From Tumor Immunology to Immunotherapy in Gastric and Esophageal Cancer

Esophageal and gastric cancers represent tumors with poor prognosis. Unfortunately, radiotherapy, chemotherapy, and targeted therapy have made only limited progress in recent years in improving the generally disappointing outcome. Immunotherapy with checkpoint inhibitors is a novel treatment approach that quickly entered clinical practice in malignant melanoma and renal cell cancer, but the role in esophageal and gastric cancer is still poorly defined. The principal prognostic/predictive biomarkers for immunotherapy efficacy currently considered are PD-L1 expression along with defects in mismatch repair genes resulting in microsatellite instability (MSI-H) phenotype. The new molecular classification of gastric cancer also takes these factors into consideration. Available reports regarding PD-1, PD-L1, PD-L2 expression and MSI status in gastric and esophageal cancer are reviewed to summarize the clinical prognostic and predictive role together with potential clinical implications. The most important recently published clinical trials evaluating checkpoint inhibitor efficacy in these tumors are also summarized

ABC Transporters and Their Role in the Neoadjuvant Treatment of Esophageal Cancer

The prognosis of esophageal cancer (EC) is poor, despite considerable effort of both experimental scientists and clinicians. The tri-modality treatment consisting of neoadjuvant chemoradiation followed by surgery has remained the gold standard over decades, unfortunately, without significant progress in recent years. Suitable prognostic factors indicating which patients will benefit from this tri-modality treatment are missing. Some patients rapidly progress on the neoadjuvant chemoradiotherapy, which is thus useless and sometimes even harmful. At the same time, other patients achieve complete remission on neoadjuvant chemoradiotherapy and subsequent surgery may increase their risk of morbidity and mortality. The prognosis of patients ranges from excellent to extremely poor. Considering these differences, the role of drug metabolizing enzymes and transporters, among other factors, in the EC response to chemotherapy may be more important compared, for example, with pancreatic cancer where all patients progress on chemotherapy regardless of the treatment or disease stage. This review surveys published literature describing the potential role of ATP-binding cassette transporters, the genetic polymorphisms, epigenetic regulations, and phenotypic changes in the prognosis and therapy of EC. The review provides knowledge base for further research of potential predictive biomarkers that will allow the stratification of patients into defined groups for optimal therapeutic outcome

Prognostic influence of internal mammary node drainage in patients with early-stage breast cancer

Background: The management of internal mammary nodes (IMNs) during multidisciplinary treatment of breast cancer has been debated for the last four decades without unequivocal conclusion. Patients and Methods: We retrospectively reviewed patients with breast cancer who underwent sentinel lymph node biopsy at our center from 2008 until 2012. IMN drainage was assessed as a potential risk factor for local and distant disease recurrence. Results: We identified 712 patients, with incidence of drainage to IMNs of 18.4%. No detrimental effect of the pattern of drainage to IMNs was found after a median follow-up of 58 months. A similar outcome was observed when drainage to IMNs was evaluated as a risk factor for patient survival. The potential risk factors for drainage to IMNs during sentinel lymph node biopsy were younger age (p=0.002) and tumor location in lower-outer, lower-inner, and upper-inner versus upper-outer quadrant (p<0.0001). Conclusion: The drainage to IMNs is unlikely to have a detrimental effect on patient outcome.[LO1304

HILIC / ESI-MS stanovení gangliosidů a dalších tříd polárních lipidů v karcinomu ledvinových buněk a v normální tkáni.

Negative-ion hydrophilic liquid chromatography-electrospray ionization mass spectrometry (HILIC/ESI-MS) method has been optimized for the quantitative analysis of ganglioside (GM3) and other polar lipid classes, such as sulfohexosylceramides (SulfoHexCer), sulfodihexosylceramides (SulfoHex2Cer), phosphatidylglycerols (PG), phosphatidylinositols (PI), lysophosphatidylinositols (LPI), and phosphatidylserines (PS). The method is fully validated for the quantitation of the studied lipids in kidney normal and tumor tissues of renal cell carcinoma (RCC) patients based on the lipid class separation and the coelution of lipid class internal standard with the species from the same lipid class. The raw data are semi-automatically processed using our software LipidQuant and statistically evaluated using multivariate data analysis (MDA) methods, which allows the complete differentiation of both groups with 100% specificity and sensitivity. In total, 21 GM3, 28 SulfoHexCer, 26 SulfoHex2Cer, 10 PG, 19 PI, 4 LPI, and 7 PS are determined in the aqueous phase of lipidomic extracts from kidney tumor tissue samples and surrounding normal tissue samples of 20 RCC patients. S-plots allow the identification of most upregulated (PI 40:5, PI 40:4, GM3 34:1, and GM3 42:2) and most downregulated (PI 32:0, PI 34:0, PS 36:4, and LPI 16:0) lipids, which are primarily responsible for the differentiation of tumor and normal groups. Another confirmation of most dysregulated lipids is performed by the calculation of fold changes together with T and p values to highlight their statistical significance. The comparison of HILIC/ESI-MS data and matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) data confirms that lipid dysregulation patterns are similar for both methods.Pro kvantitativní analýzu gangliosidu (GM3) a dalších tříd polárních lipidů, jako jsou sulfohexosylceramidy (SulfoHexCer), sulfodihexosylceramidy (SulfoHex2Cer), fosfatidylglyceroly, byla optimalizována metoda hydrofilní interakční kapalinová chromatografie s detekcí pomocí hmotnostní spekrometrie a ionizací elektrosprejem (HILIC / ESI-MS). Metoda byla optimalizována pro kvantitativní analýzu (PG), fosfatidylinositoly (PI), lysofosfatidylinositoly (LPI) a fosfatidylseriny (PS). Metoda je plně validována pro kvantifikaci studovaných lipidů v ledvinové zdravé tkáni a nádorové tkáni pacientů s karcinomem ledvinných buněk (RCC) na základě separace tříd lipidů a koeluce vnitřního standardu se stejnou třídou lipidů. Surová data byla poloautomaticky zpracovány pomocí našeho softwaru LipidQuant a statisticky vyhodnocována metodami multivariační analýzy dat (MDA). Celkem bylo ve vodné fázi lipidomických extraktů tkání ledvinových nádorů a zdravé tkání stanoveno 21 GM3, 28 SulfoHexCer, 26 SulfoHex2Cer, 10 PG, 19 PI, 4 LPI a 7 PS. S-plot grafy umožňují identifikaci nejvíce upregulovaných (PI 40: 5, PI 40: 4, GM3 34: 1 a GM3 42: 2) a nejvíce downregulated (PI 32: 0, PI 34: a LPI 16: 0), které jsou primárně odpovědné za diferenciaci nádorových a normálních skupin. Další potvrzení většiny dysregulovaných lipidů se provádí výpočtem hodnot T a p pro určení jejich statistické významnosti. Srovnání údajů z HILIC / ESI-MS a matricové laserové desorpce (MALDI-MSI) potvrzuje, že modely lipidové regulace jsou podobné u obou metod