Yan Dong, Jigeng Bai, Yuping Zhang, Guangjie Shang, Yan Zhao, Sha Li, N. Yan, Su-Juan Hao, Wenjuan Zhang
Purpose: In China the number of pathologists is far from being enough to meet the demands of ongoing population based cervical cancer screening programs. This article aims to present our experience with automated quantitative cytology imaging platform, a reading system with an artificial intelligence that we currently use routinely for cervical cancer screening in Shanxi province. Methods: From 2012-2016 a total of 40 178 women were screened. Women were divided into three groups and each group had two subgroups. Smear and liquid based technique were compared using manual and automated platform. Results: Detection rates of CIN2 + and positive rates of CIN2 were higher in all three groups when automated quantitative cytology platform was used compared with groups where reading was done by the pathologist using conventional microscope. Operator’s costs associated with automated quantitative cytology platform vs. conventional reading using light microscope were compared too. The overall costs of operations based on automated platform were proven to be lower. Conclusion: The use of automated platform and artificial intelligence as a means to overcome the lack of cytotechnologists and pathologists and to implement proper quality control in the large scale population based cervical cancer screening seems very promising.
{"title":"Automated Quantitative Cytology Imaging Analysis System in Cervical Cancer Screening in Shanxi Province, China","authors":"Yan Dong, Jigeng Bai, Yuping Zhang, Guangjie Shang, Yan Zhao, Sha Li, N. Yan, Su-Juan Hao, Wenjuan Zhang","doi":"10.5539/CCO.V6N2P51","DOIUrl":"https://doi.org/10.5539/CCO.V6N2P51","url":null,"abstract":"Purpose: In China the number of pathologists is far from being enough to meet the demands of ongoing population based cervical cancer screening programs. This article aims to present our experience with automated quantitative cytology imaging platform, a reading system with an artificial intelligence that we currently use routinely for cervical cancer screening in Shanxi province. Methods: From 2012-2016 a total of 40 178 women were screened. Women were divided into three groups and each group had two subgroups. Smear and liquid based technique were compared using manual and automated platform. Results: Detection rates of CIN2 + and positive rates of CIN2 were higher in all three groups when automated quantitative cytology platform was used compared with groups where reading was done by the pathologist using conventional microscope. Operator’s costs associated with automated quantitative cytology platform vs. conventional reading using light microscope were compared too. The overall costs of operations based on automated platform were proven to be lower. Conclusion: The use of automated platform and artificial intelligence as a means to overcome the lack of cytotechnologists and pathologists and to implement proper quality control in the large scale population based cervical cancer screening seems very promising.","PeriodicalId":89904,"journal":{"name":"Cancer and clinical oncology","volume":" ","pages":"51"},"PeriodicalIF":0.0,"publicationDate":"2017-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5539/CCO.V6N2P51","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43999058","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}
M. Ogata, H. Satake, T. Ogata, Y. Imai, Y. Hatachi, H. Yasui
Erlotinib plus gemcitabine is one of the standard chemotherapies for unresectable pancreatic cancer. Pancreatic cancer has the highest frequency of KRAS gene mutations among human cancers, and some studies suggest that KRAS status might be a predictive biomarker for anti-epidermal growth factor receptor treatment. However, the reliability of this biomarker has not been confirmed. Here, we evaluated the impact of KRAS mutations in pancreatic cancer patients treated with first line gemcitabine-based chemotherapy. 23 patients treated with gemcitabine-based chemotherapy whose KRAS status could be examined from primary or metastatic lesions were enrolled. KRAS mutations were analyzed by sequencing codons 12 and 13. We retrospectively evaluated the correlation between KRAS status, and prognosis and treatment efficacy. Patient characteristics were as follows: median age 68 years, male/female=6/17, PS 0/1=9/14, TNM stage III/IV=1/22, and gemcitabine alone/erlotinib plus gemcitabine=13/10. Among the 23 patients, KRAS codon 12 was mutated in 15, one of whom also had mutation on codon 13. Median progression-free survival (PFS) and overall survival (OS) of all patients were 4.3 months (95% confidence interval (CI): 3.1 to 5.4) and 8.1 months (95% CI: 5.9 to 10.0; events in 96%), respectively. KRAS status showed no association with PFS (p=0.310), OS (p=0.934), or the efficacy of treatment with (p=0.833) or without erlotinib (p=0.478). Thus, in this study, there was no correlation between KRAS status and the efficacy of first line chemotherapy with gemcitabine with or without erlotinib. Identification of a rationale for personalized medicine in pancreatic cancer will require further exploratory prospective studies.
{"title":"No Correlation between KRAS Status and Advanced Pancreatic Adenocarcinoma Survival","authors":"M. Ogata, H. Satake, T. Ogata, Y. Imai, Y. Hatachi, H. Yasui","doi":"10.5539/CCO.V6N2P45","DOIUrl":"https://doi.org/10.5539/CCO.V6N2P45","url":null,"abstract":"Erlotinib plus gemcitabine is one of the standard chemotherapies for unresectable pancreatic cancer. Pancreatic cancer has the highest frequency of KRAS gene mutations among human cancers, and some studies suggest that KRAS status might be a predictive biomarker for anti-epidermal growth factor receptor treatment. However, the reliability of this biomarker has not been confirmed. Here, we evaluated the impact of KRAS mutations in pancreatic cancer patients treated with first line gemcitabine-based chemotherapy. 23 patients treated with gemcitabine-based chemotherapy whose KRAS status could be examined from primary or metastatic lesions were enrolled. KRAS mutations were analyzed by sequencing codons 12 and 13. We retrospectively evaluated the correlation between KRAS status, and prognosis and treatment efficacy. Patient characteristics were as follows: median age 68 years, male/female=6/17, PS 0/1=9/14, TNM stage III/IV=1/22, and gemcitabine alone/erlotinib plus gemcitabine=13/10. Among the 23 patients, KRAS codon 12 was mutated in 15, one of whom also had mutation on codon 13. Median progression-free survival (PFS) and overall survival (OS) of all patients were 4.3 months (95% confidence interval (CI): 3.1 to 5.4) and 8.1 months (95% CI: 5.9 to 10.0; events in 96%), respectively. KRAS status showed no association with PFS (p=0.310), OS (p=0.934), or the efficacy of treatment with (p=0.833) or without erlotinib (p=0.478). Thus, in this study, there was no correlation between KRAS status and the efficacy of first line chemotherapy with gemcitabine with or without erlotinib. Identification of a rationale for personalized medicine in pancreatic cancer will require further exploratory prospective studies.","PeriodicalId":89904,"journal":{"name":"Cancer and clinical oncology","volume":"6 1","pages":"45"},"PeriodicalIF":0.0,"publicationDate":"2017-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5539/CCO.V6N2P45","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44017515","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}
T. Yong, N. Houli, G. Starkey, M. Nikfarjam, Robert Jones, M. Fink, V. Muralidharan, M. Perini, C. Christophi
Background: Hepatic resection is the standard treatment for resectable colorectal cancer liver metastases. There is evidence that lymphatics play a role in disease recurrence post-surgery. The aim of this retrospective study is to assess patterns of lymph node recurrence after liver resection. Methods: Patients who had liver resection for colorectal cancer metastasis between 1 January 2010 and 31 December 2015 at 2 institutions in Melbourne, Australia were included. Data was collected from databases located at the 2 surgical centres.Results: Seventy-four patients were included in the study. Follow-up period was for a mean of 31.4 months. Lymph node recurrence was seen in 39.2% of patients during follow-up. Initial recurrence sites after hepatectomy was mainly in visceral-site only. Lymph node recurrences became more prominent during subsequent Recurrence Stages (RS) (RS1 – 22.4%, RS2 – 50.0%, RS3 – 50.0%, RS4 – 71.4%, RS5 – 66.7%, and RS6 – 0%). No predictive factor showed statistically significant relation to development of nodal recurrence. Conclusion: Lymph node recurrences after hepatic resection for liver metastases usually occur subsequent to a visceral-site only metastasis. There is no predictive factor as to which nodal group would be involved due to the complexity of liver lymphatic drainage.
{"title":"Patterns of Lymph Node Recurrence in Colorectal Cancer Liver Metastases after Surgery: A Retrospective Longitudinal Study","authors":"T. Yong, N. Houli, G. Starkey, M. Nikfarjam, Robert Jones, M. Fink, V. Muralidharan, M. Perini, C. Christophi","doi":"10.5539/CCO.V6N2P35","DOIUrl":"https://doi.org/10.5539/CCO.V6N2P35","url":null,"abstract":"Background: Hepatic resection is the standard treatment for resectable colorectal cancer liver metastases. There is evidence that lymphatics play a role in disease recurrence post-surgery. The aim of this retrospective study is to assess patterns of lymph node recurrence after liver resection. Methods: Patients who had liver resection for colorectal cancer metastasis between 1 January 2010 and 31 December 2015 at 2 institutions in Melbourne, Australia were included. Data was collected from databases located at the 2 surgical centres.Results: Seventy-four patients were included in the study. Follow-up period was for a mean of 31.4 months. Lymph node recurrence was seen in 39.2% of patients during follow-up. Initial recurrence sites after hepatectomy was mainly in visceral-site only. Lymph node recurrences became more prominent during subsequent Recurrence Stages (RS) (RS1 – 22.4%, RS2 – 50.0%, RS3 – 50.0%, RS4 – 71.4%, RS5 – 66.7%, and RS6 – 0%). No predictive factor showed statistically significant relation to development of nodal recurrence. Conclusion: Lymph node recurrences after hepatic resection for liver metastases usually occur subsequent to a visceral-site only metastasis. There is no predictive factor as to which nodal group would be involved due to the complexity of liver lymphatic drainage.","PeriodicalId":89904,"journal":{"name":"Cancer and clinical oncology","volume":"6 1","pages":"35"},"PeriodicalIF":0.0,"publicationDate":"2017-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5539/CCO.V6N2P35","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"70723200","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}
M. Townsend, Abigail M. Felsted, Zachary E. Ence, Stephen R. Piccolo, R. Robison, K. O’Neill
Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) is a housekeeping enzyme involved in the purine synthesis of guanine and inosine in the salvage pathway. While other salvage pathway enzymes, such as TK1, have been established as biomarkers for both cancer cell proliferation and cancer development, little research been done to evaluate whether HPRT has the same potential as a cancer biomarker. We designed this study to determine if HPRT has value as an identifier of malignancy within the most common types of cancer. We utilized histological samples from lung, colon, prostate, and breast cancer with additional normal tissue to evaluate whether there was any elevation of HPRT within malignant samples. In addition, we also assessed general HPRT expression within patient’s samples from The Cancer Genome Atlas (TCGA) to confirm clinical relevance. We found that within a subset of patients, there was significant elevation of HPRT when compared to normal tissue controls. This elevation was seen in 33-55% of the malignant samples and appears to have no dependence on cancer stage. There were slight differences in staining patterns among all the organ types, but overall each organ displayed the same pattern of ‘HPRT high’ and ‘HPRT low’ populations within malignant samples. We found that in our TCGA samples, there was a similar elevation of HPRT that was significant when compared to normal controls. Overall, as an upregulated enzyme that does not directly correlate with stage, HPRT could become a valuable marker in the early diagnosis of a variety of solid tumors.
{"title":"Elevated Expression of Hypoxanthine Guanine Phosphoribosyltransferase within Malignant Tissue","authors":"M. Townsend, Abigail M. Felsted, Zachary E. Ence, Stephen R. Piccolo, R. Robison, K. O’Neill","doi":"10.5539/CCO.V6N2P19","DOIUrl":"https://doi.org/10.5539/CCO.V6N2P19","url":null,"abstract":"Hypoxanthine Guanine Phosphoribosyltransferase (HPRT) is a housekeeping enzyme involved in the purine synthesis of guanine and inosine in the salvage pathway. While other salvage pathway enzymes, such as TK1, have been established as biomarkers for both cancer cell proliferation and cancer development, little research been done to evaluate whether HPRT has the same potential as a cancer biomarker. We designed this study to determine if HPRT has value as an identifier of malignancy within the most common types of cancer. We utilized histological samples from lung, colon, prostate, and breast cancer with additional normal tissue to evaluate whether there was any elevation of HPRT within malignant samples. In addition, we also assessed general HPRT expression within patient’s samples from The Cancer Genome Atlas (TCGA) to confirm clinical relevance. We found that within a subset of patients, there was significant elevation of HPRT when compared to normal tissue controls. This elevation was seen in 33-55% of the malignant samples and appears to have no dependence on cancer stage. There were slight differences in staining patterns among all the organ types, but overall each organ displayed the same pattern of ‘HPRT high’ and ‘HPRT low’ populations within malignant samples. We found that in our TCGA samples, there was a similar elevation of HPRT that was significant when compared to normal controls. Overall, as an upregulated enzyme that does not directly correlate with stage, HPRT could become a valuable marker in the early diagnosis of a variety of solid tumors.","PeriodicalId":89904,"journal":{"name":"Cancer and clinical oncology","volume":"6 1","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2017-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5539/CCO.V6N2P19","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46290257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The objective of the paper is to elucidate how interconnected biological systems can be better mapped and understood using the rapidly growing area of Big Data. We can harness network efficiencies by analyzing diverse medical data and probe how we can effectively lower the economic cost of finding cures for rare diseases. Most rare diseases are due to genetic abnormalities, many forms of cancers develop due to genetic mutations. Finding cures for rare diseases requires us to understand the biology and biological processes of the human body. In this paper, we explore what the historical shift of focus from pharmacology to biotechnology means for accelerating biomedical solutions. With biotechnology playing a leading role in the field of medical research, we explore how network efficiencies can be harnessed by strengthening the existing knowledge base. Studying rare or orphan diseases provides rich observable statistical data that can be leveraged for finding solutions. Network effects can be squeezed from working with diverse data sets that enables us to generate the highest quality medical knowledge with the fewest resources. This paper examines gene manipulation technologies like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) that can prevent diseases of genetic variety. We further explore the role of the emerging field of Big Data in analyzing large quantities of medical data with the rapid growth of computing power and some of the network efficiencies gained from this endeavor.
{"title":"Future of Medical Research in Rare Diseases and Cancers: Shift from Pharma to Biotech and the Golden Age of Medical Advancement","authors":"Abhith Pallegar","doi":"10.5539/CCO.V6N2P12","DOIUrl":"https://doi.org/10.5539/CCO.V6N2P12","url":null,"abstract":"The objective of the paper is to elucidate how interconnected biological systems can be better mapped and understood using the rapidly growing area of Big Data. We can harness network efficiencies by analyzing diverse medical data and probe how we can effectively lower the economic cost of finding cures for rare diseases. Most rare diseases are due to genetic abnormalities, many forms of cancers develop due to genetic mutations. Finding cures for rare diseases requires us to understand the biology and biological processes of the human body. In this paper, we explore what the historical shift of focus from pharmacology to biotechnology means for accelerating biomedical solutions. With biotechnology playing a leading role in the field of medical research, we explore how network efficiencies can be harnessed by strengthening the existing knowledge base. Studying rare or orphan diseases provides rich observable statistical data that can be leveraged for finding solutions. Network effects can be squeezed from working with diverse data sets that enables us to generate the highest quality medical knowledge with the fewest resources. This paper examines gene manipulation technologies like Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) that can prevent diseases of genetic variety. We further explore the role of the emerging field of Big Data in analyzing large quantities of medical data with the rapid growth of computing power and some of the network efficiencies gained from this endeavor.","PeriodicalId":89904,"journal":{"name":"Cancer and clinical oncology","volume":"6 1","pages":"12"},"PeriodicalIF":0.0,"publicationDate":"2017-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5539/CCO.V6N2P12","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41979522","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}
Background:We have previously shown that stable transfection of the human papillomavirus (HPV) E6*I oncogene can sensitize two HPV negative oropharyngeal cancer (OSCC) cell lines to radiation. In the current study, we extended our work on OSCC to determine whether the HPV E6 oncogene can enhance the radiosensitivity of non-OSCC cell lines.Methods:Three non-OSCC cell lines (melanoma, colorectal adenocarcinoma and large cell lung cancer) were stably transfection with the HPV E6 oncogene (E6 total, E6*I and E6*II) and treated with different doses of radiation. Clonogenic assays were used to measure the radiation survival.Results:Following transfection, there was a reduction in the survival of the melanoma cell line after 2 Gy (SF2) from 0.401 (untransfected) to 0.219 (Melanoma-E6 total). This reduction was not evident at higher doses of radiation. There was no significant change in the SF2 of melanoma-E6*I (0.303) and melanoma-E6*II (0.414). The SF2 colorectal adenocarcinoma and large cell lung cancer cell lines did not change significantly after transfection.Conclusions: The radiosensitizing effect of HPV E6 oncogene is cell line specific. We found no clear evidence of a radiosensitising effect of E6 in these three non-OSCC cancer cell lines.
{"title":"The Effect of Human Papillomavirus E6 Oncogene on the Radiosensitivity of Non-Oropharyngeal Cancer Cells","authors":"A. Hong, Xiaoying Zhang, Xiao Mei Zhang, B. Rose","doi":"10.5539/CCO.V6N2P7","DOIUrl":"https://doi.org/10.5539/CCO.V6N2P7","url":null,"abstract":"Background:We have previously shown that stable transfection of the human papillomavirus (HPV) E6*I oncogene can sensitize two HPV negative oropharyngeal cancer (OSCC) cell lines to radiation. In the current study, we extended our work on OSCC to determine whether the HPV E6 oncogene can enhance the radiosensitivity of non-OSCC cell lines.Methods:Three non-OSCC cell lines (melanoma, colorectal adenocarcinoma and large cell lung cancer) were stably transfection with the HPV E6 oncogene (E6 total, E6*I and E6*II) and treated with different doses of radiation. Clonogenic assays were used to measure the radiation survival.Results:Following transfection, there was a reduction in the survival of the melanoma cell line after 2 Gy (SF2) from 0.401 (untransfected) to 0.219 (Melanoma-E6 total). This reduction was not evident at higher doses of radiation. There was no significant change in the SF2 of melanoma-E6*I (0.303) and melanoma-E6*II (0.414). The SF2 colorectal adenocarcinoma and large cell lung cancer cell lines did not change significantly after transfection.Conclusions: The radiosensitizing effect of HPV E6 oncogene is cell line specific. We found no clear evidence of a radiosensitising effect of E6 in these three non-OSCC cancer cell lines.","PeriodicalId":89904,"journal":{"name":"Cancer and clinical oncology","volume":"6 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2017-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5539/CCO.V6N2P7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46780013","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}
Sarcomatoid differentiation can occur within any subdivision of renal cell carcinoma. Although the prevalence of sarcomatoid renal cell cancer has been reported to be anywhere from 1-15% of renal cancers, sarcomatoid non-clear cell renal carcinoma is actually very rare. Studies on these cancers are generally limited to tens of patients. One reason for the paucity of patients with non-clear cell sarcomatoid renal cell cancer is the aggressive nature of this disease. We present a case of sarcomatoid non-clear cell renal carcinoma and review of the treatment for these difficult cases based on the available literature.
{"title":"Mini-Review: Sarcomatoid Non-Clear Cell Renal Cancer","authors":"Saikrishna Gadde, B. Jones, C. Old","doi":"10.5539/CCO.V6N2P1","DOIUrl":"https://doi.org/10.5539/CCO.V6N2P1","url":null,"abstract":"Sarcomatoid differentiation can occur within any subdivision of renal cell carcinoma. Although the prevalence of sarcomatoid renal cell cancer has been reported to be anywhere from 1-15% of renal cancers, sarcomatoid non-clear cell renal carcinoma is actually very rare. Studies on these cancers are generally limited to tens of patients. One reason for the paucity of patients with non-clear cell sarcomatoid renal cell cancer is the aggressive nature of this disease. We present a case of sarcomatoid non-clear cell renal carcinoma and review of the treatment for these difficult cases based on the available literature.","PeriodicalId":89904,"journal":{"name":"Cancer and clinical oncology","volume":"6 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2017-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5539/CCO.V6N2P1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45027546","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 : 2017-05-01Epub Date: 2016-11-11DOI: 10.5539/cco.v6n1p12
Raluca A Budiu, Anda M Vlad, Linda Nazario, Chandra Bathula, Kristine L Cooper, Jessica Edmed, Premal H Thaker, Julie Urban, Pawel Kalinski, Adrian V Lee, Esther L Elishaev, Thomas P Conrads, Melanie S Flint
The ability of stress to induce immune suppression is widely recognized, but the mechanisms underlying the effects of stress on the adaptive immune system during tumor progression are not completely understood. To study the effect of stress on the immune system in vivo, we used a preclinical immunocompetent mouse model bearing 4T1 mammary adenocarcinoma cells. Mice were randomized into 4 groups, including social isolation (SI), acute restraint stress (aRRS), chronic restraint stress (cRRS), or no stress (NS). We found that SI significantly decreased the number of tumor-bearing mice still alive at the end of protocol (28 days), compared to NS mice. Although we did not detect significant changes in primary tumor volume, we observed a significant increase in the endothelial marker CD31 in primary tumors of SI mice and in lung metastases in SI and RRS mice. Survival decline in SI mice was associated with significant decreases in splenic CD8 cells and in activated T cells. From a mechanistic standpoint, RRS increased expression of FOXP3, CXCL-10, and granzyme B in mouse tumors, and the effects were reversed by propranolol. Our data demonstrate that various forms of stress differentially impact adaptive immunity and tumor angiogenesis, and negatively impact survival.
应激能够诱导免疫抑制，这一点已得到广泛认可，但应激在肿瘤进展过程中对适应性免疫系统的影响机制尚未完全明了。为了研究应激对体内免疫系统的影响，我们使用了一种带有 4T1 乳腺癌细胞的临床前免疫功能正常小鼠模型。小鼠被随机分为 4 组，包括社会隔离组（SI）、急性束缚应激组（aRRS）、慢性束缚应激组（cRRS）或无应激组（NS）。我们发现，与 NS 组小鼠相比，SI 组小鼠在方案结束时（28 天）仍存活的肿瘤小鼠数量明显减少。虽然我们没有检测到原发性肿瘤体积的显著变化，但我们观察到 SI 小鼠原发性肿瘤中的内皮标志物 CD31 以及 SI 和 RRS 小鼠肺转移瘤中的内皮标志物 CD31 显著增加。SI 小鼠存活率的下降与脾脏 CD8 细胞和活化 T 细胞的显著减少有关。从机理的角度来看，RRS 增加了小鼠肿瘤中 FOXP3、CXCL-10 和颗粒酶 B 的表达，而普萘洛尔可逆转这些影响。我们的数据表明，各种形式的压力会对适应性免疫和肿瘤血管生成产生不同的影响，并对生存产生负面影响。
{"title":"Restraint and Social Isolation Stressors Differentially Regulate Adaptive Immunity and Tumor Angiogenesis in a Breast Cancer Mouse Model.","authors":"Raluca A Budiu, Anda M Vlad, Linda Nazario, Chandra Bathula, Kristine L Cooper, Jessica Edmed, Premal H Thaker, Julie Urban, Pawel Kalinski, Adrian V Lee, Esther L Elishaev, Thomas P Conrads, Melanie S Flint","doi":"10.5539/cco.v6n1p12","DOIUrl":"10.5539/cco.v6n1p12","url":null,"abstract":"<p><p>The ability of stress to induce immune suppression is widely recognized, but the mechanisms underlying the effects of stress on the adaptive immune system during tumor progression are not completely understood. To study the effect of stress on the immune system <i>in vivo</i>, we used a preclinical immunocompetent mouse model bearing 4T1 mammary adenocarcinoma cells. Mice were randomized into 4 groups, including social isolation (SI), acute restraint stress (aRRS), chronic restraint stress (cRRS), or no stress (NS). We found that SI significantly decreased the number of tumor-bearing mice still alive at the end of protocol (28 days), compared to NS mice. Although we did not detect significant changes in primary tumor volume, we observed a significant increase in the endothelial marker CD31 in primary tumors of SI mice and in lung metastases in SI and RRS mice. Survival decline in SI mice was associated with significant decreases in splenic CD8 cells and in activated T cells. From a mechanistic standpoint, RRS increased expression of <i>FOXP3, CXCL-10,</i> and <i>granzyme B</i> in mouse tumors, and the effects were reversed by propranolol. Our data demonstrate that various forms of stress differentially impact adaptive immunity and tumor angiogenesis, and negatively impact survival.</p>","PeriodicalId":89904,"journal":{"name":"Cancer and clinical oncology","volume":"6 1","pages":"12-24"},"PeriodicalIF":0.0,"publicationDate":"2017-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35079576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: Many patients describe travel to cancer treatment as inconvenient and a practical hardship and it may be perceived or experienced as a barrier to treatment. We investigated which impact cancer treatments has on the family of the patients, especially for the most frequent cancer type prostate, breast, colon and lung cancer. The aim was to identify groups of patients with an increased burden for the family. Method: All patients coming in February 2012 for chemotherapy to one of the four centres of the hospital or to the unique private practice were asked to answer a survey. The questionnaire covered items as gender, date of birth, living place, kind of cancer, kind of treatment and questions covering different aspects of the travel: how the patient travelled to the centre, how long the travel lasted, which kind of support was necessary to travel and who provided this support, whether the accompanying person had to absent herself from her workplace, whether the patient lives alone or not and how many journeys to health care providers the patients had in the last month were included in the analysis Results: 298 patients answered to all required questions (73%). 186 came accompanied, a vast majority by a member of the family and one out of four of the accompanying person had to leave the workplace. Help at home is almost exclusively provided by family members. Patients have several journeys to health care providers per month. Conclusions: The type of cancer has an impact on the support needed and must added to the previously published factors as age, gender and distance. The journey to the cancer treatment is not the unique journey to health care providers the patients have and increase the burden for the patient and the family.
{"title":"Impact of Treatments on the Family of Breast, Prostate, Colon and Lung Cancer Patients","authors":"P. Groux, S. Anchisi, T. Szucs","doi":"10.5539/cco.v6n1p61","DOIUrl":"https://doi.org/10.5539/cco.v6n1p61","url":null,"abstract":"Objective: Many patients describe travel to cancer treatment as inconvenient and a practical hardship and it may be perceived or experienced as a barrier to treatment. We investigated which impact cancer treatments has on the family of the patients, especially for the most frequent cancer type prostate, breast, colon and lung cancer. The aim was to identify groups of patients with an increased burden for the family. Method: All patients coming in February 2012 for chemotherapy to one of the four centres of the hospital or to the unique private practice were asked to answer a survey. The questionnaire covered items as gender, date of birth, living place, kind of cancer, kind of treatment and questions covering different aspects of the travel: how the patient travelled to the centre, how long the travel lasted, which kind of support was necessary to travel and who provided this support, whether the accompanying person had to absent herself from her workplace, whether the patient lives alone or not and how many journeys to health care providers the patients had in the last month were included in the analysis Results: 298 patients answered to all required questions (73%). 186 came accompanied, a vast majority by a member of the family and one out of four of the accompanying person had to leave the workplace. Help at home is almost exclusively provided by family members. Patients have several journeys to health care providers per month. Conclusions: The type of cancer has an impact on the support needed and must added to the previously published factors as age, gender and distance. The journey to the cancer treatment is not the unique journey to health care providers the patients have and increase the burden for the patient and the family.","PeriodicalId":89904,"journal":{"name":"Cancer and clinical oncology","volume":"6 1","pages":"61"},"PeriodicalIF":0.0,"publicationDate":"2017-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5539/cco.v6n1p61","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49491116","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}
H. Vaghefi, S. Agarwal, Fang Liu, B. Xiong, E. Garber, J. Wheeler
Purpose: To evaluate the toxicity, palliative benefit, and survival benefit of Radium-223 (Ra-223) in a community setting.Introduction: The ALSYMCA (Alpharadin in Symptomatic Prostate Cancer) trial demonstrated improved survival for men with painful bone metastasis from castration resistant prostate cancer who were treated with Ra-223. The median survival was 14.9 months for the Ra-223 patients compared to 11.3 months for patients treated with a placebo.Methods: We identified through the nuclear medicine records 11 patients who started Ra-223 between March 15, 2013 and December 10, 2015. The Wilcoxon signed rank test was used to compare the published results of the ALSYMPCA patients with those from our institution.Results: The Hodges-Lehman estimate of the median survival of our patients from the date of the first Ra-223 infusion was 7.8 months. The 95% confidence interval (CI) was (2.8, 14.7; p=0.0122) indicating our patients had a significantly shorter survival than the Ra-223 ALSYMPCA patients.Our patients did not have a statistically significant worse rate of anemia, neutropenia, or thrombocytopenia. We used 3 measures of treatment effectiveness: 1) reduction in the pain scores, 2) reduction in the serum PSA, and 3) reduction in the alkaline phosphatase from baseline, but the reductions were not statistically significant.Conclusions: This small study is not meant to challenge the results of the ALSYMPCA international trial. It is intended only as a caution that prior lines of therapy, especially with newer agents such as abiraterone and enzalutamide, may attenuate the benefit from this treatment, particularly in elderly patients.Radium-223 in a Community Setting for Castration Resistant Prostate Cancer
{"title":"Radium-223 in a Community Setting for Castration Resistant Prostate Cancer","authors":"H. Vaghefi, S. Agarwal, Fang Liu, B. Xiong, E. Garber, J. Wheeler","doi":"10.5539/CCO.V6N1P44","DOIUrl":"https://doi.org/10.5539/CCO.V6N1P44","url":null,"abstract":"Purpose: To evaluate the toxicity, palliative benefit, and survival benefit of Radium-223 (Ra-223) in a community setting.Introduction: The ALSYMCA (Alpharadin in Symptomatic Prostate Cancer) trial demonstrated improved survival for men with painful bone metastasis from castration resistant prostate cancer who were treated with Ra-223. The median survival was 14.9 months for the Ra-223 patients compared to 11.3 months for patients treated with a placebo.Methods: We identified through the nuclear medicine records 11 patients who started Ra-223 between March 15, 2013 and December 10, 2015. The Wilcoxon signed rank test was used to compare the published results of the ALSYMPCA patients with those from our institution.Results: The Hodges-Lehman estimate of the median survival of our patients from the date of the first Ra-223 infusion was 7.8 months. The 95% confidence interval (CI) was (2.8, 14.7; p=0.0122) indicating our patients had a significantly shorter survival than the Ra-223 ALSYMPCA patients.Our patients did not have a statistically significant worse rate of anemia, neutropenia, or thrombocytopenia. We used 3 measures of treatment effectiveness: 1) reduction in the pain scores, 2) reduction in the serum PSA, and 3) reduction in the alkaline phosphatase from baseline, but the reductions were not statistically significant.Conclusions: This small study is not meant to challenge the results of the ALSYMPCA international trial. It is intended only as a caution that prior lines of therapy, especially with newer agents such as abiraterone and enzalutamide, may attenuate the benefit from this treatment, particularly in elderly patients.Radium-223 in a Community Setting for Castration Resistant Prostate Cancer","PeriodicalId":89904,"journal":{"name":"Cancer and clinical oncology","volume":"6 1","pages":"44"},"PeriodicalIF":0.0,"publicationDate":"2017-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.5539/CCO.V6N1P44","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44112856","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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