITC-labeled. Analysis of fluorescence in XC-binding assays was visualized with an Ultra Bright Blue Light trans-illuminator equipped with an amber filter; photo-documentation was provided by a Leica V-Lux 1 digital camera; and comparative fluorescence was quantified using a Quantus benchtop fluorimeter (Promega). The tumor-targeting properties of Taxol-Tropins were tested in vitro by Taxol-aptamer binding assays and collagen-agarose binding assays and the bioactivities of PTX bound non-covalently toTaxol-Tropin aptamers were tested on XC-agarose beads. Further, the tumor targeting property of the Taxol-Tropin aptamers was tested in vivo in a murine model of metastatic cancer. Results: Here we report on the first actively targeted delivery of paclitaxel utilizing bifunctional polypeptide targeting onco-aptamers, called Taxol-Tropins, which: (i) bind PTX upon simple mixing with suitably high affinities and; (ii) bind exposed XC-proteins, thereby promoting enhanced partitioning and drug delivery into the TME. The bifunctional peptide sequence-optimized Taxol-Tropins bound tightly non-covalently to PTX and also exhibited high affinity and selectivity for XC-agarose beads in vitro. Importantly, the cytotoxic bioactivity of the Taxol-Tropin-bound-PTX molecule was well preserved in cellulo, as was demonstrated by cytocidal activity observed in MDA-MB-231 breast cancer cell cultures. Tumor-targeted PTX delivery by Taxol-Tropin onco-aptamers in vivo was modeled by subcutaneous xenografts of human pancreatic cancer in nude mice: where intense fluorescence of the PTX probe was observed in tumors of mice injected with the Taxol-Tropin-bound-PTX within minutes after intravenous","PeriodicalId":93018,"journal":{"name":"Journal of cancer research and cellular therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46366260","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}
Signet-ring cell carcinoma of the prostate gland (SRCCP) an uncommon and aggressive malignant tumour of the prostate gland which is characterized by histopathology examination features of compression of the nucleus into the form of a crescent by a large cytoplasmic vacuole. SRCCPs that have so far been reported have been either (a) primary tumours, metastatic tumours with the primary tumour elsewhere with the gastro-intestinal tract being the site of the primary tumour but the primary tumour could originate elsewhere, and additionally some reported SRCCPs have been classified as carcinoma of unknown primary. SRCCP could be a pure tumour or a tumour that is contemporaneously associated with other types of tumour including various variants of adenocarcinoma. SRCCP can manifest in various ways including: Incidental finding following prostatectomy that has been undertaken for a presumed benign prostatic hyperplasia, lower urinary tract symptoms, visible and non-visible haematuria, raised levels of serum PSA but some SRCCPs have been diagnosed with normal / low levels of serum PSA, there may be a history of dyspepsia in cases of metastatic signet-ring cell carcinoma in association with contemporaneous primary signet-ring cell carcinoma of the stomach or there may be a past history of surgical treatment for signet-ring cell carcinoma of the gastrointestinal tract, or bleeding from the gastrointestinal tract in cases of upper gastrointestinal tract and rectal bleeding as well as change in bowel habit for primary tumours of the anorectal region, retention of urine, and rarely a rectal mass in the case of SRCCP with an anorectal primary tumour. In order to exclude a primary signet ring cell carcinoma elsewhere, a detailed past medical history is required as well as radiology imaging including contrast – enhanced computed tomography (CECT) scan and contrast-enhanced magnetic resonance imaging (CEMRI) scan as well as upper gastrointestinal endoscopy and colonoscopy to exclude a primary lesion within the gastrointestinal tract. Diagnosis of SRCCP requires utilization of the histopathology and immunohistochemistry examination features of prostate biopsy, prostatic chips obtained from trans-urethral resection of prostate specimen or radical prostatectomy specimen. SRCCPs upon immunohistochemistry staining studies tend to show tumour that tend to exhibit positive staining for the following tumour markers as follows: PSA – positive staining for PSA has been variable in some studies, AE1/AE3, CAM 5.2, Ki-67 with a mean of 8%, PAS-diastase, Mucicarmine (50%), Alcian blue (60%), Alpha-methyl-acyl coenzyme A racemase (P504S), and Cytokeratin 5/6. SRCCPs also tend to exhibit negative staining for: Bcl2 (rare positive), and CEA (80%). Traditionally the treatment of Primary Signet-Ring Cell Carcinoma of the Prostate Gland has tended to be similar to the treatment of the traditional adenocarcinoma of the prostate gland which does include: hormonal treatment, radiotherap
{"title":"Signet Ring Cell Carcinoma of the Prostate Gland: A Review and Update","authors":"A. Venyo","doi":"10.31579/2640-1053/082","DOIUrl":"https://doi.org/10.31579/2640-1053/082","url":null,"abstract":"Signet-ring cell carcinoma of the prostate gland (SRCCP) an uncommon and aggressive malignant tumour of the prostate gland which is characterized by histopathology examination features of compression of the nucleus into the form of a crescent by a large cytoplasmic vacuole. SRCCPs that have so far been reported have been either (a) primary tumours, metastatic tumours with the primary tumour elsewhere with the gastro-intestinal tract being the site of the primary tumour but the primary tumour could originate elsewhere, and additionally some reported SRCCPs have been classified as carcinoma of unknown primary. SRCCP could be a pure tumour or a tumour that is contemporaneously associated with other types of tumour including various variants of adenocarcinoma. SRCCP can manifest in various ways including: Incidental finding following prostatectomy that has been undertaken for a presumed benign prostatic hyperplasia, lower urinary tract symptoms, visible and non-visible haematuria, raised levels of serum PSA but some SRCCPs have been diagnosed with normal / low levels of serum PSA, there may be a history of dyspepsia in cases of metastatic signet-ring cell carcinoma in association with contemporaneous primary signet-ring cell carcinoma of the stomach or there may be a past history of surgical treatment for signet-ring cell carcinoma of the gastrointestinal tract, or bleeding from the gastrointestinal tract in cases of upper gastrointestinal tract and rectal bleeding as well as change in bowel habit for primary tumours of the anorectal region, retention of urine, and rarely a rectal mass in the case of SRCCP with an anorectal primary tumour. In order to exclude a primary signet ring cell carcinoma elsewhere, a detailed past medical history is required as well as radiology imaging including contrast – enhanced computed tomography (CECT) scan and contrast-enhanced magnetic resonance imaging (CEMRI) scan as well as upper gastrointestinal endoscopy and colonoscopy to exclude a primary lesion within the gastrointestinal tract. Diagnosis of SRCCP requires utilization of the histopathology and immunohistochemistry examination features of prostate biopsy, prostatic chips obtained from trans-urethral resection of prostate specimen or radical prostatectomy specimen. SRCCPs upon immunohistochemistry staining studies tend to show tumour that tend to exhibit positive staining for the following tumour markers as follows: PSA – positive staining for PSA has been variable in some studies, AE1/AE3, CAM 5.2, Ki-67 with a mean of 8%, PAS-diastase, Mucicarmine (50%), Alcian blue (60%), Alpha-methyl-acyl coenzyme A racemase (P504S), and Cytokeratin 5/6. SRCCPs also tend to exhibit negative staining for: Bcl2 (rare positive), and CEA (80%). Traditionally the treatment of Primary Signet-Ring Cell Carcinoma of the Prostate Gland has tended to be similar to the treatment of the traditional adenocarcinoma of the prostate gland which does include: hormonal treatment, radiotherap","PeriodicalId":93018,"journal":{"name":"Journal of cancer research and cellular therapeutics","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41354362","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}
Sara Safaeian Laein, Bahareh Hormozi, A. Neamati, Ghorban Safaeian Layen, Masoud Homayouni-Tabrizi
To evaluate the effects of electromagnetic waves on the total number and percentage of white blood cells and also antioxidant effects of vitamin C on the effects radiation, 24 male mice (Balb/c) were used: control under the influence of low frequency electromagnetic waves and under the influence of waves with vitamin C. Total number of white blood cells in under the influence waves group significantly increased compared to control group, and also under the influence waves group with vitamin C because its antioxidant property is able to prevent the increasing impact of electromagnetic waves. The percentage of white blood cells in the under influence waves group did not significantly change compared to the control group and also, the under influence waves group with vitamin C had no significant change compared to the other group. The percentage of neutrophils in samples of the under influence waves group had significant decrease compared to control group but in the under influence waves group with vitamin C compared to the other group, this vitamin C could prevent a significant reduction in percentage of neutrophils. Our findings indicated that low electromagnetic fields have caused significant changes in the total number of white blood cells and percentage of neutrophils in mice. In the group that received vitamin C injection, significant changes were observed in the total number of white blood cells and percentage of neutrophils relative to the group under the influence of low electromagnetic waves, which indicates that vitamin C could restore the mean total number of white blood cells and percentage of neutrophils to normal value.
{"title":"Evaluating effects of electromagnetic fields on the total number and percentage of white blood cells in mice","authors":"Sara Safaeian Laein, Bahareh Hormozi, A. Neamati, Ghorban Safaeian Layen, Masoud Homayouni-Tabrizi","doi":"10.31579/2640-1053/088","DOIUrl":"https://doi.org/10.31579/2640-1053/088","url":null,"abstract":"To evaluate the effects of electromagnetic waves on the total number and percentage of white blood cells and also antioxidant effects of vitamin C on the effects radiation, 24 male mice (Balb/c) were used: control under the influence of low frequency electromagnetic waves and under the influence of waves with vitamin C. Total number of white blood cells in under the influence waves group significantly increased compared to control group, and also under the influence waves group with vitamin C because its antioxidant property is able to prevent the increasing impact of electromagnetic waves. The percentage of white blood cells in the under influence waves group did not significantly change compared to the control group and also, the under influence waves group with vitamin C had no significant change compared to the other group. The percentage of neutrophils in samples of the under influence waves group had significant decrease compared to control group but in the under influence waves group with vitamin C compared to the other group, this vitamin C could prevent a significant reduction in percentage of neutrophils. Our findings indicated that low electromagnetic fields have caused significant changes in the total number of white blood cells and percentage of neutrophils in mice. In the group that received vitamin C injection, significant changes were observed in the total number of white blood cells and percentage of neutrophils relative to the group under the influence of low electromagnetic waves, which indicates that vitamin C could restore the mean total number of white blood cells and percentage of neutrophils to normal value.","PeriodicalId":93018,"journal":{"name":"Journal of cancer research and cellular therapeutics","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45487413","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：