Pub Date : 2021-01-08DOI: 10.31487/J.COR.2021.01.03
H. Sassi, Rym Meddeb, M. Trabelsi, S. Hannachi, N. Belguith, I. Abbès, K. Rahal, K. Mrad, A. Mezlini, R. Mrad
Inherited predisposition to breast and ovarian cancer are most frequently due to germline mutations in the main genes BRCA1 (OMIM# 113705) and BRCA2 (OMIM# 600185). These inactivating mutations, essentially frameshift and nonsense variation, occurs mainly across conserved regions. The aim of the present study is to report a novel germline BRCA1 mutation identified in a Tunisian family case with early onset of breast and ovarian cancer and to evaluate the genotype phenotype correlation. The proband had high-grade tumors, invasive unilateral ductal carcinoma developed at the age of 38 and a serous ovarian adenocarcinoma after a gap of twelve years. The molecular analysis revealed a novel heterozygous nonsense BRCA1 mutation NM_007294.4: c.915T>A p.(C305*) in the proband and her daughter. This mutation leads to a truncated protein which pathogenicity was validated by bioinformatics tools. This variant is subject to nonsense-mediated mRNA decay. We also underlined the immunohistochemistry usefulness by lack of expression of BRCA1 protein in paraffin embedded breast tumor contrasting with normal tissue. Clinical and pathological data tend to be homogeneous and led to the conclusion that there is a genotype phenotype correlation in BRCA1, an element that must be taken into account in genetic counselling. Conclusively, we are the first to report this novel BRCA1 germline likely deleterious variant extending the molecular and clinical spectrum of BRCA1 pathogenic point mutations. Further in vitro functional experiments needs to be established. High-risk individuals carrying this BRCA1 mutation benefit from preventive measures to reduce morbidity.
乳腺癌和卵巢癌的遗传易感性最常见的原因是主要基因BRCA1 (OMIM# 113705)和BRCA2 (OMIM# 600185)的种系突变。这些失活突变，本质上是移码和无义变异，主要发生在保守区域。本研究的目的是报道在突尼斯早发性乳腺癌和卵巢癌家庭病例中发现的一种新的种系BRCA1突变，并评估基因型表型相关性。先证者患有高级别肿瘤，38岁时患侵袭性单侧导管癌，间隔12年后患浆液性卵巢腺癌。分子分析显示，先证者及其女儿存在一种新的杂合无义brca1突变NM_007294.4: c.915T> a p.(C305*)。该突变导致一个截短的蛋白，其致病性通过生物信息学工具得到验证。这一变异受到单义介导的mRNA衰变的影响。与正常组织相比，我们还强调了免疫组织化学在石蜡包埋乳腺肿瘤中缺乏BRCA1蛋白表达的有效性。临床和病理数据趋于一致，从而得出结论，即BRCA1存在基因型表型相关，这是遗传咨询中必须考虑的因素。最后，我们首次报道了这种新的BRCA1种系可能有害的变异，扩展了BRCA1致病性点突变的分子和临床谱。进一步的体外功能实验需要建立。携带这种BRCA1突变的高危人群可通过预防措施降低发病率。
{"title":"Identification of Novel BRCA1 Germline Deleterious Variant Among a Tunisian Family","authors":"H. Sassi, Rym Meddeb, M. Trabelsi, S. Hannachi, N. Belguith, I. Abbès, K. Rahal, K. Mrad, A. Mezlini, R. Mrad","doi":"10.31487/J.COR.2021.01.03","DOIUrl":"https://doi.org/10.31487/J.COR.2021.01.03","url":null,"abstract":"Inherited predisposition to breast and ovarian cancer are most frequently due to germline mutations in the\u0000main genes BRCA1 (OMIM# 113705) and BRCA2 (OMIM# 600185). These inactivating mutations,\u0000essentially frameshift and nonsense variation, occurs mainly across conserved regions. The aim of the\u0000present study is to report a novel germline BRCA1 mutation identified in a Tunisian family case with early\u0000onset of breast and ovarian cancer and to evaluate the genotype phenotype correlation. The proband had\u0000high-grade tumors, invasive unilateral ductal carcinoma developed at the age of 38 and a serous ovarian\u0000adenocarcinoma after a gap of twelve years. The molecular analysis revealed a novel heterozygous nonsense\u0000BRCA1 mutation NM_007294.4: c.915T>A p.(C305*) in the proband and her daughter. This mutation leads\u0000to a truncated protein which pathogenicity was validated by bioinformatics tools. This variant is subject to\u0000nonsense-mediated mRNA decay. We also underlined the immunohistochemistry usefulness by lack of\u0000expression of BRCA1 protein in paraffin embedded breast tumor contrasting with normal tissue. Clinical\u0000and pathological data tend to be homogeneous and led to the conclusion that there is a genotype phenotype\u0000correlation in BRCA1, an element that must be taken into account in genetic counselling. Conclusively, we\u0000are the first to report this novel BRCA1 germline likely deleterious variant extending the molecular and\u0000clinical spectrum of BRCA1 pathogenic point mutations. Further in vitro functional experiments needs to be\u0000established. High-risk individuals carrying this BRCA1 mutation benefit from preventive measures to reduce\u0000morbidity.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"254 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78526662","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 : 2020-12-31DOI: 10.31487/j.cor.2020.12.04
M. Inomata, K. Azechi, N. Takata, K. Hayashi, K. Tokui, C. Taka, S. Okazawa, K. Kambara, S. Imanishi, T. Miwa, Ryuji Hayashi, Shoko Matsui, K. Tobe
Purpose: We analysed the relationship between a history of immune checkpoint inhibitor (ICI) and overall survival in elderly patients with non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of the data of patients with NSCLC aged ≥70-year-old who had received systemic anticancer therapy between 2015 and 2019. Results: The analysis included the data of a total of 63 patients. Multivariate analysis revealed a significant association between a history of treatment with ICI and the overall survival. A significant interaction was also observed between a history of treatment with an ICI and the tumor histology. Conclusion: A significant association between history of ICI therapy and the overall survival was detected in elderly NSCLC patients aged ≥70-year-old in a clinical practice setting. Our results also suggested that the impact of ICI therapy on the survival differed depending on the tumor histology.
{"title":"Impact of Immune Checkpoint Inhibitor on the Survival in Elderly Patients with Non-Small Cell Lung Cancer","authors":"M. Inomata, K. Azechi, N. Takata, K. Hayashi, K. Tokui, C. Taka, S. Okazawa, K. Kambara, S. Imanishi, T. Miwa, Ryuji Hayashi, Shoko Matsui, K. Tobe","doi":"10.31487/j.cor.2020.12.04","DOIUrl":"https://doi.org/10.31487/j.cor.2020.12.04","url":null,"abstract":"Purpose: We analysed the relationship between a history of immune checkpoint inhibitor (ICI) and overall\u0000survival in elderly patients with non-small cell lung cancer (NSCLC).\u0000Methods: We conducted a retrospective analysis of the data of patients with NSCLC aged ≥70-year-old\u0000who had received systemic anticancer therapy between 2015 and 2019.\u0000Results: The analysis included the data of a total of 63 patients. Multivariate analysis revealed a significant\u0000association between a history of treatment with ICI and the overall survival. A significant interaction was\u0000also observed between a history of treatment with an ICI and the tumor histology.\u0000Conclusion: A significant association between history of ICI therapy and the overall survival was detected\u0000in elderly NSCLC patients aged ≥70-year-old in a clinical practice setting. Our results also suggested that\u0000the impact of ICI therapy on the survival differed depending on the tumor histology.\u0000","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83109456","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 : 2020-12-30DOI: 10.31487/J.COR.2020.08.12
W. Brooks, Yuri Pevzner, E. Pevzner, K. Daniel, W. Guida, M. Malafa
In recent years, evidence has mounted that a particular form of vitamin E (its δ-tocotrienol variant) may have cellular functions beyond that of an antioxidant, a role commonly ascribed to the tocotrienol class of compounds. In particular, numerous studies of δ-tocotrienol’s effect on cancer cells have identified it as a potent anticancer and antitumor agent. However, this important revelation of potential therapeutic use poses a series of new challenges, with arguably the most important being the elucidation of the precise mechanism of action responsible for the anticancer activity of δ-tocotrienol. As an initial step to address this question, we have used a computational tool, Virtual Target Screening (a molecular docking-based tool that identifies potential binding partners for small molecules), to identify potential biomolecular targets of δ-tocotrienol. Then, to gain a consensus as to the type of biomolecular entity that could be a target for δ-tocotrienol, we utilized PharmMapper and PASS (a ligand-based chemoinformatic approach), and ProBiS (a tool that analyses binding site similarities across known proteins). The results of our multipronged computational consensus-seeking approach showed that such a strategy can identify potential cellular targets of small molecules. This is evidenced by our identification of estrogen receptor-beta, a protein that has been previously shown to bind δ-tocotrienol, which elicited a cellular response. This study supports the use of such a computational approach as an initial step in target identification to avoid time-consuming, costly large-scale experimental screening, greatly reducing the experimental work to just one or a few candidate proteins.
{"title":"Identifying Biomolecular Targets of the Anticancer Vitamin-E-δ-Tocotrienol Using a Computational Approach: Virtual Target Screening","authors":"W. Brooks, Yuri Pevzner, E. Pevzner, K. Daniel, W. Guida, M. Malafa","doi":"10.31487/J.COR.2020.08.12","DOIUrl":"https://doi.org/10.31487/J.COR.2020.08.12","url":null,"abstract":"In recent years, evidence has mounted that a particular form of vitamin E (its δ-tocotrienol variant) may\u0000have cellular functions beyond that of an antioxidant, a role commonly ascribed to the tocotrienol class of\u0000compounds. In particular, numerous studies of δ-tocotrienol’s effect on cancer cells have identified it as a\u0000potent anticancer and antitumor agent. However, this important revelation of potential therapeutic use poses\u0000a series of new challenges, with arguably the most important being the elucidation of the precise mechanism\u0000of action responsible for the anticancer activity of δ-tocotrienol. As an initial step to address this question,\u0000we have used a computational tool, Virtual Target Screening (a molecular docking-based tool that identifies\u0000potential binding partners for small molecules), to identify potential biomolecular targets of δ-tocotrienol.\u0000Then, to gain a consensus as to the type of biomolecular entity that could be a target for δ-tocotrienol, we\u0000utilized PharmMapper and PASS (a ligand-based chemoinformatic approach), and ProBiS (a tool that\u0000analyses binding site similarities across known proteins). The results of our multipronged computational\u0000consensus-seeking approach showed that such a strategy can identify potential cellular targets of small\u0000molecules. This is evidenced by our identification of estrogen receptor-beta, a protein that has been\u0000previously shown to bind δ-tocotrienol, which elicited a cellular response. This study supports the use of\u0000such a computational approach as an initial step in target identification to avoid time-consuming, costly\u0000large-scale experimental screening, greatly reducing the experimental work to just one or a few candidate\u0000proteins.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"2008 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82516993","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 : 2020-12-24DOI: 10.31487/j.cor.2020.12.03
R. Pileckyte, T. Žvirblis, R. Matuzevičienė, A. Janiulionienė, L. Griškevičius
Higher circulating T regulatory cell (Treg) numbers have been found in untreated patients with chronic lymphocytic leukemia (CLL) compared to healthy subjects and correlated with progressive disease as well as time to first treatment in low-risk patients [1]. Some agents can reduce Treg numbers in CLL patients, but there are no data on the prognostic role of Treg dynamics and patient outcome. We present data from the LT-CLL-001 study, in which the clinical benefit of dose-dense high dose methylprednisolone (HDMP) and rituximab (Rtx) combination in relapsed or refractory high-risk patients with CLL was evaluated [2]. During the study, the change of T regulatory cell frequencies was measured in relation to overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Twenty-nine CLL patients with clinically or biologically high-risk disease were included. Treg frequency was evaluated at screening, after three treatment courses, and at the end of therapy. Significant reduction of the median frequencies of Treg during treatment was observed: median (range) of Treg0-3 after three treatment courses was 2.14% (-1.84%- 9.42%), p < 0.001 and median (range) of Treg0-6 was 1.01% (-2.95%- 8.35%, p = 0.004). Patients with deeper Treg reduction between screening and three treatment courses had significantly better PFS and OS (Table 1 & 2). Our data for the first time show that HDMP and Rtx combination reduces Treg frequency in pretreated CLL patients. Early and deeper Treg reduction is an independent prognostic factor for longer PFS and OS. (ClinicalTrials.gov identifier: NCT005 58181).
{"title":"T Regulatory Cells in Relapsed/Refractory Chronic Lymphocytic Leukemia Treated with High Dose Methylprednisolone and Rituximab","authors":"R. Pileckyte, T. Žvirblis, R. Matuzevičienė, A. Janiulionienė, L. Griškevičius","doi":"10.31487/j.cor.2020.12.03","DOIUrl":"https://doi.org/10.31487/j.cor.2020.12.03","url":null,"abstract":"Higher circulating T regulatory cell (Treg) numbers have been found in untreated patients with chronic\u0000lymphocytic leukemia (CLL) compared to healthy subjects and correlated with progressive disease as well\u0000as time to first treatment in low-risk patients [1]. Some agents can reduce Treg numbers in CLL patients,\u0000but there are no data on the prognostic role of Treg dynamics and patient outcome. We present data from\u0000the LT-CLL-001 study, in which the clinical benefit of dose-dense high dose methylprednisolone (HDMP)\u0000and rituximab (Rtx) combination in relapsed or refractory high-risk patients with CLL was evaluated [2].\u0000During the study, the change of T regulatory cell frequencies was measured in relation to overall response\u0000rate (ORR), progression-free survival (PFS), and overall survival (OS). Twenty-nine CLL patients with\u0000clinically or biologically high-risk disease were included. Treg frequency was evaluated at screening, after\u0000three treatment courses, and at the end of therapy. Significant reduction of the median frequencies of Treg\u0000during treatment was observed: median (range) of Treg0-3 after three treatment courses was 2.14% (-1.84%-\u00009.42%), p < 0.001 and median (range) of Treg0-6 was 1.01% (-2.95%- 8.35%, p = 0.004). Patients with\u0000deeper Treg reduction between screening and three treatment courses had significantly better PFS and OS\u0000(Table 1 & 2). Our data for the first time show that HDMP and Rtx combination reduces Treg frequency in\u0000pretreated CLL patients. Early and deeper Treg reduction is an independent prognostic factor for longer PFS\u0000and OS. (ClinicalTrials.gov identifier: NCT005 58181).\u0000","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75290757","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 : 2020-11-25DOI: 10.26226/morressier.5fa3ee5d55b1fd4cc4dd93a1
S. Jones, I. Murray, K. Lim, Robert Howells, R. Jones, Aarti Sharma
Objective: The objective of this study was to assess the ability of the American College of Surgeons (ACS) NSQIP surgical risk calculator to accurately identify patients at increased risk of perioperative complication following surgery for gynaecological malignancy. Methods: A retrospective review of 142 patients who underwent major surgery under the gynae-oncology team between 06/08/2018-16/04/2019 at the University Hospital of Wales. Pre-operative factors combined with a procedure-specific code generated the predicted risk of 13 post-operative complications for each patient. Brier scores assessed calibration and receiver operated curves (AUC) evaluated the discriminative power of NSQIP. Results: Complications were experienced by 50/142 (35.2%) patients. The calculator displayed adequate calibration when used to predict serious complications (Brier = 0.070), readmission (Brier = 0.058), return to OR (Brier = 0.000) and UTI (Brier = 0.001). It had the greatest discriminative power when predicting the risk of serious complications (AUC = 0.672; 95% CI, 0.481-0.863). The calculator successfully identified a majority of patients who had a complication as being of ‘above average risk’ for all complications, apart from return to OR, based on their pre-operative factors. Discussion: NSQIP has previously been demonstrated to be a useful pre-operative tool for evaluating the risk of post-operative complications in colorectal surgery. This study suggests that in the setting of gynaeoncology surgery the calculator does not have adequate discriminative power to be an absolute predictor of all complications, however, it may be useful in identifying patients who are likely to develop serious complications and those at above average risk of complications.
{"title":"The Utility of a Personalised Risk Calculator in Gynae-Oncology Surgery","authors":"S. Jones, I. Murray, K. Lim, Robert Howells, R. Jones, Aarti Sharma","doi":"10.26226/morressier.5fa3ee5d55b1fd4cc4dd93a1","DOIUrl":"https://doi.org/10.26226/morressier.5fa3ee5d55b1fd4cc4dd93a1","url":null,"abstract":"Objective: The objective of this study was to assess the ability of the American College of Surgeons (ACS)\u0000NSQIP surgical risk calculator to accurately identify patients at increased risk of perioperative complication\u0000following surgery for gynaecological malignancy.\u0000Methods: A retrospective review of 142 patients who underwent major surgery under the gynae-oncology\u0000team between 06/08/2018-16/04/2019 at the University Hospital of Wales. Pre-operative factors combined\u0000with a procedure-specific code generated the predicted risk of 13 post-operative complications for each\u0000patient. Brier scores assessed calibration and receiver operated curves (AUC) evaluated the discriminative\u0000power of NSQIP.\u0000Results: Complications were experienced by 50/142 (35.2%) patients. The calculator displayed adequate\u0000calibration when used to predict serious complications (Brier = 0.070), readmission (Brier = 0.058), return\u0000to OR (Brier = 0.000) and UTI (Brier = 0.001). It had the greatest discriminative power when predicting the\u0000risk of serious complications (AUC = 0.672; 95% CI, 0.481-0.863). The calculator successfully identified a\u0000majority of patients who had a complication as being of ‘above average risk’ for all complications, apart\u0000from return to OR, based on their pre-operative factors.\u0000Discussion: NSQIP has previously been demonstrated to be a useful pre-operative tool for evaluating the\u0000risk of post-operative complications in colorectal surgery. This study suggests that in the setting of gynaeoncology surgery the calculator does not have adequate discriminative power to be an absolute predictor of\u0000all complications, however, it may be useful in identifying patients who are likely to develop serious\u0000complications and those at above average risk of complications.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86318248","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 : 2020-10-30DOI: 10.31487/J.COR.2020.10.02
J. O. Rosa, Udofia Cynthia Emmanuel, Nwanosike Ahamefula Okeosisi
The rapid development of malignant cancers is characterized by inflammation, which poses a significant drawback in cancer therapy. Both cancer and inflammation operate on very similar mechanisms involving angiogenesis and cell proliferation. Currently, cancer-intrinsic inflammations have been shown to promote cancer progression and hinder apoptosis of cancerous cells. Thus, an effective strategy for chemoprevention and therapy would involve the control of inflammation. This research work aims to investigate the antiinflammatory activity of the extracts of the root bark of Rutidea parviflora (Rubiaceae), a plant I previously reported for anti-ovarian cancer activities and the isolation of palmatine; an anti-cancer compound and a second compound; urs-12-ene-24-oic acid, 3-oxo, methyl ester. This plant is renowned for its antiinflammatory properties amongst locals in Delta state, Nigeria, which has necessitated this present research. Organic and aqueous extracts were obtained from the pulverized root bark by use of the America national cancer institute protocol (NCI). The organic extract was partitioned sequentially in increasing order of polarity with n-hexane, ethyl acetate, n-butanol and distilled water to obtain four fractions. Phytochemical screening was done using standard procedures. Results from the phytochemical screening indicated the presence of alkaloids, flavonoids, saponins, tannins, glycosides and carbohydrates. Anti-inflammatory investigations of the extracts and fractions were carried out by the induction of inflammation. The animals were grouped into 12 test groups and 2 control groups with 6 rats per group. Egg albumin (0.1 ml) was administered sub-plantarly followed by treatment. Group A received a dose of 200 mg/kg of the plant extracts and Group B received a dose of 400 mg/kg of the plant extracts. Group C (positive control) received indomethacin (10 mg/kg), while Group D (negative control) received 1 ml of normal saline. Statistical analysis showed significance against the negative control indicated by P<0.05 for extracts and fractions. While for the fourth hour post induction of inflammation; the activities of the Group B organic extract, ethyl acetate and n-butanol fractions were comparable with indomethacin indicating that the plant possess significant anti-inflammatory activity and warrants further anti-inflammatory studies.
{"title":"Phytochemical Screening and In Vivo Anti-Inflammatory Activities of Anti-Cancer Plant: Rutidea parviflora (Rubiaceae)","authors":"J. O. Rosa, Udofia Cynthia Emmanuel, Nwanosike Ahamefula Okeosisi","doi":"10.31487/J.COR.2020.10.02","DOIUrl":"https://doi.org/10.31487/J.COR.2020.10.02","url":null,"abstract":"The rapid development of malignant cancers is characterized by inflammation, which poses a significant\u0000drawback in cancer therapy. Both cancer and inflammation operate on very similar mechanisms involving\u0000angiogenesis and cell proliferation. Currently, cancer-intrinsic inflammations have been shown to promote\u0000cancer progression and hinder apoptosis of cancerous cells. Thus, an effective strategy for chemoprevention\u0000and therapy would involve the control of inflammation. This research work aims to investigate the antiinflammatory activity of the extracts of the root bark of Rutidea parviflora (Rubiaceae), a plant I previously\u0000reported for anti-ovarian cancer activities and the isolation of palmatine; an anti-cancer compound and a\u0000second compound; urs-12-ene-24-oic acid, 3-oxo, methyl ester. This plant is renowned for its antiinflammatory properties amongst locals in Delta state, Nigeria, which has necessitated this present research.\u0000Organic and aqueous extracts were obtained from the pulverized root bark by use of the America national\u0000cancer institute protocol (NCI). The organic extract was partitioned sequentially in increasing order of\u0000polarity with n-hexane, ethyl acetate, n-butanol and distilled water to obtain four fractions. Phytochemical\u0000screening was done using standard procedures. Results from the phytochemical screening indicated the\u0000presence of alkaloids, flavonoids, saponins, tannins, glycosides and carbohydrates. Anti-inflammatory\u0000investigations of the extracts and fractions were carried out by the induction of inflammation. The animals\u0000were grouped into 12 test groups and 2 control groups with 6 rats per group. Egg albumin (0.1 ml) was\u0000administered sub-plantarly followed by treatment. Group A received a dose of 200 mg/kg of the plant\u0000extracts and Group B received a dose of 400 mg/kg of the plant extracts. Group C (positive control) received\u0000indomethacin (10 mg/kg), while Group D (negative control) received 1 ml of normal saline. Statistical\u0000analysis showed significance against the negative control indicated by P<0.05 for extracts and fractions.\u0000While for the fourth hour post induction of inflammation; the activities of the Group B organic extract, ethyl\u0000acetate and n-butanol fractions were comparable with indomethacin indicating that the plant possess\u0000significant anti-inflammatory activity and warrants further anti-inflammatory studies.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79861709","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 : 2020-10-09DOI: 10.21203/rs.3.rs-88926/v1
Xinyi Zhou, N. Jin, Bao‐an Chen
BackgroundAcute myeloid leukemia (AML) is a dangerous type of leukemia. The emergence of multidrug resistance (MDR) and recurrence limits the prognosis and survival of patients. In recent studies, we have known that the bone marrow microenvironment was closely related to the poor prognosis of AML. However, the underlying mechanisms are still far from fully understood. By utilizing the bioinformatics analysis, we screened out integrin β1 (ITGB1) as the hub gene, which is associated with the bone marrow microenvironment mediated changes of AML cells, with expression profile GSE73157 downloaded from National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database.MethodsR studio software was used to screen out candidate hub genes and further visualize the differential expression. R package “limma” was to find out differentially expressed genes (DEGs). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were conducted by R package “cluster Profiler”. Furthermore, protein-protein interaction (PPI) network was also performed by online tool STRING and software Cytoscape. Last but not least, online tool PrognoScan and GEPIA was utilized for the evaluation of clinical significance of the selected hub gene. P and Cox p value <0.05 was considered to be statistical significance.ResultsITGB1 was filtrated as the only hub gene in this profile. We found that patients with high expression of ITGB1 had significantly longer overall survival (OS) than those with low expression (COX p value= 0.016730). Besides, the expression of the ITGB1 gene in AML patients is lower than that in normal people significantly (p value<0.01).ConclusionWe identified ITGB1 as a key gene in the bone marrow microenvironment mediated poor prognosis in AML. The down-regulated expression of ITGB1 was related to AML patients’ poor outcome. ITGB1 may be a potential marker for predicting and guiding AML treatment.
{"title":"Comprehensive Expression and Prognosis Analyses of ITGB1 in AML","authors":"Xinyi Zhou, N. Jin, Bao‐an Chen","doi":"10.21203/rs.3.rs-88926/v1","DOIUrl":"https://doi.org/10.21203/rs.3.rs-88926/v1","url":null,"abstract":"\u0000 BackgroundAcute myeloid leukemia (AML) is a dangerous type of leukemia. The emergence of multidrug resistance (MDR) and recurrence limits the prognosis and survival of patients. In recent studies, we have known that the bone marrow microenvironment was closely related to the poor prognosis of AML. However, the underlying mechanisms are still far from fully understood. By utilizing the bioinformatics analysis, we screened out integrin β1 (ITGB1) as the hub gene, which is associated with the bone marrow microenvironment mediated changes of AML cells, with expression profile GSE73157 downloaded from National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database.MethodsR studio software was used to screen out candidate hub genes and further visualize the differential expression. R package “limma” was to find out differentially expressed genes (DEGs). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were conducted by R package “cluster Profiler”. Furthermore, protein-protein interaction (PPI) network was also performed by online tool STRING and software Cytoscape. Last but not least, online tool PrognoScan and GEPIA was utilized for the evaluation of clinical significance of the selected hub gene. P and Cox p value <0.05 was considered to be statistical significance.ResultsITGB1 was filtrated as the only hub gene in this profile. We found that patients with high expression of ITGB1 had significantly longer overall survival (OS) than those with low expression (COX p value= 0.016730). Besides, the expression of the ITGB1 gene in AML patients is lower than that in normal people significantly (p value<0.01).ConclusionWe identified ITGB1 as a key gene in the bone marrow microenvironment mediated poor prognosis in AML. The down-regulated expression of ITGB1 was related to AML patients’ poor outcome. ITGB1 may be a potential marker for predicting and guiding AML treatment.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77666502","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 : 2020-09-18DOI: 10.31487/j.cor.2020.09.07
A. Szász
Hyperthermia treatment for solid tumors is a long-used, but poorly accepted method in clinical use. Modulated electro-hyperthermia (mEHT, trade name: oncothermia®) changes the paradigm, introduces a novel, cellularly selective and immunogenic cell-ruination. The mEHT method produces tumor-vaccination, presenting the unharmed genetic information of cancer cells to immune cells [1]. The mEHT method is approved in more than 30 countries. Its phase II/III clinical applications indicate a broad perspective.
{"title":"Towards the Immunogenic Hyperthermic Action: Modulated ElectroHyperthermia","authors":"A. Szász","doi":"10.31487/j.cor.2020.09.07","DOIUrl":"https://doi.org/10.31487/j.cor.2020.09.07","url":null,"abstract":"Hyperthermia treatment for solid tumors is a long-used, but poorly accepted method in clinical use.\u0000Modulated electro-hyperthermia (mEHT, trade name: oncothermia®) changes the paradigm, introduces a\u0000novel, cellularly selective and immunogenic cell-ruination. The mEHT method produces tumor-vaccination,\u0000presenting the unharmed genetic information of cancer cells to immune cells [1]. The mEHT method is\u0000approved in more than 30 countries. Its phase II/III clinical applications indicate a broad perspective.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79279867","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 : 2020-08-31DOI: 10.31487/j.cor.2020.08.28
T. Ishikawa, Saori Endo, M. Imai, Motoi Azumi, Yujiro Nozawa, Tomoe Sano, A. Iwanaga, T. Honma, Toshiaki Yoshida
Objective: Lenvatinib is considered the first-line treatment for unresectable advanced hepatocellular carcinoma (HCC); however, in some clinical cases, discontinuation of lenvatinib is unavoidable. It is important to elucidate if transcatheter arterial infusion (TAI) with drug-eluting beads transarterial chemoembolization (DEB-TACE) is a feasible second-line treatment after discontinuing lenvatinib. In this study, we aimed to evaluate the efficacy, hepatic function and nutritional status associated with TAI with DEB-TACE for patients who previously discontinued lenvatinib. Materials and Methods: We included 35 patients who were prescribed lenvatinib for unresectable HCC between July 2018 and December 2019, of whom 12 discontinued lenvatinib during the study. The changes in the albumin-bilirubin (ALBI) score and the controlling nutritional status (CONUT) score before and after discontinuing lenvatinib were examined. Furthermore, the tolerability and survival of patients treated using TAI with DEB-TACE as a second-line treatment were analysed. Results: The ALBI and CONUT scores were significantly worse when lenvatinib was started and stopped (p<0.05). The CONUT score was significantly worse in the second-line group than in the follow-up group when beginning and discontinuing lenvatinib; however, this score tended to improve after DEB-TACE. The group that underwent TAI with DEB-TACE as a second-line treatment had significantly better survival than the follow-up group (log‑rank test, p=0.029; generalized Wilcoxon test, p=0.042). Conclusion: In patients who could undergo TAI with DEB-TACE as a second-line treatment after discontinuing lenvatinib, the CONUT score improved, while the ALBI score was maintained and welltolerated; these scores may have contributed to improved survival compared with follow-up patients. Future studies with larger sample sizes are necessary to confirm our findings.
{"title":"Additional Treatment Using Transcatheter Arterial Infusion with Drug-Eluting Beads Transarterial Chemoembolization Contributes to Prolonged Survival of Patients with BCLC Stage C Hepatocellular Carcinoma after Discontinuing Lenvatinib: Preliminary Study","authors":"T. Ishikawa, Saori Endo, M. Imai, Motoi Azumi, Yujiro Nozawa, Tomoe Sano, A. Iwanaga, T. Honma, Toshiaki Yoshida","doi":"10.31487/j.cor.2020.08.28","DOIUrl":"https://doi.org/10.31487/j.cor.2020.08.28","url":null,"abstract":"Objective: Lenvatinib is considered the first-line treatment for unresectable advanced hepatocellular\u0000carcinoma (HCC); however, in some clinical cases, discontinuation of lenvatinib is unavoidable. It is\u0000important to elucidate if transcatheter arterial infusion (TAI) with drug-eluting beads transarterial\u0000chemoembolization (DEB-TACE) is a feasible second-line treatment after discontinuing lenvatinib. In this\u0000study, we aimed to evaluate the efficacy, hepatic function and nutritional status associated with TAI with\u0000DEB-TACE for patients who previously discontinued lenvatinib.\u0000Materials and Methods: We included 35 patients who were prescribed lenvatinib for unresectable HCC\u0000between July 2018 and December 2019, of whom 12 discontinued lenvatinib during the study. The changes\u0000in the albumin-bilirubin (ALBI) score and the controlling nutritional status (CONUT) score before and after\u0000discontinuing lenvatinib were examined. Furthermore, the tolerability and survival of patients treated using\u0000TAI with DEB-TACE as a second-line treatment were analysed.\u0000Results: The ALBI and CONUT scores were significantly worse when lenvatinib was started and stopped\u0000(p<0.05). The CONUT score was significantly worse in the second-line group than in the follow-up group\u0000when beginning and discontinuing lenvatinib; however, this score tended to improve after DEB-TACE. The\u0000group that underwent TAI with DEB-TACE as a second-line treatment had significantly better survival than\u0000the follow-up group (log‑rank test, p=0.029; generalized Wilcoxon test, p=0.042).\u0000Conclusion: In patients who could undergo TAI with DEB-TACE as a second-line treatment after\u0000discontinuing lenvatinib, the CONUT score improved, while the ALBI score was maintained and welltolerated; these scores may have contributed to improved survival compared with follow-up patients. Future\u0000studies with larger sample sizes are necessary to confirm our findings.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86881333","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 : 2020-08-20DOI: 10.31487/j.cor.2020.08.08
Jongwha Chang, M. Angayen, J. Heo, S. Lopez
Background: Breast cancer is the most commonly diagnosed cancer among women in the United States and it is the leading cause of death among the Hispanic population. Little evidence exists the association of health-related quality of life (HRQoL) by the presence of breast cancer survival among the Latina population. This study was to look at the association of the presence of breast cancer survival on HRQoL measure in the US Hispanic population. Methods: This was a cross-sectional study analyzing data from the 2006-2015 Medical Expenditure Panel Survey (MEPS). The target population was comprised of Hispanic community-dwelling residents with breast cancer in the US. Two multivariate regression models were used to predict HRQoL measure by the presence of breast cancer survival among the Hispanic population. Results: A total 207 breast cancer survivors met the study inclusion criteria, and the estimated population size was 1.200,337 breast cancer survivors. In the multiple regression analysis on the SF-12 PCS scores, age, census region, poverty level, perceived health status, BMI, and employment were associated with SF12 PCS scores. The multiple regression analysis on the SF-12 MCS scores presented that age, census region, insurance type, perceived mental health status, and CCI were associated with SF-12 MCS scores. Conclusion: This study presents data on the HRQoL of Hispanic breast cancer survivors in the U.S. It builds on previous research that examines the HRQoL as expressed through the SF-12 PCS and SF-12 MCS surveys, rather than other types of measurement. This study may also be used as a guide in the implementation of clinical interventions and plans for survivorship care in improving the HRQoL of Hispanic breast cancer survivors.
{"title":"Association of Health-Related Quality of Life with Breast Cancer Survival among Hispanic Population Using 10 Years of MEPS National Sample Cohort Data","authors":"Jongwha Chang, M. Angayen, J. Heo, S. Lopez","doi":"10.31487/j.cor.2020.08.08","DOIUrl":"https://doi.org/10.31487/j.cor.2020.08.08","url":null,"abstract":"Background: Breast cancer is the most commonly diagnosed cancer among women in the United States\u0000and it is the leading cause of death among the Hispanic population. Little evidence exists the association of\u0000health-related quality of life (HRQoL) by the presence of breast cancer survival among the Latina\u0000population. This study was to look at the association of the presence of breast cancer survival on HRQoL\u0000measure in the US Hispanic population.\u0000Methods: This was a cross-sectional study analyzing data from the 2006-2015 Medical Expenditure Panel\u0000Survey (MEPS). The target population was comprised of Hispanic community-dwelling residents with\u0000breast cancer in the US. Two multivariate regression models were used to predict HRQoL measure by the\u0000presence of breast cancer survival among the Hispanic population.\u0000Results: A total 207 breast cancer survivors met the study inclusion criteria, and the estimated population\u0000size was 1.200,337 breast cancer survivors. In the multiple regression analysis on the SF-12 PCS scores,\u0000age, census region, poverty level, perceived health status, BMI, and employment were associated with SF12 PCS scores. The multiple regression analysis on the SF-12 MCS scores presented that age, census region,\u0000insurance type, perceived mental health status, and CCI were associated with SF-12 MCS scores.\u0000Conclusion: This study presents data on the HRQoL of Hispanic breast cancer survivors in the U.S. It builds\u0000on previous research that examines the HRQoL as expressed through the SF-12 PCS and SF-12 MCS\u0000surveys, rather than other types of measurement. This study may also be used as a guide in the\u0000implementation of clinical interventions and plans for survivorship care in improving the HRQoL of\u0000Hispanic breast cancer survivors.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86607106","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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