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1.
Chin Med Sci J ; 38(3): 191-205, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37503721

ABSTRACT

Background Kidney renal clear cell carcinoma (KIRC) is one of the most common renal malignancies with a high mortality rate. Cuproptosis, a novel form of cell death, is strongly linked to mitochondrial metabolism and is mediated by protein lipoylation, leading to a proteotoxic stress response and cell death. To date, few studies have ellucidated the holistic role of cuproptosis-related genes (CRGs) in the pathogenesis of KIRC.Methods We comprehensively and completely analyzed the RNA sequencing data and corresponding clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We screened for differentially expressed CRGs and constructed a prognostic risk model using univariate and multivariate Cox proportional regression analyses. Kaplan-Meier analysis was performed and receiver operating characteristic (ROC) curves were plotted to predict the prognosis of KIRC patients. Functional enrichment analysis was utilized to explore the internal mechanisms. Immune-related functions were analyzed using single-sample gene set enrichment analysis (ssGSEA), tumour immune dysfunction and exclusion (TIDE) scores, and drug sensitivity analysis.Results We established a concise prognostic risk model consisting of four CRGs (DBT, DLAT, LIAS and PDHB) to predict the overall survival (OS) in KIRC patients. The results of the survival analysis indicated a significantly lower OS in the high-risk group as compared to the patients in the low-risk group. The area under the time-dependent ROC curve (AUC) at 1, 3, and 5 year was 0.691, 0.618, and 0.614 in KIRC. Functional enrichment analysis demonstrated that CRGs were significantly enriched in tricarboxylic acid (TCA) cycle-related processes and metabolism-related pathways. Sorafenib, doxorubicin, embelin, and vinorelbine were more sensitive in the high-risk group.Conclusions We constructed a concise CRGs risk model to evaluate the prognosis of KIRC patients and this may be a new direction for the diagnosis and treatment of KIRC.


Subject(s)
Apoptosis , Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/genetics , Immunotherapy , Kidney , Kidney Neoplasms/drug therapy , Kidney Neoplasms/genetics , Prognosis , Copper
2.
Front Oncol ; 13: 1103145, 2023.
Article in English | MEDLINE | ID: mdl-37035165

ABSTRACT

Objective: As a common breast cancer-related complaint, pathological nipple discharge (PND) detected by ductoscopy is often missed diagnosed. Deep learning techniques have enabled great advances in clinical imaging but are rarely applied in breast cancer with PND. This study aimed to design and validate an Intelligent Ductoscopy for Breast Cancer Diagnostic System (IDBCS) for breast cancer diagnosis by analyzing real-time imaging data acquired by ductoscopy. Materials and methods: The present multicenter, case-control trial was carried out in 6 hospitals in China. Images for consecutive patients, aged ≥18 years, with no previous ductoscopy, were obtained from the involved hospitals. All individuals with PND confirmed from breast lesions by ductoscopy were eligible. Images from Beijing Chao-Yang Hospital were randomly assigned (8:2) to the training (IDBCS development) and internal validation (performance evaluation of the IDBCS) datasets. Diagnostic performance was further assessed with internal and prospective validation datasets from Beijing Chao-Yang Hospital; further external validation was carried out with datasets from 5 primary care hospitals. Diagnostic accuracies, sensitivities, specificities, and positive and negative predictive values for IDBCS and endoscopists (expert, competent, or trainee) in the detection of malignant lesions were obtained by the Clopper-Pearson method. Results: Totally 11305 ductoscopy images in 1072 patients were utilized for developing and testing the IDBCS. Area under the curves (AUCs) in breast cancer detection were 0·975 (95%CI 0·899-0·998) and 0·954 (95%CI 0·925-0·975) in the internal validation and prospective datasets, respectively, and ranged between 0·922 (95%CI 0·866-0·960) and 0·965 (95%CI 0·892-0·994) in the 5 external validation datasets. The IDBCS had superior diagnostic accuracy compared with expert (0.912 [95%CI 0.839-0.959] vs 0.726 [0.672-0.775]; p<0.001), competent (0.699 [95%CI 0.645-0.750], p<0.001), and trainee (0.703 [95%CI 0.648-0.753], p<0.001) endoscopists. Conclusions: IDBCS outperforms clinical oncologists, achieving high accuracy in diagnosing breast cancer with PND. The novel system could help endoscopists improve their diagnostic efficacy in breast cancer diagnosis.

3.
Clin Breast Cancer ; 22(5): 410-417, 2022 07.
Article in English | MEDLINE | ID: mdl-35473920

ABSTRACT

BACKGROUND: Male breast cancer is a rare malignant tumor, and outcomes of breast conservation therapy (BCT) are currently lacking. METHOD: The retrospective, population-based cohort study included 1369 stage I-II (T1-2 N0-1 M0) male breast cancer patients from the SEER database (2000-2018). The patients were grouped in two groups: BCT group and mastectomy group, according to surgical and radiation therapy. Kaplan-Meier method and univariable Cox proportional hazard analysis were used to compare overall survival (OS) and breast cancer-specific survival (BCSS) between two treatment groups. Propensity score matching (PSM) was performed to balance the confounding factors. RESULTS: Of the 1369 men, 97 (7%) patients received BCT, 1272 (93%) received mastectomy alone. The 5- and 10-year OS rates were 92.3% and 80.7% for BCT group compared with 80.4% and 61.4% for mastectomy group. The 5- and 10-year BCSS rates were 96.5% and 93.9% for patients undergoing BCT, as compared with 93.1% and 84.4% for patients undergoing mastectomy. Compared with mastectomy group, BCT group showed improved OS (hazard ratio [HR], 0.294; 95% CI 0.138-0.623, P = .002) and BCSS (hazard ratio [HR], 0.182; 95% CI 0.040-0.820, P = .027). Of the 791 patients with T1 stage, BCT showed insignificant association with OS (hazard ratio [HR], 0.555; 95% CI 0.207-1.488, P = .242) and BCSS (hazard ratio [HR], 1.217; 95% CI 0.171-8.675, P = .844). CONCLUSION: The results of this cohort study suggest that BCT is at least equivalent to mastectomy in male breast cancer patients. The underlying mechanism of this association needs further research.


Subject(s)
Breast Neoplasms, Male , Breast Neoplasms , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Breast Neoplasms, Male/surgery , Cohort Studies , Humans , Male , Mastectomy , Mastectomy, Segmental , Retrospective Studies
4.
Medicine (Baltimore) ; 99(43): e22652, 2020 Oct 23.
Article in English | MEDLINE | ID: mdl-33120755

ABSTRACT

RATIONALE: Poorly differentiated neuroendocrine carcinoma of the breast is a rare cancer with poor prognosis. There is no standard treatment for the disease. Neoadjuvant therapies and surgery are considered to be the main treatment when the tumor diameter is greater than 5.0 cm. Neoadjuvant therapies include chemotherapy and endocrine therapy. However, the effect of neoadjuvant endocrine therapy is not clear in the disease. PATIENT CONCERNS: In August 2014, a 28-year-old premenopausal woman noted a mass that was approximately 3.0 cm*2.0 cm in size on her right breast with pain. Subsequently, the mass has been always increasing significantly. In August 2015, the mass was approximately 7.0 cm*5.0 cm in size, accompanied by pain, no nipple retraction and discharge, no orange peel-like skin changes, and no dimples. In addition, she had no salient past history. DIAGNOSES: Histopathological examinations by a biopsy with a thick needle (hollow needle) and surgical resection confirmed poorly differentiated neuroendocrine carcinoma of the right breast. INTERVENTIONS: First and remarkably, she underwent 3 months of neoadjuvant endocrine therapy (goserelin once every 28 days, and letrozole 10 mg every day). Then, she underwent surgery - stage I breast reconstruction by using prosthesis. Adjuvant endocrine therapy has been used since the operation. OUTCOMES: According to response evaluation criteria in solid tumors 1.1, the tumor was shrunk by 78.87% after neoadjuvant endocrine therapy. No salient complications were observed. We have followed her for 48 months, and there are no signs of recurrence and metastasis. LESSONS: Poorly differentiated neuroendocrine carcinoma of the breast is rare and has a poor prognosis. Currently, there is no standard treatment for this disease. Studies show estrogen receptor and progesterone receptor of neuroendocrine carcinoma of the breast are often highly expressed. In the case, it can be observed that estrogen receptor and progesterone receptor are highly expressed. Therefore, neoadjuvant endocrine therapy may be considered in neuroendocrine carcinoma of the breast when the mass is large and the patient refuses neoadjuvant chemotherapy. We hope to provide an attractive evidence for neoadjuvant endocrine therapy of neuroendocrine carcinoma of the breast. However, more cases are still being needed for research.


Subject(s)
Antineoplastic Agents, Hormonal/administration & dosage , Aromatase Inhibitors/administration & dosage , Breast Neoplasms/drug therapy , Carcinoma, Neuroendocrine/drug therapy , Goserelin/administration & dosage , Letrozole/administration & dosage , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/diagnosis , Breast Neoplasms/pathology , Carcinoma, Neuroendocrine/diagnosis , Carcinoma, Neuroendocrine/pathology , Female , Humans , Neoadjuvant Therapy/methods
5.
Med Sci Monit ; 25: 9272-9279, 2019 Dec 05.
Article in English | MEDLINE | ID: mdl-31802780

ABSTRACT

BACKGROUND Breast cancer is one of the most commonly diagnosed cancers in women worldwide, and sonographic elastography has previously demonstrated good performance in detecting breast malignancies. However, the exact relationship between elastographic measures and clinical prognostic factors is still not well understood. Thus, the aim of this study was to evaluate any associations between major clinical prognostic factors and strain elastography and to validate the diagnostic value of elastography in breast cancer. MATERIAL AND METHODS A total of 373 subjects with breast masses, of which 196 were benign and 177 were malignant, were included in the study. All subjects underwent routine ultrasound examination and strain elastography before biopsy. The elastographic measures - strain ratio (SR) for qualitative measures and Tsukuba score (TS) for quantitative measures - were obtained and compared with prognostic factors, including nuclear grade, lymph node status, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER-2). The SR demonstrated the best diagnostic performance in differentiation between malignant and benign lesions. RESULTS With the best cut-off value at 2.42, the SR achieved a sensitivity of 96.0% and specificity of 98.5%. Moreover, higher SRs and TSs were associated with breast lesions with a high nuclear grade and lymph node metastasis and with being ER-negative, PR-negative, and HER-2 negative. CONCLUSIONS Elastography is a useful imaging technique in differentiating benign breast masses from malignant ones. The strong relationship between prognostic factors and elastographic measures also demonstrated its excellent performance in predicting the prognosis of breast malignancies.


Subject(s)
Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Elasticity Imaging Techniques/methods , Adult , Aged , Biopsy , Breast/pathology , China , Cross-Sectional Studies , Diagnosis, Differential , Female , Humans , Lymphatic Metastasis/pathology , Middle Aged , Prognosis , ROC Curve , Sensitivity and Specificity , Ultrasonography/methods
6.
Onco Targets Ther ; 11: 7787-7793, 2018.
Article in English | MEDLINE | ID: mdl-30464526

ABSTRACT

BACKGROUND: Phyllodes tumor (PT) is a rare breast fibroepithelial biphasic tumor composed of stromal and epithelial components. The patients suffering from this disease present with a large, round, mobile, fast-growing lump, and the giant PT of more than 10 cm in diameter is so uncommon. Surgery is regarded as the primary treatment, but curative efficiency of adjuvant chemotherapy and radiotherapy is so indefinite. CASE PRESENTATION: We reported one case of a middle-aged woman with a huge borderline PT in the right breast, over 20 cm in size. The pathology of needle core biopsy of the lump was suggestive of PT of the borderline subgroup, and then she underwent mastectomy of the right breast. The patient had recovered well without any postoperative treatment until a local recurrence occurred 1 year after operation. The tumor was removed with lumpectomy, which was pathologically diagnosed as malignant PT. We followed up her by telephone and heard about her postoperative adjuvant radiotherapy and chemotherapy, as well as her well recovery. CONCLUSION: The pathology of PT with low incidence is mostly benign, but local recurrence is common, and the histopathology progresses toward worsen trend. Besides, due to the difficulty in precise diagnosis of the borderline PTs, it is recommended that this subtype of patients should undergo total mastectomy. Although the curative effect of postoperative treatment has not been recognized internationally, patients, especially those with huge tumors, may benefit from these treatments.

7.
IUBMB Life ; 68(5): 394-402, 2016 05.
Article in English | MEDLINE | ID: mdl-27079864

ABSTRACT

MicroRNA-409-3p (miR-409-3p) is an miRNA expressed by embryonic stem cells, and our previous study demonstrated depressed miR-409-3p expression in human breast cancer (BC) cell lines; however, its role and function in BC metastasis are still unknown. The purpose of this study was to examine the expression levels of miR-409-3p in human BC and its role in the metastasis of BC. We analyzed the status of miR-409-3p expression in BC tissues by quantitative real-time polymerase chain reaction (PCR) and its relationship to the clinicopathologic features of patients with BC. To study the role of miR-409-3p in BC metastasis, the invasion ability of BC cells was detected by transwell invasion assays and wound healing assays. WST-1 assays and colony formation assays were used to investigate cell proliferation. Luciferase reporter assays were used to verify that miR-409-3p targeted zinc-finger E-box-binding homeobox 1 (ZEB1). Western blot analyses and transwell assays were carried out to assess ZEB1 expression and its role in BC cell metastasis. The expression of miR-409-3p was lower in tumor tissues than in noncancerous breast tissues. We verified that miR-409-3p levels were downregulated and significantly correlated with poor outcomes in patients with BC. Overexpression of miR-409-3p inhibited cellular proliferation and suppressed cellular migration and invasion in vitro and in vivo. Dual-luciferase reporter assays showed that miR-409-3p binds the 3'-untranslated region (3'-UTR) of ZEB1, suggesting that ZEB1 is a direct target of miR-409-3p. Western blot analysis confirmed that overexpression of miR-409-3p reduced ZEB1 protein levels. These data demonstrate that miR-409-3p plays an important role in regulating the metastasis of BC, which is involved in the post-transcriptional repression of ZEB1. Our results indicate that miR-409-3p can regulate the invasion and metastasis process of BC by targeting ZEB1 and may serve as a new prognostic marker and therapeutic target for treating BC metastasis. © 2016 IUBMB Life, 68(5):394-402, 2016.


Subject(s)
Breast Neoplasms/metabolism , Gene Expression Regulation, Neoplastic , MicroRNAs/physiology , Zinc Finger E-box-Binding Homeobox 1/genetics , 3' Untranslated Regions , Adult , Animals , Base Sequence , Binding Sites , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Down-Regulation , Female , Gene Expression , Humans , Lymphatic Metastasis , Male , Mice, Nude , Middle Aged , Neoplasm Invasiveness , Neoplasm Transplantation , RNA Interference , Zinc Finger E-box-Binding Homeobox 1/metabolism
8.
Int J Clin Exp Pathol ; 8(11): 14989-94, 2015.
Article in English | MEDLINE | ID: mdl-26823833

ABSTRACT

The objective of this study was to examine the expression and significance of ß-catenin in the diagnosis and prognosis of breast cancer. Overall, 241 patients with histologically confirmed breast cancer who had undergone radical surgery were enrolled in this study. ß-catenin protein expression in breast cancer samples was evaluated by immunohistochemistry. ß-catenin was expressed in Nuclei/Plasma of the samples from 41 patients. ß-catenin protein expression correlated with the histological grade of the tumor (P<0.05) and Ki-67 labeling (P<0.01). Survival analysis showed that ß-catenin expression negatively correlated with breast cancer-specific survival. Our results showed prominent expression of ß-catenin in breast cancer and strongly implicate the ß-catenin in tumor promotion.


Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms/pathology , beta Catenin/biosynthesis , Adult , Aged , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Middle Aged , Prognosis , Proportional Hazards Models , Survival Analysis , beta Catenin/analysis
9.
ScientificWorldJournal ; 2014: 387640, 2014.
Article in English | MEDLINE | ID: mdl-24757420

ABSTRACT

Intestinal ischemia-reperfusion (I/R) injury is a serious clinical pathophysiological process that may result in acute local intestine and remote liver injury. Protocatechuic acid (PCA), which has been widely studied as a polyphenolic compound, induces expression of antioxidative genes that combat oxidative stress and cell apoptosis. In this study, we investigated the effect of PCA pretreatment for protecting intestinal I/R-induced local intestine and remote liver injury in mice. Intestinal I/R was established by superior mesenteric artery occlusion for 45 min followed by reperfusion for 90 min. After the reperfusion period, PCA pretreatment markedly alleviated intestine and liver injury induced by intestinal I/R as indicated by histological alterations, decreases in serological damage parameters and nuclear factor-kappa B and phospho-foxo3a protein expression levels, and increases in glutathione, glutathione peroxidase, manganese superoxide dismutase protein expression, and Bcl-xL protein expression in the intestine and liver. These parameters were accompanied by PCA-induced adaptor protein p66shc suppression. These results suggest that PCA has a significant protective effect in the intestine and liver following injury induced by intestinal I/R. The protective effect of PCA may be attributed to the suppression of p66shc and the regulation of p66shc-related antioxidative and antiapoptotic factors.


Subject(s)
Hydroxybenzoates/therapeutic use , Intestinal Mucosa/metabolism , Liver Diseases/metabolism , Reperfusion Injury/metabolism , Shc Signaling Adaptor Proteins/physiology , Signal Transduction/physiology , Animals , Hydroxybenzoates/pharmacology , Intestines/blood supply , Intestines/drug effects , Liver Diseases/drug therapy , Male , Mice , Mice, Inbred ICR , Protective Agents/pharmacology , Protective Agents/therapeutic use , Random Allocation , Reperfusion Injury/prevention & control , Signal Transduction/drug effects , Src Homology 2 Domain-Containing, Transforming Protein 1
10.
Tumour Biol ; 35(4): 3809-17, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24347489

ABSTRACT

The objective of this study is to clarify the possible role and mechanism of Axl in the tumorigenicity and metastasis process of hepatocellular carcinoma. The mRNA and protein expression levels of Axl in MHCC97-H and MHCC97-L cell lines were evaluated by real-time PCR and Western blot analysis. The key factor of phosphatidylinositol-3-kinase (PI3K)/Akt-p21-activated kinases-1 (PAK1) signaling pathway was studied after Axl expression was downregulated by shRNA. Finally, we analyzed the expression status of Axl protein expression in hepatocellular carcinoma tissues and its relationship with the prognosis of hepatocellular carcinoma. Axl was observed to be higher expressed in MHCC97-H cell lines compared to MHCC97-L cell lines. The downregulation of Axl in MHCC97-H cell lines resulted in the inhibition of the invasion ability of MHCC97-H cells both in vitro and in vivo. Interestingly, blocking PI3K/Akt signaling pathway by LY294002 or Akt siRNA could remarkably inhibit the PAK1 activation and cell invasion. Finally, the Axl protein expression was positively correlated with differentiation, lymph node metastasis, and clinical stage in patients with hepatocellular carcinoma patients (all P < 0.01). These findings suggest that Axl can also regulate the metastasis process of hepatocellular carcinoma and may serve as a new prognostic marker and therapeutic target for treating hepatocellular carcinoma metastasis.


Subject(s)
Carcinoma, Hepatocellular/secondary , Liver Neoplasms/pathology , Phosphatidylinositol 3-Kinases/physiology , Proto-Oncogene Proteins c-akt/physiology , Proto-Oncogene Proteins/physiology , Receptor Protein-Tyrosine Kinases/physiology , p21-Activated Kinases/physiology , Adult , Aged , Cell Line, Tumor , Female , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasm Invasiveness , Proto-Oncogene Proteins/analysis , Proto-Oncogene Proteins/genetics , Receptor Protein-Tyrosine Kinases/analysis , Receptor Protein-Tyrosine Kinases/genetics , Signal Transduction , Axl Receptor Tyrosine Kinase
11.
Oncol Lett ; 5(6): 1955-1957, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23833674

ABSTRACT

Inflammatory pseudotumor of the spleen (IPTS) is an extremely rare condition. To the best of our knowledge, only ∼113 cases have been reported in the literature since the first 2 cases were reported in 1984. The present study reports the case of an IPTS in a 72-year-old male patient. The splenic tumor was identified incidentally 1 year prior to the patient being admitted to the Second Affiliated Hospital of Dalian Medical University (Dailan, China). There were no specific clinical symptoms. The initial diagnosis was of splenic lymphoma based on the pre-operative radiological findings. However, the patient underwent a splenectomy and the final pathological diagnosis of IPTS was declared. The present study also highlighted the difficulty of forming accurate pre-operative diagnoses, even when using modern imaging techniques. A partial resection of the spleen or splenectomy was considered to be the required treatment to form a definitive diagnosis and exclude malignancy. The prognosis of IPTS is generally considered to be favorable following splenectomy. The clinical and pathological features of previously reported cases are also briefly reviewed in the present study to aid in improving the accuracy of the diagnosis of this rare disease.

12.
Oncol Lett ; 5(6): 1976-1978, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23833679

ABSTRACT

Desmoid tumors (DTs) are rare lesions that do not possess any metastatic potential. However, they have a strong tendency to invade locally and recur. They constitute 3% of all soft tissue tumors and 0.03% of all neoplasms. Abdominal DTs occur sporadically or are associated with certain familial syndromes, such as familial adenomatous polyposis (FAP). The single form of this neoplasm most frequently occurs in females of reproductive age and during pregnancy. A female patient with a DT of the abdominal wall who had no relevant family history was admitted to hospital. The patient, who presented with a painless mass in the left anterolateral abdomen, had no history of trauma, surgery or childbearing. According to the medical history, physical examination and CT report, the patient was diagnosed with DT. Radical resection of the affected abdominal wall musculature was performed, and the defect was replaced with a polypropylene mesh. The histological diagnosis was of DT. The patient remains in good health and complete remission without any other treatment following surgery. DTs exhibit aggressive growth and have a high rate of recurrence. Surgery is the optimal treatment, and subsequent radiotherapy may decrease the local recurrence rate. Further research into their aetiology is required combined with multicentre clinical trials of new treatments in order to improve management of this disease. This case report provides general knowledge of DT, and may be used as a guidance for diagnosis and treatment.

13.
Exp Ther Med ; 4(4): 621-626, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23170115

ABSTRACT

The present study aimed to investigate the influence of COL8A1 expression on cell invasiveness, drug sensitivity and tumorigenicity of hepatocellular carcinoma Hepa1-6 cells with low metastatic potential. COL8A1-1-pEGFP-N2 and pEGFP-N2 were transfected into experimental and control group cells. The COL8A1 expression in transfected Hepa1-6 cells was analyzed with RT-PCR and western blot analysis. The invasive potential of transfected Hepa1-6 cells was tested in invasion experiments in vitro and the tumorigenic ability of the transfected Hepa1-6 cells was tested in mouse tumors in vivo. Hepa1-6 cell proliferation and D-limonene sensitivity was analyzed using the MTT method. Expression of COL8A1 in the Hepa1-6/COL8A1 group showed a significant increase when compared with the untransfected cells of the Hepa1-6 control group and empty-plasmid transfected cells from the Hepa1-6/mock control group. Enhanced COL8A1 expression increased cell proliferation and matrix adhesion ability via invasion and tumorigenesis in vivo while the sensitivity to D-limonene was concurrently inhibited. The expression of COL8A1 in hepatocarcinoma cells was correlated with increased tumor cell proliferation, invasion, in vivo tumorigenicity and reduced antitumor drug sensitivity, and may provide novel targets for tumor therapy.

14.
World J Gastroenterol ; 18(38): 5369-76, 2012 Oct 14.
Article in English | MEDLINE | ID: mdl-23082053

ABSTRACT

AIM: To investigate the effects of Axl deglycosylation on tumor lymphatic metastases in mouse hepatocellular carcinoma cell lines. METHODS: Western blotting was used to analyze the expression profile of Axl glycoprotein in mouse hepatocellular carcinoma cell line Hca-F treated with tunicamycin and PNGase F 3-(4,5)-dimethylthiazol(-zyl)-3,5-diphenyltetrazolium bromide (MTT) assay, extracellular matrix (ECM) invasion assay (in vitro) and tumor metastasis assay (in vivo) were utilized to evaluate the effect of Axl deglycosylation on the Hca-F cell proliferation, invasion and lymphatic metastasis. RESULTS: Tunicamycin and PNGase F treatment markedly inhibited Axl glycoprotein synthesis and expression, proliferation, invasion, and lymphatic metastasis both in vitro and in vivo. In the MTT assay, proliferation was apparent in untreated Hca-F cells compared with treated Hca-F cells. In the ECM invasion assay (in vitro), treated cells passed through the ECMatrix gel in significantly smaller numbers than untreated cells (tunicamycin 5 µg/mL: 68 ± 8 vs 80 ± 9, P = 0.0222; 10 µg/mL: 50 ± 6 vs 80 ± 9, P = 0.0003; 20 µg/mL: 41 ± 4 vs 80 ± 9, P = 0.0001); (PNGase F 8 h: 66 ± 7 vs 82 ± 8, P = 0.0098; 16 h: 49 ± 4 vs 82 ± 8, P = 0.0001; 24 h: 34 ± 3 vs 82 ± 8, P = 0.0001). In the tumor metastasis assay (in vivo), average lymph node weights of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 µg/mL: 0.84 ± 0.21 g vs 0.72 ± 0.19 g, P = 0.3237; 10 µg/mL: 0.84 ± 0.21 g vs 0.54 ± 0.11 g, P = 0.0113; 20 µg/mL: 0.84 ± 0.21 g vs 0.42 ± 0.06 g, P = 0.0008); (PNGase F 8 h: 0.79 ± 0.15 g vs 0.63 ± 0.13 g, P = 0.0766; 16 h: 0.79 ± 0.15 g vs 0.49 ± 0.10 g, P = 0.0022; 24 h: 0.79 ± 0.15 g vs 0.39 ± 0.05 g, P = 0.0001). Also, average lymph node volumes of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 µg/mL: 815 ± 61 mm³ vs 680 ± 59 mm³, P = 0.0613; 10 µg/mL: 815 ± 61 mm³ vs 580 ± 29 mm³, P = 0.0001; 20 µg/mL: 815 ± 61 mm³ vs 395 ± 12 mm³, P = 0.0001); (PNGase F 8 h: 670 ± 56 mm³ vs 581 ± 48 mm³, P = 0.0532; 16 h: 670 ± 56 mm³ vs 412 ± 22 mm³, P = 0.0001; 24 h: 670 ± 56 mm³ vs 323 ± 11 mm³, P = 0.0001). CONCLUSION: Alteration of Axl glycosylation can attenuate neoplastic lymphatic metastasis. Axl N-glycans may be a universal target for chemotherapy.


Subject(s)
Biomarkers, Tumor/metabolism , Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/metabolism , Proto-Oncogene Proteins/metabolism , Receptor Protein-Tyrosine Kinases/metabolism , Animals , Blotting, Western , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation , Glycosylation , Liver Neoplasms/pathology , Liver Neoplasms, Experimental/metabolism , Liver Neoplasms, Experimental/pathology , Lymphatic Metastasis , Mice , Neoplasm Invasiveness , Axl Receptor Tyrosine Kinase
15.
Zhonghua Wei Chang Wai Ke Za Zhi ; 14(10): 793-5, 2011 Oct.
Article in Chinese | MEDLINE | ID: mdl-22030780

ABSTRACT

OBJECTIVE: To analyze the clinicopathological characteristics and prognosis of familial gastric cancer and to improve the treatment outcome. METHODS: Clinical data of 67 patients with familial gastric cancer and 820 patients with sporadic gastric cancer in the Second Affiliated Hospital of Dalian Medical University from 1995 to 2005 were retrospectively analyzed. RESULTS: Compared to sporadic gastric cancer, the percentage of familial gastric cancer patients less than 45 years old was higher (34.3% vs. 14.6%). Early gastric cancer(23.9% vs. 13.8%), diffuse gastric cancer(79.1% vs. 29.0%), and lymph node metastasis (91.0% vs. 70.9%) were more common in patients with familial cancer(P<0.05). The 5-year survival rate of familial gastric cancer patients was lower than that of patients with sporadic gastric cancer(20.5% vs. 45.1%)(P<0.05). CONCLUSIONS: Familial gastric cancer has characteristics of younger onset age, advanced disease staging, higher positive lymph node ratio and poorer prognosis. Therefore, early diagnosis should be emphasized in the management of familial gastric cancer.


Subject(s)
Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Adult , Female , Humans , Male , Middle Aged , Pedigree , Prognosis , Retrospective Studies , Stomach Neoplasms/genetics , Survival Rate
16.
Zhonghua Wei Chang Wai Ke Za Zhi ; 10(4): 353-5, 2007 Jul.
Article in Chinese | MEDLINE | ID: mdl-17659461

ABSTRACT

OBJECTIVE: To summarize the clinical characteristics, diagnosis and treatment of gastric neurogenic tumors. METHODS: Clinical data of 11 patients with gastric neurogenic tumors confirmed by pathology, operation and immunohistochemistry were analysed retrospectively. RESULTS: There were 7 males and 4 females with a median age of 55.5 years. The main manifestations were gastrointestinal hemorrhage, abdominal pain, upper abdominal discomfort and anaemia. Nine patients underwent gastroscopy and only one case was confirmed by the examination. Two patients were diagnosed during operation. Eight patients were submitted to subtotal gastrectomy, three were partial gastrectomy. All patients were followed up, and perioperative death occurred in one patient because of respiratory failure, recurrence occurred in two patients. Other patients with long- term follow- up had a good prognosis. CONCLUSIONS: Gastric neurogenic tumors have no specific clinical characteristics preoperatively, and the misdiagnosis rate is high. Once the diagnosis of gastric neurogenic tumors is made, an operation should be performed as early as possible.


Subject(s)
Stomach Neoplasms/diagnosis , Stomach Neoplasms/surgery , Adult , Aged , Female , Humans , Male , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Prognosis , Retrospective Studies , Stomach Neoplasms/pathology
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