Pub Date : 2016-09-01DOI: 10.4103/2395-3977.192930
Shu-yao Zhang, M. Sun, Yun Yuan, Miaojun Wang, Y. She, Li Zhou, Cong-zhu Li, Chen Chen, Sheng-qi Zhang
Aim: Although paclitaxel (PTX) is a widely used chemotherapeutic agent across many cancer types, the correlation between its concentration and treatment efficacy and toxicity is yet to be clarified. Hence, the study aims to determine the correlation between PTX Tc > 0.05 and its therapeutic efficacy and toxicity. Methods: Using MyPaclitaxel™, we measured the blood concentration of PTX in 96 ovarian cancer (stage IIIB to IV) patients, who were admitted to the Cancer Hospital of Shantou University Medical College in Chaoshan, China. PTX Tc > 0.05, the time during which PTX plasma concentration exceed 0.05 μmol/L, is calculated using nonlinear mixed effect model. Results: (1) The PTX Tc > 0.05 was constant and significantly correlated with treatment response and the range of Tc > 0.05 of PTX was 14-36 h. (2) There was no correlation between relative PTX dose and the PTX Tc > 0.05. (3) There was a statistically significant difference in the PTX Tc > 0.05 between complete remission (CR) + partial remission (PR) and stable disease (SD) + progressive disease (P = 0.00185). The PTX Tc > 0.05 in most patients with CR and PR was in the range of 26-30 h. (4) The PTX Tc > 0.05 significantly correlated with the occurrence of leukopenia (P = 0.0002) and leukopenic fever (P = 0.0211), and higher PTX Tc > 0.05 correlated with increased incidence of severe leukopenia and leukopenic fever. (5) Occurrence and severity of peripheral neuropathy significantly correlated with the level of PTX Tc > 0.05 (P = 0.0003, 0.0118). Conclusion: These results indicated that the PTX Tc > 0.05 correlated with therapeutic efficacy and drug toxicity. Therefore, monitoring the PTX Tc > 0.05 other than blood concentration of PTX is necessary to optimize individual treatment.
{"title":"Correlation between paclitaxel Tc > 0.05 and its therapeutic efficacy and severe toxicities in ovarian cancer patients","authors":"Shu-yao Zhang, M. Sun, Yun Yuan, Miaojun Wang, Y. She, Li Zhou, Cong-zhu Li, Chen Chen, Sheng-qi Zhang","doi":"10.4103/2395-3977.192930","DOIUrl":"https://doi.org/10.4103/2395-3977.192930","url":null,"abstract":"Aim: Although paclitaxel (PTX) is a widely used chemotherapeutic agent across many cancer types, the correlation between its concentration and treatment efficacy and toxicity is yet to be clarified. Hence, the study aims to determine the correlation between PTX Tc > 0.05 and its therapeutic efficacy and toxicity. Methods: Using MyPaclitaxel™, we measured the blood concentration of PTX in 96 ovarian cancer (stage IIIB to IV) patients, who were admitted to the Cancer Hospital of Shantou University Medical College in Chaoshan, China. PTX Tc > 0.05, the time during which PTX plasma concentration exceed 0.05 μmol/L, is calculated using nonlinear mixed effect model. Results: (1) The PTX Tc > 0.05 was constant and significantly correlated with treatment response and the range of Tc > 0.05 of PTX was 14-36 h. (2) There was no correlation between relative PTX dose and the PTX Tc > 0.05. (3) There was a statistically significant difference in the PTX Tc > 0.05 between complete remission (CR) + partial remission (PR) and stable disease (SD) + progressive disease (P = 0.00185). The PTX Tc > 0.05 in most patients with CR and PR was in the range of 26-30 h. (4) The PTX Tc > 0.05 significantly correlated with the occurrence of leukopenia (P = 0.0002) and leukopenic fever (P = 0.0211), and higher PTX Tc > 0.05 correlated with increased incidence of severe leukopenia and leukopenic fever. (5) Occurrence and severity of peripheral neuropathy significantly correlated with the level of PTX Tc > 0.05 (P = 0.0003, 0.0118). Conclusion: These results indicated that the PTX Tc > 0.05 correlated with therapeutic efficacy and drug toxicity. Therefore, monitoring the PTX Tc > 0.05 other than blood concentration of PTX is necessary to optimize individual treatment.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"89 1","pages":"131 - 136"},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85470856","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 : 2016-07-01DOI: 10.4103/2395-3977.189302
N. Murray, E. Reyes, N. Orellana, C. Fuentealba, O. Jacob
Aim: The aim of this study was to determine the association of age with the clinicopathological findings, phenotypic expression of circulating prostate cells (CPCs) and micrometastasis, biochemical failure and effect of androgen blockade after radical prostatectomy for prostate cancer in Chilean men. Methods: This is a prospective, observational, single-center study of Chilean men who underwent radical prostatectomy. Three months after surgery, the peripheral blood was collected to analyze the biochemical failure by measuring prostate-specific antigen (PSA) levels in the serum. The blood and bone marrow were collected to detect the presence of CPCs and the bone marrow micrometastasis by checking the expression of PSA, human epidermal growth factor receptor 2 (HER-2), and matrix metalloproteinase 2 (MMP-2) using standard immunocytochemistry. The clinicopathological findings, phenotypic expression of CPCs and micrometastasis, biochemical failure and effect of androgen blockade were analyzed for association with age. Results: In total, 120/338 (36.6%) of patients were ≥ 70 years (older men). A higher frequency of biochemical failure occurred in older men with negative surgical margins, a Gleason score ≥ 8, and pT3 tumors compared to patients < 70 years of age (younger men). The expression of HER-2 and MMP-2 was higher in CPCs and micrometastasis in older men. After androgen blockade, the expression of HER-2 and MMP-2 was similar in both groups. With androgen blockade, more younger men became micrometastasis negative (49% vs. 15%) while more older men became castrate resistant (83% vs. 43%). Conclusion: After radical prostatectomy, the older men with pathological features of Gleason score ≥ 8, pT3 tumors, and positive extracapsular extension had higher frequency of biochemical failure and the presence of CPCs. The treatment of androgen blockade was less successful to suppress the disease relapse in the older men than that in the younger man.
{"title":"Impact of age on the biochemical failure and androgen suppression after radical prostatectomy for prostate cancer in chilean men","authors":"N. Murray, E. Reyes, N. Orellana, C. Fuentealba, O. Jacob","doi":"10.4103/2395-3977.189302","DOIUrl":"https://doi.org/10.4103/2395-3977.189302","url":null,"abstract":"Aim: The aim of this study was to determine the association of age with the clinicopathological findings, phenotypic expression of circulating prostate cells (CPCs) and micrometastasis, biochemical failure and effect of androgen blockade after radical prostatectomy for prostate cancer in Chilean men. Methods: This is a prospective, observational, single-center study of Chilean men who underwent radical prostatectomy. Three months after surgery, the peripheral blood was collected to analyze the biochemical failure by measuring prostate-specific antigen (PSA) levels in the serum. The blood and bone marrow were collected to detect the presence of CPCs and the bone marrow micrometastasis by checking the expression of PSA, human epidermal growth factor receptor 2 (HER-2), and matrix metalloproteinase 2 (MMP-2) using standard immunocytochemistry. The clinicopathological findings, phenotypic expression of CPCs and micrometastasis, biochemical failure and effect of androgen blockade were analyzed for association with age. Results: In total, 120/338 (36.6%) of patients were ≥ 70 years (older men). A higher frequency of biochemical failure occurred in older men with negative surgical margins, a Gleason score ≥ 8, and pT3 tumors compared to patients < 70 years of age (younger men). The expression of HER-2 and MMP-2 was higher in CPCs and micrometastasis in older men. After androgen blockade, the expression of HER-2 and MMP-2 was similar in both groups. With androgen blockade, more younger men became micrometastasis negative (49% vs. 15%) while more older men became castrate resistant (83% vs. 43%). Conclusion: After radical prostatectomy, the older men with pathological features of Gleason score ≥ 8, pT3 tumors, and positive extracapsular extension had higher frequency of biochemical failure and the presence of CPCs. The treatment of androgen blockade was less successful to suppress the disease relapse in the older men than that in the younger man.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"32 1","pages":"105 - 112"},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78933894","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 : 2016-07-01DOI: 10.4103/2395-3977.189305
J. Qi, Hongwei Yang, Xin Wang, Y. Tu
Malignant glioma, a common form of central nervous system tumor, has a poor prognosis. The overall survival of these patients is as low as 12–14 months only. In general, the progress in personal precision medication has been gradually directed toward the molecular profiling of the tumors. Malignant glioma is one such tumor in which treatment response relies largely on its molecular characteristics, thus making the understanding of these markers essential to deliver the best treatment possible. Representative molecular markers (isocitrate dehydrogenase 1 mutation, 1p19q codeletion, epidermal growth factor receptor variant III amplification, human telomerase reverse transcriptase promoter mutations, alpha thalassemia/mental retardation syndrome X-linked mutation, and O[6]-methylguanine DNA methyltransferase promoter methylation) are described/discussed in this article. Furthermore, the research prospects of cell-free DNA, regarded as a new developing trend of molecular markers, are discussed. There is an immense hope in these promising molecular markers which are expected to improve the overall survival and quality of life of malignant glioma patients.
{"title":"The progress in molecular biomarkers of gliomas","authors":"J. Qi, Hongwei Yang, Xin Wang, Y. Tu","doi":"10.4103/2395-3977.189305","DOIUrl":"https://doi.org/10.4103/2395-3977.189305","url":null,"abstract":"Malignant glioma, a common form of central nervous system tumor, has a poor prognosis. The overall survival of these patients is as low as 12–14 months only. In general, the progress in personal precision medication has been gradually directed toward the molecular profiling of the tumors. Malignant glioma is one such tumor in which treatment response relies largely on its molecular characteristics, thus making the understanding of these markers essential to deliver the best treatment possible. Representative molecular markers (isocitrate dehydrogenase 1 mutation, 1p19q codeletion, epidermal growth factor receptor variant III amplification, human telomerase reverse transcriptase promoter mutations, alpha thalassemia/mental retardation syndrome X-linked mutation, and O[6]-methylguanine DNA methyltransferase promoter methylation) are described/discussed in this article. Furthermore, the research prospects of cell-free DNA, regarded as a new developing trend of molecular markers, are discussed. There is an immense hope in these promising molecular markers which are expected to improve the overall survival and quality of life of malignant glioma patients.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"73 1","pages":"125 - 129"},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83969149","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 : 2016-07-01DOI: 10.4103/2395-3977.189304
R. Mahmood, M. Aldehaim, F. Hussain, T. Elhassan, Z. A. Khan, M. Memon
Aim: To assess the incidence and characteristics of carcinoma of unknown primary (CUP). Methods: We retrospectively collected the clinical data of CUP cases treated in our medical center between 1975 and 2010, the results of which were statistically analyzed. Further, a comprehensive literature search, using PubMed database, on CUP cases was performed, and the results were discussed. Results: A total of 1250 cases were identified, with male to female ratio of 1.2:1. Median age at diagnosis was 56 ± 16 years. Liver was the most common site of metastasis, followed by neck and peritoneum. Majority of cases (54.5%) received supportive treatment only, with the overall survival, over 1 year period, being 49%. Univariate analysis revealed pathology, gender, and site of disease as the significant predictors of survival, whereas pathology failed to reach significance on multivariate analysis, with “lymph nodes only” carrying the best prognosis. Conclusion: Our data confirm the heterogeneity of CUP cases and variable treatment courses. This highlights the importance of establishing a national registry for this subgroup of cancer patients. Moreover, there is a need to develop multidisciplinary specialist teams and protocols to manage this group of patients, and participation in clinical trials should be strongly encouraged.
{"title":"Carcinoma of unknown primary: 35 years of a single institution's experience","authors":"R. Mahmood, M. Aldehaim, F. Hussain, T. Elhassan, Z. A. Khan, M. Memon","doi":"10.4103/2395-3977.189304","DOIUrl":"https://doi.org/10.4103/2395-3977.189304","url":null,"abstract":"Aim: To assess the incidence and characteristics of carcinoma of unknown primary (CUP). Methods: We retrospectively collected the clinical data of CUP cases treated in our medical center between 1975 and 2010, the results of which were statistically analyzed. Further, a comprehensive literature search, using PubMed database, on CUP cases was performed, and the results were discussed. Results: A total of 1250 cases were identified, with male to female ratio of 1.2:1. Median age at diagnosis was 56 ± 16 years. Liver was the most common site of metastasis, followed by neck and peritoneum. Majority of cases (54.5%) received supportive treatment only, with the overall survival, over 1 year period, being 49%. Univariate analysis revealed pathology, gender, and site of disease as the significant predictors of survival, whereas pathology failed to reach significance on multivariate analysis, with “lymph nodes only” carrying the best prognosis. Conclusion: Our data confirm the heterogeneity of CUP cases and variable treatment courses. This highlights the importance of establishing a national registry for this subgroup of cancer patients. Moreover, there is a need to develop multidisciplinary specialist teams and protocols to manage this group of patients, and participation in clinical trials should be strongly encouraged.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"32 1","pages":"113 - 118"},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80880328","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}
Overweight and obesity are dramatically increasing worldwide. In addition to being the most important factor for the increase in diabetes prevalence, there is a growing evidence of obesity being also significantly associated with the risks and poor outcome in ovarian cancer (OVC). Metformin is the most widely used first-line type 2 diabetes drug, currently being studied for its association with the decreased risk of occurrence and better survival of OVC patients. In this review, we discussed the proposed mechanisms of metformin-exerted anticancer effects, as well as the preclinical and clinical data suggesting its beneficial effect against this devastating condition.
{"title":"Metformin in ovarian cancer therapy: A discussion","authors":"Yeling Ouyang, X. Chen, Chun-Chen Zhang, Vichitra Bunyamanop, Jianfeng Guo","doi":"10.4103/2395-3977.189306","DOIUrl":"https://doi.org/10.4103/2395-3977.189306","url":null,"abstract":"Overweight and obesity are dramatically increasing worldwide. In addition to being the most important factor for the increase in diabetes prevalence, there is a growing evidence of obesity being also significantly associated with the risks and poor outcome in ovarian cancer (OVC). Metformin is the most widely used first-line type 2 diabetes drug, currently being studied for its association with the decreased risk of occurrence and better survival of OVC patients. In this review, we discussed the proposed mechanisms of metformin-exerted anticancer effects, as well as the preclinical and clinical data suggesting its beneficial effect against this devastating condition.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"12 1","pages":"119 - 124"},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90190568","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 : 2016-07-01DOI: 10.4103/2395-3977.189303
K. Deepalakshmi, S. Mirunalini
Aim: The aim of this study was to explore the antiproliferative and apoptotic effect of Pleurotus ostreatus ethanolic extract (POEet) on human mammary carcinoma cell line (Michigan cancer foundation-7 [MCF-7]). Methods: Gas chromatography-mass spectrometry (GC-MS) was performed to isolate and quantify the active constituent of POEet chloroform fraction. Cytotoxic property of POEet on MCF-7 and Vero cells was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. We further evaluated the apoptotic effect by measuring the mitochondrial membrane potential (ΔΨm), dual staining (acridine orange/ethidium bromide), comet assay, DNA fragmentation, and oxidant/antioxidant status in MCF-7 cells treated with and without POEet. Results: GC-MS analysis identified 30 phytochemical constituents from the POEet chloroform fraction. MTT assay revealed a greater degree of cytotoxicity at almost all doses of POEet, with IC30 value (164.59 µg/mL) and IC50 value (1024.02 µg/mL) greatly inhibiting the cell growth. In addition, POEet could modulate the levels of oxidant/antioxidant status and induce a potent loss mitochondrial membrane potential, DNA damage, and apoptosis in MCF-7 cells. Conclusion: The study demonstrates a potent anticancer property of P. ostreatus against human mammary carcinoma cells which might be of value in nutraceutical industry. Further investigations are essential to establish it as a treatment against breast cancer.
目的:探讨平菇乙醇提取物(POEet)对人乳腺癌细胞系(Michigan cancer foundation-7 [MCF-7])的抗增殖和凋亡作用。方法:采用气相色谱-质谱法(GC-MS)分离并定量分析了三氯甲烷部分的有效成分。采用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)法研究了POEet对MCF-7和Vero细胞的细胞毒性。我们通过测定线粒体膜电位(ΔΨm)、双染色(吖啶橙/溴化乙啶)、彗星试验、DNA片段化和氧化/抗氧化状态,进一步评估了POEet对MCF-7细胞的凋亡作用。结果:气相色谱-质谱分析鉴定出30种植物化学成分。MTT实验显示,几乎所有剂量的POEet都具有更大程度的细胞毒性,IC30值(164.59µg/mL)和IC50值(1024.02µg/mL)显著抑制细胞生长。此外,POEet可以调节氧化/抗氧化状态水平,诱导MCF-7细胞线粒体膜电位丧失、DNA损伤和凋亡。结论:本研究证实了白藜芦醇对人乳腺癌细胞具有较强的抗癌作用,在营养保健行业具有一定的应用价值。进一步的研究是必要的,以确定它是一种治疗乳腺癌的方法。
{"title":"Antiproliferative and apoptotic effect of Pleurotus ostreatus on human mammary carcinoma cell line (michigan cancer foundation-7)","authors":"K. Deepalakshmi, S. Mirunalini","doi":"10.4103/2395-3977.189303","DOIUrl":"https://doi.org/10.4103/2395-3977.189303","url":null,"abstract":"Aim: The aim of this study was to explore the antiproliferative and apoptotic effect of Pleurotus ostreatus ethanolic extract (POEet) on human mammary carcinoma cell line (Michigan cancer foundation-7 [MCF-7]). Methods: Gas chromatography-mass spectrometry (GC-MS) was performed to isolate and quantify the active constituent of POEet chloroform fraction. Cytotoxic property of POEet on MCF-7 and Vero cells was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. We further evaluated the apoptotic effect by measuring the mitochondrial membrane potential (ΔΨm), dual staining (acridine orange/ethidium bromide), comet assay, DNA fragmentation, and oxidant/antioxidant status in MCF-7 cells treated with and without POEet. Results: GC-MS analysis identified 30 phytochemical constituents from the POEet chloroform fraction. MTT assay revealed a greater degree of cytotoxicity at almost all doses of POEet, with IC30 value (164.59 µg/mL) and IC50 value (1024.02 µg/mL) greatly inhibiting the cell growth. In addition, POEet could modulate the levels of oxidant/antioxidant status and induce a potent loss mitochondrial membrane potential, DNA damage, and apoptosis in MCF-7 cells. Conclusion: The study demonstrates a potent anticancer property of P. ostreatus against human mammary carcinoma cells which might be of value in nutraceutical industry. Further investigations are essential to establish it as a treatment against breast cancer.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"4 1","pages":"95 - 104"},"PeriodicalIF":0.0,"publicationDate":"2016-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91099258","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 : 2016-05-01DOI: 10.4103/2395-3977.184319
A. Marolla, J. Waisberg, G. T. Saba, D. Germini, M. Pinhal
Aim: The aim of the study was to analyze the expression of hyaluronic acid (HA) and its type in human colorectal cancer (CRC) and non-neoplastic mucosa tissues. Methods : The study included 64 adult CRC patients, who met all the inclusion and exclusion criteria. Two tissue samples (neoplastic and non-neoplastic mucosa) from each patient′s large intestine were collected and were subjected to electrospray ionization mass spectrometry (ESI-MS) and fluorimetric assays. Results: The analysis of colorectal neoplastic tissue and non-neoplastic mucosa by ESI-MS allowed the identification of HA and its oligosaccharide fragments. Low molecular weight (LMW), nonbiotinylated isoform of HA, and its fragments were identified in both neoplastic and non-neoplastic mucosa. The expression of HA was found to be slightly lower in tumor tissue (0.561 mg HA/g tissue) than in colorectal non-neoplastic mucosa (0.579 mg HA/g tissue), although the difference was not statistically significant (P = 0.87). This result was probably influenced by the nonbiotinylated LMW-HA. For the specific group of patients that did not present lymph node metastasis, the average HA levels were higher in tumor tissue (0.674 mg HA/g tissue) than in non-neoplastic tissue (0.529 mg HA/g tissue), which managed to reach statistical significance (P = 0.04). For the group of patients with lymph node involvement, no difference between tumor and nontumor tissue was observed. The HA expression among the tumor tissues within the variables of each clinicopathological parameters assessed failed to elicit any significant difference (location, P = 0.62; size, P = 0.13; lymph node invasion, P = 0.57; degree of cellular differentiation, P = 0.46; venous infiltration, P = 0.73; lymphatic infiltration, P = 0.36; neural infiltration, P = 0.28; tumor node metastasis classification, P = 0.15; and presence of synchronous metastases, P = 0.35; initial versus advanced stage, P = 0.37). Conclusions: The expression of HA was found to be slightly lower in tumor tissue than in colorectal non-neoplastic mucosa, although this difference was not statistically significant. This finding probably influenced the lower expression of HA in tumor tissue than in colorectal non-neoplastic mucosa. Compared to normal tissues, HA levels are significantly increased in the tumor tissues unless they exhibit lymph node metastasis. Otherwise, the expression of HA in tumor tissue did not correlated with the other clinicopathological parameters.
{"title":"Hyaluronic Acid in Normal and Neoplastic Colorectal Tissue: Electrospray Ionization Mass Spectrometric and Fluor Metric Analysis","authors":"A. Marolla, J. Waisberg, G. T. Saba, D. Germini, M. Pinhal","doi":"10.4103/2395-3977.184319","DOIUrl":"https://doi.org/10.4103/2395-3977.184319","url":null,"abstract":"Aim: The aim of the study was to analyze the expression of hyaluronic acid (HA) and its type in human colorectal cancer (CRC) and non-neoplastic mucosa tissues. Methods : The study included 64 adult CRC patients, who met all the inclusion and exclusion criteria. Two tissue samples (neoplastic and non-neoplastic mucosa) from each patient′s large intestine were collected and were subjected to electrospray ionization mass spectrometry (ESI-MS) and fluorimetric assays. Results: The analysis of colorectal neoplastic tissue and non-neoplastic mucosa by ESI-MS allowed the identification of HA and its oligosaccharide fragments. Low molecular weight (LMW), nonbiotinylated isoform of HA, and its fragments were identified in both neoplastic and non-neoplastic mucosa. The expression of HA was found to be slightly lower in tumor tissue (0.561 mg HA/g tissue) than in colorectal non-neoplastic mucosa (0.579 mg HA/g tissue), although the difference was not statistically significant (P = 0.87). This result was probably influenced by the nonbiotinylated LMW-HA. For the specific group of patients that did not present lymph node metastasis, the average HA levels were higher in tumor tissue (0.674 mg HA/g tissue) than in non-neoplastic tissue (0.529 mg HA/g tissue), which managed to reach statistical significance (P = 0.04). For the group of patients with lymph node involvement, no difference between tumor and nontumor tissue was observed. The HA expression among the tumor tissues within the variables of each clinicopathological parameters assessed failed to elicit any significant difference (location, P = 0.62; size, P = 0.13; lymph node invasion, P = 0.57; degree of cellular differentiation, P = 0.46; venous infiltration, P = 0.73; lymphatic infiltration, P = 0.36; neural infiltration, P = 0.28; tumor node metastasis classification, P = 0.15; and presence of synchronous metastases, P = 0.35; initial versus advanced stage, P = 0.37). Conclusions: The expression of HA was found to be slightly lower in tumor tissue than in colorectal non-neoplastic mucosa, although this difference was not statistically significant. This finding probably influenced the lower expression of HA in tumor tissue than in colorectal non-neoplastic mucosa. Compared to normal tissues, HA levels are significantly increased in the tumor tissues unless they exhibit lymph node metastasis. Otherwise, the expression of HA in tumor tissue did not correlated with the other clinicopathological parameters.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"4 1","pages":"79 - 84"},"PeriodicalIF":0.0,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73389821","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 : 2016-05-01DOI: 10.4103/2395-3977.184313
Jing Cai, K. Turner, Xiao Liang, WPaul Segars, ChrisR Kelsey, D. Yoo, L. Ren, F. Yin
Aim: To investigate the effect of irregular respiratory on target-matching accuracy in lung stereotactic-body radiation therapy (SBRT). Methods: The four-dimensional extended cardiac torso (4D-XCAT) phantom was used to generate 4D computed tomography (4DCT) and cone-beam CT (CBCT) images. Images were generated for 1 regular and 10 irregular trajectories, and for 3 tumor size groups (1, 2, and 3 cm). Image registrations between CBCT and average intensity projection (AIP) images of 4DCT were performed based on target volume matching. Error of registration was determined as the difference between manual CBCT-to-AIP registration and known registration between the two. In addition, internal target volumes (ITVs) were contoured on and compared between AIP, maximum intensity projection (MIP), and CBCT. Results: Small inter-observer variations of registration were found: 0.2, 0.3, and 0.7 mm in the medial-lateral (ML), anterior-posterior (AP), and superior-inferior (SI) direction, respectively. Small errors of registration (median ≤ 0.5 mm) were found in all three directions for the regular respiratory profile. For the irregular profiles and on average of all tumor size groups, the median ± standard deviation (SD) errors of registration were 0.5 ± 0.3 mm, 0.4 ± 0.5 mm, and 1.9 ± 1.6 mm in the ML, AP, and SI direction, respectively. Significant differences were found between MIP and CBCT-based ITV volumes for the three tumor size groups (P = 0.011, 0.010, and 0.006 for 1, 2, and 3 cm tumor size group, respectively). Conclusion: Irregular breathing can induce error in CBCT-to-AIP registration in lung SBRT. This error increases as the breathing irregularity increases.
{"title":"Target-Matching Accuracy in Stereotactic Body Radiation Therapy of Lung Cancer: An Investigation Based on Four-Dimensional Digital Human Phantom","authors":"Jing Cai, K. Turner, Xiao Liang, WPaul Segars, ChrisR Kelsey, D. Yoo, L. Ren, F. Yin","doi":"10.4103/2395-3977.184313","DOIUrl":"https://doi.org/10.4103/2395-3977.184313","url":null,"abstract":"Aim: To investigate the effect of irregular respiratory on target-matching accuracy in lung stereotactic-body radiation therapy (SBRT). Methods: The four-dimensional extended cardiac torso (4D-XCAT) phantom was used to generate 4D computed tomography (4DCT) and cone-beam CT (CBCT) images. Images were generated for 1 regular and 10 irregular trajectories, and for 3 tumor size groups (1, 2, and 3 cm). Image registrations between CBCT and average intensity projection (AIP) images of 4DCT were performed based on target volume matching. Error of registration was determined as the difference between manual CBCT-to-AIP registration and known registration between the two. In addition, internal target volumes (ITVs) were contoured on and compared between AIP, maximum intensity projection (MIP), and CBCT. Results: Small inter-observer variations of registration were found: 0.2, 0.3, and 0.7 mm in the medial-lateral (ML), anterior-posterior (AP), and superior-inferior (SI) direction, respectively. Small errors of registration (median ≤ 0.5 mm) were found in all three directions for the regular respiratory profile. For the irregular profiles and on average of all tumor size groups, the median ± standard deviation (SD) errors of registration were 0.5 ± 0.3 mm, 0.4 ± 0.5 mm, and 1.9 ± 1.6 mm in the ML, AP, and SI direction, respectively. Significant differences were found between MIP and CBCT-based ITV volumes for the three tumor size groups (P = 0.011, 0.010, and 0.006 for 1, 2, and 3 cm tumor size group, respectively). Conclusion: Irregular breathing can induce error in CBCT-to-AIP registration in lung SBRT. This error increases as the breathing irregularity increases.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"2 1","pages":"65 - 71"},"PeriodicalIF":0.0,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85879354","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 : 2016-05-01DOI: 10.4103/2395-3977.184316
Ye Song, Tianshi Que, Hao Long, Xi'an Zhang, Luxiong Fang, Zhi-yong Li, S. Qi
Aim: To investigate the role of death-associated protein kinase 3 (DAPK3) and activated caspase-3 in glioma condition. Methods: Immunohistochemical staining for DAPK3 and activated caspase-3 was performed on 136 paraffin-embedded glioma samples and 15 normal brain tissues, and the relationship between their expression levels and clinico-pathological features of glioma was statistically analyzed. Univariate and multivariate analyses were used to evaluate their prognostic value and patients′ survival. Results: The expression of both DAPK3 and activated caspase-3 was found suppressed in glioma tissues (P = 0.001 and P = 0.043). Further, DAPK3 and activated caspase-3 expression were markedly correlated with World Health Organization (WHO) Grading (I-II vs. III-IV) of the glioma condition (P = 0.002 and P < 0.001). A significantly positive correlation was observed between DAPK3 and activated caspase-3 expression (Spearman′s correlation coefficient = 0.706; P < 0.001). Univariate analysis revealed that both DAPK3 and activated caspase-3 were significantly associated with the overall survival of glioma patients (P < 0.001 and P < 0.001). In addition, multivariate analysis demonstrated that only DAPK3 and activated caspase-3 protein levels, but not WHO grading, significantly correlated with patients′ survival (P = 0.008 and P = 0.042). Conclusion: Downregulation of DAPK3 and activated caspase-3 is strongly associated with the clinical progression and poor prognosis of glioma, suggesting their use as a reliable clinical predictor.
{"title":"Downregulation of Death-associated Protein Kinase 3 and Caspase-3 Correlate to the Progression and Poor Prognosis of Gliomas","authors":"Ye Song, Tianshi Que, Hao Long, Xi'an Zhang, Luxiong Fang, Zhi-yong Li, S. Qi","doi":"10.4103/2395-3977.184316","DOIUrl":"https://doi.org/10.4103/2395-3977.184316","url":null,"abstract":"Aim: To investigate the role of death-associated protein kinase 3 (DAPK3) and activated caspase-3 in glioma condition. Methods: Immunohistochemical staining for DAPK3 and activated caspase-3 was performed on 136 paraffin-embedded glioma samples and 15 normal brain tissues, and the relationship between their expression levels and clinico-pathological features of glioma was statistically analyzed. Univariate and multivariate analyses were used to evaluate their prognostic value and patients′ survival. Results: The expression of both DAPK3 and activated caspase-3 was found suppressed in glioma tissues (P = 0.001 and P = 0.043). Further, DAPK3 and activated caspase-3 expression were markedly correlated with World Health Organization (WHO) Grading (I-II vs. III-IV) of the glioma condition (P = 0.002 and P < 0.001). A significantly positive correlation was observed between DAPK3 and activated caspase-3 expression (Spearman′s correlation coefficient = 0.706; P < 0.001). Univariate analysis revealed that both DAPK3 and activated caspase-3 were significantly associated with the overall survival of glioma patients (P < 0.001 and P < 0.001). In addition, multivariate analysis demonstrated that only DAPK3 and activated caspase-3 protein levels, but not WHO grading, significantly correlated with patients′ survival (P = 0.008 and P = 0.042). Conclusion: Downregulation of DAPK3 and activated caspase-3 is strongly associated with the clinical progression and poor prognosis of glioma, suggesting their use as a reliable clinical predictor.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"3 1","pages":"72 - 78"},"PeriodicalIF":0.0,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84627971","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 : 2016-05-01DOI: 10.4103/2395-3977.184321
Kaijun Huang, P. Vlachostergios, Wanhua Yang, R. L. Balmiki
Chronic lymphocytic leukemia (CLL)-induced immunodeficiency has been implicated in the occurrence of several secondary or concurrent malignancies. We hereby present the first case of combined CLL and pancreatic neuroendocrine tumor as collision neoplasms within metastatic periportal lymphadenopathy in a 62-year-old patient who presented with obstructive jaundice. An ovoid nodular mass was seen posterior to the head of the pancreas on magnetic resonance cholangiopancreatography and the patient subsequently underwent endoscopic retrograde cholangiopancreatography, with successful placement of two stents within the identified hilar stricture. Tn-111 pentetreotide scintigraphy with single-photon emission computed tomography (CT)/CT disclosed two foci of somatostatin receptor positive tissue in the upper abdomen correlating to the previously seen porta hepatis and portacaval lymphadenopathy and the patient was treated with octreotide. Simultaneous onset of CLL and secondary malignancies that each has a different disease status is a rare phenomenon but is important to diagnose for establishing an appropriate treatment strategy, which in certain cases may involve the use of agents active in both types of malignancy to minimize toxicity.
{"title":"Combined Chronic Lymphocytic Leukemia and Pancreatic Neuroendocrine Carcinoma: A Collision Tumor Variation","authors":"Kaijun Huang, P. Vlachostergios, Wanhua Yang, R. L. Balmiki","doi":"10.4103/2395-3977.184321","DOIUrl":"https://doi.org/10.4103/2395-3977.184321","url":null,"abstract":"Chronic lymphocytic leukemia (CLL)-induced immunodeficiency has been implicated in the occurrence of several secondary or concurrent malignancies. We hereby present the first case of combined CLL and pancreatic neuroendocrine tumor as collision neoplasms within metastatic periportal lymphadenopathy in a 62-year-old patient who presented with obstructive jaundice. An ovoid nodular mass was seen posterior to the head of the pancreas on magnetic resonance cholangiopancreatography and the patient subsequently underwent endoscopic retrograde cholangiopancreatography, with successful placement of two stents within the identified hilar stricture. Tn-111 pentetreotide scintigraphy with single-photon emission computed tomography (CT)/CT disclosed two foci of somatostatin receptor positive tissue in the upper abdomen correlating to the previously seen porta hepatis and portacaval lymphadenopathy and the patient was treated with octreotide. Simultaneous onset of CLL and secondary malignancies that each has a different disease status is a rare phenomenon but is important to diagnose for establishing an appropriate treatment strategy, which in certain cases may involve the use of agents active in both types of malignancy to minimize toxicity.","PeriodicalId":9428,"journal":{"name":"Cancer Translational Medicine","volume":"41 1","pages":"90 - 94"},"PeriodicalIF":0.0,"publicationDate":"2016-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74740241","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}