Pub Date : 2020-04-30DOI: 10.31487/j.cor.2020.04.12
A. Gerger, Austrian Breast, E. Bareck, G. V. Pelt, H. Rabl, H. Gelderblom, K. Geissler, M. Filipits, M. Gnant, P. Götzinger, R. Schaberl-Moser, R. Greil, R. Tollenaar, Stefan W. de Vroome, S. Zunder, T. Bachleitner-Hofmann, W. Mesker, W. Hilbe
Background: Tumor-stroma ratio (TSR) is an independent prognosticator in colon cancer. Objective: We set out to investigate the predictive power, as well as to validate the prognostic power of TSR in stage II colon cancer patients. Better identification of patients who could benefit from adjuvant chemotherapy remains an important issue in stage II disease. Methods: TSR was microscopically determined on haematoxylin and eosin-stained primary tumor tissue slides of 212 patients who received either adjuvant chemotherapy or surveillance after curative resection in a prospective randomized clinical trial (ABCSG-91). Results: Stroma-high tumors were associated with significantly more cancer-related death ((CaDeath) HR 2.30, 95% CI 1.05−5.03; p=0.037) and significantly shorter distant recurrence-free survival ((DRFS) HR 2.32, 95% CI 1.10−4.87; p=0.027) compared to stroma-low tumors. Backward multivariate Cox-regression analysis demonstrated TSR as an independent prognosticator for DRFS (p=0.027) and CaDeath (p=0.031). TSR did not validate as a predictive biomarker; CaDeath (HR 0.87, 95% CI 0.18−4.17; p=0.87), DRFS (HR 0.76, 95% CI 0.17−3.36; p=0.71) and OS (HR 0.96, 95% CI 0.29−3.21; p=0.95) for the type of chemotherapy given in ABCSG-91. Conclusions: TSR, an easily applicable and inexpensive observer-based method, is an independent predictor of poor prognosis in stage II colon cancer. Predictive value for adjuvant 5-FU/leucovorin could not be demonstrated.
背景:肿瘤间质比(TSR)是结肠癌的独立预后指标。目的:探讨tsr在II期结肠癌患者中的预测能力，并验证其预后能力。在II期疾病中，更好地识别可以从辅助化疗中获益的患者仍然是一个重要问题。方法:在前瞻性随机临床试验(ABCSG-91)中，对212例接受辅助化疗或治疗性切除后接受监测的患者的原发肿瘤组织切片，在显微镜下测定血色素和伊红染色的TSR。结果:间质高的肿瘤与更多的癌症相关死亡相关((CaDeath) HR2.30, 95% CI 1.05−5.03;p=0.037)，远端无复发生存期显著缩短((DRFS) HR2.32, 95% CI 1.10−4.87;P =0.027)。多变量反向cox回归分析显示TSR是DRFS (p=0.027)和CaDeath (p=0.031)的独立预测因子。TSR未被证实为预测性生物标志物;CaDeath (HR 0.87, 95% CI 0.18−4.17;p=0.87)， DRFS (HR0.76, 95% CI 0.17−3.36;p=0.71)和OS (HR 0.96, 95% CI 0.29−3.21;p=0.95)与ABCSG-91的化疗类型有关。结论:TSR是一种易于应用且价格低廉的基于观察者的方法，是II期结肠癌预后不良的独立预测指标。辅助5-FU/亚叶酸素的预测价值无法证明。
{"title":"Prognostic and Predictive Value of the Tumor-Stroma Ratio in STAGE II Colon Cancer","authors":"A. Gerger, Austrian Breast, E. Bareck, G. V. Pelt, H. Rabl, H. Gelderblom, K. Geissler, M. Filipits, M. Gnant, P. Götzinger, R. Schaberl-Moser, R. Greil, R. Tollenaar, Stefan W. de Vroome, S. Zunder, T. Bachleitner-Hofmann, W. Mesker, W. Hilbe","doi":"10.31487/j.cor.2020.04.12","DOIUrl":"https://doi.org/10.31487/j.cor.2020.04.12","url":null,"abstract":"Background: Tumor-stroma ratio (TSR) is an independent prognosticator in colon cancer.\u0000Objective: We set out to investigate the predictive power, as well as to validate the prognostic power of\u0000TSR in stage II colon cancer patients. Better identification of patients who could benefit from adjuvant\u0000chemotherapy remains an important issue in stage II disease.\u0000Methods: TSR was microscopically determined on haematoxylin and eosin-stained primary tumor tissue\u0000slides of 212 patients who received either adjuvant chemotherapy or surveillance after curative resection in\u0000a prospective randomized clinical trial (ABCSG-91).\u0000Results: Stroma-high tumors were associated with significantly more cancer-related death ((CaDeath) HR\u00002.30, 95% CI 1.05−5.03; p=0.037) and significantly shorter distant recurrence-free survival ((DRFS) HR\u00002.32, 95% CI 1.10−4.87; p=0.027) compared to stroma-low tumors. Backward multivariate Cox-regression\u0000analysis demonstrated TSR as an independent prognosticator for DRFS (p=0.027) and CaDeath (p=0.031).\u0000TSR did not validate as a predictive biomarker; CaDeath (HR 0.87, 95% CI 0.18−4.17; p=0.87), DRFS (HR\u00000.76, 95% CI 0.17−3.36; p=0.71) and OS (HR 0.96, 95% CI 0.29−3.21; p=0.95) for the type of\u0000chemotherapy given in ABCSG-91.\u0000Conclusions: TSR, an easily applicable and inexpensive observer-based method, is an independent\u0000predictor of poor prognosis in stage II colon cancer. Predictive value for adjuvant 5-FU/leucovorin could\u0000not be demonstrated.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81029494","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 : 2020-04-29DOI: 10.31487/j.cor.2020.04.11
H. Heers, L. Mina, S. Bahadur, S. Lim
Use of adjuvant endocrine therapy for women with hormone-receptor (HR)-positive breast cancer has become the standard of care. Tamoxifen, an orally available selective estrogen receptor modulator (SERM), is a commonly used endocrine therapy agent currently recommended for use in pre- or post-menopausal women with HR-positive breast cancer. Current evidence suggests that prolonged tamoxifen use may be implicated in causing hepatotoxicity which may manifest as non-alcoholic steatohepatitis (NASH), cholestasis, cirrhosis, or hepatic necrosis. We herein present two cases of suspected tamoxifen-induced NASH resulting in fulminant liver failure. We also discuss literature surrounding tamoxifen-related hepatoxicity and implications in clinical practice.
{"title":"Accelerated Onset of Liver Failure after Prolonged Adjuvant Tamoxifen Use in Breast Cancer Patients","authors":"H. Heers, L. Mina, S. Bahadur, S. Lim","doi":"10.31487/j.cor.2020.04.11","DOIUrl":"https://doi.org/10.31487/j.cor.2020.04.11","url":null,"abstract":"Use of adjuvant endocrine therapy for women with hormone-receptor (HR)-positive breast cancer has\u0000become the standard of care. Tamoxifen, an orally available selective estrogen receptor modulator (SERM),\u0000is a commonly used endocrine therapy agent currently recommended for use in pre- or post-menopausal\u0000women with HR-positive breast cancer. Current evidence suggests that prolonged tamoxifen use may be\u0000implicated in causing hepatotoxicity which may manifest as non-alcoholic steatohepatitis (NASH),\u0000cholestasis, cirrhosis, or hepatic necrosis. We herein present two cases of suspected tamoxifen-induced\u0000NASH resulting in fulminant liver failure. We also discuss literature surrounding tamoxifen-related\u0000hepatoxicity and implications in clinical practice.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77894550","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 : 2020-04-29DOI: 10.31487/j.cor.2020.04.09
C. Nathan, Chunjing Zhang, Hong-yan Du, M. Panchatcharam, Sumitra Miriyala, Yunfeng Zhao
Background: New adjuvant therapies for human head and neck (H&N) cancer to improve the quality of life of the patients are in great demand. Our early studies have demonstrated that uncoupling protein 2 (UCP2) is upregulated in the tumor tissues of H&N cancer compared to the adjacent normal tissues; however, the role of UCP2 in H&N cancer has not been studied. Objective: In this manuscript, we aim to examine whether UCP2 contributes to H&N cancer progression in vitro. Methods: We generated UCP2 stable knockdown H&N cancer cells and detected the effects of UCP2 inhibition on cell proliferation, migration, invasion, 3D spheroid formation, and the sensitivity to a chemodrug treatment. Results: Knockdown of UCP2 suppressed the progression of H&N cancer in vitro, which might be mediated via the following mechanism: 1) increased the G1 phase whereas decreased the S phase of the cell cycle, which could be mediated by suppression of the G1/S regulators including CDK4/6 and cyclin D1. 2) Decreased mitochondrial oxygen consumption, ATP production, and lactate formation, which is consistent with the downregulation of c-Myc. 3) FAK may serve as the upstream signaling molecule, and its action was mediated by Akt and ERK. Conclusions: Our studies first demonstrate that targeting UCP2 may suppress H&N cancer progression in vitro.
背景:人们对头颈部肿瘤的新型辅助治疗有很大的需求，以提高患者的生活质量。我们早期的研究表明，与邻近正常组织相比，解偶联蛋白2(uncoupling protein 2, UCP2)在H&N癌的肿瘤组织中表达上调，但UCP2在H&N癌中的作用尚未研究。目的:在本文中，我们旨在研究UCP2是否有助于体外H&N癌症的进展。方法:制备稳定敲除UCP2的H&N肿瘤细胞，检测UCP2抑制对细胞增殖、迁移、侵袭、三维球体形成及化疗药物敏感性的影响。结果:UCP2基因下调可抑制体外H&N癌的进展，其机制可能是:1)细胞周期G1期延长，S期缩短，其机制可能是通过抑制G1/S调控因子CDK4/6和cyclin D1介导。2)线粒体耗氧量、ATP生成和乳酸形成减少，这与c-Myc下调一致。3) FAK可能是上游信号分子，其作用由Akt和ERK介导。结论:我们的研究首次证明靶向UCP2可能抑制H&N癌症的体外进展。
{"title":"Targeting UCP2 Suppresses the FAK Signaling and Progression of Human Head and Neck Cancer Cells","authors":"C. Nathan, Chunjing Zhang, Hong-yan Du, M. Panchatcharam, Sumitra Miriyala, Yunfeng Zhao","doi":"10.31487/j.cor.2020.04.09","DOIUrl":"https://doi.org/10.31487/j.cor.2020.04.09","url":null,"abstract":"Background: New adjuvant therapies for human head and neck (H&N) cancer to improve the quality of\u0000life of the patients are in great demand. Our early studies have demonstrated that uncoupling protein 2\u0000(UCP2) is upregulated in the tumor tissues of H&N cancer compared to the adjacent normal tissues;\u0000however, the role of UCP2 in H&N cancer has not been studied.\u0000Objective: In this manuscript, we aim to examine whether UCP2 contributes to H&N cancer progression\u0000in vitro.\u0000Methods: We generated UCP2 stable knockdown H&N cancer cells and detected the effects of UCP2\u0000inhibition on cell proliferation, migration, invasion, 3D spheroid formation, and the sensitivity to a chemodrug treatment.\u0000Results: Knockdown of UCP2 suppressed the progression of H&N cancer in vitro, which might be mediated\u0000via the following mechanism: 1) increased the G1 phase whereas decreased the S phase of the cell cycle,\u0000which could be mediated by suppression of the G1/S regulators including CDK4/6 and cyclin D1. 2)\u0000Decreased mitochondrial oxygen consumption, ATP production, and lactate formation, which is consistent\u0000with the downregulation of c-Myc. 3) FAK may serve as the upstream signaling molecule, and its action\u0000was mediated by Akt and ERK.\u0000Conclusions: Our studies first demonstrate that targeting UCP2 may suppress H&N cancer progression in\u0000vitro.\u0000","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"100 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74355182","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 : 2020-04-27DOI: 10.31487/j.cor.2020.04.07
Basappa, D. Rangappa, K. Thanuja, K. Rangappa, M. Rani, T. Swaroop
Naturally occurring anacardic acid based benzamides were reported to show anti-inflammatory and anticancer activities, where we synthesized and characterized by NMR and HRMS analysis and also tested a series of anacardic acid based benzamides and evaluated against the proliferation of human liver cancer cells (HepG2). Among the tested compounds, 6j-m showed good inhibitory activity against HepG2 cells with IC50 values ranging from 78.2-91.9 μM. In conclusion, we herein reported the newer series of an academic acid benzamides for the first time.
{"title":"Synthesis, Characterization and Cytotoxic Studies of Benzamide Derivatives of Anacardic Acid using Human Liver Cancer Cells","authors":"Basappa, D. Rangappa, K. Thanuja, K. Rangappa, M. Rani, T. Swaroop","doi":"10.31487/j.cor.2020.04.07","DOIUrl":"https://doi.org/10.31487/j.cor.2020.04.07","url":null,"abstract":"Naturally occurring anacardic acid based benzamides were reported to show anti-inflammatory and\u0000anticancer activities, where we synthesized and characterized by NMR and HRMS analysis and also tested\u0000a series of anacardic acid based benzamides and evaluated against the proliferation of human liver cancer\u0000cells (HepG2). Among the tested compounds, 6j-m showed good inhibitory activity against HepG2 cells\u0000with IC50 values ranging from 78.2-91.9 μM. In conclusion, we herein reported the newer series of an\u0000academic acid benzamides for the first time.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"47 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91350354","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 : 2020-04-21DOI: 10.31487/j.cor.2020.04.05
A. Zuk, Beata Burczyńska, Dong Li, L. Ghali, S. Dilworth, X. Wen
In this study three dimensional (3-D) in vitro models of normal breast and breast cancer tissues were developed to mimic closely the in vivo tissue microenvironment and therefore providing reliable models for in vitro studies as well as testing of novel cancer therapies. Normal and cancerous human breast cell lines were used to construct 3-D artificial tissues, where de-epidermalised dermis (DED) was used as a scaffold for both models. Morphological analyses were conducted using haematoxylin and eosin staining. Biomarkers including keratin 5 and 19 as well as α smooth muscle actin and mucin 1 were used to confirm and validate the reliability of the proposed models using immunohistochemical techniques. Findings suggest that the 3-D in vitro models described in this work can serve as functional models of both human normal and cancerous breast tissues. Multiple structures similar to ducts and lobules of human breast in vivo were observed in 3-D in vitro models by the use of H&E, some breast cancer colonies seen in the cancerous 3-D model were similar to the ducto-lobular structures observed in normal 3-D model of the breast but the former cells were more loosely connected, irregular and largely disorganized. The established 3-D in vitro model of normal breast showed the development of ducto-lobular structures composed of an inner cell layer which was stained positive with α mucin 1 antibody, a biomarker that is characteristic for luminal cells; and also an outer basal layer of cells that was stained positive for α smooth muscle actin, a biomarker of myoepithelial cells.. Keratin staining in 3-D in vitro models also resembled the pattern observed in vivo where keratin 5 was detected in both luminal and myoepithelial cells of normal breast model (NTERT cells), whereas keratin 19 was present in breast cancer model (C2321 cells). These 3-D models successfully recapitulate both normal and pathological tissue architecture of breast tissue and has the potential for various applications in the evaluation of breast cancer progression and treatment.
{"title":"Modelling and Validating Three-Dimensional Human Breast and Cancerous Human Breast Tissues In Vitro","authors":"A. Zuk, Beata Burczyńska, Dong Li, L. Ghali, S. Dilworth, X. Wen","doi":"10.31487/j.cor.2020.04.05","DOIUrl":"https://doi.org/10.31487/j.cor.2020.04.05","url":null,"abstract":"In this study three dimensional (3-D) in vitro models of normal breast and breast cancer tissues were\u0000developed to mimic closely the in vivo tissue microenvironment and therefore providing reliable models for\u0000in vitro studies as well as testing of novel cancer therapies. Normal and cancerous human breast cell lines\u0000were used to construct 3-D artificial tissues, where de-epidermalised dermis (DED) was used as a scaffold\u0000for both models. Morphological analyses were conducted using haematoxylin and eosin staining.\u0000Biomarkers including keratin 5 and 19 as well as α smooth muscle actin and mucin 1 were used to confirm\u0000and validate the reliability of the proposed models using immunohistochemical techniques. Findings suggest\u0000that the 3-D in vitro models described in this work can serve as functional models of both human normal\u0000and cancerous breast tissues. Multiple structures similar to ducts and lobules of human breast in vivo were\u0000observed in 3-D in vitro models by the use of H&E, some breast cancer colonies seen in the cancerous 3-D\u0000model were similar to the ducto-lobular structures observed in normal 3-D model of the breast but the former\u0000cells were more loosely connected, irregular and largely disorganized. The established 3-D in vitro model\u0000of normal breast showed the development of ducto-lobular structures composed of an inner cell layer which\u0000was stained positive with α mucin 1 antibody, a biomarker that is characteristic for luminal cells; and also\u0000an outer basal layer of cells that was stained positive for α smooth muscle actin, a biomarker of myoepithelial\u0000cells.. Keratin staining in 3-D in vitro models also resembled the pattern observed in vivo where keratin 5\u0000was detected in both luminal and myoepithelial cells of normal breast model (NTERT cells), whereas keratin\u000019 was present in breast cancer model (C2321 cells). These 3-D models successfully recapitulate both\u0000normal and pathological tissue architecture of breast tissue and has the potential for various applications in\u0000the evaluation of breast cancer progression and treatment.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"97 6 Pt 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89543549","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 : 2020-04-20DOI: 10.31487/j.cor.2020.04.03
C. Moazez, Dawood Findakly, S. Amar
Background: Hodgkin's lymphoma (HL) is a hematopoietic tumor that is distinguished by the presence of Reed-Sternberg cells in a background of inflammatory cells. Advancements in cancer research have driven significant motions in cancer-related overall survival outcomes, which has led to higher rates of developing secondary neoplasms. Case Presentation: A 22-year-old-woman with a past medical history of non-Hodgkin's lymphoma (NHL) who presents to the hospital for respiratory manifestations and unintentional weight loss. Chest Computed Tomography (CT) scan showed left axillary lymphadenopathy; biopsy proved nodular sclerosing stage IVB HL. The patient started an anthracycline free regimen, but unfortunately, she developed an acute kidney injury, and thus, cisplatin was discontinued and switched to brentuximab therapy with hemodialysis. After the second cycle of salvage brentuximab therapy, the patient was admitted to the hospital for post obstructive pneumonia-causing acute hypoxic respiratory failure, and the decision was made to start the patient on immunotherapy with pembrolizumab. However, during administering pembrolizumab, the patient developed acute respiratory distress, and she ended up requiring emergent intubation and was admitted to the medical intensive care unit. Therefore, it was decided that pembrolizumab will not be given again. The patient later stabilized, and surprisingly, upon follow-up, the patient was found to have negative fluorodeoxyglucose (FDG) PET/CT scan, which indicates the remission of her HL. Conclusion: Recognize the critical role of the anti-programmed cell death protein-1 monoclonal antibodies in patients with chemo-resistant Hodgkin's Lymphoma (HL).
{"title":"Single-Dose Pembrolizumab Achieving Remission in Patient with Refractory Hodgkin’s Lymphoma","authors":"C. Moazez, Dawood Findakly, S. Amar","doi":"10.31487/j.cor.2020.04.03","DOIUrl":"https://doi.org/10.31487/j.cor.2020.04.03","url":null,"abstract":"Background: Hodgkin's lymphoma (HL) is a hematopoietic tumor that is distinguished by the presence of\u0000Reed-Sternberg cells in a background of inflammatory cells. Advancements in cancer research have driven\u0000significant motions in cancer-related overall survival outcomes, which has led to higher rates of developing\u0000secondary neoplasms.\u0000Case Presentation: A 22-year-old-woman with a past medical history of non-Hodgkin's lymphoma (NHL)\u0000who presents to the hospital for respiratory manifestations and unintentional weight loss. Chest Computed\u0000Tomography (CT) scan showed left axillary lymphadenopathy; biopsy proved nodular sclerosing stage IVB\u0000HL. The patient started an anthracycline free regimen, but unfortunately, she developed an acute kidney\u0000injury, and thus, cisplatin was discontinued and switched to brentuximab therapy with hemodialysis. After\u0000the second cycle of salvage brentuximab therapy, the patient was admitted to the hospital for post obstructive\u0000pneumonia-causing acute hypoxic respiratory failure, and the decision was made to start the patient on\u0000immunotherapy with pembrolizumab. However, during administering pembrolizumab, the patient\u0000developed acute respiratory distress, and she ended up requiring emergent intubation and was admitted to\u0000the medical intensive care unit. Therefore, it was decided that pembrolizumab will not be given again. The\u0000patient later stabilized, and surprisingly, upon follow-up, the patient was found to have negative\u0000fluorodeoxyglucose (FDG) PET/CT scan, which indicates the remission of her HL.\u0000Conclusion: Recognize the critical role of the anti-programmed cell death protein-1 monoclonal antibodies\u0000in patients with chemo-resistant Hodgkin's Lymphoma (HL).","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77260449","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 : 2020-04-10DOI: 10.31487/j.cor.2020.03.09
B. Ljungberg, G. Roos, M. Landström, Raviprakash T. Sitaram
Renal cell carcinoma (RCC) encompasses various tumor types characterized by a variety of genetic abnormalities. The genetic changes, like mutations, deletions, and epigenetic alterations, can affect the signaling components and signaling networks, causing the modification of tumor pathogenesis and prognosis of RCC. The most prevalent RCC, clear cell RCC (ccRCC), is asymptomatic in the early stages, refractory to chemotherapy and radiation therapy, and has a poorer prognosis compared with the papillary and chromophobe ccRCC types. Loss of the VHL gene and upregulation of oxygen sensors, hypoxiainducible factor alphas (HIF-α), which promote different growth factors, is a signature of sporadic ccRCC. The VHL-HIF-α and Wnt/β-catenin pathways are closely connected and contribute to the ontogeny of ccRCC. This review confines to ccRCC and the role of the Wnt/β-catenin signaling pathways and its crosstalk with VHL/HIF.
{"title":"Role of Wnt Signaling Pathways in Clear Cell Renal Cell Carcinoma Pathogenesis in Relation to VHL and HIF Status","authors":"B. Ljungberg, G. Roos, M. Landström, Raviprakash T. Sitaram","doi":"10.31487/j.cor.2020.03.09","DOIUrl":"https://doi.org/10.31487/j.cor.2020.03.09","url":null,"abstract":"Renal cell carcinoma (RCC) encompasses various tumor types characterized by a variety of genetic\u0000abnormalities. The genetic changes, like mutations, deletions, and epigenetic alterations, can affect the\u0000signaling components and signaling networks, causing the modification of tumor pathogenesis and\u0000prognosis of RCC. The most prevalent RCC, clear cell RCC (ccRCC), is asymptomatic in the early stages,\u0000refractory to chemotherapy and radiation therapy, and has a poorer prognosis compared with the papillary\u0000and chromophobe ccRCC types. Loss of the VHL gene and upregulation of oxygen sensors, hypoxiainducible factor alphas (HIF-α), which promote different growth factors, is a signature of sporadic ccRCC.\u0000The VHL-HIF-α and Wnt/β-catenin pathways are closely connected and contribute to the ontogeny of\u0000ccRCC. This review confines to ccRCC and the role of the Wnt/β-catenin signaling pathways and its\u0000crosstalk with VHL/HIF.\u0000","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87933274","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 : 2020-04-10DOI: 10.31487/j.cor.2020.03.10
Ming‐Jen Chen, T. Hsu, Wen-Chun Sun
A 56-years-old female had a history of radical proctectomy for carcinoma of rectum on 2003/4/29. Pathology report was Dukes’ C adenocarcinoma with 12 of 24 lymph node showing metastasis. She was managed to have six months of adjuvant chemotherapy of 5- fluorouracil with leucovorin. Computed Tomography (CT) scan on 2013/4/16 was reported as having recurrent tumor in left presacral region with. associated left hydronephrosis and hydroureter. 5400 cGy of radiotherapy was given. CT scan on 2013/8/14 was reported as decreased size of recurrent tumor in left presacral region as compared to last CT with persistent left hydronephrosis and hydroureter due to tumor invasion of middle left ureter. She was then arranged to have chemotherapy of capecitabine, irinotecan oxaliplatin, uracil-futrafur with bevacizumab and Ziv-Aflibercept. Above knee amputation of left leg was performed on 2016/3/29 following poor result of fasciectomy for necrotizing fasciitis. CT scan on 2016/6/6 was reported as interval stable of presacral and left pelvic wall soft tissue mass with calcification, associated left hydronephrosis and hydroureter. 160 mg per day of regorafenib was started from 2016/7/14. She was taking regorafenib regularly in the past three years and 6 months with stable disease. Her last CT scan on 2019/12/27 was reported as stationary appearance of the calcified soft tissue lesion in left presacral region with ipsilateral hydronephroureter and obliteration ipsilateral common iliac vein with prominent venous collaterals in anterior wall of pelvis and with mild left thigh edematous change.
{"title":"Long Term Survival of a Patient with Metastatic Rectal Cancer Treated with Oral Regorafenib - A Case Report","authors":"Ming‐Jen Chen, T. Hsu, Wen-Chun Sun","doi":"10.31487/j.cor.2020.03.10","DOIUrl":"https://doi.org/10.31487/j.cor.2020.03.10","url":null,"abstract":"A 56-years-old female had a history of radical proctectomy for carcinoma of rectum on 2003/4/29.\u0000Pathology report was Dukes’ C adenocarcinoma with 12 of 24 lymph node showing metastasis. She\u0000was managed to have six months of adjuvant chemotherapy of 5- fluorouracil with leucovorin.\u0000Computed Tomography (CT) scan on 2013/4/16 was reported as having recurrent tumor in left\u0000presacral region with. associated left hydronephrosis and hydroureter. 5400 cGy of radiotherapy was\u0000given. CT scan on 2013/8/14 was reported as decreased size of recurrent tumor in left presacral region\u0000as compared to last CT with persistent left hydronephrosis and hydroureter due to tumor invasion of\u0000middle left ureter. She was then arranged to have chemotherapy of capecitabine, irinotecan oxaliplatin,\u0000uracil-futrafur with bevacizumab and Ziv-Aflibercept. Above knee amputation of left leg was\u0000performed on 2016/3/29 following poor result of fasciectomy for necrotizing fasciitis. CT scan on\u00002016/6/6 was reported as interval stable of presacral and left pelvic wall soft tissue mass with\u0000calcification, associated left hydronephrosis and hydroureter. 160 mg per day of regorafenib was started\u0000from 2016/7/14. She was taking regorafenib regularly in the past three years and 6 months with stable\u0000disease. Her last CT scan on 2019/12/27 was reported as stationary appearance of the calcified soft\u0000tissue lesion in left presacral region with ipsilateral hydronephroureter and obliteration ipsilateral\u0000common iliac vein with prominent venous collaterals in anterior wall of pelvis and with mild left thigh\u0000edematous change.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90157002","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 : 2020-04-01DOI: 10.31487/j.cor.2020.03.08
Lei-ming Guo, Cheng-zhe Yang, Chun-yu He, Ke Li, L. Qiao, Shuning Xu, Xiaoyuan Wu, Y. Liu
Majority Chinese esophageal cancer patients have squamous cell carcinoma (ESCC) and with metastasis at initial diagnosis. Treatment for metastatic ESCC where first-line chemotherapy failed is an unmet medical need. Targeting human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor receptor 2 (KDR) have been approved to be effective for esophageal adenocarcinoma (EAC). We explored the clinical relevance of these molecular signaling in ESCC cohorts and collected clinical evidence on applying apatinib, a Chinese FDA-approved KDR inhibitor for late-stage gastric carcinoma, in 26 patients with chemotherapy-refractory metastatic ESCC. The clinical response rate and disease control rate of these patients to apatinib 500mg once daily regimen was 12% and 60%, respectively. The patients’ median progression-free survival time (PFS) was 3.2 months (95% CI, 2.23-4.17 months) and overall survival time (OS) was 5.3 months (95% CI, 4.46-6.14 months). The most common grade 3-4 treatment-related adverse events included leukopenia (7.7%) and anemia (7.7%). No drug-related death occurred. In conclusion, apatinib has favorable activity and acceptable safety, and could be a new treatment option for patients with chemotherapy refractory metastatic ESCC.
{"title":"Clinical Evidence on Apatinib in Treating Chemotherapy-Refractory Metastatic Esophageal Squamous Cell Carcinoma","authors":"Lei-ming Guo, Cheng-zhe Yang, Chun-yu He, Ke Li, L. Qiao, Shuning Xu, Xiaoyuan Wu, Y. Liu","doi":"10.31487/j.cor.2020.03.08","DOIUrl":"https://doi.org/10.31487/j.cor.2020.03.08","url":null,"abstract":"Majority Chinese esophageal cancer patients have squamous cell carcinoma (ESCC) and with metastasis at\u0000initial diagnosis. Treatment for metastatic ESCC where first-line chemotherapy failed is an unmet medical\u0000need. Targeting human epidermal growth factor receptor 2 (HER2) and vascular endothelial growth factor\u0000receptor 2 (KDR) have been approved to be effective for esophageal adenocarcinoma (EAC). We explored\u0000the clinical relevance of these molecular signaling in ESCC cohorts and collected clinical evidence on\u0000applying apatinib, a Chinese FDA-approved KDR inhibitor for late-stage gastric carcinoma, in 26 patients\u0000with chemotherapy-refractory metastatic ESCC. The clinical response rate and disease control rate of these\u0000patients to apatinib 500mg once daily regimen was 12% and 60%, respectively. The patients’ median\u0000progression-free survival time (PFS) was 3.2 months (95% CI, 2.23-4.17 months) and overall survival time\u0000(OS) was 5.3 months (95% CI, 4.46-6.14 months). The most common grade 3-4 treatment-related adverse\u0000events included leukopenia (7.7%) and anemia (7.7%). No drug-related death occurred. In conclusion,\u0000apatinib has favorable activity and acceptable safety, and could be a new treatment option for patients with\u0000chemotherapy refractory metastatic ESCC.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79469872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-03-31DOI: 10.31487/j.cor.2020.03.07
Dawood Findakly, S. Amar
Background: Phosphatidylinositol 3-kinase (PI3K) is an essential target in lymphoid tumors therapy. Copanlisib is a novel class of medication that targets PI3K and used for the treatment of relapsing or refractory B-cell lymphomas. Case Presentation: A 42-year-old woman presents to our hospital for worsening abdominal pain. Examination pertinent for axillary lymphadenopathy, and abdominal ascites. CT chest, abdomen and pelvis reported multiple lung nodules, pleural effusions, extensive retroperitoneal lymphadenopathy, and peritoneal carcinomatosis. Lymph node and bone marrow biopsies confirmed B-cell follicular lymphoma and fluorescent in situ hybridization (FISH) testing was positive for translocation t(14:18). Her disease was refractory to multiple chemotherapy regimens. Thus, initiated copanlisib therapy with a remarkable response, but the patient developed a diffuse maculopapular rash and skin biopsy-proven to be drug rash. Therefore, copanlisib was discontinued. Conclusion: Here, we report a case of a middle-aged woman who developed a rash after the fifth cycle of copanlisib therapy. This case report will create awareness of evolving possible side effects in this novel chemotherapeutic agent.
{"title":"Copanlisib-Associated Skin Toxicity: A Peculiar Case of Copanlisib-Induced Skin Rash in a Patient with Refractory Follicular Lymphoma","authors":"Dawood Findakly, S. Amar","doi":"10.31487/j.cor.2020.03.07","DOIUrl":"https://doi.org/10.31487/j.cor.2020.03.07","url":null,"abstract":"Background: Phosphatidylinositol 3-kinase (PI3K) is an essential target in lymphoid tumors therapy.\u0000Copanlisib is a novel class of medication that targets PI3K and used for the treatment of relapsing or\u0000refractory B-cell lymphomas.\u0000Case Presentation: A 42-year-old woman presents to our hospital for worsening abdominal pain.\u0000Examination pertinent for axillary lymphadenopathy, and abdominal ascites. CT chest, abdomen and pelvis\u0000reported multiple lung nodules, pleural effusions, extensive retroperitoneal lymphadenopathy, and\u0000peritoneal carcinomatosis. Lymph node and bone marrow biopsies confirmed B-cell follicular lymphoma\u0000and fluorescent in situ hybridization (FISH) testing was positive for translocation t(14:18). Her disease was\u0000refractory to multiple chemotherapy regimens. Thus, initiated copanlisib therapy with a remarkable\u0000response, but the patient developed a diffuse maculopapular rash and skin biopsy-proven to be drug rash.\u0000Therefore, copanlisib was discontinued.\u0000Conclusion: Here, we report a case of a middle-aged woman who developed a rash after the fifth cycle of\u0000copanlisib therapy. This case report will create awareness of evolving possible side effects in this novel\u0000chemotherapeutic agent.","PeriodicalId":10487,"journal":{"name":"Clinical Oncology and Research","volume":"108 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91550259","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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