elastin and Stomach-Neoplasms

Gastric cancer (GC) is the fifth most frequent cancer in the world and shows the highest incidence in Latin America and Asia. An increasing amount of evidence demonstrates that lysyl oxidase isoforms, a group of extracellular matrix crosslinking enzymes, should be considered as potential biomarkers and therapeutic targets in GC. In this review, we focus on the expression levels of lysyl oxidase isoforms, its functions and the clinical implications in GC. Finding novel proteins related to the processing of these extracellular matrix enzymes might be helpful in the design of new therapies, which, in combination with classic pharmacology, could be used to delay the progress of this aggressive cancer and offer a wider temporal window for clinical intervention.

Topics: Biomarkers, Tumor; Chelating Agents; Collagen; Elastin; Fibrosis; Humans; Neoplasm Metastasis; Protein Isoforms; Protein-Lysine 6-Oxidase; Stomach Neoplasms

Lymphatic invasion (LI) and venous invasion (VI) are the strongest risk factors for lymph node metastasis in patients with early gastric cancer, and may predict their prognosis. We aimed to investigate interobserver agreement among pathologists before and after adding ancillary staining for diagnosing LI and VI in this setting.. This retrospective study included 100 specimens of submucosal invasive gastric cancer from 100 patients treated using endoscopic resection. Three pathologists (expert, intermediate and trainee experience levels) independently evaluated individual LI and VI status using haematoxylin and eosin (H&E)-stained slides, and re-evaluated their decisions by reviewing corresponding D2-40-stained and elastin-stained slides. Interobserver agreement was assessed using κ statistics. With the ancillary D2-40 staining, there was an improved agreement for LI diagnoses between the expert and intermediate pathologist (H&E κ = 0.78, D2-40 κ = 0.85) and between the expert and trainee pathologist (H&E κ = 0.37, D2-40 κ = 0.56). With the ancillary elastin staining, there was an improved agreement for VI diagnoses between the expert and intermediate pathologists (H&E κ = 0.25, elastin κ = 0.63) and between the expert and trainee pathologists (H&E κ = 0.29, elastin κ = 0.45).. With both the ancillary D2-40 and elastin staining there was an improved interobserver agreement for LI and VI diagnoses, regardless of the pathologist's experience. This ancillary staining may be useful in improving the accuracy of LI and VI diagnoses, helping to improve the risk stratification of early gastric cancer patients.

Topics: Aged; Antibodies, Monoclonal, Murine-Derived; Biomarkers, Tumor; Elastin; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Observer Variation; Retrospective Studies; Staining and Labeling; Stomach Neoplasms

The presence of vessel invasion is considered indicative of a poor prognosis in many malignant tumors. We aimed to compare the sensitivity of elastin stains (van Gieson's and orcein methods) with 2 smooth muscle markers (h-caldesmon and desmin) in gastric, pancreatic, and colorectal adenocarcinoma specimens.. We used 27 (29.3%) gastric, 35 (38.0%) pancreatic, and 30 (32.6%) colorectal resection specimens. We applied a provisional classification of vessel invasion patterns: type A, a focus with a nearby artery unaccompanied by a vein; type T, a focus at the invasive front without an unaccompanied artery; and type X, foci that only appeared by any of the 4 stains used.. There were 369 foci. The smooth muscle markers were more sensitive than the elastin stains, and h-caldesmon more sensitive than desmin, in all types. Among the 139 type A foci, 33 (23.7%) were positive by desmin and h-caldesmon, whereas the elastin stains were not ( P = .001). h-Caldesmon was the only positive marker in 11 (7.9%; P = .011). Among the 78 type T foci, 21 (26.9%) were positive by desmin and h-caldesmon, when both elastin stains were negative ( P = .000). In 16 (20.5%) foci, h-caldesmon was the only positive marker ( P = .002). Among 152 type X foci, 91 (59.9%) were positive by all markers, 26 (17.1%) by both desmin and h-caldesmon, and 9 (5.9%) by only the 2 elastin stains ( P = .001).. We recommend these stains for suspect foci in gastric, pancreatic, and colorectal adenocarcinoma specimens. They might highlight both predictable and unpredictable foci.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Calmodulin-Binding Proteins; Colorectal Neoplasms; Desmin; Elastin; Female; Humans; Immunohistochemistry; Male; Middle Aged; Neovascularization, Pathologic; Pancreatic Neoplasms; Staining and Labeling; Stomach Neoplasms; Young Adult

Endoscopic submucosal dissection (ESD) can successfully resect large lesions en bloc by using a submucosal injection solution, but the cost of currently available submucosal injection solutions is not satisfactory. The authors' aim was to evaluate the feasibility and effectiveness of a thermally sensitive elastin-like polypeptide (ELP) used as submucosal injection solution in ESD.. We conducted an ex vivo study to determine the optimal concentration of ELPs in rabbits, an in vivo study to evaluate the effectiveness of mucosal elevation in rats, and a large animal study to confirm the feasibility of preclinical application by using conventional clinical procedure in pigs.. ELP (500 μM) was proved to be the optimal injectable submucosal injection solution and elevated mucosa more efficiently than any control. The same concentration of ELP exhibited an equivalent effectiveness of mucosal elevation, the retention of the elevation, and minimal bleeding with sodium hyaluronate. The ESD procedure time with 500 μM ELP in a preclinical study with pigs was significantly shorter than with any other concentration of ELP and normal saline solution.. Use of ELP as submucosal injection solution was feasible, with higher and longer-lasting elevation and fewer adverse events.

Topics: Animals; Disease Models, Animal; Dissection; Elastin; Endoscopy, Gastrointestinal; Feasibility Studies; Gastric Mucosa; Injections, Intralesional; Male; Neoplasms, Experimental; Rabbits; Rats; Rats, Sprague-Dawley; Stomach Neoplasms; Swine; Swine, Miniature; Temperature; Treatment Outcome

The use of the traditional xenograft subcutaneous tumor model has been contested because of its limitations, such as a slow tumorigenesis, inconsistent chemotherapeutic results, etc. In light of these challenges, we aim to revamp the traditional model by employing an electrospun scaffold composed of polydioxanone, gelatin and elastin to boost the tumorigenesis. The scaffold featured a highly porous microstructure and successfully supported the growth of tumor cells in vitro without provoking apoptosis. In vivo studies showed that in the scaffold model the tumor volume increased by 43.27% and the weight by 75.58%, respectively, within a 12-week period. In addition, the scaffold model saw an increase of CD24(+) and CD44(+) cells in the tumor mass by 42% and 313%, respectively. The scaffolding materials did not lead to phenotypic changes during the tumorigenesis. Thereafter, in the scaffold model, we found that the chemotherapeutic regimen of docetaxel, cisplatin and fluorouracil unleashed a stronger capability than the regimen comprising cisplatin and fluorouracil to deplete the CD44(+) subpopulation. This discovery sheds mechanistic lights on the role of docetaxel for its future chemotherapeutic applications. This revamped model affords cancer scientists a convenient and reliable platform to mechanistically investigate the chemotherapeutic drugs on gastric cancer stem cells.

Topics: Animals; Antineoplastic Agents; Apoptosis; CD24 Antigen; Cell Survival; Cisplatin; Drug Screening Assays, Antitumor; Elastin; Female; Fluorouracil; Gelatin; Humans; Hyaluronan Receptors; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplastic Stem Cells; Phenotype; Polydioxanone; Porosity; Stomach Neoplasms; Time Factors; Tissue Engineering; Tissue Scaffolds

The present study was undertaken to examine malignant alterations of collagen and elastin in human stomach cancer. Results of the study are as follows: 1. Content of hydroxyproline which in characteristic amino acid in collagen was elevated in stomach cancer tissues of Bormann types I to IV as compared to that of the uninvolved stomach. 2. When hydroxyproline content in stomach cancer of type IV (scirrhous) was compared to that in other types (I to III) of the cancer, the content in scirrhous was significantly elevated compared with that in cancers of other types, in terms of dry weight of whole tissue, number of cancer cells, and of insoluble proteins which are rich in collagen and elastin. However, when hydroxyproline was determined on two histological layers (mucosa plus submucosa layer and muscular plus serosa layer) separated from the involved and uninvolved stomach tissues, no significant difference in hydroxyproline content was observed between the scirrhous and non-scirrhous cancers. These observations may imply that an increased collagen synthesis in the scirrhous occurs in many layers of stomach tissue but is not restricted in a particular layer. 3. Non-reducing cross-link amino acids of collagen, pyridinoline and histidinoalanine, were assayed on the involved and uninvolved tissues. Pyridinoline content was higher in stomach cancers of Bormann types I to IV, while no significant difference of histidinoalanine content was found. These observations suggest that there is an increased cross-linking of collagen in stomach cancer. 4. Elastin concentration in stomach cancer was determined through the assay of desmosine and isodesmosine which are specific cross-link amino acids in elastin. The contents of these amino acids was increased in stomach cancer tissues of types I to IV as compared with that in the uninvolved tissue. 5. A ratio of desmosine plus isodesmosine to hydroxyproline was higher in the involved stomach than was in the uninvolved, suggesting that increased elastinosis exceeds collagenosis in stomach cancer.

Topics: Amino Acids; Collagen; Dipeptides; Elastin; Humans; Hydroxyproline; Stomach Neoplasms