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Lenalidomide regulates the CCL21/CCR7/ERK1/2 axis to inhibit migration and proliferation in diffuse large B-cell lymphoma

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Oncology research 2025年第1期33卷 199-212页

作者： Wen Yang Bin Tang Dan Xu Wenxiu Yang department of pathology Guizhou Medical University The Affiliated Hospital of Guizhou Medical University Guiyang 550004 China.

Background:The prognostic significance of the chemokine receptor CCR7 in diffuse large B-cell lymphoma (DLBCL) has been reported previously. However, the detailed mechanisms of CCR7 in DLBCL, particularly regarding its interaction with lenalidomide treatment, are not fully understood.Methods:Our study utilized bioinformatics approaches to identify hub genes in SU-DHL-2 cell lines treated with lenalidomide compared to control groups. Immunohistochemical data and clinical information from 122 patients with DLBCL were analyzed to assess the correlation of CCR7 and p-ERK1/2 expression with the prognosis of DLBCL. Furthermore, and experiments were conducted to clarify the role of CCR7 in the response of DLBCL to lenalidomide treatment.Results:Our bioinformatics analysis pinpointed CCR7 as a hub gene in the context of lenalidomide treatment in DLBCL. Notably, 31.14% and 36.0% (44/122) of DLBCL cases showed positive expression for CCR7 and ERK1/2 respectively, establishing them as independent prognostic factors for adverse outcomes in DLBCL via multivariate Cox regression analysis. Additionally, our studies demonstrated that the external application of the protein CCL21 promoted proliferation, migration, invasion, and activation of the ERK1/2 pathway in SU-DHL-2 and OCI-LY3 cell lines with high levels of CCR7 expression. This effect was mitigated by CCR7 silencing through siRNA, application of ERK inhibitors, or lenalidomide treatment. experiments reinforced the efficacy of lenalidomide, significantly reducing tumor growth rate, tumor mass, serum total LDH levels, and expression of CCR7 and p-ERK1/2 in a SU-DHL-2 xenograft model in nude mice ( < 0.05).Conclusion:Our study clarifies the potential role of the CCL21/CCR7/ERK1/2 axis in the therapeutic effects of lenalidomide in DLBCL treatment.

关键词： CCL21 CCR7 Diffuse large B-cell lymphoma (DLBCL) ERK1/2 Lenalidomide

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Overexpression of carbonic anhydrase Ⅱ and Ki-67 proteins in prognosis of gastrointestinal stromal tumors

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World Journal of Gastroenterology 2013年第16期19卷 2473-2480页

作者： Li-Cheng Liu Wen-Tong Xu Xin Wu Po Zhao Ya-Li Lv Lin Chen department of General surgery General Hospital of PLA department of pathology General Hospital of PLA

AIM: To investigate the expression and prognostic value of carbonic anhydrase Ⅱ (CA Ⅱ) and Ki-67 in gastrointestinal stromal tumors (GISTs). METHODS: One hundred and thirteen GIST patients admitted to Chinese People's Liberation Army General Hospital from January 2004 to December 2010 were retrospectively followed up, and immunohistochemistry was used to detect CA Ⅱ, Ki-67 and CD117 expression in tumor samples. The survival rates of the patients were analyzed using the Kaplan-Meier method. Log-rank test, χ 2 test and Cox proportional hazards model were used to determine the relationships between CA Ⅱ, Ki-67 and CD117 expression and prognostic value in GISTs. RESULTS: The survival rates at 1, 3 and 5 years were 90.0%, 82.0% and 72.0% in all patients. However, in patients with positive CA Ⅱ or Ki-67, the survival rates were 92.0%, 83.0% and 77.0% or 83.0%, 66.6% and 53.0%, respectively. Compared with the negative groups, the survival rates in the positive groups were significantly lower (CA Ⅱ log-rankP = 0.000; Ki-67 logrank P = 0.004). Multivariate Cox analysis revealed that CA Ⅱ, CD117 and Ki-67 were considerable immune factors in prognosis of GIST patients (CA Ⅱ P = 0.043; CD117 P = 0.042; Ki-67 P = 0.007). Besides, tumor diameter, mitotic rate, tumor site, depth of invasion, complete resection, intraoperative rupture, and adjuvant therapy were important prognosis predictive factors. Our study indicated that CA Ⅱ had strong expression in GISTs and the prognosis of GISTs with high CA Ⅱ expression was better than that of GISTs with low or no expression, suggesting that CA Ⅱ is both a diagnostic and prognostic biomarker for GIST. CONCLUSION: CA Ⅱ and Ki-67 are significant prognostic factors for GISTs. CA Ⅱ associated with neovascular endothelia could serve as a potential target for cancer therapy.

关键词： Gastrointestinal stromal tumors Carbonic anhydrase CD117 Ki-67 Prognostic factor

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Acinar cell carcinoma of the pancreas in a young patient with chronic pancreatitis

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Hepatobiliary & Pancreatic Diseases International 2010年第1期9卷 103-106页

作者： Fatima-Zahra Kebir Ahlem Lahmar Nafaa Arfa Saber Manai Mohamed Ali El Ouaer Saadia Bouraoui Carole Gouttalier Sabah Mezabi-Regaya department of pathology Mongi Slim Hospital department of surgery Mongi Slim Hospital

BACKGROUND:Acinar cell carcinoma (ACC) is a rare malignancy of the pancreas arising from acinar *** ductal adenocarcinoma,this tumor rarely presents with ***:We present a case of ACC associated with chronic calcifying pancreatitis,and a review of the literature focusing on diagnosis and ***:A 43-year-old man was proposed for Wirsungojejunal derivation for chronic *** examination of the tissue extracted revealed an *** was *** months postoperatively,the patient developed hepatic metastasis and was treated with gemcitabine as palliative ***:The clinical presentation of ACC of the pancreas is not specific and the tumor can be underdiagnosed when associated with chronic *** regarding course,treatment,and prognosis of this tumor are generally lacking.

关键词： pancreas acinar cell carcinoma pancreatitis

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Acquired segmental colonic hypoganglionosis in an adult Caucasian male:A case report

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World Journal of Gastrointestinal surgery 2019年第2期11卷 101-111页

作者： Allan MF Kwok Andrew B Still Kimberly Hart department of surgery Wollongong Hospital department of Anatomical pathology Wollongong Hospital

BACKGROUND Hypoganglionosis is a rare condition that most often presents with abnormal gastrointestinal transit and usually arises in early childhood or adolescence. Two types have been described(Type I and Type II). The adult-onset form(acquired hypoganglionosis) is extremely uncommon and is thought to arise due to cellular remodelling as a result of chronic inflammation. It differs from Hirschprung's disease in that there is a reduction in ganglion cells in the colonic neural plexuses as opposed to being completely *** SUMMARY A 31 year-old male presented to hospital with recurrent abdominal pain and vomiting over thirteen months. Abdominal computed tomography scans demonstrated thickening and stranding affecting the transverse, descending and sigmoid colon. Endoscopic appearances were non-specific but confirmed a mixed picture of mucosal inflammation and necrosis in various stages of *** investigations were performed to elucidate an underlying aetiology but neither an infective nor ischaemic cause could be proven. Biopsy features were not typical of inflammatory bowel disease. Due to persistence of his symptoms and failure of medical management, a segmental colectomy was performed. Histological examination of the specimen revealed an unexpected finding of segmental hypoganglionosis. Complete surgical excision of the diseased segment of colon was curative and since his operation the patient has had no recurrence of symptoms requiring *** Our case serves to raise awareness of acquired hypoganglionosis as a rare condition that can result from chronic colitis.

关键词： Acquired hypoganglionosis Hirschprung’s disease Adult Ganglion cells Acetylcholinesterase Calretinin Case report

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Detection of fusion gene in cell-free DNA of a gastric synovial sarcoma

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World Journal of Gastroenterology 2018年第8期24卷 949-956页

作者： Shinpei Ogino Hirotaka Konishi Daisuke Ichikawa Junichi Hamada Katsutoshi Shoda Tomohiro Arita Shuhei Komatsu Atsushi Shiozaki Kazuma Okamoto Sanae Yamazaki Satoru Yasukawa Eiichi Konishi Eigo Otsuji Division of Digestive surgery Department of Surgery Kyoto Prefectural University of Medicine department of Surgical pathology Kyoto Prefectural University of Medicine

Synovial sarcoma(SS) is genetically characterized by chromosomal translocation, which generates SYT-SSX fusion transcripts. Although SS can occur in any body part, primary gastric SS is substantially rare. Here we describe a detection of the fusion gene sequence of gastric SS in plasma cell-free DNA(cf DNA). A gastric submucosal tumor was detected in the stomach of a 27-year-old woman and diagnosed as SS. Candidate intronic primers were designed to detect the intronic fusion breakpoint and this fusion sequence was confirmed in intron 10 of SYT and intron 5 of SSX2 by genomic polymerase chain reaction(PCR) and direct sequencing. A locked nucleic acid(LNA) probe specificto the fusion sequence was designed for detecting the fusion sequence in plasma and the fusion sequence was detected in preoperative plasma cfD NA, while not detected in postoperative plasma cfD NA. This technique will be useful for monitoring translocation-derived diseases such as SS.

关键词： Fusion gene Gastric synovial sarcoma Plasma Cell free DNA

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Single skip metastasis in sentinel lymph node: In an early gastric cancer

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World Journal of Gastroenterology 2015年第33期21卷 9803-9807页

作者： Tivadar Jr Bara Simona Gurzu Ioan Jung Zoltan Kadar Haruhiko Sugimura Tivadar Bara department of surgery University of Medicine and Pharmacy department of pathology University of Medicine and Pharmacy department of Tumor pathology Hamamatsu UniversitySchool of Medicine

Lymph node status is considered a key prognostic and predictive factor in patients with gastric cancer(GC).Although there is a practical approach to the intraoperative detection of sentinel lymph nodes(SLNs),such a procedure is not included in the European surgical *** this report,we present a practical approach to SLN mapping in a representative case with early gastric cancer(EGC).A 74-year-old female was hospitalized with an endoscopically observed,superficially ulcerated tumor located in the antral *** gastrectomy with D2 lymphadenectomy and SLN mapping was performed by injecting methylene blue dye into the peritumoral submucosal *** incidentally detected blue-stained lymph node located along the middle colic artery was also *** was detected 40 min after injection of the methylene *** examination showed a p T1b-staged well-differentiated HER-2-negative *** of the 41 LNs located at the first,third,and fifth station of the regional LN compartments were found to be free of tumor *** only lymph node with metastasis was located along the middle colicartery and was considered a non-regional lymph *** incidentally identified skip metastasis indicated stage Ⅳ GC.A classic chemotherapy regimen was given,and no recurrences were observed six months after *** this representative case,low-cost SLN mapping,with a longer intraoperative waiting time,totally changed the stage of the tumor in a patient with EGC.

关键词： Early gastric cancer Sentinel lymph node Lymph nod

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Clinical significance of nerve growth factor and tropomyosin-receptor-kinase signaling pathway in intrahepatic cholangiocarcinoma

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World Journal of Gastroenterology 2014年第14期20卷 4076-4084页

作者： Xiao-Qing Yang Yun-Fei Xu Sen Guo Yi Liu Shang-Lei Ning Xiao-Fei Lu Hui Yang Yu-Xin Chen department of Hepatobiliary surgery Qilu Hospital of Shandong University department of pathology Shandong University department of Gastrointestinal surgery Central Hospital of Shandong University

AIM: To investigate the correlation between nerve growth factor-tropomyosin-receptor-kinase (NGF-TrkA) signaling pathway and prognosis in intrahepatic cholangiocarcinoma (IHCC).

关键词： Nerve growth factor Tropomyosin-receptor-kinase Prognosis Intrahepatic cholangiocarcinoma Progression

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Epithelial turnover in duodenal familial adenomatous polyposis: A possible role for estrogen receptors?

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World Journal of Gastroenterology 2016年第11期22卷 3202-3211页

作者： Alfredo Di Leo Gabriella Nesi Mariabeatrice Principi Domenico Piscitelli Bruna Girardi Maria Pricci Giuseppe Losurdo Andrea Iannone Enzo Ierardi Francesco Tonelli Gastroenterology Section Department of Emergency and Organ TransplantationUniversity of Bari pathology Section Department of Surgery and Translational MedicineUniversity of Florence pathology Section Department of Emergency and Organ TransplantationUniversity of Bari General surgery Section Department of Surgery and Translational MedicineUniversity of Florence

AIM: To investigate estrogen receptors expression in duodenal familial adenomatous polyposis (FAP) and any relationship with epithelial proliferation/apoptosis ***: Twenty-two patients affected by FAP undergoing duodenal resection for malignancies were recruited. Controls were 15 healthy subjects undergoing endoscopy for dyspeptic symptoms. ER-α, ER-α, Ki-67, TUNEL and caspase 3 expression (labeling index: percentage of positive cells) were evaluated by immunohistochemistry or immunofluorescence and examined by light or confocal microscopy. Samples were assigned to four groups: normal tissue, low (LGD) and high-grade dysplasia (HGD), adenocarcinoma (AC). One-way analysis of variance, corrected by Bonferroni’s test, and Pearson’s correlation test were applied for statistical ***: ER-beta showed a progressive decline: normal tissue (23.5 ± 4.9), LGD (21.1 ± 4.8), HGD (9.3 ± 3.5), AC (7.1 ± 3.1). The normal tissue of FAP subjects expressed ER-beta like the controls (23.9 ± 6.2). Conversely, ER-α showed a progressive increase from normal tissue (24.8 ± 5.6) to AC (52.0 ± 8.2); the expression in normal tissue was similar to controls (22.5 ± 5.3). Ki67 demonstrated a statistically significant progressive increase at each disease stage up to AC. TUNEL did not reveal differences between controls and normal tissue of FAP subjects, but progressive decreases were observed in LGD, through HGD to AC. Pearson’s correlation test showed a direct relationship between ER-β and TUNEL LI (r = 0.8088, P < 0.0001). Conversely, ER-α was inversely correlated with TUNEL LI (r = - 0.7257, P < 0.0001). The co-expression of ER-β and caspase 3 declined progressively from normal to neoplastic ***: This study confirmed that ER-β is strongly decreased in duodenal FAP carcinomas, declining in a multiple

关键词： Familial adenomatous polyposis Duodenal cancer Estrogen receptors Immunohistochemistry Confocal microscopy Dysplasia

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Hepatopancreatoduodenectomy for metastatic duodenal gastrointestinal stromal tumor

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Hepatobiliary & Pancreatic Diseases International 2006年第1期5卷 147-150页

作者： Charalabos Stratopoulos Zahir Soonawalla Juan Piris Peter J Friend Nuffield department of surgery and the department of Cellular pathology

BACKGROUND: Duodenal gastrointestinal stromal tumors, which are rare, comprise 3%-5% of all gastrointestinal stromai tumors. We present a case of a metastatic duodenal gastrointestinal stromal tumor that was successfully treated by simultaneous tight hemihepatectomy and pancreaticoduodenectomy. METHODS: A 50-year-old woman was admitted to our department for the treatment of a possible metastatic duodenal gastrointestinal stromal tumor (GIST). At laparotomy a large duodenal tumor was found displacing the head of the pancreas. A 3 cm in diameter lesion in the posterior aspect of segment Ⅷ of the liver was also noted. Simultaneous right hepatectomy and pancreaticoduodenectomy were performed. RESULTS: Histological examination revealed a high grade metastatic duodenal GIST strongly positive for c-kit, CD34, and vimentin. The patient had no additional therapy. A follow-up of 21 months showed that the patient is very well and there is no evidence of recurrent diseases. CONCLUSIONS: Malignant stromai tumors of the duodenum are rarely encountered. They are usually slow growing, and may be amenable to curative surgery, even after occurrence of metastases. Resection of localized liver metastasis is still advocated when feasible, since imatinib does not provide a complete or long-term response. Combined surgical resection is an efficacious treatment for patients with metastatic duodenal gastrointestinal stromal tumor.

关键词： duodenal neoplasms hepatectomy pancreaticoduodenectomy liver metastasis gastrointestinal stromal tumor

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Two cases of pancreatic ductal adenocarcinoma with intrapancreatic metastasis

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World Journal of Gastroenterology 2016年第41期22卷 9222-9228页

作者： Yusuke Fujita Minoru Kitago Yohei Masugi Osamu Itano Masahiro Shinoda Yuta Abe Taizo Hibi Hiroshi Yagi Yoko Fujii-Nishimura Michiie Sakamoto Yuko Kitagawa department of surgery Keio University School of Medicine department of pathology Keio University School of Medicine

There are no standardized diagnostic criteria for intrapancreatic metastasis of pancreatic ductal adenocarcinoma(PDAC). Here, we report two cases of patients with PDAC who were pathologically diagnosed as harboring intrapancreatic metastasis. In both cases, the main lesions were located in the pancreatic body, and no other lesion was detected preoperatively. The patients were diagnosed with pancreatic body cancers and distal pancreatectomy was performed. Pathological findings revealed microscopic cancer nests, which had connections to neither the main lesion nor the premalignant lesion in the pancreatic tail parenchyma. In both cases, the histological type of the daughter lesion was quite similar to that of the main lesion. Hence, we diagnosed the daughter lesions as metastatic foci in the pancreas. Although intrapancreatic metastasis of PDAC has been regarded as a poor prognostic factor, few reports of intrapancreatic metastasis are available. This article reports two such cases and provides a review of the literature.

关键词： Carcinoma Pancreatic ductal Neoplasm micrometastasis Recurrence Carcinogenesis

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