Browsing by Subject "Pancreatic cancer"

Now showing 1 - 17 of 17
  • Thumbnail Image
    Publication
    Open Access
    Decreased survival in patients with pancreatic cancer may be associated with an increase in histopathological expression of inflammasome marker NLRP3
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Fraile Martínez, Oscar; García Montero, Cielo; Pekarek, Leonel; Saz, Jose V.; Álvarez Mon, Miguel Ángel; Barrena Blázquez, Silvestra; García Honduvilla, Natalio; Buján, Julia; Asúnsolo, Ángel; Coca, Santiago; Álvarez Mon, Melchor; Guijarro, Luis G.; Saez, Miguel A.; Ortega, Miguel A.
    Pancreatic cancer is a malignant neoplasm that, despite its low frequency, has a 5-year survival rate of less than 10%. The study of different histopathological markers has allowed a better understanding of the onset and development of this type of tumor as well as facilitating an approach to clinical variables based on their diagnostic, prognostic, and predictive value. In this sense, the NLRP3 protein of the inflammasome has been shown to be a component of great relevance in the initiation and progression of pancreatic cancer, although the value of this biomarker in patients has not yet been clarified. In this study, we selected 41 patients with pancreatic cancer and followed them for 60 months (5 years), evaluating their NLRP3 expression using immunohistochemical techniques. Furthermore, by performing Kaplan-Meier curves, we evaluated the survival of these patients in relation to their NLRP3 expression. Our results show that a significant percentage of our cohort had high expression of this component (90.74%) and that there is an inverse relationship between the expression of NLRP3 and patient survival. High levels of NLRP3 expression are related to lower survival and worse prognosis in these patients, possibly due to an ineffective immune system response and increased tumor-promoted inflammation. Future studies should be aimed at confirming these results in larger groups and evaluating various clinical strategies based on this knowledge.
  • Thumbnail Image
    Publication
    Open Access
    Effects of single, double or triple combinations of octreotide, galanin and serotonin on a human pancreatic cancer cell line
    (Murcia : F. Hernández, 2005) Tjomsland, V.; El-Salhy, M.
    The human pancreatic cancer cell line (SW 1990) was exposed to 0.2 µg/ml of octreotide, galanin or serotonin as single, double or triple combinations. The tumor cells were checked at 3, 6 and 12 hours. In order to determine the number of viable cancer cells, the MTTassay was used. Proliferation, apoptosis and the expression of epidermal growth factor were detected with immunohistochemistry using the avidin-biotin complex method. In addition, apoptosis was also detected with (TUNEL) method. The primary antibodies used were proliferating cell nuclear antigen (PCNA), anti-poly (ADP-ribose) polymerase (PARP) and antihuman epidermal growth factor. Single treatment with octreotide or serotonin reduced, the number of viable cells and the proliferation index at all observation times. Galanin increased the number of viable cells and the proliferation index. Whereas double treatments containing octreotide reduced the number of viable cells, those containing galanin increased the number. The effect of single, double or triple treatment on the apoptotic index obtained with both TUNEL method and PARP expression varied depending on the combination and the observation time. Octreotide did not affect the tumor cell expression of EGF. Galanin and serotonin, on the other hand, increased the expression of EGF Whereas triple combination increased the expression of EGF after 6 h, all the other double combinations decreased this expression. It has been concluded that treatment with a combination of octreotide and serotonin may be useful in clinical settings.
  • Thumbnail Image
    Publication
    Open Access
    Epigenetic upregulation of MNAT1 by SMYD2 is linked to PI3K/AKT activation and tumorigenesis of pancreatic adenocarcinoma
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Xu, Zhen; Liu, Yan; Pan, Zhi; Qin, Lei
    Dysregulation of histone methyltransferase SET and MYND domain-containing protein 2 (SMYD2) has been correlated with human developmental disorders and cancers. This research aims to investigate the roles of SMYD2 and its interacted molecules in pancreatic adenocarcinoma (PAAD). Two PAAD-related gene expression datasets were downloaded to screen key molecules involved in tumor progression. SMYD2 was expressed at high levels in PAAD tissues and cells. SMYD2 silencing suppressed while its overexpression promoted proliferation, invasiveness, migration, apoptosis resistance, and cell cycle progression of PAAD cells. Target molecules of SMYD2 were predicted by online tools and validated by chromatin immunoprecipitation and luciferase assays. SMYD2 catalyzed H3K36me2 modification at the promoter region of MNAT1 component of CDK activating kinase (MNAT1) to promote its transcription. MNAT1 was correlated with an unfavorable clinical outcome of PAAD patients. Alteration of MNAT1 alone also affected the malignant behavior of PAAD cells. Moreover, MNAT1 overexpression in cells rescued the malignant phenotype of cells suppressed by SMYD2 silencing. MNAT1 activated the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) signaling. In vivo, SMYD2 silencing decreased the growth rate and weight of xenograft tumors in nude mice. Overall, this paper demonstrates that SMYD2-mediated MNAT1 upregulation is linked to PAAD tumorigenesis via PI3K/ AKT pathway activation.
  • Thumbnail Image
    Publication
    Open Access
    Expression analysis of MAC30 in human pancreatic cancer and tumors of the gastrointestinal tract
    (Murcia : F. Hernández, 2004) Kayed, Hany; Kleeff, Jörg; Ding, J.; Hammer, J.; Giese, T.; Zentgraf, H.; Büchler, M.W.; Friess, Helmut
    Meningioma-associated protein, MAC30, is a protein with unknown function and cellular localization that is differentially expressed in certain malignancies. In the present study, the expression of MAC30 in a variety of normal and cancerous human gastrointestinal tissues, with special emphasis on pancreatic tissues was analyzed. Quantitative RT-PCR was utilized to compare MAC30 expression levels. In situ hybridization and immunohistochemistry were carried out to localize MAC30 mRNA and protein expression in normal and cancerous tissue samples of the esophagus, stomach, colon and pancreas. Furthermore, the effects of TGF-ß on the transcription of MAC30 mRNA were examined in pancreatic cancer cells. MAC30 mRNA was expressed in a wide variety of normal human tissues, being most abundant in testicular and gastric tissue samples. MAC30 mRNA levels were significantly increased in breast and colon cancer, but significantly decreased in pancreatic and renal cancer. TGF-ß down-regulated MAC30 mRNA levels in certain pancreatic cancer cells. MAC30 protein was localized in normal pancreatic tissues, mainly in acinar and islet cells, and in normal colon, gastric and esophageal tissues especially in the mucosal cells. MAC30 was strongly present in tubular complexes in pancreatic cancer tissues but weak to absent in pancreatic cancer cells of primary tumors and metastases. In contrast, esophageal, gastric and colon tumors displayed strong MAC30 immunoreactivity in the cancer cells. In conclusion, MAC30 is expressed in various normal and diseased human tissues. MAC30 up-regulation in certain tumors and down-regulation in others suggests that this protein plays a distinct role in human malignancies.
  • Thumbnail Image
    Publication
    Open Access
    Expression and regulation of nicotine receptor and osteopontin isoforms in human pancreatic ductal adenocarcinoma
    (F. Hernández y J.F. Madrid. Murcia: Universidad de Murcia, Departamento de Biología Celular e Histología., 2011) Sullivan, Jennifer; Blair, Laurel; Alnajar, Amer; Aziz, Tamer; Chipitsyna, Galina; Gong, Qiaoke; Yeo, Charles J.; Arafat, Hwyda A.
    Osteopontin (OPN) is a secreted phospho-protein that confers on cancer cells a migratory phenotype. We have recently shown that nicotine, a risk factor in pancreatic ductal adenocarcinoma (PDA), induces an alpha7-nicotine acetylcholine receptor (α7-nAChR)-mediated increase of OPN in PDA cells. In this study, we tested nicotine’s effect on the expression of OPN splice variants (OPNa, b, c) in PDA cells. We also analyzed the correlation between patients’ smoking history with OPN and α7-nAChR levels. RT-PCR and UV-light-illumination of ethidium-bromide staining were used to examine the mRNA expression in tissue and PDA cells treated with or without nicotine (3-300 nM). Localization of total OPN, OPNc and α7-nAChR was analyzed by immunohistochemistry, and their mRNA tissue expression levels were correlated with the patients’ smoking history. PDA cells expressed varying levels of OPNa, OPNb, and α7-nAChR. Nicotine treatment selectively induced denovo expression of OPNc and increased α7-nAChR expression levels. In PDA tissue, OPNc was found in 87% of lesions, of which 73% were smokers. OPNc and total OPN levels were correlated in the tissue from patients with invasive PDA. Nicotine receptor was expressed in the invasive and premalignant lesions without clear correlation with smoking history. We show here for the first time that α7-nAChR is expressed in PDA cells and tissues and is regulated by nicotine in PDA cells. This, together with our previous findings that α7-nAChR mediates the metastatic effects of nicotine in PDA, suggest that combined targeting of α7-nAChR and OPNc could be a valid novel therapeutic strategy for invasive PDA, especially in the smoking population.
  • Thumbnail Image
    Publication
    Open Access
    High Annexin A10 expression is correlated with poor prognosis in pancreatic ductal adenocarcinoma
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Ishikawa, Akira; Kuraoka, Kazuya; Zaitsu, Junichi; Saito, Akihisa; Yamaguch, Atsushi; Kuwai, Toshio; Sudo, Takeshi; Hadano, Naoto; Tashiro, Hirotaka; Taniyama, Kiyomi; Yasui, Wataru
    Pancreatic ductal adenocarcinoma (PDAC) is the third-leading cause of cancer-related death. Owing to its poor prognosis, new molecular biomarkers for PDAC are needed. Annexin A10 (ANXA10) is a calcium- /phospholipid-binding protein belonging to the annexin family of proteins. ANXA10 is not only associated with gastric phenotypes, but also acts an independent prognostic factor in several cancers. However, the role of ANXA10 in PDAC remains unknown. Therefore, we examined the relationship between ANXA10 and the prognosis of PDAC. We analyzed the expression of ANXA10 using data from public databases, and performed immunohistochemistry analysis for 81 PDAC cases. We then investigated the relationship between ANXA10 expression and clinicopathological features. ANXA10 was detected in 47 of 81 PDAC cases (58%). High expression of ANXA10 was significantly related to poor overall survival (OS; p=0.011). Univariate analysis of OS revealed three prognostic parameters: tumor grade (p=0.046), perineural invasion (p=0.017), and ANXA10 expression (p=0.012). Multivariate analysis indicated that ANXA10 expression (p<0.01) alone was a prognostic factor in PDAC cases. Our findings suggest that ANXA10 expression is an independent prognostic factor in PDAC cases and shows promise as a new biomarker in PDAC.
  • Thumbnail Image
    Publication
    Open Access
    Knockdown of TBRG4 suppresses the migration, invasion, and epithelial-to-mesenchymal transition of pancreatic cancer cells via TGF-β/smad3 signaling
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Ye, Xiao; Zheng, Xiaolin; Zhu, Ling; Biología Celular e Histología
    Introduction. Pancreatic cancer (PC) is one of the deadliest malignancies worldwide, with a low five-year survival rate of less than 10%. Transforming growth factor β regulator 4 (TBRG4) is differentially expressed in PC tissues, but its specific functions and regulatory role in PC have not been clarified. Methods. TBRG4 mRNA expression in PC cells was measured by qRT-PCR. Protein levels of TBRG4, key markers related to the epithelial-mesenchymal transition (EMT) process, and factors related to the TGF-β/smad3 pathway were quantified by western blot. The migratory and invasive abilities of PC cells were evaluated by wound healing and Transwell assays, respectively. Spearman’s correlation analysis was performed to analyze the expression correlation between TBRG4 and TGF-β1 (or SMAD3). Xenograft mouse models were established to explore the in vivo role of TBRG4. Results. The mRNA and protein expression of TBRG4 were elevated in PC cells. TBRG4 knockdown repressed PC cell migration, invasion, and the EMT process. Moreover, TBRG4 activated TGF-β/smad3 signaling in PC cells and positively correlated with TGF-β1 (or SMAD3) expression in PC tissues based on bioinformatics analysis. Furthermore, SRI-011381 (an agonist of TGF-β1) counteracted the inhibitory influence of TBRG4 knockdown on PC cellular behaviors, and SB431542 (an inhibitor of the TGF-β type I receptor) treatment countervailed the promoting influence of TBRG4 overexpression on PC cell invasion, migration, and EMT. Results of in vivo assays verified that TBRG4 silencing inhibited tumorigenesis and TGF-β/smad3 signaling. Conclusion. The silencing of TBRG4 inhibits PC cell invasion, migration, EMT, and tumorigenesis by inactivating TGF-β/smad3 signaling.
  • Thumbnail Image
    Publication
    Open Access
    Melatonin influences pancreatic cancerogenesis
    (F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2014) Jaworek, Jolanta; Leja-Szpak, Anna
    Pancreatic cancer has fatal prognosis because of the absence of early symptoms, late diagnosis and the resistance to radio- and chemotherapy. Melatonin, an indoleamine discovered in the pineal gland, has also been detected in the gastrointestinal system and its specific receptors have been identified in the pancreas. Some evidence indicates that melatonin could modulate the process of pancreatic oncogenesis: 1) Melatonin, as direct scavenger of radical oxygen and nitrogen species (ROS and RNS) and activator of antioxidant enzymes effectively protects the pancreatic tissue against oxidative stress and inflammatory damage. 2) In pancreatic carcinoma cell line (PANC-1) melatonin used at high doses affects the Bax/Bcl protein balance, and stimulates the expressions of caspase-9 and caspase-3, thus activating the mitochondrial pathway of apoptosis. On the contrary, low concentrations of melatonin turn on the production of anti-apoptotic heat shock proteins: HSP27, HSP70, and HSP90, which prevents the activation of caspase-3. 3) Melatonin reduces angiogenesis and decreases proliferation of endothelial cells through inhibition of vascular endothelial factor (VEGF). 4) Melatonin strengthens the immune defense of the organism via activation of peripheral effector T cells and suppression of T regulatory cells. 5) In animal studies melatonin has been found to increase the efficacy of oncostatic drugs, to reduce the side effects of chemotherapy and to decrease morbidity. These observations suggest that melatonin at high doses could be potentially taken into consideration as the supportive treatment in the therapy of pancreatic cancer, although the effect of melatonin on apoptosis requires further study. Histol Histopathol 29, 423-431 (2014)
  • Thumbnail Image
    Publication
    Open Access
    Mixed acinar-neuroendocrine carcinoma of the pancreas: a case report and a review
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2016) Jakobsen, Mark; Klöppel, Günter; Detlefsen, Sönke
    A 62-year-old woman presented with abdominal discomfort. Imaging studies showed a tumor in the pancreatic tail. At contrast-enhanced CT and macroscopy, the tumor showed cystic, solid and hemorrhagic areas. Histologically, the tumor was wellcircumscribed and entirely encapsulated. Some of the tumor cells in the cystic areas were reminiscent of acinar cells, and the majority was arranged in a solid growth pattern. Immunohistochemistry revealed >30% positivity for chymotrypsin, chromogranin A, synaptophysin, and CD56. The diagnosis of a mixed acinar-neuroendocrine carcinoma (MAEC) was made. Review of the English language literature revealed 44 previously published cases of resected MAECs. We found that, compared to pure acinar cell carcinoma, patients with MAEC have a slightly higher age and are less frequently males, as the male/female ratio was almost equal. The histogenesis of MAEC is still controversial. Due to the small number of cases it is at present not possible to define an evidencebased optimal treatment strategy for these patients.
  • Thumbnail Image
    Publication
    Open Access
    Morphometric studies in human pancreatic cancer argues against the etiological role of type 2 diabetes in pancreatic cancer
    (Murcia : F. Hernández, 2010) Saruc, Murat; Iki, Katsumichi; Pour, Parviz M.
    Background: To understand the role of islet amyloid polypeptide (IAPP) in type 2 diabetes and pancreatic cancer (PC), we investigated the patterns of its expression and its ratio to insulin, glucagon, somatostatin and pancreatic polypeptide cells by morphometry in tissues from these two diseases in comparison to the normal pancreas. Materials and Methods: Pancreatic tissues from 11 donors (five without pancreatic disease and six with type 2 diabetes) and 11 surgical specimens from PC patients obtained from the cancer area (zone A) and the adjacent tumor-free area (zone B) were examined immunohistochemically. The size of islets, the number on ß-, α-, δ- pp- and IAPP-expressing cells and their ratios in the islets of these tissues were determined. Results: In the normal pancreas, only 50% of the ß-cells while α- and δ-cells co-expressed IAPP only sporadically. In tissues from diabetics as well as in zone A, the number of the ß-cells and the IAPP-expressing cells was reduced significantly, while the number of α- and δ-cells was increased. In zone B, however, significantly more ß-cell and IAPP-expressing cells and a significantly lower number of α-cells were found compared to those in zone A. Significant differences were also found between the specimens from type 2 diabetics and pancreatic cancer relative to the ratios of IAPP/ß-cell, IAPP/α-cells and ß-cell/δ-cells. Conclusion: The morphometric data show a decrease rather than an increase in the number of IAPP-expressing cells in PC. Differences in abnormalities in type-2 diabetics and in zone B of PC tissue strongly argue against the role of type 2 diabetes in PC. Rather, the development of diabetes in subjects prone to pancreatic cancer could be a red flag for malignancy
  • Thumbnail Image
    Publication
    Open Access
    On the role of the islets of Langerhans in pancreatic cancer
    (Murcia : F. Hernández, 2004) Hennig, R.; Ding, X.Z.; Adrian, T.E.
    Pancreatic cancer is a devastating disease characterized by a dismal prognosis with most patients dying within six months after diagnosis. Surgery is an option in less than one in five of these patients, and even with tumor resection the majority of patients succumb to the disease. Other effective treatment options are not available. Common features of pancreatic cancer are severe cachexia, marked insulin resistance and diabetes mellitus. Several studies have demonstrated connections between pancreatic cancers and the endocrine pancreas and this has raised questions regarding the role of the islets of Langerhans in pancreatic adenocarcinoma. This manuscript reviews the recent literature in this field and addresses several questions regarding the interaction between the islets of Langerhans and pancreatic cancer. This review considers the histological findings in pancreatic cancer, cell culture and animal experiments, the four islet cell types and the hormones they secrete, as well as the influence of the arachidonic acid pathways on islet cell function and pancreatic cancer. While pancreatic adenocarcinomas are ductal in nature, the cell of origin has not been identified and there is even some evidence that the islets may harbor the precursor cell. Considerable evidence suggests that the diabetes is caused by the tumor, while other studies have identified diabetes as a risk factor. Clearly, the islets are important in many aspects of this disease. However, even though progress has been made, some questions regarding the interaction of pancreatic cancer and the endocrine pancreas remain unanswered.
  • Thumbnail Image
    Publication
    Open Access
    Preferential expression of cystein-rich secretory protein-3 (CRISP-3) in chronic pancreatitis
    (Murcia : F. Hernández, 2003) Liao, Q.; Kleeff, Jörg; Xiao, Y.; Guweidhi, A.; Schambony, A.; Töpfer-Petersen, E.; Zimmermann, Astrid; Büchler, M.W.; Friess, Helmut
    Background: Chronic pancreatitis (CP) is a progressive inflammatory process resulting in exocrine and endocrine pancreatic insufficiency in advanced stages. Cysteine-rich secretory protein (CRISP-3) has been identified as a defense-associated molecule with predominant expression in the salivary gland, pancreas and prostate. Aims: In this study, we investigated CRISP-3 expression in normal pancreatic tissues, chronic pancreatitis tissues, pancreatic cancer tissues and pancreatic cancer cell lines, as well as in other gastrointestinal organs. Materials and Methods: 15 normal pancreatic tissues, 14 chronic pancreatitis tissues and 14 pancreatic cancer tissues as well as three pancreatic cancer cell lines were analyzed. Moreover, hepatocellular carcinoma and esophageal, stomach and colon cancers were also analyzed together with the corresponding normal controls. Results: CRISP-3 was expressed at moderate to high levels in chronic pancreatitis tissues and at moderate levels in pancreatic cancer tissues but at low levels in normal pancreatic tissues, and was absent in three pancreatic cancer cell lines. CRISP-3 expression was below the level of detection in all cancerous gastrointestinal tissues and in all normal tissues except 2 of 16 colon tissue samples. CRISP-3 mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells and in small proliferating ductal cells in CP tissues and CP-like lesions in pancreatic cancer tissues. In contrast, CRISP-3 expression was weak to absent in the cytoplasm of cancer cells as well as in acinar cells and ductal cells in pancreatic cancer tissues and normal pancreatic tissues. Conclusion: These results reveal that the distribution of CRISP-3 in gastrointestinal tissues is predominantly in the pancreas. High levels of CRISP-3 in acinar cells dedifferentiating into small proliferating ductal cells in CP and CP-like lesions in pancreatic cancer suggests a role of this molecule in the pathophysiology of CP.
  • Thumbnail Image
    Publication
    Open Access
    Prognostic role of IRS-4 in the survival of patients with pancreatic cancer
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2022) Ortega, Miguel A; Pekarek, Leonel; Garcia Montero, Cielo; Fraile Martinez, Oscar; Saez, Miguel A; Asúnsolo, Angel; Alvarez Mon, Miguel A; Monserrat, Jorge; Coca, Santiago; Toledo Lobo, M. Val; García Honduvilla, Natalio; Albillos, Agustin; Buján, Julia; Alvarez Mon, Melchor; Guijarro, Luis G
    Pancreatic cancer is a malignancy of rising incidence, especially in developed countries due to causes such as sedentary lifestyles, tobacco smoking and ultraprocessed high fat and high sugar diets, amongst others. It is in fact the 7th cause of cancer-related deaths worldwide, and, in the following years, it is expected to climb upwards to 2nd position, after lung cancer. This is because it may have an asymptomatic course, and when it becomes evident it is in advanced stages, accompanied by metastasis generally. For this reason, survival rates are so low and, even in the few successful cases there is a high possibility of recurrence. Identifying new molecular biomarkers is arising as a highly useful tool for pancreatic cancer clinical management, although much research and work remain to be done in this field. Thus, the present study aims to analyze a series of molecules (IRS-4, Rb1, Ki-67 y COX-2) as candidates for prognosis and survival by immunohistochemistry techniques. Additionally, a 60-month longitudinal surveillance program was conducted, associated with diverse clinical parameters. Kaplan-Meier curves estimating the time of survival according to tumoral expression of those molecules denoted a low cumulative survival rate. Importantly, we observed that high levels of IRS-4 were significantly associated with a bad prognosis of the disease, increasing 160 times the mortality risk. In this way, our research showed a relevant value of these biomarkers in pancreatic cancer patients’ survival, opening a pathway for future research areas designed to inhibit these components
  • Thumbnail Image
    Publication
    Open Access
    Reduced expression of the membrane skeleton protein beta1-spectrin (SPTBN1) is associated with worsened prognosis in pancreatic cancer
    (Murcia : F. Hernández, 2010) Jiang, Xiaohua; Gillen, Sonja; Esposito, Irene; Giese, Nathalia A.; Michalski, Christoph W.; Friess, Helmut; Kleeff, Jörg
    Spectrins are members of the superfamily of F-actin cross linking proteins that are important as scaffolding proteins for protein sorting, cell adhesion, and migration. In addition, spectrins have been implicated in TGF-beta signaling. The aim of the present study was to analyze the expression and localization of beta1-spectrin (SPTBN1) in pancreatic tissues. mRNA levels of SPTBN1 in cultured pancreatic cancer cell lines, as well as in normal pancreatic tissues (n=18), chronic pancreatitis (n=48) and pancreatic cancer tissues (n=66) were analyzed by real time quantitative RT-PCR. Localization of SPTBN1 in pancreatic tissues was determined by immunohistochemistry. SPTBN1 staining was assessed semi-quantitatively in 55 cancer tissues and survival analysis was carried out using the KaplanMeier method. Median SPTBN1 mRNA levels were 6.0- fold higher in pancreatic cancer tissues compared to the normal pancreas (p<0.0001) and 2.2–fold higher compared to chronic pancreatitis tissues (p=0.0002). In the normal pancreas, SPTBN1 was present in the cytoplasm of normal ductal cells and occasionally in pancreatic acinar and centroacinar cells. In pancreatic cancer tissues, SPTBN1 was present in the cytoplasm of pancreatic cancer cells. Low SPTBN1 protein expression indicated a tendency for worsened prognosis with a median survival of 14.0 months, versus 23.8 months for patients whose tumors expressed moderate/high levels of SPTBN1. In conclusion, reduced SPTBN1 expression correlated with shorter survival of pancreatic cancer patients, suggesting a tumor suppressor function of this gene, as has already been shown for other malignancies of the gastrointestinal tract.
  • Thumbnail Image
    Publication
    Open Access
    Shifting epidemiology of pancreatic cancer in Southeast Spain (1983-2018): emerging patterns in younger women and neuroendocrine neoplasms
    (2026-02-17) Colorado-Yohar, Sandra M.; Vaamonde-Martín, Ricardo J.; Ballesta Ruiz, Mónica; Salmerón Martínez, Diego; Marcos-Gragera, Rafael; Sánchez-Gil, Antonia; Corral de la Calle, Javier; Chirlaque López, María Dolores; Ciencias Sociosanitarias
  • Thumbnail Image
    Publication
    Open Access
    Spatial and phenotypic characterization of pancreatic cancer-associated fibroblasts after neoadjuvant treatment
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2020) Nielsen, Michael Friberg Bruun; Mortensen, Michael Bau; Sörensen, Mia Dahl; Wirenfeldt, Martin; Kristensen, Bjarne Winther; Schröder, Henrik Daa; Pfeiffer, Per; Detlefsen, Sönke
    Pancreatic ductal adenocarcinoma (PC) is characterized by a highly fibrotic desmoplastic stroma. Subtypes of cancer-associated fibroblasts (CAFs) have been identified in chemotherapy-naïve PC (CTN-PC), but their precise functions are still unclear. Our knowledge regarding the properties of CAFs in the regressive stroma after neoadjuvant treatment (NAT) of PC (NAT-PC) is particularly limited. We aimed to examine the marker phenotypic properties of CAFs in the regressive stroma of PC. Surgical specimens from patients with CTN-PC (n=10) and NAT-PC (n=10) were included. Juxtatumoural, peripheral, lobular, septal, peripancreatic, and regressive stromal compartments were manually outlined using digital imaging analysis (DIA) for area quantification. The compartment-specific expression of CD271, cytoglobin, DOG-1, miR-21, osteonectin, PDGF-Rβ, and tenascin C was evaluated by immunohistochemistry or in situ hybridization, using manual scoring and automated DIA. The area fraction of the regressive stroma was significantly higher in NAT-PC than in CTN-PC (P=0.0002). CD271 (P<0.01), cytoglobin (P<0.05), DOG1 (P<0.05), miR-21 (P<0.05), and tenascin C (P<0.05) exhibited significant differences in their expression profiles between the juxtatumoural compared to the peripheral and regressive stroma. PDGF-Rβ expression was significantly higher in juxtatumoural than in peripheral CAFs (P<0.05). Our data provide further support of the concept of stromal heterogeneity and phenotypic different CAF subtypes in PC. CAFs in the regressive stroma of NAT- PC show a marker phenotype similar to some (namely, peripheral) and different from other (namely, juxtatumoural) previously defined CAF subtypes. It may be hypothesized that phenotypic CAF subtypes, at least in part, also may share functional properties. Studies examining the precise functional characteristics of CAF subtypes in PC are needed
  • Thumbnail Image
    Publication
    Open Access
    Stroma composition and proliferative activity are related to therapy response in neoadjuvant treated pancreatic ductal adenocarcinoma
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2021) Haeberle, Lena; Insilla, Andrea Cacciato; Kap, Anne-Christine; Steiger, Katja; Schlitter, Anna Melissa; Konukiewitz, Björn; Demir, Ihsan Ekin; Friess, Helmut; Esposito, Irene
    Background. Tumor regression grading (TRG) based on histopathology is the main tool to assess therapy effects after neoadjuvant therapy (NAT) of pancreatic ductal adenocarcinoma (PDAC). However, reliable markers to distinguish therapy effects from preexisting tumor features are lacking. The aim of this study was the characterization of PDAC after NAT, focusing on the stroma. Material and Methods. Tissue samples from patients resected for PDAC after NAT (n=27) were analyzed. TRG was assessed using the Royal North Shore (RNS) system. Stromal composition was evaluated by Movat's stain. Immunohistochemistry (IH) for Ki-67 and five previously established stroma markers (alpha-Crystallin B, alpha-Smooth muscle actin (alpha-SMA), Neurotrophin-3 (NT-3), SPARC and Tenascin C) was also performed. Results were compared with therapynaïve PDACs (n=10). Results. Most cases showed a moderate response (RNS 2; 74%), while 15% displayed a poor response (RNS 3), and 11% a good response (RNS 1). No complete response was observed. Poor regression was associated with mucin-rich stroma, while good regression was associated with collagen-rich stroma. Cases with poorer therapy response had significantly higher proliferation. Higher peritumoral staining intensity for alpha-SMA and Tenascin C also showed a trend towards an association with poor regression. Conclusions. Similar to the stroma in therapy-naïve PDAC, the stroma of PDAC after NAT is heterogeneous. Distinguishing between desmoplastic stroma and therapy-induced fibrosis by single markers is not possible. Movat's pentachrome stain, IH for Ki-67, and to some extent for Tenascin C and alpha-SMA, can help detect poor histopathological response to NAT.