Triple-negative breast cancers (TNBC) lack estrogen receptor (ER), progesterone receptor and epidermal growth factor receptor HER2 and share many features of basal-like breast cancer (BLBC). Therefore, these patients have to rely on chemotherapy. The mechanistic target of rapamycin complex 1 (mTORC1) as well as its downstream targets p70 S6 kinase (S6K1) and S6K2 have been implicated in breast cancer. The 40S ribosomal protein S6 kinase 2 (S6K2) has been associated with endocrine resistance. We have previously shown that S6K2 protects against apoptotic cell death in ER-positive breast cancer cells. In the present study, we investigated if S6K2 could serve as a potential target for TNBC. Our analysis of TCGA dataset as well as immunohistochemistry of patient samples revealed that S6K2 is overexpressed not only in ER-positive but also in TN breast tumors compared to normal breast tissues. Silencing of S6K2 by siRNA enhanced sensitivity of BLBC MCF10CA1d cells to chemotherapeutic drugs cisplatin and doxorubicin. S6K2 knockdown also increased sensitivity of BLBC MCF10CA1a and TNBC HCC1395 cells to TRAIL. While S6K2 knockdown alone had little effect on apoptosis, it enhanced TRAIL-induced apoptosis as judged by the increase in caspase-3 activity, PARP cleavage and annexin V/PI staining. Overexpression of constitutively-active S6K2 construct in MDA-MB-231 cells protected against TRAIL-induced apoptosis. These results suggest that S6K2 also promotes survival of TNBC. Therefore, targeting S6K2 in combination with chemotherapeutic agents could improve therapy of TNBC.
{"title":"https://researchopenworld.com/ribosomal-s6-kinase-2-promotes-survival-of-triple-negative-breast-cancer-cells-to-apoptotic-stimuli/#","authors":"Savitha Sridharan, Zhenyu Xuan, A. Basu","doi":"10.31038/cst.2019432","DOIUrl":"https://doi.org/10.31038/cst.2019432","url":null,"abstract":"Triple-negative breast cancers (TNBC) lack estrogen receptor (ER), progesterone receptor and epidermal growth factor receptor HER2 and share many features of basal-like breast cancer (BLBC). Therefore, these patients have to rely on chemotherapy. The mechanistic target of rapamycin complex 1 (mTORC1) as well as its downstream targets p70 S6 kinase (S6K1) and S6K2 have been implicated in breast cancer. The 40S ribosomal protein S6 kinase 2 (S6K2) has been associated with endocrine resistance. We have previously shown that S6K2 protects against apoptotic cell death in ER-positive breast cancer cells. In the present study, we investigated if S6K2 could serve as a potential target for TNBC. Our analysis of TCGA dataset as well as immunohistochemistry of patient samples revealed that S6K2 is overexpressed not only in ER-positive but also in TN breast tumors compared to normal breast tissues. Silencing of S6K2 by siRNA enhanced sensitivity of BLBC MCF10CA1d cells to chemotherapeutic drugs cisplatin and doxorubicin. S6K2 knockdown also increased sensitivity of BLBC MCF10CA1a and TNBC HCC1395 cells to TRAIL. While S6K2 knockdown alone had little effect on apoptosis, it enhanced TRAIL-induced apoptosis as judged by the increase in caspase-3 activity, PARP cleavage and annexin V/PI staining. Overexpression of constitutively-active S6K2 construct in MDA-MB-231 cells protected against TRAIL-induced apoptosis. These results suggest that S6K2 also promotes survival of TNBC. Therefore, targeting S6K2 in combination with chemotherapeutic agents could improve therapy of TNBC.","PeriodicalId":72517,"journal":{"name":"Cancer studies and therapeutics","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87931124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Grossert, Silvia Heinz, Livia Müller, J. Gaab, C. Urech, T. Berger, Viviane Hess
Background: Online health interventions are becoming increasingly frequent. However, to prove effective and satisfy the specific needs of cancer patients, the standardized steps of development are crucial. This includes structured usability testing to identify potential usability issues in the patient-specific context early during the development process of a new program. Methods: Usability of a newly developed online stress management program was prospectively assessed in patients with solid tumors undergoing systemic treatment. In an academic computer-lab facility, each patient was asked to fulfill 16 tasks, which covered key components of the program including website navigation, login-in to secure area, filling-in forms, accessing audio files, and contacting the trial team. Usability problems during these tasks were identified via the think-aloud method and video recording and categorized. General usability was tested with the System Usability Scale (SUS). Results: A total of 165 tasks from 11 patients were analyzed. Overall usability was high (mean System Usability Scale score 83.6) exceeding the pre-defined cut-off of 70. Participants solved 97% (160/165) of all tasks, the majority (76%) independently. A total of 122 specific usability problems were identified, predominantly concerning website functionality (50.8%) and navigation (29.5%). Conclusions: Structured usability testing of a novel online intervention in the target population of cancer patients allowed for identification and subsequent correction of a significant number of usability problems. This crucial step allowed for a patient-friendly, self-explanatory online program with enhanced user-specific functionality, navigation and terminology before embarking on the subsequent randomized trial.
{"title":"https://researchopenworld.com/usability-testing-of-the-online-stress-management-intervention-stream-for-cancer-patients-results-and-implementations/#","authors":"A. Grossert, Silvia Heinz, Livia Müller, J. Gaab, C. Urech, T. Berger, Viviane Hess","doi":"10.31038/cst.2019422","DOIUrl":"https://doi.org/10.31038/cst.2019422","url":null,"abstract":"Background: Online health interventions are becoming increasingly frequent. However, to prove effective and satisfy the specific needs of cancer patients, the standardized steps of development are crucial. This includes structured usability testing to identify potential usability issues in the patient-specific context early during the development process of a new program. Methods: Usability of a newly developed online stress management program was prospectively assessed in patients with solid tumors undergoing systemic treatment. In an academic computer-lab facility, each patient was asked to fulfill 16 tasks, which covered key components of the program including website navigation, login-in to secure area, filling-in forms, accessing audio files, and contacting the trial team. Usability problems during these tasks were identified via the think-aloud method and video recording and categorized. General usability was tested with the System Usability Scale (SUS). Results: A total of 165 tasks from 11 patients were analyzed. Overall usability was high (mean System Usability Scale score 83.6) exceeding the pre-defined cut-off of 70. Participants solved 97% (160/165) of all tasks, the majority (76%) independently. A total of 122 specific usability problems were identified, predominantly concerning website functionality (50.8%) and navigation (29.5%). Conclusions: Structured usability testing of a novel online intervention in the target population of cancer patients allowed for identification and subsequent correction of a significant number of usability problems. This crucial step allowed for a patient-friendly, self-explanatory online program with enhanced user-specific functionality, navigation and terminology before embarking on the subsequent randomized trial.","PeriodicalId":72517,"journal":{"name":"Cancer studies and therapeutics","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91138708","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}
B. Traore, A. Barry, T. Kourouma, M. Keita, M. Cissé
Purpose: To determine the frequency of albino skin cancers and to describe the difficulties related to the diagnostic and therapeutic management of these patients in Guinea. Material and methods: This was a retrospective cohort study on albinos attending Surgical Oncology Unit of Donka National Hospital for skin cancer from March 17, 2007, to December 17, 2016. Results: We identified the 30 albinoes who presented 41 skin cancer lesions. There were 18 (60.0%) women and 12 (40.0%) men. The average consultation delay was 28.3 months. Patients were housewives in 10 cases (33%), merchants in 8 cases (26.6%) and students in 6 cases (20.0%). The primary sites were the face in 22 cases (73.3%), trunk in 4 cases (13.3%) and neck in 3 cases (10.0%). There were squamous cell carcinoma in 29 cases (96.7%) and sarcoma 1 case (3.3%). The clinical stage was localized in 16 cases (53, 3%), locally advanced in 13 cases (43.3%) and metastatic in 1 case (3.3%). Wide surgical excision performed in 17 (56.7%) for 28 lesions. Wound closure was achieved by a myocutaneous flap in 15 cases, directed scarring in 7 cases, direct suture in 4 cases and skin graft in 2 cases. After a median follow-up of 8 months, 2 patients presented with relapse and 3 new tumor lesions and 9 (30.0%) died. At 24 months, overall survival was 29.0%. Conclusion: The incidence of skin cancer is high among albinos. Late diagnosis and inaccessibility to means of treatment are factors limiting the management of this vulnerable group.
{"title":"https://researchopenworld.com/skin-cancers-in-albinos-at-surgical-oncology-unit-of-donka-national-hospital-conakry/#","authors":"B. Traore, A. Barry, T. Kourouma, M. Keita, M. Cissé","doi":"10.31038/cst.2019413","DOIUrl":"https://doi.org/10.31038/cst.2019413","url":null,"abstract":"Purpose: To determine the frequency of albino skin cancers and to describe the difficulties related to the diagnostic and therapeutic management of these patients in Guinea. Material and methods: This was a retrospective cohort study on albinos attending Surgical Oncology Unit of Donka National Hospital for skin cancer from March 17, 2007, to December 17, 2016. Results: We identified the 30 albinoes who presented 41 skin cancer lesions. There were 18 (60.0%) women and 12 (40.0%) men. The average consultation delay was 28.3 months. Patients were housewives in 10 cases (33%), merchants in 8 cases (26.6%) and students in 6 cases (20.0%). The primary sites were the face in 22 cases (73.3%), trunk in 4 cases (13.3%) and neck in 3 cases (10.0%). There were squamous cell carcinoma in 29 cases (96.7%) and sarcoma 1 case (3.3%). The clinical stage was localized in 16 cases (53, 3%), locally advanced in 13 cases (43.3%) and metastatic in 1 case (3.3%). Wide surgical excision performed in 17 (56.7%) for 28 lesions. Wound closure was achieved by a myocutaneous flap in 15 cases, directed scarring in 7 cases, direct suture in 4 cases and skin graft in 2 cases. After a median follow-up of 8 months, 2 patients presented with relapse and 3 new tumor lesions and 9 (30.0%) died. At 24 months, overall survival was 29.0%. Conclusion: The incidence of skin cancer is high among albinos. Late diagnosis and inaccessibility to means of treatment are factors limiting the management of this vulnerable group.","PeriodicalId":72517,"journal":{"name":"Cancer studies and therapeutics","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82040598","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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