Association of pancreatic cancer stem cells with tumor stroma type.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15771-e15771
Author(s):  
Ibrahim Halil Sahin ◽  
Gokce Askan ◽  
Joanne F Chou ◽  
Marinela Capanu ◽  
Kenneth H. Yu ◽  
...  

e15771 Background: Pancreatic ductal adenocarcinoma (PDA) is a heterogeneous disease with distinct stroma features. Cancer stem cells (CSC) in PDA may express CD44 (C) +/- Epithelial Specific Antigen (E). We investigated the relationship of CSC markers with tumor stroma and clinical outcomes in PDA patients (pts) who had surgical resection. Methods: Pts who underwent PDA resection with IRB #00-032/#06-107 consent between 01/2012-06/2014 at Memorial Sloan Kettering were identified. C and E immunohistochemical (IHC) expression scored as follow: 0, none; 1, 1%–10%; 2, 11%–50%; 3, 51%–80%; 4, 81%–100%. Staining intensity was scored as 0, none; 1, weak; 2, moderate; 3, strong. The total scores (0-12) were averaged and was considered positive when average score > median. Stroma was classified as loose, moderate and dense based on fibroblast content using H&E stain. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier and compared by log-rank test; association between CSC markers and stroma type was assessed by Fisher`s exact test. Results: N = 93 PDA pts identified. PDA with C(+) E(-) had significantly higher loose stroma and PDA with C(-) E(+) and C(-) E(-) had more moderate and dense stroma (p = 0.0033). The number of PDA pts with dense, moderate, and loose stroma was: 11, 31, and 51 respectively. No local recurrence in pts with dense stroma observed and 8/11 had either lung or liver recurrence. Six of 31pts with loose stroma had a local recurrence and 13/31 pts had either liver or lung recurrence. No statistically significant difference in OS and RFS were observed among subgroups (P = 0.089). Median time from relapse to death was: 2, 11.5, 10,5 and months 7 in C+/E-, C-/E+, C+/E+, and C-/E- groups respectively. Conclusions: PDA CSCs appears to have an association with PDA stroma type. We also observed different recurrence patterns among stroma subgroups. Respecting small sample size, these data indicate CSCs may have an important role in stroma differentiation in PDA. CSC markers do not predict OS and RFS, however, resected PDA with C(+) E(-) may have more aggressive behavior following recurrence. [Table: see text]

2020 ◽  
Author(s):  
Gokce Askan ◽  
Ibrahim Halil Sahin ◽  
Joanne F. Chou ◽  
Aslihan Yavas ◽  
Marinela Capanu ◽  
...  

Abstract Background: Herein, we investigate the relationship between pancreatic stem cell markers (PCSC markers), CD44, and epithelial-specific antigen (ESA), tumor stroma, and the impact on recurrence outcomes in pancreatic ductal adenocarcinoma (PDAC) patients.Methods: PDAC patients who underwent surgical resection between 01/2012 -06/2014 were identified. CD44 and ESA expression was assessed by immunohistochemistry. Stroma was classified as loose, moderate, and dense based on fibroblast content. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared between subgroups by log-rank test. The association between PCSC markers and stroma type was assessed by Fisher`s exact test. Results: N= 93 PDAC patients were identified. The number of PDAC patients with dense, moderate density, and loose stroma was 11 (12%), 51 (54%), and 31 (33%) respectively. PDAC with CD44+/ESA- had highest rate of loose stroma (63%) followed by PDAC CD44+/ESA+ (50%), PDAC CD44-/ESA+ (35%), CD44-/ESA- (9%) (p=0.0033). No local recurrence was observed in patients with dense stroma and 9 had distant recurrence. The highest rate of cumulative local recurrence observed in patients with loose stroma. No statistically significant difference in RFS and OS were observed among subgroups (P=0.089). Conclusions: These data indicate PCSCs may have an important role in stroma differentiation in PDAC. Although not reaching statistical significance, we observed more local recurrences in patients with loose stroma, and no local recurrence was seen in patients with dense stroma suggesting tumor stroma may influence the recurrence pattern in PDAC patients.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Gokce Askan ◽  
Ibrahim Halil. Sahin ◽  
Joanne F. Chou ◽  
Aslihan Yavas ◽  
Marinela Capanu ◽  
...  

Abstract Background Herein, we investigate the relationship between pancreatic stem cell markers (PCSC markers), CD44, and epithelial-specific antigen (ESA), tumor stroma, and the impact on recurrence outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. Methods PDAC patients who underwent surgical resection between 01/2012–06/2014 were identified. CD44 and ESA expression was assessed by immunohistochemistry. Stroma was classified as loose, moderate, and dense based on fibroblast content. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared between subgroups by log-rank test. The association between PCSC markers and stroma type was assessed by Fisher’s exact test. Results N = 93 PDAC patients were identified. The number of PDAC patients with dense, moderate density, and loose stroma was 11 (12%), 51 (54%), and 31 (33%) respectively. PDAC with CD44+/ESA− had highest rate of loose stroma (63%) followed by PDAC CD44+/ESA+ (50%), PDAC CD44−/ESA+ (35%), CD44−/ESA− (9%) (p = 0.0033). Conversely, lack of CD44 and ESA expression was associated with the highest rate of moderate and dense stroma (91% p = 0.0033). No local recurrence was observed in patients with dense stroma and 9 had distant recurrence. The highest rate of cumulative local recurrence was observed in patients with loose stroma. No statistically significant difference in RFS and OS was observed among subgroups (P = 0.089). Conclusions These data indicate PCSCs may have an important role in stroma differentiation in PDAC. Our results further suggest that tumor stroma may influence the recurrence pattern in PDAC patients.


2020 ◽  
Author(s):  
Gokce Askan ◽  
Ibrahim Halil Sahin ◽  
Joanne F. Chou ◽  
Aslihan Yavas ◽  
Marinela Capanu ◽  
...  

Abstract Background Herein, we investigate the relationship between pancreatic stem cell markers (PCSC markers), CD44, and epithelial-specific antigen (ESA), tumor stroma, and the impact on recurrence outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. Methods PDAC patients who underwent surgical resection between 01/2012 -06/2014 were identified. CD44 and ESA expression was assessed by immunohistochemistry. Stroma was classified as loose, moderate density, and dense based on fibroblast content. Overall survival (OS) and relapse-free survival (RFS) were estimated using the Kaplan-Meier method and compared between subgroups by log-rank test. The association between PCSC markers and stroma type was assessed by Fisher`s exact test. Results N = 93 PDAC patients were identified. The number of PDAC patients with dense, moderate density, and loose stroma was 11 (12%), 51 (54%), and 31 (33%) respectively. PDAC with CD44+/ESA− had highest rate of loose stroma (63%) followed by PDAC CD44+/ESA+ (50%), PDAC CD44−/ESA+ (35%), CD44−/ESA− (9%) (p = 0.0033). No local recurrence was observed in patients with dense stroma and 9 had distant recurrence. The highest rate of cumulative local recurrence observed in patients with loose stroma. No statistically significant difference in RFS and OS were observed among subgroups (P = 0.089). Conclusions These data indicate PCSCs may have an important role in stroma differentiation in PDAC. Although not reaching statistical significance, we observed more local recurrences in patients with loose stroma, and no local recurrence was seen in patients with dense stroma suggesting tumor stroma may influence the recurrence pattern in PDAC patients.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15721-e15721
Author(s):  
Gokce Askan ◽  
Ibrahim Halil Sahin ◽  
Marinela Capanu ◽  
Mesruh Turkekul ◽  
Kenneth H. Yu ◽  
...  

e15721 Background: Recent studies indicate that pancreatic cancer stem cells (CSC) may predict disease behavior and survival outcomes of pancreatic ductal adenocarcinomas (PDACs) patients (pts). Several CSC markers have been reported in PDAC (Fitzgerald, TL, 2014). We herein evaluated the impact of CSC markers including CD44 and Epithelial Specific Antigen (ESA) on survival outcome of PDAC pts who had liver or lung metastasis after initial surgical resection (IR). Methods: Clinicopathologic features and survival of 59 PDACs were analyzed. Pts with IRB approval, and whom had available primary tumor tissue, were included. All neoplasms were immuno labeled with CD44 and ESA. Staining intensity was scored as weak (1), moderate (2), strong (3), while the staining pattern was scored as: few (1), patchy (2), and diffuse (3). The expression for CD44 and ESA was accepted positive if total score ≥4. Time from relapse to death (TRD) was estimated using the Kaplan-Meier method censoring patients that were alive at the last follow up. Survival curves were compared using the log-rank test Results: Of 59 pts, 42 (71 %) had liver, 10 (17%) had lung and 7 (12%) had both liver and lung metastasis. M/F = 34/25; mean age = 64.2 (range, 34-90). Patients were subcategorized as follows; thirteen cases were CD44 (+)/ESA (-) (group1) and 13 were CD44 (-)/ESA (+) (group 2). Eight (61.5%) of group 1 tumors and 2 (15.3%) of group 2 were poorly differentiated. At last follow-up, except one with 63 months survival, all pts died of disease with 23.3 months (range, 3-67) median OS. No significant difference in TRD was observed between group 1 (6.9 months) and 2 (13.8 months) (p = 0.62). However, we observed group 1 tumors had worse OS (12 months) compared to group 2 (36 months). Conclusions:A worse outcome trend was observed for pts with CD44 (+)/ESA (-), albeit not statistically significant and likely limited by small numbers. Further studies are warranted to evaluate the robustness of this observation.


2017 ◽  
Vol 39 (3) ◽  
pp. 224-228 ◽  
Author(s):  
D E Ryspayeva ◽  
I I Smolanka ◽  
A S Dudnichenko ◽  
A A Lyashenko ◽  
Yu A Grinevich ◽  
...  

Identification and characterization of the population of cancer stem cells (CSC) depends on several cellular markers, which combination is specific for the phenotype of CSC in the corresponding tumor. Several markers of CSC have already been identified in breast cancer (BC), but there are no universal indicators that could specifically identify the CSC in BC. Aims: To determine the validation of the CSC model for cell surface markers such as CD44 and CD24 and their clinical significance. Materials and Methods: Primary tumor samples of 45 patients with invasive BC without chemotherapy prior to surgery exposure were examined in paraffin blocks. CD44 and CD24 antigens expression was evaluated by the percentage of positive cells using different chromogens and the MultiVision detection system by immunohistochemical method. In this research the evaluation was determined by the following criteria: (-), negative — expression in < 10% of tumor cells; (+), positive — expression in ≥10% of cells. The same scoring system was applied for the expression of CD44+/CD24−. Results: 62.2% of investigated patients are patients older than 50 years and most of them with stage II of disease (71.0%) and luminal tumor subtypes (68.9%). We analysed the expression of CD44, CD24 and CD44+/CD24− for different patients with dividing them into two groups. The group A consists of patients with unfavorable prognosis (relapses and metastases have occurred in the first three years after diagnosis), and the group B — with a favourable prognosis (the development of metastases after three years). Median disease-free survival in the group A is 19 months, in the group B — 46 months. The difference between the overall survival (OS) curves in the groups A and B is statistically significant (p < 0.001), the risk of death was higher in the group A (hazard ratio (HR) 5.9; confidence interval (CI) 2.3–15.2). The content of CD44 cells did not differ statistically between groups A and B (p = 0.18), but there was a tendency for increasing in OS with the existence of CD44+ cells (p = 0.056). The distribution of the expression of CD24 marker did not differ between the groups (p = 0.36) as well as the OS curves (p = 0.59). Analysis of the expression of CD44+/CD24− which were considered as possible CSC, revealed a paradoxical increase (p = 0.03) of the frequency in patients of the group B (40.9%) compared to the group A (8.7%). Nevertheless, the comparison of the clinical outcomes did not reveal a statistically significant difference in the survival curves in the groups with existence and absence of CD44+/CD24– expression (p = 0.08). The analysis showed the increasing of the risk of worse clinical outcomes in the cases of expression absence of CD44+/CD24− (HR 2.8; CI 1.1–6.8). Conclusions: As a result of our research, the analysis of the quantity of assumed stem cells of the BC, which were identified by immunohistochemistry as CD44 and CD24 cells, failed to detect a statistically significant relation between groups of patients with different prognosis, and the identification of their expression is not enough for the characteristics of CSC. The obtained data demonstrating the worst clinical outcome in the cases of absence of CD44+/CD24− expression apparently require further investigations and the validation of the immunohistochemical method with the determination of the cut-off line in defining of CD44 and CD24 status.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ana Golić Jelić ◽  
Ljiljana Tasić ◽  
Ranko Škrbić ◽  
Valentina Marinković ◽  
Svjetlana Stoisavljević Šatara ◽  
...  

Abstract Background Pharmacists are often the first healthcare professionals that patients contact with their illnesses and requests for medical information, which is enhanced following the recent COVID-19 pandemic. Community pharmacists are expected and required to possess a broad spectrum of knowledge and skills. Self-assessment of these competencies is needed for their self-improvement. Purpose of the study To assess pharmacists’ clinical knowledge and practice in the safe use of contraceptives, and to compare the scores obtained by external observation with pharmacists’ self-assessment of their knowledge as well as investigate the significance of preceptorship experiences. Contraceptives was chosen as the subject area in view of high rates of abortions as a means of contraception in Bosnia and Herzegovina. Methods A questionnaire approach was used. The questionnaire included the following: the first domain contained two case scenarios (safe use of contraceptives), which evaluated clinical knowledge, a second domain in which pharmacists self-assessed their knowledge to resolve cases from the first domain and a third domain that measured the demographics of pharmacists (including experience in preceptorship). Dispensing practice was evaluated in the second domain. The questionnaires were distributed to a convenient sample of 100 pharmacists at the Annual Meeting of Bosnia and Herzegovina Pharmacists. The results were presented as counts (%). The groups (preceptors and non-preceptors) were compared using Mann-Whitney U test, paired assessments were analyzed by Wilcoxon signed-rank test and Spearman’s correlation was used to assess the correlation between variables. Results Of the 100 pharmacists invited to participate, 84 completed the questionnaire (84 % response rate). There was no agreement between pharmacists’ real knowledge (average score - case 1: 2.71, case 2: 3.3) and their self-assessment (average score - case 1: 3.77, case 2: 3.91). There was no statistically significant difference in the actual knowledge of pharmacists (experienced/non-experienced in precepting), while the difference in the self-assessment was significant between these two groups. Conclusion Pharmacists appear to overrate themselves, which leads to self-enhancement bias, in which the experience in precepting has some influence. Pharmacists’ capability in performing an objective self-assessment of their clinical knowledge needs to be carefully studied in the future to fully benefit patients.


Author(s):  
Camila Juliano Salvador Rodrigues ◽  
Elita Ferreira da Silveira ◽  
Rafael da Silveira Vargas ◽  
Giordano Gatti de Giacomo ◽  
Marino Muxfeldt Bianchin

Background: Cancer stem cells, also known as tumor-initiating cells, are suggested to be responsible for drug resistance and cancer development due in part to their ability to self-renew themselves and differentiate into heterogeneous lineages of cancer cells. Objective: This study was designed to investigate the role of cancer stem cells in pancreatic cancer. Methods: A retrospective clinicopathological analysis was undertaken in 112 patients diagnosed with pancreatic ductal adenocarcinoma between 2005 and 2010, and immunohistochemistry was performed with antibodies against CD133, CD24, and OCT4. Positive nuclear, cytoplasmic or membrane staining for each antibody was rated on staining intensity, being classified into low/moderate or strong staining groups. Results were analyzed relative to each patient’s clinicopathological parameters. Results: There was an established relationship between the staining of the markers with some variables associated with worse prognosis, being the three markers present in most tumor cells and associated with tumor progression. We suppose that cancer stem cells are present from the beginning of tumor initiation and are intrinsically related to tumor development. Although the presence of stem cells has been associated with molecular biology of various tumors, their expression in pancreatic cancer has not yet been clinically reported. Conclusion: The presence of stem cells and their role in pancreatic cancer tumorigenesis may be considered as valuable prognostic factors, although the mechanism involved needs further investigation. Increasing insights into role of cancer stem cells and carcinogenesis can ultimately generate new ideas for molecularly based diagnostic and therapeutic approaches.


2018 ◽  
Vol 12 (1) ◽  
pp. 89 ◽  
Author(s):  
Giyati Retnowati ◽  
Rose Mini Agoes Salim ◽  
Airin Y Saleh

This research aimed to determine the effectiveness of picture in storybook reading to increase kindness in children. This research involved 31 children aged 5-6 years; they were taken from the kindergarten in Bandung as the participants. The intervention was done by reading eight picture books in eight days. The kindness was measured using a measurement instrument created by the researcher, in the form of nine coloured cards that described the behaviour of kindness. The measurement was also done by seeing through the kindness tree and observation sheets that filled out by the teacher. The data analysis using the Wilcoxon Signed-rank test shows a significant difference in the average score of kindness (p<0,05) before and after picture storybook reading. Two weeks after the intervention, the improvement on all kindness behaviours with the post-test score is greater than pre-test score that still can be found. Observation through kindness tree and observational sheets shows the same result.


2019 ◽  
Vol 20 (20) ◽  
pp. 5107 ◽  
Author(s):  
Larisa Ryskalin ◽  
Carla L. Busceti ◽  
Francesca Biagioni ◽  
Fiona Limanaqi ◽  
Pietro Familiari ◽  
...  

The cellular prion protein (PrPc) is an evolutionarily conserved cell surface protein encoded by the PRNP gene. PrPc is ubiquitously expressed within nearly all mammalian cells, though most abundantly within the CNS. Besides being implicated in the pathogenesis and transmission of prion diseases, recent studies have demonstrated that PrPc contributes to tumorigenesis by regulating tumor growth, differentiation, and resistance to conventional therapies. In particular, PrPc over-expression has been related to the acquisition of a malignant phenotype of cancer stem cells (CSCs) in a variety of solid tumors, encompassing pancreatic ductal adenocarcinoma (PDAC), osteosarcoma, breast cancer, gastric cancer, and primary brain tumors, mostly glioblastoma multiforme (GBM). Thus, PrPc is emerging as a key in maintaining glioblastoma cancer stem cells’ (GSCs) phenotype, thereby strongly affecting GBM infiltration and relapse. In fact, PrPc contributes to GSCs niche’s maintenance by modulating GSCs’ stem cell-like properties while restraining them from differentiation. This is the first review that discusses the role of PrPc in GBM. The manuscript focuses on how PrPc may act on GSCs to modify their expression and translational profile while making the micro-environment surrounding the GSCs niche more favorable to GBM growth and infiltration.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2932-2932
Author(s):  
Farzana A. Sayani ◽  
Nizar J. Bahlis ◽  
Peter Faris ◽  
Mary Lynn Savoie ◽  
Ahsan Chaudhry ◽  
...  

Abstract Multiple dose intensive chemotherapy regimens have been used for induction/mobilization of stem cells for autologous stem cell transplantation (ASCT) in multiple myeloma. However, the exact role and regimens of such dose intensive chemotherapy has not been clearly defined. We therefore did a retrospective study to determine if dose intensive cyclophosphamide (Cyclo) 5.25 g/m2, etoposide 1.05 g/m2 and cisplatin 105 mg/m2 (DICEP) results in improved relapse rate and survival compared to standard mobilization with only Cyclo 2 g/m2. Between January 1998 and March 2004, a consecutive series of 57 newly diagnosed multiple myeloma patients receiving DICEP (38) or Cyclo (19) for in-vivo purging/mobilization were analyzed. Both groups were similar in regards to age and sex. There were no significant differences in IPI score, Durie-Salmon stage, B2 microglobulin, calcium, creatinine and albumin levels between treatment groups. Outcomes included time to relapse and time to death. Median follow up time was 799 days. Kaplan-Meier plots for time to relapse showed no significant difference (p=0.0992). Median relapse time in the DICEP group was 905 days (95% CI 580–1604) compared to 1112 days (95% CI 742-infinity) in the Cyclo group. Kaplan-Meier plots for overall survival showed no significant difference between both groups (p=0.8664). The median survival times have not yet been reached in either group and are not reported. Analysis revealed no discernable confounding risk factors. Effects of treatment on outcomes were not altered after adjusting for IPI score and Durie-Salmon staging using the stratified log-rank test. Small sample size and short duration of followup are potential limiting factors for this study, however, preliminary analysis of a larger sample of 91 multiple myeloma patients receiving either DICEP or a less intense induction/mobilization regimen, also revealed no significant difference in disease free or overall survival. Monoclonal plasma cell contamination of stem cell products was not significantly different between both groups (DICEP 42.9%, Cyclo 56.3%, p=0.5573). This study therefore suggests that the very intense DICEP induction/mobilization regimen results in no significant difference in survival outcomes. The more intense regimen does not significantly decrease tumor contamination of autograft stem cells. Overall, our experience suggests that novel induction therapies such as bortezomib, lenolidomide etc. should be pursued in preference to any further study of high dose cytotoxic chemotherapy induction. Figure Figure


Sign in / Sign up

Export Citation Format

Share Document