Carney triad is a multitumor syndrome affecting almost exclusively young women in a nonfamilial setting, which manifests by multifocal gastric gastrointestinal stromal tumors, paragangliomas, and pulmonary chondroma. The Carney triad-associated tumors are characterized by a deficiency of the mitochondrial succinate dehydrogenase enzymatic complex. Recently, it has been observed that the deficiency results from epigenetic silencing of the SDHC gene by its promoter hypermethylation. To elucidate anatomic distribution of SDHC promoter methylation in Carney triad patients and thus to shed some light on the possible natural development of this epigenetic change, both neoplastic and available non-neoplastic tissues of 3 patients with Carney triad were tested for hypermethylation at the SDHC promoter site. SDHC promoter hypermethylation was proven in all tumors studied. Lack of SDHC epigenetic silencing in the non-neoplastic lymphoid and duodenal tissue (ie, tissues not involved in the development of Carney triad-associated tumors) together with the finding of SDHC promoter hypermethylation in the non-neoplastic gastric wall favors the hypothesis of postzygotic somatic mosaicism as the biological background of Carney triad; it also offers an explanation of the multifocality of gastrointestinal stromal tumors of the stomach occurring in this scenario as well. However, the precise mechanism responsible for the peculiar organ-specific distribution of Carney triad-associated tumors is still unknown.
- MeSH
- chondrom * genetika metabolismus patologie MeSH
- DNA nádorová * genetika metabolismus MeSH
- leiomyosarkom * genetika metabolismus patologie MeSH
- lidé MeSH
- membránové proteiny * genetika metabolismus MeSH
- metylace DNA * MeSH
- mozaicismus * MeSH
- nádorové proteiny * genetika metabolismus MeSH
- nádory plic * genetika metabolismus patologie MeSH
- nádory žaludku * genetika metabolismus patologie MeSH
- nechromafinní paragangliom * genetika metabolismus patologie MeSH
- promotorové oblasti (genetika) * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Intraperitoneal malignant cells detection in patients with gastric cancer is associated with a significant decrease in overall survival. The overall accuracy of cytological examination of peritoneal lavages, however, is quite low, and intraperitoneal recurrence has been observed even in patients with negative cytology. Immunocytochemistry and molecular techniques have been investigated to improve high-risk patients' identification with variable results. The aim of this study was to compare the performance of different laboratory methods applied to peritoneal washing, to improve the cytological identification of malignant cells. METHODS: We prospectively evaluated 21 patients who underwent surgery and peritoneal lavage for gastric cancer. Among them, 18 had negative cytology and three were positive for malignant cells. For each patient, immunohistochemistry with BerEP4 antibody was performed on seriate sections of cellblock preparation at different levels, using the method reported for sentinel nodes in other types of cancer. Paired frozen quotes of washing fluids were evaluated by qRT-PCR with primer for mRNA of Ceacam5. RESULTS: In 4 of 18 patients with previous negative routine cytology, isolated neoplastic cells in seriate sections of the cellblock inclusion have been found. Results showed to be coherent with molecular analysis for CEA mRNA. CONCLUSION: The sensitivity and specificity of peritoneal washing analyses should be notably improved by immunohistochemistry applied to multilevel cellblock sectioning. The method is less expensive and more widely applicable than molecular analysis, in each laboratory setting. This approach allows detection of minimum peritoneal seeding in patients with gastric cancer.
- MeSH
- ascitická tekutina metabolismus patologie MeSH
- GPI-vázané proteiny genetika metabolismus MeSH
- karcinoembryonální antigen genetika metabolismus MeSH
- lidé MeSH
- nádorové biomarkery genetika metabolismus MeSH
- nádory žaludku metabolismus patologie MeSH
- peritoneální výplach metody normy MeSH
- senzitivita a specificita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
denokarcinom jícnu a žaludku je onemocnění s vážnou prognózou. Použitím moderní multimodální léčby bylo u lokálně pokročilého karcinomu dosaženo maxima v mediánu celkového přežití. K dalším pokrokům může dojít stratifikací pacientů k léčbě podle moderních molekulárních prediktorů definovaných například skupinou The Cancer Genome Atlas. Hybridní vyšetření pozitronovou emisní tomografií a výpočetní tomografií je přínosnou metodou v časné identifikaci skupiny pacientů, která nemá prospěch z podávané léčby, a přináší možnost časné modifikace léčebného schématu. Metastazující adenokarcinom distálního jícnu a žaludku je heterogenní onemocnění. V praxi je jediným cíleným lékem s molekulárním prediktorem trastuzumab, v druhé linii je standardní součástí terapie antiangiogenní léčba. Přes slibné výsledky ve studiích fáze I a II ostatní moderní léky, jako jsou multikinázové inhibitory, inhibitory receptoru pro epidermální růstový, receptory pro růstový faktor hepatocytů (MET/HGF) či inhibitory savčího rapamycinového cílového receptoru (mammalian target of rapamycine receptor, mTOR) selhaly. Nové léčebné možnosti zahrnují aktivaci imunitní odpovědi prostřednictvím checkpoint inhibitorů, inhibici signálních drah STAT3 nádorových kmenových buněk, inhibitory PARP (poly-adenozindifosfát-ribózo-polymeráza), protilátky proti matrixové metaloproteináze 9 a protilátku proti claudinu 18.2.
Adenocarcinoma of distal oesophagus and gastric adenocarcinoma still have a poor clinical outcome. In locally advanced adenocarcinoma multimodal treatment has reached maximum of median overall survival. New molecular predictors defined recently by The Cancer Genome Atlas offer an opportunity of patient stratification to optimal treatment approach. PET/CT is a valuable method providing earlier identification of non-responders and enabling a well-timed change of ineffective treatment. Metastatic gastric cancer is very heterogeneous disease. Trastuzumab is the only clinically valid targeted therapy with a known molecular predictor. Antiangiogenic treatment is a standard of care in the second line treatment. Despite promising phase I/II clinical trials results, several phase III studies assessing receptor tyrosine kinase-related signaling pathways such as epidermal growth factor receptor, hepatocyte growth factor receptor (MET/HGF) or mammalian target of rapamycine receptor (mTOR) failed. Novel treatment targets include activation of immune response by PD-1/PD-L1 checkpoint inhibitors, inhibition of cancer stemness-related signaling pathways like STAT3, targeting DNA damage repair, stroma modification by matrix metalloproteinase-9 inhibition and Claudin-18.2, a tight junction protein antibody.
- Klíčová slova
- ramucirumab,
- MeSH
- adenokarcinom farmakoterapie patologie radioterapie MeSH
- adjuvantní chemoterapie MeSH
- antitumorózní látky terapeutické užití MeSH
- chemoradioterapie MeSH
- cílená molekulární terapie MeSH
- gastroezofageální junkce patologie MeSH
- inhibitory angiogeneze terapeutické užití MeSH
- kombinovaná farmakoterapie MeSH
- lidé MeSH
- metastázy nádorů farmakoterapie MeSH
- monoklonální protilátky terapeutické užití MeSH
- nádory jícnu * diagnostické zobrazování patologie terapie MeSH
- nádory žaludku * metabolismus patologie terapie MeSH
- neoadjuvantní terapie MeSH
- PET/CT MeSH
- přežití po terapii bez příznaků nemoci MeSH
- protokoly antitumorózní kombinované chemoterapie terapeutické užití MeSH
- receptor erbB-2 MeSH
- trastuzumab terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
Metastatic gastric cancer is an incurable disease. Systemic chemotherapy prolongs survival, improves symptom control, and helps maintain a better quality of life of patients with metastatic gastric cancer. HER2 testing of the primary tumor and/or the metastases is warranted before initiation of first-line treatment. This review article outlines the indication and clinical data of medical treatment of advanced gastric cancer and highlights aspects of quality of life.
PURPOSE OF REVIEW: The purpose of the review is to delineate novel approaches for biology-based treatment in advanced gastric cancer. We reviewed the latest translational and clinical research articles and congress presentations. RECENT FINDINGS: A new molecular classification of gastric cancer based on histology, genetic and proteomic alterations has evolved. It provides a roadmap for development of new drugs and combinations and for patient stratification. Anti-HER2 treatment, which is an effective strategy in metastatic gastric cancer, is now also being studied in the perioperative setting. However, resistance mechanisms in advanced disease are poorly understood and optimal patient selection remains challenging. Targeting angiogenesis is an emerging concept in the management of advanced gastric cancer, and ramucirumab has prolonged survival in the second line either as a monotherapy or in combination with paclitaxel. Biomarkers for selecting patients who benefit from ramucirumab are still lacking. Immune checkpoint blockade and inhibition of cancer stemness targets are other emerging directions for the medical treatment of gastric cancer. Large-scale international studies are ongoing. SUMMARY: Promising biology-based treatment strategies are evolving. But tumor heterogeneity which is an inherent feature of gastric cancer challenges the development of molecularly targeted and personalized treatment strategies.
- MeSH
- lidé MeSH
- nádory žaludku genetika metabolismus patologie terapie MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Kalcifikujúci fibrózny tumor žalúdka je zriedkavý benígny fibrózny tumor, ktorý vzniká v podkožných alebo hlbokých mäkkých tkanivách u detí a mladých dospelých, avšak možno sa s ním stretnúť aj u starších ľudí, najmä v oblasti pleury alebo peritoneálnej dutiny. Z literatúry sú známe len ojedinelé prípady výskytu v gastrointestinálnom trakte, respektíve v žalúdku. V práci prezentujeme našu skúsenosť s touto neobvyklou léziou objavenou u 68 ročnej ženy. Klinicky bol zistený pendulujúci, submukózne uložený tumor malej kurvatúry žalúdka. Histologicky je kalcifikujúci fibrózny tumor jedinečná lézia, ktorú tvoria denzné hyalinizované kolagénové vlákna, nevýrazné roztrúsené fibroblasty, rôzne množstvo psamomatóznych teliesok alebo dystrofických kalcifikátov a ložiská lymfoplazmocytárnej infiltrácie. Naša práca je zameraná na krátky prehľad a diferenciálnu diagnostiku kalcifikujúceho fibrózneho tumoru a iných známejších alebo naopak nezvyčajných vretenobunkových lézií žalúdka.
The calcifying fibrous tumor is a rare benign fibrous tumor which occurs in subcutaneous or deep soft tissues in children and young adults, but also is frequently seen in pleural and intraabdominal locations in older people. Gastric involvement has been only sporadically reported in the literature. We present here our experience with this unusual lesion discovered in a 68-year-old woman. Clinically, the tumor was described as a pendulating, submucosally located mass, in the body of the stomach on a lesser curvature. The calcifying fibrous tumor is a histologically distinct lesion composed of dense hyalinized collagen fibers, inconspicuous scattered fibroblasts, a varying amount of psammoma bodies or dystrophic calcifications and foci of lymphoplasmacytic infiltration. In this report we will focus on a brief review and differential diagnosis of this tumor and other more common or not widely known gastric spindle cell lesions.
- Klíčová slova
- kalcifikující fibrózní tumor,
- MeSH
- diferenciální diagnóza MeSH
- imunohistochemie MeSH
- kalcinóza * metabolismus patologie MeSH
- lidé MeSH
- nádory z fibrózní tkáně * diagnóza genetika metabolismus patologie MeSH
- nádory žaludku * diagnóza genetika metabolismus patologie MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The regulation and stem cell origin of normal and neoplastic gastric glands are uncertain. Here, we show that Mist1 expression marks quiescent stem cells in the gastric corpus isthmus. Mist1(+) stem cells serve as a cell-of-origin for intestinal-type cancer with the combination of Kras and Apc mutation and for diffuse-type cancer with the loss of E-cadherin. Diffuse-type cancer development is dependent on inflammation mediated by Cxcl12(+) endothelial cells and Cxcr4(+) gastric innate lymphoid cells (ILCs). These cells form the perivascular gastric stem cell niche, and Wnt5a produced from ILCs activates RhoA to inhibit anoikis in the E-cadherin-depleted cells. Targeting Cxcr4, ILCs, or Wnt5a inhibits diffuse-type gastric carcinogenesis, providing targets within the neoplastic gastric stem cell niche.
- MeSH
- anoikis MeSH
- antitumorózní látky farmakologie MeSH
- buněčný rodokmen MeSH
- časové faktory MeSH
- chemokin CXCL12 metabolismus MeSH
- endoteliální buňky metabolismus patologie MeSH
- epitelové buňky účinky léků metabolismus patologie MeSH
- kadheriny metabolismus MeSH
- lidé MeSH
- lymfocyty metabolismus patologie MeSH
- mezibuněčná komunikace MeSH
- myši transgenní MeSH
- myši MeSH
- nádorová transformace buněk genetika metabolismus patologie MeSH
- nádorové buněčné linie MeSH
- nádorové kmenové buňky účinky léků metabolismus patologie MeSH
- nádorové mikroprostředí * MeSH
- nádory žaludku farmakoterapie genetika metabolismus patologie MeSH
- nika kmenových buněk * MeSH
- proteiny Wnt metabolismus MeSH
- receptory CXCR4 metabolismus MeSH
- rho proteiny vázající GTP metabolismus MeSH
- signální dráha Wnt MeSH
- signální transdukce MeSH
- stárnutí buněk MeSH
- transkripční faktory bHLH genetika metabolismus MeSH
- transplantace kostní dřeně MeSH
- žaludeční sliznice účinky léků metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Isolated porcine pepsinogen A was used for the preparation of polyclonal rabbit and polyclonal chicken anti-pepsinogen A antibodies. Immunochemical properties of both immunoglobulin fractions were compared. The rabbit anti-serum was further purified using immobilized porcine pepsinogen A on magnetic cellulose beads and the resulting anti-pepsinogen A fraction proved to be applicable for the separation and the determination of porcine pepsinogen A. In contrary, antibodies prepared from chicken eggs by the same way have been found not suitable for the evaluation of the pepsinogen A level. Unexpectedly, the pre-immune fraction of chicken antibodies showed reactivity against porcine pepsinogen A and the affinity separation of specific polyclonal chicken anti-pepsinogen A antibodies on immobilized porcine pepsinogen A did not result in an enrichment of anti-pepsinogen A antibodies.
- MeSH
- ELISA MeSH
- imunohistochemie MeSH
- králíci MeSH
- kur domácí MeSH
- nádory žaludku imunologie metabolismus MeSH
- pepsinogen A imunologie metabolismus MeSH
- prasata MeSH
- protilátky imunologie MeSH
- skot MeSH
- žaludeční sliznice imunologie metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: The present study assessed whether exhaled breath analysis using Selected Ion Flow Tube Mass Spectrometry could distinguish esophageal and gastric adenocarcinoma from noncancer controls. BACKGROUND: The majority of patients with upper gastrointestinal cancer present with advanced disease, resulting in poor long-term survival rates. Novel methods are needed to diagnose potentially curable upper gastrointestinal malignancies. METHODS: A Profile-3 Selected Ion Flow Tube Mass Spectrometry instrument was used for analysis of volatile organic compounds (VOCs) within exhaled breath samples. All study participants had undergone upper gastrointestinal endoscopy on the day of breath sampling. Receiver operating characteristic analysis and a diagnostic risk prediction model were used to assess the discriminatory accuracy of the identified VOCs. RESULTS: Exhaled breath samples were analyzed from 81 patients with esophageal (N = 48) or gastric adenocarcinoma (N = 33) and 129 controls including Barrett's metaplasia (N = 16), benign upper gastrointestinal diseases (N = 62), or a normal upper gastrointestinal tract (N = 51). Twelve VOCs-pentanoic acid, hexanoic acid, phenol, methyl phenol, ethyl phenol, butanal, pentanal, hexanal, heptanal, octanal, nonanal, and decanal-were present at significantly higher concentrations (P < 0.05) in the cancer groups than in the noncancer controls. The area under the ROC curve using these significant VOCs to discriminate esophageal and gastric adenocarcinoma from those with normal upper gastrointestinal tracts was 0.97 and 0.98, respectively. The area under the ROC curve for the model and validation subsets of the diagnostic prediction model was 0.92 ± 0.01 and 0.87 ± 0.03, respectively. CONCLUSIONS: Distinct exhaled breath VOC profiles can distinguish patients with esophageal and gastric adenocarcinoma from noncancer controls.
- MeSH
- adenokarcinom diagnóza metabolismus MeSH
- dechové testy MeSH
- hmotnostní spektrometrie * MeSH
- hodnocení rizik MeSH
- lidé středního věku MeSH
- lidé MeSH
- metody pro podporu rozhodování MeSH
- nádorové biomarkery metabolismus MeSH
- nádory jícnu diagnóza metabolismus MeSH
- nádory žaludku diagnóza metabolismus MeSH
- ROC křivka MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- těkavé organické sloučeniny metabolismus MeSH
- vydechnutí MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
In the current study, the sensitivity and specificity of methods of HER2 status detection were studied in 55 patients presenting with gastric/gastroesophageal junction carcinoma (30 intestinal and 25 diffuse), in small biopsy (endoscopy; n=33) and resection specimens (n=22). The primary objective of the present study was to compare various methods for the assessment of HER2 status, with regards to the sensitivity and specificity of each method, as well as their concordance. In all cases, the status of HER2 was determined using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), silver in situ hybridization (SISH), and quantitative polymerase chain reaction (qPCR). The concordance rate between IHC and ISH was 100% for IHC 0 and 3+. The concordance rate for IHC 1+ was 100% between IHC and SISH, and 92.9% between IHC and FISH. The concordance rate among different FISH methods was 100%, between FISH and SISH it was 96.2%, and between qPCR and ISH methods it was 88.5%. Thus, the results demonstrate that different in situ hybridization methods are comparable and that none were superior. Furthermore, the IHC and FISH methods were found to be comparable and the concordance rate was particularly good. qPCR analysis correlated well with the other methods and appears to be a possible alternative tool for detection of the HER2 status. However, the concordance rate of qPCR with other methods was identified to be lower in the diffuse carcinoma group of endoscopy biopsy specimens; therefore investigation of further cases is required.
- MeSH
- adenokarcinom diagnóza metabolismus MeSH
- diagnostické techniky molekulární MeSH
- dospělí MeSH
- gastroezofageální junkce patologie MeSH
- hybridizace in situ fluorescenční MeSH
- imunohistochemie MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory žaludku diagnóza metabolismus MeSH
- receptor erbB-2 genetika metabolismus MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
