Pub Date : 2021-09-16DOI: 10.31487/j.cor.2021.09.05
M. Velázquez-Flores, R. R. Esparza-Garrido
Non-coding RNAs are conformed by a large repertoire of RNA molecules with unimaginable tridimensional structures and functions. Small nuclear RNAs are an essential part of the spliceosome machinery, which is crucial for proper mRNA maturation. It is important to add that U6, one of the four snRNAs forming the spliceosome has been extensively studied. Full-length U6 (U6-1) loci are widely dispersed throughout the genome (200-900 copies), but a few U6 full-length loci have been identified to date as potentially active genes. The importance of U6 to carry out, together with other snRNAs, the catalytic activity and recognition of annealing target sequences, its evolution in the genome and the fact that the genome has many U6 copies and pseudogenes, its association with retrotransposition, as well as their implication in diseases is discussed in this review.
{"title":"The Potential of U6 and Its Copies in the Regulation of the Human Genome","authors":"M. Velázquez-Flores, R. R. Esparza-Garrido","doi":"10.31487/j.cor.2021.09.05","DOIUrl":"https://doi.org/10.31487/j.cor.2021.09.05","url":null,"abstract":"Non-coding RNAs are conformed by a large repertoire of RNA molecules with unimaginable tridimensional structures and functions. Small nuclear RNAs are an essential part of the spliceosome machinery, which is crucial for proper mRNA maturation. It is important to add that U6, one of the four snRNAs forming the spliceosome has been extensively studied. Full-length U6 (U6-1) loci are widely dispersed throughout the genome (200-900 copies), but a few U6 full-length loci have been identified to date as potentially active genes. The importance of U6 to carry out, together with other snRNAs, the catalytic activity and recognition of annealing target sequences, its evolution in the genome and the fact that the genome has many U6 copies and pseudogenes, its association with retrotransposition, as well as their implication in diseases is discussed in this review.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88081231","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 : 2021-08-31DOI: 10.31487/j.cor.2021.08.09
M. Moslim, Hailan Liu, M. Lefton, K. Ruth, Rajeswari Nagarathinam, H. Cooper, S. Reddy
Background: Ampullary carcinoma is rare with a more favourable prognosis compared to pancreatic ductal adenocarcinoma. The role of histological classification, including pancreatobiliary (PB) and intestinal (INT), on survival and recurrence outcomes in ampullary cancer is still debatable. Methods: 42 patients were identified between 1996-2010. Results: Nineteen classic pancreatoduodenectomies (PD) and 23 pylorus-preserving PDs were performed. Pathological review revealed 23, 18 and 1 patients with the PB, INT and mixed histology, respectively. Adjuvant chemoradiation (ACRT), chemotherapy, and radiation were given to 14 (33.3%), 4 (9.5%) and 2 (4.8%) patients, respectively. Recurrence-free survival (RFS) and overall survival (OS) from time of surgery were higher in the PB histological variant compared to INT (p=0.005 and 0.012, respectively). A landmark (LM) analysis found higher survival in the PB variant patients compared to INT (RFS p=0.023; OS p=0.048). There was no difference in RFS between both histological variants for patients who underwent surgery alone (p=0.42). However, the PB had higher RFS compared to the INT histology for patients who underwent ACRT (p=0.008). Conclusion: Ampullary carcinoma with PB histological variant was associated with significant survival benefit. The PB versus INT survival benefit was seen in the setting of ACRT, but not with surgery alone.
{"title":"Survival and Recurrence in Pancreatobiliary Versus Intestinal Histology of Ampullary Carcinoma","authors":"M. Moslim, Hailan Liu, M. Lefton, K. Ruth, Rajeswari Nagarathinam, H. Cooper, S. Reddy","doi":"10.31487/j.cor.2021.08.09","DOIUrl":"https://doi.org/10.31487/j.cor.2021.08.09","url":null,"abstract":"Background: Ampullary carcinoma is rare with a more favourable prognosis compared to pancreatic ductal adenocarcinoma. The role of histological classification, including pancreatobiliary (PB) and intestinal (INT), on survival and recurrence outcomes in ampullary cancer is still debatable.\u0000Methods: 42 patients were identified between 1996-2010.\u0000Results: Nineteen classic pancreatoduodenectomies (PD) and 23 pylorus-preserving PDs were performed. Pathological review revealed 23, 18 and 1 patients with the PB, INT and mixed histology, respectively. Adjuvant chemoradiation (ACRT), chemotherapy, and radiation were given to 14 (33.3%), 4 (9.5%) and 2 (4.8%) patients, respectively. Recurrence-free survival (RFS) and overall survival (OS) from time of surgery were higher in the PB histological variant compared to INT (p=0.005 and 0.012, respectively). A landmark (LM) analysis found higher survival in the PB variant patients compared to INT (RFS p=0.023; OS p=0.048). There was no difference in RFS between both histological variants for patients who underwent surgery alone (p=0.42). However, the PB had higher RFS compared to the INT histology for patients who underwent ACRT (p=0.008).\u0000Conclusion: Ampullary carcinoma with PB histological variant was associated with significant survival benefit. The PB versus INT survival benefit was seen in the setting of ACRT, but not with surgery alone.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75886370","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 : 2021-08-31DOI: 10.31487/j.cor.2021.08.08
C. Bellcross, April Hermstad, Christine Tallo, C. Leonard, Ioana Pencea, Christine Stanislaw
Purpose: The Breast Cancer Genetics Referral Screening Tool (B-RST™) has been endorsed as one of several validated screening tools to identify women appropriate for cancer genetics referral. We conducted a randomized trial to determine the most effective means of follow-up for women who screened positive on B-RST™ 3.0. Methods: Women undergoing screening mammography at one of four Emory clinics were approached to complete the B-RST™. Participants who screened positive were randomized to one of three follow-up groups: self-referral (Group 1), electronic health record (EHR) clinician messaging (Group 2), or direct contact (Group 3). We compared genetic counseling appointment scheduling and completion rates by group. Results: Of 2,422 participants, 658 (27.2%) screened positive. Genetic counseling appointments were scheduled by 9.2%, 20.1% and 9.7% of Group 1, 2 and 3 participants respectively (p=0.001). Challenges to scheduling included lack of physician response to EHR messages and unsuccessful direct contact. Among those scheduled (n=78) 70.5% completed the appointment, with no difference between the three groups. Conclusion: B-RST™ can be used effectively in mammography settings to identify high-risk women for cancer genetics referral. Follow-up via EHR appears an acceptable and efficient approach, but additional strategies are needed to facilitate completion of the genetic counseling process.
{"title":"A Randomized Trial to Maximize Identification and Genetic Counseling Referral of Women at Risk for Hereditary Breast and Ovarian Cancer","authors":"C. Bellcross, April Hermstad, Christine Tallo, C. Leonard, Ioana Pencea, Christine Stanislaw","doi":"10.31487/j.cor.2021.08.08","DOIUrl":"https://doi.org/10.31487/j.cor.2021.08.08","url":null,"abstract":"Purpose: The Breast Cancer Genetics Referral Screening Tool (B-RST™) has been endorsed as one of \u0000several validated screening tools to identify women appropriate for cancer genetics referral. We conducted \u0000a randomized trial to determine the most effective means of follow-up for women who screened positive on \u0000B-RST™ 3.0.\u0000Methods: Women undergoing screening mammography at one of four Emory clinics were approached to \u0000complete the B-RST™. Participants who screened positive were randomized to one of three follow-up \u0000groups: self-referral (Group 1), electronic health record (EHR) clinician messaging (Group 2), or direct \u0000contact (Group 3). We compared genetic counseling appointment scheduling and completion rates by group.\u0000Results: Of 2,422 participants, 658 (27.2%) screened positive. Genetic counseling appointments were \u0000scheduled by 9.2%, 20.1% and 9.7% of Group 1, 2 and 3 participants respectively (p=0.001). Challenges to \u0000scheduling included lack of physician response to EHR messages and unsuccessful direct contact. Among \u0000those scheduled (n=78) 70.5% completed the appointment, with no difference between the three groups.\u0000Conclusion: B-RST™ can be used effectively in mammography settings to identify high-risk women for \u0000cancer genetics referral. Follow-up via EHR appears an acceptable and efficient approach, but additional \u0000strategies are needed to facilitate completion of the genetic counseling process.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"181 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74084653","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 : 2021-08-30DOI: 10.31487/j.cor.2021.08.10
J. Gootee, C. Willman, S. Aurit, P. Silberstein
Background: Signet ring cell carcinoma of the esophagus (SRCCE) is an aggressive tumor that represents approximately 3.5-5.0% of all esophageal cancers. Prior studies have shown a strong correlation between treating facility and survival for different cancers, but this has not been studied in SRCCE. The goal of this study is to assess differences in survival based on the type of treatment facility. Methods: There were 2,021 patients with SRCCE identified using the histology 8490 and topography codes C15.0-C15.9 in the National Cancer Database (NCDB). Descriptive analysis, Kaplan-Meier curves, and a multivariable Cox hazard regression analysis were all utilized to determine the significance of treatment facility type and other variables. Results: The cohort mostly received treatment at academic centers (47.7%). As age increased, mortality also increased (HR=1.01; 95% CI:1.01-1.02, p<0.001). Africans Americans (HR=1.44; 95% CI:1.02-2.02, p=0.036) had an increased risk of mortality when compared to Non-Hispanic Caucasians. Patients at academic facilities demonstrated a decreased risk of mortality when compared to community programmes (HR=0.73; 95% CI:0.64-0.84, p<0.001) and integrated cancer programmes (HR=0.69; 95% CI:0.58-0.83, p=0.008). Neoadjuvant chemoradiation resulted decreased mortality when compared to adjuvant chemoradiation (HR=1.41; 95% CI:1.21-1.63, p<0.001) and no chemoradiation (HR=1.84; 95% CI:1.58- 2.14, p<0.001). Conclusion: For patients diagnosed with SRCCE, receiving treatment at academic centers resulted in better survival probabilities compared to nonacademic facilities. Older patients, African Americans, increasing tumor stage, no and adjuvant chemoradiation, and comorbidities with Charlson-Deyo scores of 1 and 2+ were all associated with an increased risk of mortality from SRCCE.
{"title":"The Effect of Treatment Facility, Race, and Chemoradiation on Survival for Signet Ring Cell Carcinoma of the Esophagus: An Analysis of the National Cancer Database","authors":"J. Gootee, C. Willman, S. Aurit, P. Silberstein","doi":"10.31487/j.cor.2021.08.10","DOIUrl":"https://doi.org/10.31487/j.cor.2021.08.10","url":null,"abstract":"Background: Signet ring cell carcinoma of the esophagus (SRCCE) is an aggressive tumor that represents \u0000approximately 3.5-5.0% of all esophageal cancers. Prior studies have shown a strong correlation between \u0000treating facility and survival for different cancers, but this has not been studied in SRCCE. The goal of this \u0000study is to assess differences in survival based on the type of treatment facility.\u0000Methods: There were 2,021 patients with SRCCE identified using the histology 8490 and topography codes \u0000C15.0-C15.9 in the National Cancer Database (NCDB). Descriptive analysis, Kaplan-Meier curves, and a \u0000multivariable Cox hazard regression analysis were all utilized to determine the significance of treatment \u0000facility type and other variables.\u0000Results: The cohort mostly received treatment at academic centers (47.7%). As age increased, mortality \u0000also increased (HR=1.01; 95% CI:1.01-1.02, p<0.001). Africans Americans (HR=1.44; 95% CI:1.02-2.02, \u0000p=0.036) had an increased risk of mortality when compared to Non-Hispanic Caucasians. Patients at \u0000academic facilities demonstrated a decreased risk of mortality when compared to community programmes \u0000(HR=0.73; 95% CI:0.64-0.84, p<0.001) and integrated cancer programmes (HR=0.69; 95% CI:0.58-0.83, \u0000p=0.008). Neoadjuvant chemoradiation resulted decreased mortality when compared to adjuvant \u0000chemoradiation (HR=1.41; 95% CI:1.21-1.63, p<0.001) and no chemoradiation (HR=1.84; 95% CI:1.58-\u00002.14, p<0.001). \u0000Conclusion: For patients diagnosed with SRCCE, receiving treatment at academic centers resulted in better \u0000survival probabilities compared to nonacademic facilities. Older patients, African Americans, increasing \u0000tumor stage, no and adjuvant chemoradiation, and comorbidities with Charlson-Deyo scores of 1 and 2+ \u0000were all associated with an increased risk of mortality from SRCCE.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81133118","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 : 2021-08-30DOI: 10.31487/j.cor.2021.08.12
Cynthia Osemeke, X. Wen, H. Garelick, Sandra S. Appiah
Acute myeloid leukemia (AML) is associated with numerous mutations, with the Feline McDonough Sarcoma (FMS) like tyrosine kinase 3 (FLT3) mutation resulting in with poor prognosis and outcome. Therapies have been developed using FLT3 inhibitors, however, drug resistance often leads to disease relapse. In this study, α-Mangostin and doxorubicin (Dox) were evaluated, singly and in combination, for their anti-leukemic effect on MOLM-13, an AML cell line with FLT3-ITD mutation. Cell viability and apoptosis were determined using CyQUANTGR and TUNEL assay, respectively. Cell cycle analysis was conducted on propidium iodide-stained cells using flow cytometry. Cellular proteins were quantified using Western blot technique, with additional study by ELISA for FLT3 kinase activity. The results revealed that cell treatment by the combined drug, Dox (1 µM) and α-Mangostin (20 µM), compared to Dox (1 µM) alone, caused a significant inhibitory effect (P<0.001) and indicated synergistic cell growth inhibition. The combined drug also showed increased TUNEL positive apoptotic cells and increased expression of the pro-apoptotic protein Bak compared to Dox alone (P<0.05). Dox treated cells, as well as the combined drug induced cell cycle arrest at G2/M phase compared to untreated cells (P<0.05 and P<0.001, respectively). There was also statistically significant (P<0.05) reduction of cdc25 phosphatases (enzymes which play an important role in G2/M transition) by the combination drug compared to sole cell treatment by Dox. Furthermore, phosphorylated FLT3 protein expression was reduced when the combined treatment was compared to Dox only after 2 h (P<0.05) and after 24 h (P<0.001). Thus, Dox and α-Mangostin combined treatment inhibited FLT3 phosphorylation in MOLM-13 cells which could have contributed to G2M cell arrest and apoptosis via cdc25s and Bak proteins respectively. Further studies are warranted to further evaluate the potential of Dox and α-Mangostin combined drug as inhibitors of FLT3-ITD phosphorylation and its potential clinical relevance in AML treatment.
急性髓性白血病(AML)与许多突变相关，其中猫麦克多诺肉瘤(FMS)如酪氨酸激酶3 (FLT3)突变导致预后和预后较差。已经开发出使用FLT3抑制剂的治疗方法，然而，耐药性经常导致疾病复发。本研究对α-山竹苷和阿霉素(Dox)单独和联合对FLT3-ITD突变的AML细胞株MOLM-13的抗白血病作用进行了评价。采用CyQUANTGR法和TUNEL法分别测定细胞活力和凋亡。用流式细胞术分析碘化丙啶染色细胞的细胞周期。采用Western blot技术对细胞蛋白进行定量分析，同时采用ELISA法检测FLT3激酶活性。结果表明，与Dox(1µM)联合用药相比，Dox(1µM)与α-山竹苷(20µM)联合用药对细胞的抑制作用显著(P<0.001)，并表现出协同抑制细胞生长的作用。联合用药组TUNEL阳性凋亡细胞增多，促凋亡蛋白Bak表达增加(P<0.05)。与未处理的细胞相比，Dox处理的细胞以及联合药物诱导的细胞周期阻滞在G2/M期(分别P<0.05和P<0.001)。与Dox单细胞治疗相比，联合用药降低cdc25磷酸酶(在G2/M转变中起重要作用的酶)的水平也有统计学意义(P<0.05)。此外，与Dox相比，联合治疗后2 h (P<0.05)和24 h (P<0.001)磷酸化FLT3蛋白表达均降低。因此，Dox和α-山竹苷联合处理可以抑制MOLM-13细胞中FLT3的磷酸化，而FLT3可能分别通过cdc25s和Bak蛋白参与G2M细胞的阻滞和凋亡。需要进一步的研究来进一步评估Dox和α-山竹苷联合用药作为FLT3-ITD磷酸化抑制剂的潜力及其在AML治疗中的潜在临床意义。
{"title":"α-Mangostin and Doxorubicin Combination Synergistically Inhibited Cell Growth, Induced Cell Apoptosis with Increased Bak Protein and Decreased FLT3-ITD Phosphorylation in AML MOLM-13 Cell Line","authors":"Cynthia Osemeke, X. Wen, H. Garelick, Sandra S. Appiah","doi":"10.31487/j.cor.2021.08.12","DOIUrl":"https://doi.org/10.31487/j.cor.2021.08.12","url":null,"abstract":"Acute myeloid leukemia (AML) is associated with numerous mutations, with the Feline McDonough Sarcoma (FMS) like tyrosine kinase 3 (FLT3) mutation resulting in with poor prognosis and outcome. Therapies have been developed using FLT3 inhibitors, however, drug resistance often leads to disease relapse. In this study, α-Mangostin and doxorubicin (Dox) were evaluated, singly and in combination, for their anti-leukemic effect on MOLM-13, an AML cell line with FLT3-ITD mutation. Cell viability and apoptosis were determined using CyQUANTGR and TUNEL assay, respectively. Cell cycle analysis was conducted on propidium iodide-stained cells using flow cytometry. Cellular proteins were quantified using Western blot technique, with additional study by ELISA for FLT3 kinase activity. The results revealed that cell treatment by the combined drug, Dox (1 µM) and α-Mangostin (20 µM), compared to Dox (1 µM) alone, caused a significant inhibitory effect (P<0.001) and indicated synergistic cell growth inhibition. The combined drug also showed increased TUNEL positive apoptotic cells and increased expression of the pro-apoptotic protein Bak compared to Dox alone (P<0.05). Dox treated cells, as well as the combined drug induced cell cycle arrest at G2/M phase compared to untreated cells (P<0.05 and P<0.001, respectively). There was also statistically significant (P<0.05) reduction of cdc25 phosphatases (enzymes which play an important role in G2/M transition) by the combination drug compared to sole cell treatment by Dox. Furthermore, phosphorylated FLT3 protein expression was reduced when the combined treatment was compared to Dox only after 2 h (P<0.05) and after 24 h (P<0.001). Thus, Dox and α-Mangostin combined treatment inhibited FLT3 phosphorylation in MOLM-13 cells which could have contributed to G2M cell arrest and apoptosis via cdc25s and Bak proteins respectively. Further studies are warranted to further evaluate the potential of Dox and α-Mangostin combined drug as inhibitors of FLT3-ITD phosphorylation and its potential clinical relevance in AML treatment.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"129 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77855762","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 : 2021-08-20DOI: 10.31487/j.cor.2021.08.03
Yiao Tan, Fangfang Zhao, Chun-bao Zang, Shuhan Liu, Tao Huang, Lingsuo Kong, Fangfang Ge, Dabing Huang, Y. Pu
Objectives: Bladder cancer is the second most common urological cancer worldwide with low early diagnosis and high mortality. The limited progress on the diagnostics and treatment largely impedes the survival of bladder cancer patients. Methods: Potential therapeutic biomarkers are urgently needed for future clinic treatment. We performed the RNA-seq assays and identified a new gene zinc finger protein 485, termed ZNF485, which is highly expressed in the tissues of bladder cancer patients. Results: We found that inhibition of ZNF485 in bladder cancer cell line T24 and 5637 can obviously inhibit the proliferation and promotes the apoptosis of cancer cells. Furthermore, the wound healing and invasion assays showed that down-regulation of ZNF485 significantly decreased the mobility and invasion of T24 and 5637 cells. In addition, ZNF485-siRNA transfected obviously inhibited tumor growth in nude mice. Conclusion: Taken together, the results provide evidence that ZNF485 is involved in the tumorigenesis of bladder cancer, which might be a potential therapeutic biomarker for the treatment of this disease.
{"title":"Effects of the Zinc Finger Protein 485 (ZNF485) on the Proliferation, Metastasis and Invasion of Bladder Cancer Cells","authors":"Yiao Tan, Fangfang Zhao, Chun-bao Zang, Shuhan Liu, Tao Huang, Lingsuo Kong, Fangfang Ge, Dabing Huang, Y. Pu","doi":"10.31487/j.cor.2021.08.03","DOIUrl":"https://doi.org/10.31487/j.cor.2021.08.03","url":null,"abstract":"Objectives: Bladder cancer is the second most common urological cancer worldwide with low early diagnosis and high mortality. The limited progress on the diagnostics and treatment largely impedes the survival of bladder cancer patients.\u0000Methods: Potential therapeutic biomarkers are urgently needed for future clinic treatment. We performed the RNA-seq assays and identified a new gene zinc finger protein 485, termed ZNF485, which is highly expressed in the tissues of bladder cancer patients.\u0000Results: We found that inhibition of ZNF485 in bladder cancer cell line T24 and 5637 can obviously inhibit the proliferation and promotes the apoptosis of cancer cells. Furthermore, the wound healing and invasion assays showed that down-regulation of ZNF485 significantly decreased the mobility and invasion of T24 and 5637 cells. In addition, ZNF485-siRNA transfected obviously inhibited tumor growth in nude mice.\u0000Conclusion: Taken together, the results provide evidence that ZNF485 is involved in the tumorigenesis of bladder cancer, which might be a potential therapeutic biomarker for the treatment of this disease.\u0000","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75809959","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 : 2021-08-18DOI: 10.31487/j.cor.2021.08.05
Savanah D Gisriel, Kristle L. Haberichter, Sara Huang, James Z. Huang
Objectives: We recently examined the utility of flow cytometric analysis in the diagnosis of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) by examining reactive T-cell features. This study aims to compare these features in sequential biopsies of persistent or recurrent lymphadenopathy in patients with NLPHL. Methods: We reanalysed the histopathology and flow cytometry findings of 9 patients with multiple biopsies for persistent or recurrent lymphadenopathy and either initial or recurrent NLPHL. A flow cytometry signature was considered suggestive of NLPHL if ≥12% of T-cells expressed CD57 or ≥3% of T-cells co-expressed CD4 and CD8. Results: A flow cytometry signature considered suggestive of NLPHL was seen in 18 of 20 specimens. Based on histopathology, 11 were diagnosed as NLPHL, 3 were initially underdiagnosed as atypical lymphoid proliferation, and 4 were initially incorrectly diagnosed as negative or progressive transformation of germinal centers. Flow cytometry showed similar expression patterns of CD57 and CD4/CD8 in T-cells between initial and subsequent biopsies. The remaining 2 specimens lacked the flow cytometry signature suggestive of NLPHL and were histopathologically diagnosed as reactive hyperplasia. Conclusion: Flow cytometry analysis based on our criteria is highly sensitive in detecting NLPHL. Correlation with the cytospin cytology may increase the diagnostic specificity. A negative flow essentially ruled out the possibility of NHLPHL.
{"title":"Flow Cytometry Analysis of Recurrent or Persistent Lymphadenopathy in Patients with Nodular Lymphocyte-Predominant Hodgkin Lymphoma","authors":"Savanah D Gisriel, Kristle L. Haberichter, Sara Huang, James Z. Huang","doi":"10.31487/j.cor.2021.08.05","DOIUrl":"https://doi.org/10.31487/j.cor.2021.08.05","url":null,"abstract":"Objectives: We recently examined the utility of flow cytometric analysis in the diagnosis of nodular \u0000lymphocyte predominant Hodgkin lymphoma (NLPHL) by examining reactive T-cell features. This study \u0000aims to compare these features in sequential biopsies of persistent or recurrent lymphadenopathy in patients \u0000with NLPHL.\u0000Methods: We reanalysed the histopathology and flow cytometry findings of 9 patients with multiple \u0000biopsies for persistent or recurrent lymphadenopathy and either initial or recurrent NLPHL. A flow \u0000cytometry signature was considered suggestive of NLPHL if ≥12% of T-cells expressed CD57 or ≥3% of \u0000T-cells co-expressed CD4 and CD8.\u0000Results: A flow cytometry signature considered suggestive of NLPHL was seen in 18 of 20 specimens. \u0000Based on histopathology, 11 were diagnosed as NLPHL, 3 were initially underdiagnosed as atypical \u0000lymphoid proliferation, and 4 were initially incorrectly diagnosed as negative or progressive transformation \u0000of germinal centers. Flow cytometry showed similar expression patterns of CD57 and CD4/CD8 in T-cells \u0000between initial and subsequent biopsies. The remaining 2 specimens lacked the flow cytometry signature \u0000suggestive of NLPHL and were histopathologically diagnosed as reactive hyperplasia.\u0000Conclusion: Flow cytometry analysis based on our criteria is highly sensitive in detecting NLPHL. \u0000Correlation with the cytospin cytology may increase the diagnostic specificity. A negative flow essentially \u0000ruled out the possibility of NHLPHL.\u0000","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"10 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91425884","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 : 2021-08-17DOI: 10.31487/j.cor.2021.08.07
J. Fries, M. Saleh, R. Büttner
The pleural lobes are the origin of different pathologies, including malignant tumors, e.g., pleural mesothelioma. In some cases, clinical and macroscopic presentation point strongly to the diagnosis but often enough the patient has another underlying disease; malignant neoplasms of the lung as well as other organs (skin, pancreas, prostate or kidney) can mimic pleural mesothelioma and if so, are defined as ‘pseudo-mesothelioma’. We present eight cases that are clinically and macroscopically highly suspicious for pleural mesothelioma. All patients were autopsied due to medico-legal issues and work-related diseases. Six out of eight patients underwent autopsy to exclude possibility of asbestos-related malignancy and two out of eight due to exclusion of silicosis. From the eight cases, only three were real pleural mesotheliomas. Another three were adenocarcinomas of the lung mimicking pleural mesotheliomas. One had squamous cell carcinoma of the lung. Lastly, one patient had an extraordinary case of papillary renal cell carcinoma metastasizing universally in both pleura lobes. Due to striking morphological similarities, the exact final diagnosis was only possible after extended immunohistochemical analysis of the tissues. In summary, not only is it difficult to distinguish between real or pseudo pleural mesothelioma in patients having had contact with asbestos. Even patients with no evidence of asbestos contact can have clinical and pathological events strongly suggesting asbestosis and mesothelioma, without having it.
{"title":"Differentiation between Pleural Mesothelioma versus Pseudo-Mesothelioma Demonstrated in Eight Autopsy Cases","authors":"J. Fries, M. Saleh, R. Büttner","doi":"10.31487/j.cor.2021.08.07","DOIUrl":"https://doi.org/10.31487/j.cor.2021.08.07","url":null,"abstract":"The pleural lobes are the origin of different pathologies, including malignant tumors, e.g., pleural \u0000mesothelioma. In some cases, clinical and macroscopic presentation point strongly to the diagnosis but often \u0000enough the patient has another underlying disease; malignant neoplasms of the lung as well as other organs \u0000(skin, pancreas, prostate or kidney) can mimic pleural mesothelioma and if so, are defined as ‘pseudo-mesothelioma’. We present eight cases that are clinically and macroscopically highly suspicious for pleural \u0000mesothelioma. All patients were autopsied due to medico-legal issues and work-related diseases. Six out of \u0000eight patients underwent autopsy to exclude possibility of asbestos-related malignancy and two out of eight \u0000due to exclusion of silicosis. From the eight cases, only three were real pleural mesotheliomas. Another \u0000three were adenocarcinomas of the lung mimicking pleural mesotheliomas. One had squamous cell \u0000carcinoma of the lung. Lastly, one patient had an extraordinary case of papillary renal cell carcinoma \u0000metastasizing universally in both pleura lobes. Due to striking morphological similarities, the exact final \u0000diagnosis was only possible after extended immunohistochemical analysis of the tissues. In summary, not \u0000only is it difficult to distinguish between real or pseudo pleural mesothelioma in patients having had contact \u0000with asbestos. Even patients with no evidence of asbestos contact can have clinical and pathological events \u0000strongly suggesting asbestosis and mesothelioma, without having it.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83060084","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 : 2021-08-17DOI: 10.31487/j.cor.2021.06.03
K. Dharanipragada, N. Ghimire, N. Ghimire, Shanmugam Dasarathan, B. Zachariah, P. Toi, Sunitha Vc, S. Selvarajan
Background: In India breast cancer forms the commonest malignancy after cervical cancer in females and is detected in 20 per 1,00,000 women. Metformin acts as oral hypoglycemia drug and anti-tumor drug. Mechanism of action of metformin is to inhibit cellular proliferation as well as to increases pathological Complete Response in breast cancer patients when used in addition to neoadjuvant chemotherapy. Methods: This randomized control trial study was conducted on 54 patients to assess the effect of adding metformin to neoadjuvant chemotherapy in pathologic response in Breast Cancer patients as well as to establish safety and tolerance of metformin as a neoadjuvant drug in Breast cancer and to measure the effect of metformin on sex hormones, tumor and insulin resistance dated from November 2016 to June 2018. Study group received metformin along with neoadjuvant chemotherapy and Control group received neoadjuvant chemotherapy only. In every visit, side effects of metformin were assessed like nausea, vomiting, abdominal discomfort, dizziness. Pre NACT-BMI and Post NACT- BMI were calculated and differences were assessed. Any post-operative complication was looked for post-surgery. Data was analysed by SPSS version 19. Results: Our study showed that DHEAS level decreased by 5.65 in study group while the fall in DHEAS in non-metformin arm was 2.1. 7.1% of participants in metformin group showed complete response, 78.6% participants showed partial response and 14.3% had progressive disease. In non-metformin group, complete, partial response and progressive disease were seen in 40.0%, 60.0% and 0.0% respectively. Patient in control group had higher complete response. However, the difference in pathologic complete response between metformin and non-metformin group has no statistical significance (p= 0.057). Conclusion: Our study supports the view that patient without insulin resistance treated with NACT alone has higher pathologic complete response than the patient treated with NACT with metformin. However, sample size of present study is small to support the results.
{"title":"Efficacy of Combining Metformin with Neoadjuvant Chemotherapy on Pathologic Response in Non-diabetic Patients with Carcinoma Breast- A Randomized Controlled Trial","authors":"K. Dharanipragada, N. Ghimire, N. Ghimire, Shanmugam Dasarathan, B. Zachariah, P. Toi, Sunitha Vc, S. Selvarajan","doi":"10.31487/j.cor.2021.06.03","DOIUrl":"https://doi.org/10.31487/j.cor.2021.06.03","url":null,"abstract":"Background: In India breast cancer forms the commonest malignancy after cervical cancer in females and is detected in 20 per 1,00,000 women. Metformin acts as oral hypoglycemia drug and anti-tumor drug. Mechanism of action of metformin is to inhibit cellular proliferation as well as to increases pathological Complete Response in breast cancer patients when used in addition to neoadjuvant chemotherapy.\u0000Methods: This randomized control trial study was conducted on 54 patients to assess the effect of adding metformin to neoadjuvant chemotherapy in pathologic response in Breast Cancer patients as well as to establish safety and tolerance of metformin as a neoadjuvant drug in Breast cancer and to measure the effect of metformin on sex hormones, tumor and insulin resistance dated from November 2016 to June 2018. Study group received metformin along with neoadjuvant chemotherapy and Control group received neoadjuvant chemotherapy only. In every visit, side effects of metformin were assessed like nausea, vomiting, abdominal discomfort, dizziness. Pre NACT-BMI and Post NACT- BMI were calculated and differences were assessed. Any post-operative complication was looked for post-surgery. Data was analysed by SPSS version 19.\u0000Results: Our study showed that DHEAS level decreased by 5.65 in study group while the fall in DHEAS in non-metformin arm was 2.1. 7.1% of participants in metformin group showed complete response, 78.6% participants showed partial response and 14.3% had progressive disease. In non-metformin group, complete, partial response and progressive disease were seen in 40.0%, 60.0% and 0.0% respectively. Patient in control group had higher complete response. However, the difference in pathologic complete response between metformin and non-metformin group has no statistical significance (p= 0.057).\u0000Conclusion: Our study supports the view that patient without insulin resistance treated with NACT alone has higher pathologic complete response than the patient treated with NACT with metformin. However, sample size of present study is small to support the results.\u0000","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"129 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86387768","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 : 2021-08-16DOI: 10.31487/j.cor.2021.08.06
Kaylee Chen, M. Raja
Conventional cancer chemotherapy aims to kill highly proliferating tumor cells and is often immunosuppressive due to its off-target side effects. However, certain cytotoxic cancer chemotherapeutic drugs can kill tumor cells by triggering immunogenic cell death (ICD). Cells undergoing ICD release damage-associated molecular patterns (DAMPs) to activate robust innate and adaptive anti-tumor immune responses. Despite many compounds being able to trigger one or two hallmarks of ICD, very few bona fide ICD inducers are available. Identification of bioactive natural ICD inducers with low side effects and high tolerability represents a priority in biomedical research. In this review, we discuss the various strategies to regulate the hallmarks of ICD and enhance immunogenic potentials. We focus on evaluating the potential of natural compounds of marine origin to amplify the effects of ICD and therefore serve as novel therapeutic anti-cancer agents alone or in combination with existent chemo- or immune-therapies.
{"title":"Harnessing Natural Products of Marine Origin for Induction of Immunogenic Cell Death","authors":"Kaylee Chen, M. Raja","doi":"10.31487/j.cor.2021.08.06","DOIUrl":"https://doi.org/10.31487/j.cor.2021.08.06","url":null,"abstract":"Conventional cancer chemotherapy aims to kill highly proliferating tumor cells and is often immunosuppressive due to its off-target side effects. However, certain cytotoxic cancer chemotherapeutic drugs can kill tumor cells by triggering immunogenic cell death (ICD). Cells undergoing ICD release damage-associated molecular patterns (DAMPs) to activate robust innate and adaptive anti-tumor immune responses. Despite many compounds being able to trigger one or two hallmarks of ICD, very few bona fide ICD inducers are available. Identification of bioactive natural ICD inducers with low side effects and high tolerability represents a priority in biomedical research. In this review, we discuss the various strategies to regulate the hallmarks of ICD and enhance immunogenic potentials. We focus on evaluating the potential of natural compounds of marine origin to amplify the effects of ICD and therefore serve as novel therapeutic anti-cancer agents alone or in combination with existent chemo- or immune-therapies.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82164436","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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