Lysyl hydroxylase LH1 promotes confined migration and metastasis of cancer cells by stabilizing Septin2 to enhance actin network.

BACKGROUND: Excessive extracellular matrix deposition and increased stiffness are typical features of solid tumors such as hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). These conditions create confined spaces for tumor cell migration and metastasis. The regulatory mechanism of confined migration remains unclear. METHODS: LC-MS was applied to determine the differentially expressed proteins between HCC tissues and corresponding adjacent tissue. Collective migration and single cell migration microfluidic devices with 6 µm-high confined channels were designed and fabricated to mimic the in vivo confined space. 3D invasion assay was created by Matrigel and Collagen I mixture treat to adherent cells. 3D spheroid formation under various stiffness environment was developed by different substitution percentage GelMA. Immunoprecipitation was performed to pull down the LH1-binding proteins, which were identified by LC-MS. Immunofluorescent staining, FRET, RT-PCR, Western blotting, FRAP, CCK-8, transwell cell migration, wound healing, orthotopic liver injection mouse model and in vivo imaging were used to evaluate the target expression and cellular phenotype. RESULTS: Lysyl hydroxylase 1 (LH1) promoted the confined migration of cancer cells at both collective and single cell levels. In addition, LH1 enhanced cell invasion in a 3D biomimetic model and spheroid formation in stiffer environments. High LH1 expression correlated with poor prognosis of both HCC and PDAC patients, while it also promoted in vivo metastasis. Mechanistically, LH1 bound and stabilized Septin2 (SEPT2) to enhance actin polymerization, depending on the hydroxylase domain. Finally, the subpopulation with high expression of both LH1 and SEPT2 had the poorest prognosis. CONCLUSIONS: LH1 promotes the confined migration and metastasis of cancer cells by stabilizing SEPT2 and thus facilitating actin polymerization.

iTRAQ-MS/MS Proteomic Analysis Reveals Differentially Expressed Proteins During Post-harvest Maturation of the White Button Mushroom Agaricus bisporus.

Agaricus bisporus (J. E. Lange) Imbach, well known as the common cultivated mushroom or white button mushroom, is widely cultivated all over the world. We used iTRAQ-MS/MS (i.e., isobaric tags for relative and absolute quantification-coupled two-dimensional liquid chromatography-tandem mass spectrometry) to identify protein expression changes that occur during the post-harvest maturation of Agaricus bisporus fruitbodies at 0, 6, 12, and 48 h after harvest. A total of 5878 unique peptides, representing 1063 proteins, were identified. Quantitative data were obtained from 1012 out of the 1063 proteins. A total of 102, 106, and 160 differentially expressed proteins (>twofolds differences) were identified from samples collected at 6, 12, and 48 h compared to sample from 0 h post harvest, accounting for 10.1, 10.5, and 15.8% of the total proteins identified, respectively. All identified proteins including the differentially expressed proteins among different post-harvest stages were subjected to bioinformatic analysis. Furthermore, seven representative proteins either up or down-regulated at different post-harvest stages were analyzed by real-time PCR. Three out of the seven proteins, the mismatched base pair and cruciform DNA recognition protein, hydrophobin-B and protein transporter, exhibited similar expression patterns as their corresponding proteins. The 260 differentially expressed proteins identified from our study laid a foundation for future studies aiming to understand the post-harvest maturation process of A. bisporus and eventually, might help in the development of breeding program to identify strains with extended shelf life.

Prognostic significance of USP10 as a tumor-associated marker in gastric carcinoma.

Ubiquitin-specific protease 10 (USP10), a novel deubiquitinating enzyme, had been associated with growth of tumor cell. However, the role of USP10 in gastric cancer carcinogenesis had not been elucidated yet. The aim of this study was to investigate the expression level of USP10 in gastric carcinoma (GC) tissues and cell lines, then to evaluate the clinical significance of USP10 in GC patients. USP10, E-cadherin, Ki67 and p53 expressions were detected in 365 GC and 40 non-cancerous mucosa tissues by immunohistochemistry. Western blot for USP10 was performed on additional fresh GC tissues and GC cell lines. The expression level of USP10 in GC tissues was proved lower than that in non-cancerous mucosa tissues (p < 0.05). It was also lower in GC cell lines (AGS, BGC-823 and MKN45 cells) than that in gastric epithelial immortalized cell line (GES-1). Clinicopathological analysis showed that USP10 expression was negatively correlated with gastric wall invasion (p = 0.009), nodal metastasis (p = 0.002), and TNM stage (p = 0.000). In contrast, a positively correlation between the expression of USP10 and E-cadherin was found (p < 0.05), but there was no relationship proved between Ki67, p53 and USP10 (p > 0.05). On the Kaplan-Meier survival curves, we found poor prognosis in GC patients was associated with negative USP10 expression (p < 0.05). Moreover, USP10 expression was an independent prognostic factor for the overall survival in multivariate analysis. Our findings suggested that USP10 was an independent predictor of prognosis of GC patients.

Investigating the optimal parathyroid autotransplantation strategy in transareolar endoscopic thyroidectomy: A retrospective cohort study.

BACKGROUND: There is ongoing debate about whether intraoperative parathyroid autotransplantation effectively prevents permanent hypoparathyroidism after thyroidectomy. This study aims to examine its impact on postoperative parathyroid function and determine the best autotransplantation strategy. METHODS: A retrospective analysis was conducted on 194 patients who underwent total thyroidectomy with central lymph node dissection (CLND) for papillary thyroid carcinoma (PTC). Patients were divided into four groups based on the number of parathyroid autotransplants during surgery: Group 1 (none, n = 43), Group 2 (1 transplant, n = 60), Group 3 (2 transplants, n = 67), and Group 4 (3 transplants, n = 24). Various clinical parameters were collected and compared among the groups. RESULTS: Parathyroid autotransplantation was identified as a risk factor for temporary hypoparathyroidism (OR: 1.74; 95% CI: 1.27-2.39, P = 0.001) and a protective factor for permanent hypoparathyroidism (OR: 0.27; 95% CI: 0.14-0.55, P < 0.001). At 12 months postoperative, systemic parathyroid hormone (PTH) levels increased progressively from Groups 1 to 4, with significant differences observed only between Group 1 and Group 2 (P < 0.02). Difference values in systemic PTH levels between Month 1 and Day 1 postoperative increased progressively from Groups 1 to 4, with statistically significant differences observed between adjacent groups (P < 0.02). The number of dissected positive lymph nodes increased progressively across the four groups, showing statistical differences (P < 0.02). CONCLUSION: Parathyroid autotransplantation can prevent permanent hypoparathyroidism. Additionally, we recommend preserving parathyroids in situ whenever possible. If autotransplantation is required, it should involve no more than two glands.

Extracellular Vesicle Preparation and Analysis: A State-of-the-Art Review.

In recent decades, research on Extracellular Vesicles (EVs) has gained prominence in the life sciences due to their critical roles in both health and disease states, offering promising applications in disease diagnosis, drug delivery, and therapy. However, their inherent heterogeneity and complex origins pose significant challenges to their preparation, analysis, and subsequent clinical application. This review is structured to provide an overview of the biogenesis, composition, and various sources of EVs, thereby laying the groundwork for a detailed discussion of contemporary techniques for their preparation and analysis. Particular focus is given to state-of-the-art technologies that employ both microfluidic and non-microfluidic platforms for EV processing. Furthermore, this discourse extends into innovative approaches that incorporate artificial intelligence and cutting-edge electrochemical sensors, with a particular emphasis on single EV analysis. This review proposes current challenges and outlines prospective avenues for future research. The objective is to motivate researchers to innovate and expand methods for the preparation and analysis of EVs, fully unlocking their biomedical potential.

Size and shape control of microgel-encapsulating tumor spheroid via a user-friendly solenoid valve-based sorter and its application on precise drug testing.

The precision of previous cancer research based on tumor spheroids, especially the microgel-encapsulating tumor spheroids, was limited by the high heterogeneity in the tumor spheroid size and shape. Here, we reported a user-friendly solenoid valve-based sorter to reduce this heterogeneity. The artificial intelligence algorithm was employed to detect and segmentate the tumor spheroids in real-time for the size and shape calculation. A simple off-chip solenoid valve-based sorting actuation module was proposed to sort out target tumor spheroids with the desired size and shape. Utilizing the developed sorter, we successfully uncovered the drug response variations on cisplatin of lung tumor spheroids in the same population but with different sizes and shapes. Moreover, with this sorter, the precision of drug testing on the spheroid population level was improved to a level comparable to the precise but complex single spheroid analysis. The developed sorter also exhibits significant potential for organoid morphology and sorting for precision medicine research.

Immune checkpoint inhibitor for different age patients with NSCLC in efficacy: A systematic review and meta-analysis.

OBJECTIVE: This article is a Meta-analysis aiming to systematically evaluate the difference in efficacy of immune checkpoint inhibitor in patients with non-small cell lung cancer (NSCLC) by age. METHODS: We performed a Meta-analysis of published randomized controlled trials concerning for patients with NSCLC by age. We compared overall survival among three groups (age <65 years, age 65-75 years, age ≥75 years). Hazard ratios (HRs) and 95% confidence intervals (CIs) were collected and pooled. RESULTS: A total of 10,291 patients from 17 RCTs were included. In the group under age 65 years, immune checkpoint inhibitor can significantly prolong the overall survival of patients with NSCLC (HR = 0.73, 95% CI: 0.66∼0.81, P < 0.00001). In the age 65-75 years group, immune checkpoint inhibitors prolonged overall survival in patients with NSCLC (HR = 0.78, 95% CI:0.71∼0.84, P < 0.00001). However, it has no significant effect on the overall survival of NSCLC patients (HR = 0.88, 95% CI:0.72∼1.08, P > 0.05) in the group older than 75 years. CONCLUSIONS: Immune checkpoint inhibitors prolonged the overall survival of NSCLC patients in the age <65 years group and the age 65-75 years group, but in the age ≥75 years group, there was no significant effect on overall survival. This may be related to innate immune and adaptive immune dysregulation due to "immunosenescence" in older patients.

Cellulose Nanofibrils of High Immunoaffinity for Efficient Enrichment of Small Extracellular Vesicles.

Extracellular vesicles (EVs), crucial in facilitating the transport of diverse molecular cargoes for intercellular communication, have shown great potential in diagnostics, therapeutics, and drug delivery. The challenge of developing effective preparation methods for EVs is heightened by their intrinsic heterogeneity and complexity. Here, a novel strategy for high EV enrichment is developed by utilizing EV-affinitive-modified cellulose nanofibrils. Specifically, modified cellulose with rich carboxyl groups has outstanding dispersing properties, able to be dispersed into cellulose nanofibrils in solution. These cellulose nanofibrils are utilized as scaffolds for the immobilization of EV-affinitive antibody of CD63 by chemical conjugation. The CD63-modified nanofibrils demonstrate a superior EV capture efficiency of 86.4% compared with other reported methods. The high performance of this system is further validated by the efficient capture of EVs from biological blood plasma, allowing the detection of bioactive markers from EV-derived miRNAs and proteins. The authors envision that these modified cellulose nanofibrils of enhanced capability on EV enrichment will open new avenues in various biomedical applications.

Predicting the potential suitable distribution area of Emeia pseudosauteri in Zhejiang Province based on the MaxEnt model.

Human activities, including urbanization, industrialization, agricultural pollution, and land use, have contributed to the increased fragmentation of natural habitats and decreased biodiversity in Zhejiang Province as a result of socioeconomic development. Numerous studies have demonstrated that the protection of ecologically significant species can play a crucial role in restoring biodiversity. Emeia pseudosauteri is regarded as an excellent environmental indicator, umbrella and flagship species because of its unique ecological attributes and strong public appeal. Assessing and predicting the potential suitable distribution area of this species in Zhejiang Province can help in the widespread conservation of biodiversity. We used the MaxEnt ecological niche model to evaluate the habitat suitability of E. pseudosauteri in Zhejiang Province to understand the potential distribution pattern and environmental characteristics of suitable habitats for this species, and used the AUC (area under the receiver operating characteristic curve) and TSS (true skill statistics) to evaluate the model performance. The results showed that the mean AUC value was 0.985, the standard deviation was 0.011, the TSS average value was 0.81, and the model prediction results were excellent. Among the 11 environmental variables used for modeling, temperature seasonality (Bio_4), altitude (Alt) and distance to rivers (Riv_dis) were the key variables affecting the distribution area of E. pseudosauteri, with contributions of 33.5%, 30% and 15.9%, respectively. Its main suitable distribution area is in southern Zhejiang Province and near rivers, at an altitude of 50-300 m, with a seasonal variation in temperature of 7.7-8 °C. Examples include the Ou River, Nanxi River, Wuxi River, and their tributary watersheds. This study can provide a theoretical basis for determining the scope of E. pseudosauteri habitat protection, population restoration, resource management and industrial development in local areas.

[Predictive value of PTH level on day 1 after surgery for papillary thyroid carcinoma in patients with permanent hypoparathyroidism].

Objective:To investigate the relationship between parathyroid hormone（PTH） level and permanent hypoparathyroidism（PHPP） on the first day after radical papillary thyroidectomy, and its predictive value. Methods:A total of 80 patients with papillary thyroid cancer who underwent total thyroid resection and central lymph node dissection were collected and analyzed from January 2021 to January 2022. According to whether PHPP occurred after surgery, the patients were divided into hypoparathyroidism group and normal parathyroid function group, and univariate and binary logistics regression were used to analyze the correlation between PTH and serum calcium levels and PHPP on the first day after surgery in two groups. The dynamic changes of PTH at different time points after operation were analyzed. The area under the receiver operating characteristic was used to evaluate the predictive power of PTH on the development of PHPP after surgery. Results:Among the 80 patients with papillary thyroid cancer, 10 cases developed PHPP, with an incidence rate of 12.5%. Binary logistics regression analysis showed that PTH on the first postoperative day（OR=14.534, 95%CI: 2.377-88.858, P=0.004） was an independent predictive risk factor for postoperative PHPP. Taking PTH=8.75 ng/L on the first postoperative day as the cut-off value, the AUC of the area under the curve was 0.874（95%CI: 0.790-0.958, P<0.001）, the sensitivity was 71.4%, the specificity was 100%, and the Yoden index was 0.714. Conclusion:PTH level on the first day after total thyroid papillary carcinoma surgery is closely related to PHPP, and is an independent predictor of PHPP.

The non-receptor tyrosine kinase c-Src mediates the PDGF-induced association between Furin and pro-MT1-MMP in HPAC pancreatic cells.

Furin is a member of the proprotein convertase family, which is capable of cleaving the precursors of a wide variety of substrates including membrane-type 1 matrix metalloproteinase (MT1-MMP) proenzyme. c-Src is activated by growth factors, and has been linked with a poor prognosis in pancreatic cancer (PCa). Both c-Src and Furin play crucial roles in tumorigenesis, and the mechanism controlling their association is not understood. Modulation of the association between Furin and pro-MT1-MMP by c-Src inhibitor PP2 was evaluated by western blotting, assay of in vitro enzyme, co-immunoprecipitation (co-IP), and confocal immunofluorescence microscopy. Human platelet-derived growth factor BB (PDGF-BB) activated c-Src and induced c-Src-dependent association of Furin with pro-MT1-MMP in HPAC pancreatic cancer cells. Co-IP and confocal immunofluorescence assays revealed that c-Src interacts with Furin in vivo. The SH2 domain appeared to be important for c-Src interaction with Furin. In addition, we showed that Furin protein is tyrosine phosphorylated. Association between Furin and MT1-MMP is regulated by the tyrosine kinase c-Src.

Clinical application of parathyroid autotransplantation in endoscopic radical resection of thyroid carcinoma.

Purpose: This study aimed to examine the effect of selective inferior parathyroid gland autotransplantation on central lymph node dissection(CLND) and incidence of postoperative hypoparathyroidism in patients undergoing endoscopic radical resection of thyroid carcinoma. Methods: The data of 310 patients undergoing endoscopic radical resection of thyroid carcinoma will be retrospectively analyzed. The patients will be divided into the experimental group and the control group according to whether they combined with parathyroid autotransplantation. Statistics of the incidence rate of postoperative hypoparathyroidism, the concentration of PTH and Calcium in the systemic circulation at different time points in the two groups, the concentration of PTH in the cubital fossa vein in the transplantation region in the experimental group, and the number of central lymph nodes and positive lymph nodes dissection will be carried out. Results: The incidence rate of temporary and permanent hypoparathyroidism in the experimental group was 33.75% and 0.625%, respectively, and in the control group was 22% and 5%, respectively; its difference was statistically significant (X2 = 10.255, P=0.006). Parathyroid autotransplantation increased incidence of transient hypoparathyroidism (OR, 1.806; Cl, 1.088-2.998; P=0.022), and lower incidence of permanent hypoparathyroidism (OR, 0.112; Cl, 0.014-0.904; P=0.040). The diameters of thyroid cancer nodules was not associated with the occurrence of transient hypoparathyroidism (OR, 0.769; Cl, 0.467-1.265; P=0.301) or permanent hypoparathyroidism (OR, 1.434; Cl, 0.316-6.515; P=0.641). Comparison of systemic circulation PTH, between the two groups showed that the PTH of patients in the experimental group was higher than that in the control group from 1 week to 12 months after the operation, and the difference was statistically significant (P<0.05). In the experimental group, from 1 week to 12 months after surgery, PTH concentrations was significantly higher in the cubital fossa of the transplantation side than in the contralateral side, and the differences were statistically significant (P<0.05). The mean number of central lymph node dissected per patient was significantly higher in the experimental group (7.94 ± 3.03 vs. 6.99 ± 2.86; P <0.05); The mean number of positive nodes per patient was significantly higher in the experimental group (3.16 ± 1.86 vs. 2.53 ± 1.59; P <0.05). Conclusions: In endoscopic radical resection of thyroid carcinoma, parathyroid autotransplantation is more beneficial to postoperative parathyroid glands function recovery, effectively preventing postoperative permanent hypoparathyroidism and realizing more thorough CLND.

A nomogram for predicting overall-specific survival in thyroid cancer patients with total thyroidectomy: a SEER database analysis.

BACKGROUND: A good predictive model requires patients to attend consultations for prognosis and subsequent clinical follow up. The aim of the present study was to build a nomogram chart with independent prognostic factors for thyroid cancer (TC) patients with total thyroidectomy. METHODS: This was a retrospective, observational study. Data were collected from the Surveillance, Epidemiology, End Results (SEER) database and approved by the institutional review board of our institution. In total, 11,614 patients with TC after thyroidectomy were selected from 2010 to 2015. We divided the selected patients into a modeling group and a verification group at a ratio of 7:3. The effective factors were selected to establish the nomogram model through Cox analysis. Finally, internal verification was carried out through the testing group. RESULTS: Chi-squared analysis of various factors in the modeling group and the testing group had no significant statistical significance, indicating that random grouping was meaningful. Most of the TC patients were female patients. The following variables were selected through univariate and multivariate Cox analysis for overall-specific survival: age, histological type, grade, tumor size, stage TMN, and sex. These variables were used to establish predictions of 3- and 5-year survival rates using a nomogram. Both the modeling group and the verification group had good predictive ability with their C-index all greater than 0.8. CONCLUSIONS: We established the first postoperative prediction model of TC with total thyroidectomy through the variables selected via the Cox multivariate analysis, which laid the foundation for the prognostic prediction and postoperative follow up of each patient.

Astrocytoma of the ciliary body.

PURPOSE: To report the occurrence of an astrocytoma of the ciliary body. METHODS: The patient was evaluated by ophthalmoscopic examination (including color ultrasonography and ultrasound biomicroscopy) as well as operating therapy. Histopathology and immunocytochemical analysis were performed. RESULTS: A 29-year-old woman was found to have a left ciliary body tumor. Color ultrasonography revealed a 12 x 10 mm size, a low-level echo boundary, and a bright echogenic band. Ultrasound biomicroscopy showed that the lesion was located in the superior temporal quadrant of the ciliary body and extended backward for 6 mm from the limbus. The tumor was carefully dissected free and completely removed via episcleral incision. Histopathology revealed a fibrillary astrocytoma. Staining for glial fibrillary acidic protein yielded positive results and neuron-specific enolase yielded negative results. CONCLUSIONS: We describe an astrocytoma of the ciliary body in a patient, which is an extremely rare ocular tumor. Histopathology and immunocytochemical analysis were required to establish the diagnosis.

Polymorphism of thymidylate synthase gene associated with its protein expression in human colon cancer.

AIM: To correlate the polymorphisms in the 5'-untranslated region with thymidylate synthase (TS) protein expression in Han Chinese colonic neoplasms. METHODS: Adenocarcinoma samples were from 68 patients who received no treatment before surgery. Tandem repeat length of TS gene was determined by PCR amplification of genomic DNA. Intratumoral TS protein expression was studied immunohistochemically in corresponding sections from paraffin-embedded primary foci. Immunoreactivity was semiquantitatively evaluated by immunoreactivity score (IRS). RESULTS: Double-(2R) and triple-repeated (3R) sequences of the TS gene were found in the cancer tissues. Three genotypes of TS were found: 2R/2R (n=6), 2R/3R (n=22) and 3R/3R (n=40). Patients who were homozygous for triple-repeated (3R/3R) sequences showed significantly higher IRS of TS than patients who were homozygous for double-repeated (2R/2R) sequences or heterozygous patients (2R/3R): 5.73+/-3.25 vs 2.17+/-1.47 or 3.77+/-2.64, P=0.008 or P=0.015. But no statistical significance of IRS in cancer tissues was observed between 2R/3R genotype and 2R/2R genotype. CONCLUSION: There is a relationship between TS genotype and TS protein expression in clinical specimens. The data might offer an advantage for selection of Chinese cancer patients to receive fluoropyrimidines treatment.

Spontaneous ruptured primary hepatic angiosarcoma coincident with Schistosoma Japonica liver fibrosis.

AIM: We report herein a case of spontaneous ruptured primary hepatic angiosarcoma coincident with Schistosoma Japonica liver fibrosis and review the correlative literature. METHODS: The resected specimen was examined by histopathological and immunohistochemical evaluation. RESULTS: The final diagnosis was spontaneous ruptured primary hepatic angiosarcoma coincident with Schistosoma Japonica liver fibrosis Conclusion: Considering the nature of primary hepatic angiosarcoma, in particular the ruptured hepatic angiosarcoma, it is obviously desirable to avoid any unnecessary delay or definitive surgical treatment. It is presumed that angiosarcoma in the liver has a possible association with S. japonicum and the deposition of ovae in liver.

Myxoid adrenocortical adenoma with a pseudoglandular pattern: a case report and literature review.

Adrenocortical adenoma is a benign neoplasm derived from cells of the adrenal cortex. The myxoid variant of this tumor is extremely rare. To our knowledge, only 23 cases of myxoid adrenocortical adenoma have been reported so far and 19 of them mentioned the pseudoglandular pattern. We reported a new case of 56-year-old Chinese female patient whose left adrenal gland was shown a neoplastic lesion by computed tomography (CT) and magnetic resonance (MR) imaging. Histopathological study showed that the mass was a myxoid adrenocortical adenoma with a pseudoglandular pattern. Then, we performed immunohistochemistry with 28 biomarkers to make differential diagnosis and found that tumor cells were diffusely positive for vimentin, melan-A, CD56, NSE and USP10, and focally positive for cytokeratin pan, cytokeratin 8/18 and VEGF. The labeling index of Ki-67 and Cyclin D1 were about 1% and 50%, respectively. No immunoreactivity was found for EMA, cytokeratin 7, HMB45, S-100, alpha-inhibin, calretinin, synaptophysin, chromogranin A, P53, EGFR, MMP2, DNA topo II alpha, CA125, E-cadherin, P63, P16 and Her-2. The patient has been followed up for 37 months after tumor resection and no evidence was found to suggest any local recurrence or any metastatic disease. Myxoid adrenocortical adenoma with a pseudoglandular pattern is extremely rare. The accurate diagnosis should be based on combined consideration of clinical characteristics, CT, MR imaging and pathological features, and should be distinguished from other retroperitoneal myxoid tumors.

Primary malignant fibrous histiocytoma of the small bowel: a report of an additional case in duodenum.

AIMS: We report herein an additional case of primary malignant fibrous histiocytoma (MFH) in the duodenum and provide a review of the existing literature. METHODS AND RESULTS: A 61-yr-old Chinese man was admitted to our hospital with symptoms of melena, anorexia, and weight loss. An abdominal computed tomography (CT) and gastrointestinal barium meal examination demonstrated a tumor of the duodenum suggestive of primary malignancy. The tumor was successfully treated by pancreaticoduodenectomy. It was histopathologically and immunohistochemically diagnosed to be a storiform-type primary MFH of the duodenum. There have been a total of 40 cases of primary malignant fibrous histiocytoma of the small bowel documented in the literature including our Chinese cases. CONCLUSION: Primary malignant fibrous histiocytoma of the small bowel, especially in the duodenum is extremely rare. The final diagnosis is made only after pathological and immunopathological examination of the tumor. The malignant potential of such tumors is high. The prognosis may be mainly dependent on the invasion and metastasis of tumor, while tumor size is irrelevant. The treatment should be surgery if possible. Early surgical intervention may be the best form of management that may offer the patient good result.

Presence and release of the chromogranin B-derived secretolytin-like peptide KR-11 from the porcine spleen.

Chromogranin B (CgB) is a major matrix protein in secretory granules/large dense-cored vesicles and a precursor for smaller peptides. In an earlier study, we have identified a secretolytin-like peptide (KR-11, pCgB(637-647)) from porcine chromaffin granules. Further evidence is presented here to show the processing of chromogranin B to this peptide during axonal transport in the splenic nerve and its release in the spleen upon various conditions of stimulation. Immunohistochemical staining showed that in the porcine spleen chromogranin B and NPY completely colocalize in nerve fibres and varicosities in blood vessel walls and trabeculae, and along the loose network of smooth muscle cells in the red pulp, as identified by their alpha-smooth muscle cell actin content. No antibacterial activity was found for the porcine secretolytin-like peptide, KR-11. The change of one amino acid residue (Thr-->Asn) in the porcine homologous fragment of secretolytin appears to be responsible for its loss of antibacterial activity.

Presence and release of SR-17 (chromogranin B(586-602)) in the porcine splenic nerve and its enzymatic degradation by CD26/dipeptidyl peptidase IV.

Using the pig splenic nerve as a model, we investigated the proteolytic processing of porcine chromogranin B (CgB) during its axonal transport. An ELISA was developed for SR-17 (CgB(586-602)), a novel CgB-derived peptide, originally found in the adrenal medulla. The results demonstrate that CgB is processed in an early stage during its axonal transport. Immunohistochemical data, based on a rabbit anti-SR-17 antiserum, show that the spleen CgB/SR-17 is exclusively present in the nerve endings. No SR-17 immunoreactivity (IR) was found in splenocytes. We also provide evidence that SR-17 is co-released with noradrenaline (NA) upon electrical stimulation of the splenic nerve. Its release is frequency-dependent and strongly enhanced in the presence of the alpha-blocking agent phentolamine. In addition, we show that the new CgB-peptide can serve as a substrate for the lymphocyte surface glycoprotein CD26, also known as dipeptidyl peptidase IV (DPP IV), generating a new peptide ER-15 (CgB(588-602)).