E. Cavalcanti, Vittoria Barchiesi, Dionigio Cerasuolo, F. Di Paola, M. Cantile, S. Cecere, S. Pignata, A. Morabito, R. Costanzo, M. Di Maio, F. Perrone
Objectives. Serum cystatin C seems to be an accurate marker of glomerular filtration rate (GFR) compared to serum creatinine. The aim of this work was to explore the possibility of using serum cystatin C instead of serum creatinine to early predict renal failure in cancer patients who received platinum based chemotherapy. Design and Methods. Serum creatinine, serum cystatin C concentrations, and GFR were determined simultaneously in 52 cancer patients received carboplatin-based or cisplatin-based chemotherapy. Serum creatinine was assayed on Cobas C6000-Roche, serum cystatin C assay was performed on AIA 360-Tosoh, and GFR was determined in all patients, before the first cycle of chemotherapy and before the subsequent administrations. Results. In the overall series, for the prediction of a fall of GFR < 80 mL/min/1.73 m2, the AUC of the ROC curve for cystatin C was 0,667 and the best threshold was 1.135 mg/L (sensitivity 90.5%, specificity 61.1%). For a GFR fall < 60 mL/min/1.73 m2, the AUC of ROC curve for cystatin C was 74.3% and the best threshold was 1.415 mg/L (sensitivity 66.7%, specificity 73.2%). Conclusions. Baseline cystatin C values were not able to predict renal failure during subsequent treatment. In conclusion, serum cystatin C is not a reliable early marker to efficiently predict renal failure in patients receiving chemotherapy.
{"title":"Correlation of Serum Cystatin C with Glomerular Filtration Rate in Patients Receiving Platinum-Based Chemotherapy","authors":"E. Cavalcanti, Vittoria Barchiesi, Dionigio Cerasuolo, F. Di Paola, M. Cantile, S. Cecere, S. Pignata, A. Morabito, R. Costanzo, M. Di Maio, F. Perrone","doi":"10.1155/2016/4918325","DOIUrl":"https://doi.org/10.1155/2016/4918325","url":null,"abstract":"Objectives. Serum cystatin C seems to be an accurate marker of glomerular filtration rate (GFR) compared to serum creatinine. The aim of this work was to explore the possibility of using serum cystatin C instead of serum creatinine to early predict renal failure in cancer patients who received platinum based chemotherapy. Design and Methods. Serum creatinine, serum cystatin C concentrations, and GFR were determined simultaneously in 52 cancer patients received carboplatin-based or cisplatin-based chemotherapy. Serum creatinine was assayed on Cobas C6000-Roche, serum cystatin C assay was performed on AIA 360-Tosoh, and GFR was determined in all patients, before the first cycle of chemotherapy and before the subsequent administrations. Results. In the overall series, for the prediction of a fall of GFR < 80 mL/min/1.73 m2, the AUC of the ROC curve for cystatin C was 0,667 and the best threshold was 1.135 mg/L (sensitivity 90.5%, specificity 61.1%). For a GFR fall < 60 mL/min/1.73 m2, the AUC of ROC curve for cystatin C was 74.3% and the best threshold was 1.415 mg/L (sensitivity 66.7%, specificity 73.2%). Conclusions. Baseline cystatin C values were not able to predict renal failure during subsequent treatment. In conclusion, serum cystatin C is not a reliable early marker to efficiently predict renal failure in patients receiving chemotherapy.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"221 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114586862","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}
Our previous study identified an elevated abundance of annexin A3 (Anxa3) as a novel prognostic biomarker of lung adenocarcinoma (LADC) through quantitative proteomics analysis. However, the biological functions of Anxa3 in LADC are not fully clear. In this study, in vitro and in vivo assays were performed to investigate the effects of Anxa3 downregulation on the growth, migration, invasion, metastasis, and signaling pathway activation of LADC cells. After Anxa3 downregulation, the growth of A549 and LTEP-a2 LADC cells was slowed and they showed decreased migration and invasion in vitro. Anxa3 knockdown significantly inhibited tumor formation by A549 cells in vivo; while many metastases were formed by control A549 cells, there were obvious reductions in the numbers of lung, liver, and brain metastases formed by Anxa3 knockdown in A549 cells. Furthermore, Anxa3 knockdown significantly decreased MMP-2 and N-cadherin expression and increased E-cadherin expression both in cell lines in vitro and in tumor nodules examined during in vivo tumorigenesis assays. Interestingly, Anxa3 downregulation reduced the phosphorylated levels of MEK and ERK. In summary, Anxa3 knockdown inhibited the growth, migration, invasion, and metastasis of LADC, decreased the activation of the MEK/ERK signaling pathway, and modulated the expression of MMP-2, E-cadherin, and N-cadherin.
{"title":"Annexin A3 Knockdown Suppresses Lung Adenocarcinoma","authors":"Ying-Fu Liu, Qing-Qing Liu, Y. Zhang, J. Qiu","doi":"10.1155/2016/4131403","DOIUrl":"https://doi.org/10.1155/2016/4131403","url":null,"abstract":"Our previous study identified an elevated abundance of annexin A3 (Anxa3) as a novel prognostic biomarker of lung adenocarcinoma (LADC) through quantitative proteomics analysis. However, the biological functions of Anxa3 in LADC are not fully clear. In this study, in vitro and in vivo assays were performed to investigate the effects of Anxa3 downregulation on the growth, migration, invasion, metastasis, and signaling pathway activation of LADC cells. After Anxa3 downregulation, the growth of A549 and LTEP-a2 LADC cells was slowed and they showed decreased migration and invasion in vitro. Anxa3 knockdown significantly inhibited tumor formation by A549 cells in vivo; while many metastases were formed by control A549 cells, there were obvious reductions in the numbers of lung, liver, and brain metastases formed by Anxa3 knockdown in A549 cells. Furthermore, Anxa3 knockdown significantly decreased MMP-2 and N-cadherin expression and increased E-cadherin expression both in cell lines in vitro and in tumor nodules examined during in vivo tumorigenesis assays. Interestingly, Anxa3 downregulation reduced the phosphorylated levels of MEK and ERK. In summary, Anxa3 knockdown inhibited the growth, migration, invasion, and metastasis of LADC, decreased the activation of the MEK/ERK signaling pathway, and modulated the expression of MMP-2, E-cadherin, and N-cadherin.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"2016 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131291962","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}
Jacqueline Nolan, M. Sarimollaoglu, D. Nedosekin, Azemat Jamshidi‐Parsian, E. Galanzha, R. Kore, R. Griffin, V. Zharov
Circulating tumor cells (CTCs) demonstrated the potential as prognostic markers of metastatic development. However, the incurable metastasis can already be developed at the time of initial diagnosis with the existing CTC assays. Alternatively, tumor-associated particles (CTPs) including exosomes can be a more valuable prognostic marker because they can be released from the primary tumor long before CTCs and in larger amount. However, little progress has been made in high sensitivity detection of CTPs, especially in vivo. We show here that in vivo integrated photoacoustic (PA) and fluorescence flow cytometry (PAFFC) platform can provide the detection of melanoma and breast-cancer-associated single CTPs with endogenously expressed melanin and genetically engineered proteins or exogenous dyes as PA and fluorescent contrast agents. The two-beam, time-of-light PAFFC can measure the sizes of CTCs and CTPs and identify bulk and rolling CTCs and CTC clusters, with no influence on blood flow instability. This technique revealed a higher concentration of CTPs than CTCs at an early cancer stage. Because a single tumor cell can release many CTPs and in vivo PAFFC can examine the whole blood volume, PAFFC diagnostic platform has the potential to dramatically improve (up to 105-fold) the sensitivity of cancer diagnosis.
{"title":"In Vivo Flow Cytometry of Circulating Tumor-Associated Exosomes","authors":"Jacqueline Nolan, M. Sarimollaoglu, D. Nedosekin, Azemat Jamshidi‐Parsian, E. Galanzha, R. Kore, R. Griffin, V. Zharov","doi":"10.1155/2016/1628057","DOIUrl":"https://doi.org/10.1155/2016/1628057","url":null,"abstract":"Circulating tumor cells (CTCs) demonstrated the potential as prognostic markers of metastatic development. However, the incurable metastasis can already be developed at the time of initial diagnosis with the existing CTC assays. Alternatively, tumor-associated particles (CTPs) including exosomes can be a more valuable prognostic marker because they can be released from the primary tumor long before CTCs and in larger amount. However, little progress has been made in high sensitivity detection of CTPs, especially in vivo. We show here that in vivo integrated photoacoustic (PA) and fluorescence flow cytometry (PAFFC) platform can provide the detection of melanoma and breast-cancer-associated single CTPs with endogenously expressed melanin and genetically engineered proteins or exogenous dyes as PA and fluorescent contrast agents. The two-beam, time-of-light PAFFC can measure the sizes of CTCs and CTPs and identify bulk and rolling CTCs and CTC clusters, with no influence on blood flow instability. This technique revealed a higher concentration of CTPs than CTCs at an early cancer stage. Because a single tumor cell can release many CTPs and in vivo PAFFC can examine the whole blood volume, PAFFC diagnostic platform has the potential to dramatically improve (up to 105-fold) the sensitivity of cancer diagnosis.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"55 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121927105","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. Ieni, V. Barresi, G. Branca, Rosario Alberto Caruso, G. Tuccari
Aim. The role of mast cells in cell-cell immune interactions has received increasing attention, although their functional interaction with neutrophils still remains to be clarified in tumors. The aim of the present study was to investigate the association between mast cells and neutrophils in a series of gastric carcinomas (GC). Patients and Methods. 52 surgically resected GC specimens were routinely processed for both light and electron microscopy. Only cases showing both mast cells and neutrophils in the tumor stroma were considered in the analysis. Results. Only 9 GC (M : F = 5 : 4; age range: 50–82 years) showed both mast cells and neutrophils in the tumor stroma. At ultrathin sections, we identified heterotypic aggregation and intermingling of mast cells and neutrophils. Mast cells had mature phenotype and showed full complement of granules with homogeneous, scroll, particle, and mixed pattern. In addition, we found normal-appearing or early apoptosis showing neutrophils. Conclusion. Our histological findings showed the likely interaction between mast cells and neutrophils in GC. We hypothesize that the granular content of mast cells may be released in small quantity through a mechanism called “kiss-and-run fusion,” which is alternative to well-known massive anaphylactic or piecemeal degranulation.
的目标。肥大细胞在细胞-细胞免疫相互作用中的作用已受到越来越多的关注,尽管它们在肿瘤中与中性粒细胞的功能相互作用仍有待阐明。本研究的目的是探讨肥大细胞和中性粒细胞在一系列胃癌(GC)中的关系。患者和方法:对52例手术切除的GC标本进行常规光镜和电镜检查。只有在肿瘤基质中显示肥大细胞和中性粒细胞的病例才被考虑在分析中。结果。只有9 GC (M: F = 5:4;年龄范围:50-82岁),肿瘤基质中可见肥大细胞和中性粒细胞。在超薄切片上,我们发现了肥大细胞和中性粒细胞的异型聚集和混合。肥大细胞表型成熟,颗粒齐全,呈均匀型、涡旋型、颗粒型和混合型。此外,我们还发现出现正常或早期凋亡的中性粒细胞。结论。我们的组织学结果显示肥大细胞和中性粒细胞可能在GC中相互作用。我们假设肥大细胞的颗粒内容物可能通过一种称为“吻跑融合”的机制少量释放,这是众所周知的大量过敏性或碎片性脱粒的替代方法。
{"title":"Mast Cell Interaction with Neutrophils in Human Gastric Carcinomas: Ultrastructural Observations","authors":"A. Ieni, V. Barresi, G. Branca, Rosario Alberto Caruso, G. Tuccari","doi":"10.1155/2016/6891971","DOIUrl":"https://doi.org/10.1155/2016/6891971","url":null,"abstract":"Aim. The role of mast cells in cell-cell immune interactions has received increasing attention, although their functional interaction with neutrophils still remains to be clarified in tumors. The aim of the present study was to investigate the association between mast cells and neutrophils in a series of gastric carcinomas (GC). Patients and Methods. 52 surgically resected GC specimens were routinely processed for both light and electron microscopy. Only cases showing both mast cells and neutrophils in the tumor stroma were considered in the analysis. Results. Only 9 GC (M : F = 5 : 4; age range: 50–82 years) showed both mast cells and neutrophils in the tumor stroma. At ultrathin sections, we identified heterotypic aggregation and intermingling of mast cells and neutrophils. Mast cells had mature phenotype and showed full complement of granules with homogeneous, scroll, particle, and mixed pattern. In addition, we found normal-appearing or early apoptosis showing neutrophils. Conclusion. Our histological findings showed the likely interaction between mast cells and neutrophils in GC. We hypothesize that the granular content of mast cells may be released in small quantity through a mechanism called “kiss-and-run fusion,” which is alternative to well-known massive anaphylactic or piecemeal degranulation.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"51 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115998418","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}
R. Gónzalez-Gónzalez, N. Molina-Frechero, Ramón G Carreón-Burciaga, Sandra López-Verdín, Carlos Robles-Bonilla, V. Pereira-Prado, R. Bologna-Molina
Ameloblastoma is a common and unpredictable odontogenic tumor with high relapse rates. Several studies assessing the proliferative capacity of these neoplasms have been published, mainly using the protein Ki-67. Cell counts must be completed to determine the cell proliferation rate. Multiple methods have been developed for this purpose. The most widely used method is the labeling index, which has undergone changes over time to better facilitate cell counting. Here, we compared manual cell counting methods with automated cell counting (ImmunoRatio) to determine the relative effectiveness of these methods. The results suggest that ImmunoRatio, a free software tool, may be highly advantageous and provide results similar to manual cell counting methods when used with the appropriate calibration. However, ImmunoRatio has flaws that may affect the labeling index results. Therefore, this automated cell counting method must be supplemented with manual cell counting methods.
{"title":"Comparison between Manual and Automated Methods for Ki-67 Immunoexpression Quantification in Ameloblastomas","authors":"R. Gónzalez-Gónzalez, N. Molina-Frechero, Ramón G Carreón-Burciaga, Sandra López-Verdín, Carlos Robles-Bonilla, V. Pereira-Prado, R. Bologna-Molina","doi":"10.1155/2016/7486989","DOIUrl":"https://doi.org/10.1155/2016/7486989","url":null,"abstract":"Ameloblastoma is a common and unpredictable odontogenic tumor with high relapse rates. Several studies assessing the proliferative capacity of these neoplasms have been published, mainly using the protein Ki-67. Cell counts must be completed to determine the cell proliferation rate. Multiple methods have been developed for this purpose. The most widely used method is the labeling index, which has undergone changes over time to better facilitate cell counting. Here, we compared manual cell counting methods with automated cell counting (ImmunoRatio) to determine the relative effectiveness of these methods. The results suggest that ImmunoRatio, a free software tool, may be highly advantageous and provide results similar to manual cell counting methods when used with the appropriate calibration. However, ImmunoRatio has flaws that may affect the labeling index results. Therefore, this automated cell counting method must be supplemented with manual cell counting methods.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"88 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132851485","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}
R. Ciortea, C. Berceanu, A. Măluţan, R. Mocan, C. Iuhas, C. Bucuri, M. Rada, D. Mihu
Introduction. The identification of biological markers that indicate an increased risk for the development or recurrence of endometrial cancer (EC) in obese women might be useful for decreasing EC mortality and morbidity. Glucose-regulated protein 78 (GRP78) is a major protein of the endoplasmic reticulum expressed in all normal cells. Overexpression of GRP78 has been reported to be a tumoral biomarker. Increased detection of GRP78 is positively correlated with the tumoral stage and prognosis. This study aimed to identify a correlation between intraperitoneal fat, plasma GRP78 levels, and EC. Materials and Methods. Two groups of patients were included in the study: group I, 44 patients diagnosed with EC, and group II, 44 patients without gynecological pathology or inflammatory disorders. Visceral fat was determined by ultrasound and plasma GRP78 levels were measured. Results. Plasma GRP78 levels were significantly higher in patients with EC compared to the control group. Intraperitoneal fat was in a positive linear correlation with the plasma GRP78 level (p < 0.0001). Conclusion. The measurement of the GRP78 level associated with the determination of intraperitoneal fat can be a useful predictor for EC.
{"title":"Intraperitoneal Fat through GRP78: A Risk Factor for Endometrial Cancer","authors":"R. Ciortea, C. Berceanu, A. Măluţan, R. Mocan, C. Iuhas, C. Bucuri, M. Rada, D. Mihu","doi":"10.1155/2016/3496538","DOIUrl":"https://doi.org/10.1155/2016/3496538","url":null,"abstract":"Introduction. The identification of biological markers that indicate an increased risk for the development or recurrence of endometrial cancer (EC) in obese women might be useful for decreasing EC mortality and morbidity. Glucose-regulated protein 78 (GRP78) is a major protein of the endoplasmic reticulum expressed in all normal cells. Overexpression of GRP78 has been reported to be a tumoral biomarker. Increased detection of GRP78 is positively correlated with the tumoral stage and prognosis. This study aimed to identify a correlation between intraperitoneal fat, plasma GRP78 levels, and EC. Materials and Methods. Two groups of patients were included in the study: group I, 44 patients diagnosed with EC, and group II, 44 patients without gynecological pathology or inflammatory disorders. Visceral fat was determined by ultrasound and plasma GRP78 levels were measured. Results. Plasma GRP78 levels were significantly higher in patients with EC compared to the control group. Intraperitoneal fat was in a positive linear correlation with the plasma GRP78 level (p < 0.0001). Conclusion. The measurement of the GRP78 level associated with the determination of intraperitoneal fat can be a useful predictor for EC.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"133 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"120930435","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}
I. Rotar, D. Dumitras, R. Popp, F. Petrişor, Paul Cotutiu, F. Stamatian, D. Muresan
Aim. The present study aims to analyze the potential role of VEGF +936 C/T polymorphism in cervical intraepithelial neoplasia. Material and Method. One hundred and eighty-six patients were included in the study: 75 cases (patients diagnosed with CIN) and 111 controls (negative for both HPV testing and cytology). For each patient a single visit was scheduled when colposcopy was performed. From cervical specimen, cytology and HPV testing were performed and from peripheral blood VEGF +936 genotyping was determined. For statistical analysis purposes OR and chi-square were used at a level of significance of <0.05. Results. No link has been found in the detection of CT genotype in cases versus controls, OR = 0.8295, [0.42, 1.62]. An inverse correlation has been found between T allele and HSIL, OR = 0.2121, [0.0473, 0.9517], p = 0.0866. Conclusion. No link has been found between VEGF +936 C/T and cervical intraepithelial neoplasia.
{"title":"VEGF +936 C/T Genetic Polymorphism in Patients with Cervical Dysplasia","authors":"I. Rotar, D. Dumitras, R. Popp, F. Petrişor, Paul Cotutiu, F. Stamatian, D. Muresan","doi":"10.1155/2016/6074275","DOIUrl":"https://doi.org/10.1155/2016/6074275","url":null,"abstract":"Aim. The present study aims to analyze the potential role of VEGF +936 C/T polymorphism in cervical intraepithelial neoplasia. Material and Method. One hundred and eighty-six patients were included in the study: 75 cases (patients diagnosed with CIN) and 111 controls (negative for both HPV testing and cytology). For each patient a single visit was scheduled when colposcopy was performed. From cervical specimen, cytology and HPV testing were performed and from peripheral blood VEGF +936 genotyping was determined. For statistical analysis purposes OR and chi-square were used at a level of significance of <0.05. Results. No link has been found in the detection of CT genotype in cases versus controls, OR = 0.8295, [0.42, 1.62]. An inverse correlation has been found between T allele and HSIL, OR = 0.2121, [0.0473, 0.9517], p = 0.0866. Conclusion. No link has been found between VEGF +936 C/T and cervical intraepithelial neoplasia.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124431588","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}
O. Kovaleva, D. Samoilova, Maria S Shitova, A. Gratchev
Tumor associated macrophages (TAMs) are an important element of tumor stroma. They originate from blood monocytes attracted by chemokines and cytokines produced by tumor cells and, being instructed by tumor microenvironment, develop into potent tumor-supporting cell population. TAMs were demonstrated to directly stimulate tumor cell proliferation and to promote angiogenesis. Further TAMs provide for efficient immune escape by producing immunosuppressive cytokines and facilitate tumor dissemination by producing extracellular matrix remodeling enzymes. In renal cell carcinoma (RCC), numerous studies were performed for elucidation of the role of TAM in tumor progression. Using pan-macrophages marker CD68 and type 2 macrophage (M2) markers CD163 and CD206, it was demonstrated that increased density of TAMs is associated with poor survival of patients. Although most of the studies are focused on M2 population in RCC, several markers rather typical for type 1 macrophages (M1) were also characterized. Macrophages isolated from RCC tumors were shown to produce proinflammatory cytokines TNFα, IL-1β, IL-6, and CCL2. It can be concluded that RCC is an excellent example of a tumor with hybrid phenotype of TAMs that share both M1 and M2 properties. Moreover, TAMs seem to be an attractive therapeutic target as well. Further investigations are needed for identification of RCC-specific TAM markers with high predictive capacity and/or suitable for therapeutic targeting.
{"title":"Tumor Associated Macrophages in Kidney Cancer","authors":"O. Kovaleva, D. Samoilova, Maria S Shitova, A. Gratchev","doi":"10.1155/2016/9307549","DOIUrl":"https://doi.org/10.1155/2016/9307549","url":null,"abstract":"Tumor associated macrophages (TAMs) are an important element of tumor stroma. They originate from blood monocytes attracted by chemokines and cytokines produced by tumor cells and, being instructed by tumor microenvironment, develop into potent tumor-supporting cell population. TAMs were demonstrated to directly stimulate tumor cell proliferation and to promote angiogenesis. Further TAMs provide for efficient immune escape by producing immunosuppressive cytokines and facilitate tumor dissemination by producing extracellular matrix remodeling enzymes. In renal cell carcinoma (RCC), numerous studies were performed for elucidation of the role of TAM in tumor progression. Using pan-macrophages marker CD68 and type 2 macrophage (M2) markers CD163 and CD206, it was demonstrated that increased density of TAMs is associated with poor survival of patients. Although most of the studies are focused on M2 population in RCC, several markers rather typical for type 1 macrophages (M1) were also characterized. Macrophages isolated from RCC tumors were shown to produce proinflammatory cytokines TNFα, IL-1β, IL-6, and CCL2. It can be concluded that RCC is an excellent example of a tumor with hybrid phenotype of TAMs that share both M1 and M2 properties. Moreover, TAMs seem to be an attractive therapeutic target as well. Further investigations are needed for identification of RCC-specific TAM markers with high predictive capacity and/or suitable for therapeutic targeting.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132903295","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. Microscopes are omnipresent throughout the field of biological research. With microscopes one can see in detail what is going on at the cellular level in tissues. Though it is a ubiquitous tool, the limitation is that with high magnification there is a small field of view. It is often advantageous to see an entire sample at high magnification. Over the years technological advancements in optics have helped to provide solutions to this limitation of microscopes by creating the so-called dedicated “slide scanners” which can provide a “whole slide digital image.” These scanners can provide seamless, large-field-of-view, high resolution image of entire tissue section. The only disadvantage of such complete slide imaging system is its outrageous cost, thereby hindering their practical use by most laboratories, especially in developing and low resource countries. Methods. In a quest for their substitute, we tried commonly used image editing software Adobe Photoshop along with a basic image capturing device attached to a trinocular microscope to create a digital pathology slide. Results. The seamless image created using Adobe Photoshop maintained its diagnostic quality. Conclusion. With time and effort photomicrographs obtained from a basic camera-microscope set up can be combined and merged in Adobe Photoshop to create a whole slide digital image of practically usable quality at a negligible cost.
{"title":"Image Montaging for Creating a Virtual Pathology Slide: An Innovative and Economical Tool to Obtain a Whole Slide Image","authors":"S. Banavar, Prashanthi Chippagiri, Rohit Pandurangappa, Saileela Annavajjula, Premalatha Bidadi Rajashekaraiah","doi":"10.1155/2016/9084909","DOIUrl":"https://doi.org/10.1155/2016/9084909","url":null,"abstract":"Background. Microscopes are omnipresent throughout the field of biological research. With microscopes one can see in detail what is going on at the cellular level in tissues. Though it is a ubiquitous tool, the limitation is that with high magnification there is a small field of view. It is often advantageous to see an entire sample at high magnification. Over the years technological advancements in optics have helped to provide solutions to this limitation of microscopes by creating the so-called dedicated “slide scanners” which can provide a “whole slide digital image.” These scanners can provide seamless, large-field-of-view, high resolution image of entire tissue section. The only disadvantage of such complete slide imaging system is its outrageous cost, thereby hindering their practical use by most laboratories, especially in developing and low resource countries. Methods. In a quest for their substitute, we tried commonly used image editing software Adobe Photoshop along with a basic image capturing device attached to a trinocular microscope to create a digital pathology slide. Results. The seamless image created using Adobe Photoshop maintained its diagnostic quality. Conclusion. With time and effort photomicrographs obtained from a basic camera-microscope set up can be combined and merged in Adobe Photoshop to create a whole slide digital image of practically usable quality at a negligible cost.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"31 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122984679","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}
C. Cai, D. Nedosekin, Y. Menyaev, M. Sarimollaoglu, M. Proskurnin, V. Zharov
Control of sickle cell disease (SCD) stage and treatment efficiency are still time-consuming which makes well-timed prevention of SCD crisis difficult. We show here that in vivo photoacoustic (PA) flow cytometry (PAFC) has a potential for real-time monitoring of circulating sickled cells in mouse model. In vivo data were verified by in vitro PAFC and photothermal (PT) and PA spectral imaging of sickle red blood cells (sRBCs) expressing SCD-associated hemoglobin (HbS) compared to normal red blood cells (nRBCs). We discovered that PT and PA signal amplitudes from sRBCs in linear mode were 2–4-fold lower than those from nRBCs. PT and PA imaging revealed more profound spatial hemoglobin heterogeneity in sRBCs than in nRBCs, which can be associated with the presence of HbS clusters with high local absorption. This hypothesis was confirmed in nonlinear mode through nanobubble formation around overheated HbS clusters accompanied by spatially selective signal amplification. More profound differences in absorption of sRBCs than in nRBCs led to notable increase in PA signal fluctuation (fluctuation PAFC mode) as an indicator of SCD. The obtained data suggest that noninvasive label-free fluctuation PAFC has a potential for real-time enumeration of sRBCs both in vitro and in vivo.
{"title":"Photoacoustic Flow Cytometry for Single Sickle Cell Detection In Vitro and In Vivo","authors":"C. Cai, D. Nedosekin, Y. Menyaev, M. Sarimollaoglu, M. Proskurnin, V. Zharov","doi":"10.1155/2016/2642361","DOIUrl":"https://doi.org/10.1155/2016/2642361","url":null,"abstract":"Control of sickle cell disease (SCD) stage and treatment efficiency are still time-consuming which makes well-timed prevention of SCD crisis difficult. We show here that in vivo photoacoustic (PA) flow cytometry (PAFC) has a potential for real-time monitoring of circulating sickled cells in mouse model. In vivo data were verified by in vitro PAFC and photothermal (PT) and PA spectral imaging of sickle red blood cells (sRBCs) expressing SCD-associated hemoglobin (HbS) compared to normal red blood cells (nRBCs). We discovered that PT and PA signal amplitudes from sRBCs in linear mode were 2–4-fold lower than those from nRBCs. PT and PA imaging revealed more profound spatial hemoglobin heterogeneity in sRBCs than in nRBCs, which can be associated with the presence of HbS clusters with high local absorption. This hypothesis was confirmed in nonlinear mode through nanobubble formation around overheated HbS clusters accompanied by spatially selective signal amplification. More profound differences in absorption of sRBCs than in nRBCs led to notable increase in PA signal fluctuation (fluctuation PAFC mode) as an indicator of SCD. The obtained data suggest that noninvasive label-free fluctuation PAFC has a potential for real-time enumeration of sRBCs both in vitro and in vivo.","PeriodicalId":313227,"journal":{"name":"Analytical Cellular Pathology (Amsterdam)","volume":"78 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134523367","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}