The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Joseph M Klausner - One of the best experts on this subject based on the ideXlab platform.
-
protective Desmoplasia in pancreatic adenocarcinoma high vitamin d receptor expression and collagen content
Anticancer Research, 2020Co-Authors: Adi Vaknine Bahat, Shoshi Bardavid, Asaf Aizic, Guy Lahat, Ido Wolf, Joseph M Klausner, Abigail Brooks, Orli Greenberg, Eran NizriAbstract:BACKGROUND/AIM Vitamin D receptor (VDR) has been shown to suppress Desmoplasia in pancreatic ductal adenocarcinoma (PDAC). Our aim was to assess the clinical effects of VDR expression and its correlation with collagen content in the Desmoplasia of PDAC patients. PATIENTS AND METHODS This is a retrospective analysis of 127 patients with peritumoral Desmoplasia resected for PDAC. VDR expression and collagen content were assessed by immunohistochemistry and correlated with clinical outcome. RESULTS Patients were classified into those with high and those with low VDR expression. High VDR expression was associated with improved overall survival (OS) in localized disease (N0) (median= 33; 95%CI=26.4-39.6 vs. 18; 15.5-20.5 months, p=0.01). Patients with high vs. low collagen content had improved OS [34, (range=22.3-45.6 months) vs. 17, (range=14.4-19.6 months), p<0.001]. The number of VDR+ cells was the same for patients with either high or low collagen content. CONCLUSION Protective Desmoplasia is associated with increased VDR expression and collagen content.
-
Desmoplasia in lymph node metastasis of pancreatic adenocarcinoma reveals activation of cancer associated fibroblasts pattern and t helper 2 immune cell infiltration
Pancreas, 2019Co-Authors: Eran Nizri, Shoshi Bardavid, Asaf Aizic, Neta Sternbach, Guy Lahat, Ido Wolf, Joseph M KlausnerAbstract:ObjectivesPancreatic ductal adenocarcinoma (PDAC) is characterized by a peritumoral proliferation of fibroblasts and extracellular matrix production known as Desmoplasia. We aimed to study Desmoplasia in PDAC lymph node (LN) metastases.MethodsWe evaluated LNs from 66 patients with PDAC and LN metast
-
analysis of histological and immunological parameters of metastatic lymph nodes from colon cancer patients reveals that t helper 1 type immune response is associated with improved overall survival
Medicine, 2016Co-Authors: Eran Nizri, Shoshi Bardavid, Guy Lahat, Nofar Greenmanmaaravi, Amir Benyehuda, Gilad Weiner, Joseph M KlausnerAbstract:Lymph node (LN) involvement in colonic carcinoma (CC) is a grave prognostic sign and mandates the addition of adjuvant treatment. However, in light of the histological variability and outcomes observed, we hypothesized that patients with LN metastases (LNM) comprise different subgroups. We retrospectively analyzed the histological sections of 82 patients with CC and LNM. We studied various histological parameters (such as tumor grade, Desmoplasia, and preservation of LN architecture) as well as the prevalence of specific peritumoral immune cells (CD8+, CD20+, T-bet+, and GATA-3+). We correlated the histological and immunological data to patient outcome. Tumor grade was a significant prognostic factor even in patients with LNM. So was the number of LN involved (N1/N2 stage). From the morphological parameters tested (LN extracapsular invasion, Desmoplasia in LN, LN architecture preservation, and mode of metastases distribution), none was found to be significantly associated with overall survival (OS). The mean OS of CD8+ low patients was 66.6 ± 6.25 versus 71.4 ± 5.1 months for CD8+ high patients (P = 0.79). However, T-helper (Th) 1 immune response skewing (measured by Th1/Th2 ratio >1) was significantly associated with improved OS. For patients with low ratio, the median OS was 35.5 ± 5 versus 83.5 months for patients with high Th1/Th2 ratio (P = 0.001). The histological presentation of LNM does not entail specific prognostic information. However, the finding of Th1 immune response in LN signifies a protective immune response. Future studies should be carried to verify this marker and develop a strategy that augments this immune response during subsequent adjuvant treatment.
Kenoki Ohuchida - One of the best experts on this subject based on the ideXlab platform.
-
degree of Desmoplasia in metastatic lymph node lesions is associated with lesion size and poor prognosis in pancreatic cancer patients
Oncology Letters, 2017Co-Authors: Hiromichi Nakayama, Kenoki Ohuchida, Masaki Yoshida, Tetsuyuki Miyazaki, Shin Takesue, Toshiya Abe, Sho Endo, Kazuhiro Koikawa, Takashi Okumura, Taiki MoriyamaAbstract:Pancreatic cancer is characterized by increased hyperplasia of fibrotic tissue, termed Desmoplasia, and lymph node metastasis is an independent prognostic factor in this disease. However, there are no reports focused on Desmoplasia in pancreatic cancer lymph node metastases. The present study evaluated a range of factors and investigated their association with poor prognosis in pancreatic cancer cases with lymph node metastasis, including the degree of Desmoplasia in lesions. To identify the poor prognostic factors associated with lymph node metastasis, the present study retrospectively reviewed the clinical data of 65 patients with lymph node metastases that underwent surgical pancreatic cancer resection between 2007 and 2012 at a single institution. The investigation focused on the degree of fibrosis in metastatic lesions in 216 lymph nodes, and investigated associations with prognosis or clinicopathological findings. The ratios of the fibrotic area in metastatic lymph node lesions were evaluated and classified into three categories, high (≥70%), moderate (10-70%) and low (<10%). Desmoplasia was not observed in cancer-free lymph nodes. The size of metastatic lymph node lesions was additionally measured, and a significant association between metastatic lesion size and the degree of Desmoplasia was observed (P<0.001). The degree of Desmoplasia was additionally associated with local extranodal invasion. In the analysis of 65 pancreatic cancer patients with metastatic lymph nodes, the presence of multiple metastatic lymph nodes with moderate or high Desmoplasia was significantly associated with poor survival (high, P=0.0048; moderate/high, P=0.0075). Of several clinicopathological factors, the presence of multiple metastatic lymph nodes with high or moderate Desmoplasia was associated with overall survival in univariate (P=0.0098) and multivariate (P=0.0466) analyses. The degree of Desmoplasia in metastatic lymph nodes is associated with lesion size, and the presence of multiple metastatic lymph nodes with Desmoplasia is an independent poor prognostic factor, suggesting that the Desmoplasia may have an important role in the malignant progression of lymph node metastases.
-
calpain inhibitor calpeptin suppresses pancreatic cancer by disrupting cancer stromal interactions in a mouse xenograft model
Cancer Science, 2016Co-Authors: Masaki Yoshida, Kenoki Ohuchida, Takashi Okumura, Yoshihiro Miyasaka, Biao Zheng, Nobuhiro Torata, Hayato Fujita, Toshinaga Nabae, Tatsuya Manabe, Masaya ShimamotoAbstract:Desmoplasia contributes to the aggressive behavior of pancreatic cancer. However, recent clinical trials testing several antifibrotic agents on pancreatic cancer have not shown clear efficacy. Therefore, further investigation of Desmoplasia-targeting antifibrotic agents by another mechanism is needed. Calpeptin, an inhibitor of calpains, suppressed fibroblast function and inhibited fibrosis. In this study, we investigated the anticancer effects of calpeptin on pancreatic cancer. We investigated whether calpeptin inhibited tumor progression using a mouse xenograft model. We used quantitative RT-PCR to evaluate the expression of calpain-1 and calpain-2 mRNA in pancreatic cancer cells (PCCs) and pancreatic stellate cells (PSCs). We also undertook functional assays, including proliferation, migration, and invasion, to evaluate the inhibitory effects of calpeptin on PCCs and PSCs. Quantitative RT-PCR indicated that PCCs and PSCs expressed calpain-2 mRNA. Calpeptin reduced tumor volume (P = 0.0473) and tumor weight (P = 0.0471) and inhibited the tumor desmoplastic reaction (P < 0.001) in xenograft tumors in nude mice. Calpeptin also inhibited the biologic functions of PCCs and PSCs including proliferation (P = 0.017), migration (P = 0.027), and invasion (P = 0.035) in vitro. Furthermore, calpeptin reduced the migration of PCCs and PSCs by disrupting the cancer-stromal interaction (P = 0.0002). Our findings indicate that calpeptin is a promising antitumor agent for pancreatic cancer, due not only to its suppressive effect on PCCs and PSCs but also its disruption of the cancer-stromal interaction.
-
podoplanin expression in cancer associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas
Molecular Cancer, 2013Co-Authors: Kenoki Ohuchida, Kenji Fujiwara, Koji Shindo, Shinichi Aishima, Minoru Fujino, Yusuke Mizuuchi, Masami HattoriAbstract:Background Interactions between cancer cells and surrounding cancer-associated fibroblasts (CAFs) play an important role in cancer progression. Invasive ductal carcinoma (IDC) of the pancreas is characterized by abundant fibrous connective tissue called Desmoplasia. Podoplanin (PDPN) is a lymphatic vessel marker (D2-40), and expression of PDPN by stromal CAFs has been reported to be a prognostic indicator in various types of cancer.
-
Pirfenidone Inhibits Pancreatic Cancer Desmoplasia by Regulating Stellate Cells
Cancer research, 2013Co-Authors: Shingo Kozono, Kenoki Ohuchida, Daiki Eguchi, Naoki Ikenaga, Kenji Fujiwara, Lin Cui, Kazuhiro Mizumoto, Masao TanakaAbstract:Pancreatic stellate cells (PSC), which are implicated in Desmoplasia in pancreatic cancer, enhance the malignancy of cancer cells and confer resistance to established treatments. We investigated whether the antifibrotic agent pirfenidone can suppress Desmoplasia and exert antitumor effects against pancreatic cancer. Primary PSCs were established from pancreatic cancer tissue obtained during surgery. In vitro, pirfenidone inhibited the proliferation, invasiveness, and migration of PSCs in a dose-dependent manner. Although supernatants of untreated PSCs increased the proliferation, invasiveness, and migration of pancreatic cancer cells (PCC), supernatants of pirfenidone-treated PSCs decreased these effects. Exposure to PCC supernatant increased the production of platelet-derived growth factor-A, hepatic growth factor, collagen type I, fibronectin, and periostin in PSCs, which was significantly reduced by pirfenidone. Mice were subcutaneously implanted with PCCs (SUIT-2 cells) and PSCs into the right flank and PCCs alone into the left flank. Oral administration of pirfenidone to these mice significantly reduced tumor growth of co-implanted PCCs and PSCs, but not of PCCs alone. Pirfenidone also decreased the proliferation of PSCs and the deposition of collagen type I and periostin in tumors. In mice with orthotopic tumors consisting of PCCs co-implanted with PSCs, pirfenidone suppressed tumor growth, reduced the number of peritoneal disseminated nodules, and reduced the incidence of liver metastasis. Pirfenidone in combination with gemcitabine more effectively suppressed orthotopic tumor growth compared with pirfenidone or gemcitabine alone. In conclusion, our findings indicate that pirfenidone is a promising antitumor agent for pancreatic cancer, owing to its suppression of Desmoplasia through regulating PSCs.
Eran Nizri - One of the best experts on this subject based on the ideXlab platform.
-
protective Desmoplasia in pancreatic adenocarcinoma high vitamin d receptor expression and collagen content
Anticancer Research, 2020Co-Authors: Adi Vaknine Bahat, Shoshi Bardavid, Asaf Aizic, Guy Lahat, Ido Wolf, Joseph M Klausner, Abigail Brooks, Orli Greenberg, Eran NizriAbstract:BACKGROUND/AIM Vitamin D receptor (VDR) has been shown to suppress Desmoplasia in pancreatic ductal adenocarcinoma (PDAC). Our aim was to assess the clinical effects of VDR expression and its correlation with collagen content in the Desmoplasia of PDAC patients. PATIENTS AND METHODS This is a retrospective analysis of 127 patients with peritumoral Desmoplasia resected for PDAC. VDR expression and collagen content were assessed by immunohistochemistry and correlated with clinical outcome. RESULTS Patients were classified into those with high and those with low VDR expression. High VDR expression was associated with improved overall survival (OS) in localized disease (N0) (median= 33; 95%CI=26.4-39.6 vs. 18; 15.5-20.5 months, p=0.01). Patients with high vs. low collagen content had improved OS [34, (range=22.3-45.6 months) vs. 17, (range=14.4-19.6 months), p<0.001]. The number of VDR+ cells was the same for patients with either high or low collagen content. CONCLUSION Protective Desmoplasia is associated with increased VDR expression and collagen content.
-
Desmoplasia in lymph node metastasis of pancreatic adenocarcinoma reveals activation of cancer associated fibroblasts pattern and t helper 2 immune cell infiltration
Pancreas, 2019Co-Authors: Eran Nizri, Shoshi Bardavid, Asaf Aizic, Neta Sternbach, Guy Lahat, Ido Wolf, Joseph M KlausnerAbstract:ObjectivesPancreatic ductal adenocarcinoma (PDAC) is characterized by a peritumoral proliferation of fibroblasts and extracellular matrix production known as Desmoplasia. We aimed to study Desmoplasia in PDAC lymph node (LN) metastases.MethodsWe evaluated LNs from 66 patients with PDAC and LN metast
-
analysis of histological and immunological parameters of metastatic lymph nodes from colon cancer patients reveals that t helper 1 type immune response is associated with improved overall survival
Medicine, 2016Co-Authors: Eran Nizri, Shoshi Bardavid, Guy Lahat, Nofar Greenmanmaaravi, Amir Benyehuda, Gilad Weiner, Joseph M KlausnerAbstract:Lymph node (LN) involvement in colonic carcinoma (CC) is a grave prognostic sign and mandates the addition of adjuvant treatment. However, in light of the histological variability and outcomes observed, we hypothesized that patients with LN metastases (LNM) comprise different subgroups. We retrospectively analyzed the histological sections of 82 patients with CC and LNM. We studied various histological parameters (such as tumor grade, Desmoplasia, and preservation of LN architecture) as well as the prevalence of specific peritumoral immune cells (CD8+, CD20+, T-bet+, and GATA-3+). We correlated the histological and immunological data to patient outcome. Tumor grade was a significant prognostic factor even in patients with LNM. So was the number of LN involved (N1/N2 stage). From the morphological parameters tested (LN extracapsular invasion, Desmoplasia in LN, LN architecture preservation, and mode of metastases distribution), none was found to be significantly associated with overall survival (OS). The mean OS of CD8+ low patients was 66.6 ± 6.25 versus 71.4 ± 5.1 months for CD8+ high patients (P = 0.79). However, T-helper (Th) 1 immune response skewing (measured by Th1/Th2 ratio >1) was significantly associated with improved OS. For patients with low ratio, the median OS was 35.5 ± 5 versus 83.5 months for patients with high Th1/Th2 ratio (P = 0.001). The histological presentation of LNM does not entail specific prognostic information. However, the finding of Th1 immune response in LN signifies a protective immune response. Future studies should be carried to verify this marker and develop a strategy that augments this immune response during subsequent adjuvant treatment.
Guy Lahat - One of the best experts on this subject based on the ideXlab platform.
-
protective Desmoplasia in pancreatic adenocarcinoma high vitamin d receptor expression and collagen content
Anticancer Research, 2020Co-Authors: Adi Vaknine Bahat, Shoshi Bardavid, Asaf Aizic, Guy Lahat, Ido Wolf, Joseph M Klausner, Abigail Brooks, Orli Greenberg, Eran NizriAbstract:BACKGROUND/AIM Vitamin D receptor (VDR) has been shown to suppress Desmoplasia in pancreatic ductal adenocarcinoma (PDAC). Our aim was to assess the clinical effects of VDR expression and its correlation with collagen content in the Desmoplasia of PDAC patients. PATIENTS AND METHODS This is a retrospective analysis of 127 patients with peritumoral Desmoplasia resected for PDAC. VDR expression and collagen content were assessed by immunohistochemistry and correlated with clinical outcome. RESULTS Patients were classified into those with high and those with low VDR expression. High VDR expression was associated with improved overall survival (OS) in localized disease (N0) (median= 33; 95%CI=26.4-39.6 vs. 18; 15.5-20.5 months, p=0.01). Patients with high vs. low collagen content had improved OS [34, (range=22.3-45.6 months) vs. 17, (range=14.4-19.6 months), p<0.001]. The number of VDR+ cells was the same for patients with either high or low collagen content. CONCLUSION Protective Desmoplasia is associated with increased VDR expression and collagen content.
-
Desmoplasia in lymph node metastasis of pancreatic adenocarcinoma reveals activation of cancer associated fibroblasts pattern and t helper 2 immune cell infiltration
Pancreas, 2019Co-Authors: Eran Nizri, Shoshi Bardavid, Asaf Aizic, Neta Sternbach, Guy Lahat, Ido Wolf, Joseph M KlausnerAbstract:ObjectivesPancreatic ductal adenocarcinoma (PDAC) is characterized by a peritumoral proliferation of fibroblasts and extracellular matrix production known as Desmoplasia. We aimed to study Desmoplasia in PDAC lymph node (LN) metastases.MethodsWe evaluated LNs from 66 patients with PDAC and LN metast
-
analysis of histological and immunological parameters of metastatic lymph nodes from colon cancer patients reveals that t helper 1 type immune response is associated with improved overall survival
Medicine, 2016Co-Authors: Eran Nizri, Shoshi Bardavid, Guy Lahat, Nofar Greenmanmaaravi, Amir Benyehuda, Gilad Weiner, Joseph M KlausnerAbstract:Lymph node (LN) involvement in colonic carcinoma (CC) is a grave prognostic sign and mandates the addition of adjuvant treatment. However, in light of the histological variability and outcomes observed, we hypothesized that patients with LN metastases (LNM) comprise different subgroups. We retrospectively analyzed the histological sections of 82 patients with CC and LNM. We studied various histological parameters (such as tumor grade, Desmoplasia, and preservation of LN architecture) as well as the prevalence of specific peritumoral immune cells (CD8+, CD20+, T-bet+, and GATA-3+). We correlated the histological and immunological data to patient outcome. Tumor grade was a significant prognostic factor even in patients with LNM. So was the number of LN involved (N1/N2 stage). From the morphological parameters tested (LN extracapsular invasion, Desmoplasia in LN, LN architecture preservation, and mode of metastases distribution), none was found to be significantly associated with overall survival (OS). The mean OS of CD8+ low patients was 66.6 ± 6.25 versus 71.4 ± 5.1 months for CD8+ high patients (P = 0.79). However, T-helper (Th) 1 immune response skewing (measured by Th1/Th2 ratio >1) was significantly associated with improved OS. For patients with low ratio, the median OS was 35.5 ± 5 versus 83.5 months for patients with high Th1/Th2 ratio (P = 0.001). The histological presentation of LNM does not entail specific prognostic information. However, the finding of Th1 immune response in LN signifies a protective immune response. Future studies should be carried to verify this marker and develop a strategy that augments this immune response during subsequent adjuvant treatment.
Frederic G Barr - One of the best experts on this subject based on the ideXlab platform.
-
pdgf a pdgf rβ tgfβ3 and bone morphogenic protein 4 in desmoplastic small round cell tumors with ews wt1 gene fusion product and their role in stromal Desmoplasia an immunohistochemical study
Modern Pathology, 2005Co-Authors: Paul J Zhang, John R Goldblum, Bruce R Pawel, Cyril Fisher, Theresa L Pasha, Frederic G BarrAbstract:PDGF-A, PDGF-R beta, TGF beta 3 and bone morphogenic protein-4 in desmoplastic small round cell tumors with EWS-WT1 gene fusion product and their role in stromal Desmoplasia: an immunohistochemical study Histologically, desmoplastic small round cell tumor is composed of the characteristic neoplastic small round cells with divergent differentiation, and distinct desmoplastic stroma. Genetically, the tumor shows a characteristic 11; 22 translocation, involving the EWS gene on chromosome 22 and the WT1gene on chromosome 11 to produce an EWS- WT1 fusion gene which generates a chimeric protein functioning as a novel transcription factor that activates expression of target genes such as PDGF- A. Expression of PDGF- A, a potent growth factor for fibroblasts, has been detected in desmoplastic small round cell tumors and has been linked to the characteristic Desmoplasia in these tumors. Bone morphogenic proteins, which are members of the TGFbeta superfamily play a complex role in regulating cell growth and differentiation and bone formation but have not been evaluated in desmoplastic small round cell tumors. In all, 24 desmoplastic small round cell tumors with EWS- WT1 fusion product confirmed by RT- PCR analysis were evaluated for expression of PDGF- A, PDGF- Rbeta, TGFbeta3 and bone morphogenic protein- 4 by standard immunohistochemical methods with antigen retrieval on paraffin sections. Immunoreactivity was evaluated semiquantitively. Tumor- associated Desmoplasia was quantified using a three- tier scale on hematoxylin- and eosin- stained sections. Desmoplastic small round cell tumors showed variable immunoreactivity with TGFbeta3 ( 21/ 24), BMP4 ( 14/ 21), PDGF- A ( 19/ 24) and PDGF- Rbeta ( 16/ 22). Less frequently, the stromal cells showed reactivity with TGFbeta3, PDGF- Rbeta and PDGF- A. Tumor- associated Desmoplasia was prominent in eight, intermediate in seven and weak in nine cases. There was no correlation between tumor- associated Desmoplasia and the markers tested except PDGF- A. In contrast to a previous study, our study showed that the level of PDGF- A expression inversely correlated with tumor-associated Desmoplasia. Other targets of the EWS- WT1 transcription factor other than PDGF- A may be directly responsible for the prominent tumor- associated Desmoplasia seen in desmoplastic small round cell tumor.