IntroductionHodgkin lymphoma (HL) is characterized by a minority of neoplastic cells, the Hodgkin and Reed-Sternberg cells (HRS cells), and an extensive inflammatory background. Many studies have documented that HL is associated with disturbed cytokine production. 1 Cytokine and chemokine production may not only promote growth of HRS cells and help to evade immune surveillance, but also cause the characteristic histology and the clinical symptoms of HL. 2 Cross-talk between HRS cells and surrounding lymphocytes has been studied for many years, and this interaction is regarded to be important for the pathogenesis of HL.The application of proteomics techniques has been proven to be a powerful tool for the identification of new biomarkers involved in pathogenesis of many diseases (reviewed by Hanash 3 ). Some studies on hematologic malignancies using proteomics approaches have been reported, 4,5 but application of proteomics technology to HL is still limited. Fujii et al compared HL cell line proteome to anaplastic large cell lymphoma (ALCL) and non-Hodgkin lymphoma (NHL) using a 2-dimensional difference gel electrophoresis approach of total cell lysates. 6,7 HL expressed higher levels of pyridoxine-5Ј-phosphate oxidase, vinculin, dihydropyrimidinase-related protein-2 and NADHubiquinone oxidoreductase compared with ALCL. In comparison to NHL cell lines, HL cell lines showed higher expression of pyridoxine-5Ј-phosphate oxidase, ␥-enolase, vinculin, vimentin, galectin-1, annexin A5, and protein kinase C substrate. 7 Carvalho et al identified changes in the spectrum using quadrupole-time-of-flight hybrid mass spectrometer in serum of HL patients compared with normal controls, but no further protein identification was performed. 8 Overall, only very limited proteomics data are available for HL.To gain more insight into the proteins secreted by HRS cells that might be involved in the cross-talk with infiltrating lymphocytes or might serve as tumor biomarkers, the secretome of HL cell lines was determined in cell culture supernatant. Protein identification was performed by nanoscale reversed-phase liquid chromatography tandem mass spectrometry (LC-MS/MS) after 1D-SDS-PAGE fractionation. Proteins related to immune response were validated in cell culture supernatant and patient plasma by enzyme-linked immunosorbent assay (ELISA) and in tumor tissues by immunohistochemistry. Methods Cell lines and cultureThe HL cell lines L1236 and KMH2 were established from HL patients with mixed cellularity subtype, L428 from nodular sclerosis subtype and DEV from nodular lymphocyte predominant HL (NLPHL) subtype. They were cultured in RPMI 1640 medium (Lonza Walkersville, Walkersville, MD) supplemented with fetal calf serum (Lonza Walkersville). For analysis of secreted proteins, to avoid the masking effects of high-abundance serum proteins in the culture medium, the cells were washed 3 times with RPMI 1640 medium to deplete all serum proteins, and cultured in RPMI 1640 medium without serum for 24 hours. Under these conditions, cell via...

Little is known about the gene expression profile and significance of the rosetting CD4 þ CD26À T cells in classical Hodgkin's lymphoma (cHL). To characterize these T cells, CD4 þ CD26À and CD4 þ CD26 þ T-cell populations were sorted from lymph node (LN) cell suspensions from nodular sclerosis HL (NSHL) and reactive LNs. mRNA profiles of stimulated and resting cell subsets were evaluated with quantitative RT-PCR for 46 genes. We observed a higher percentage of CD4 þ CD26À T cells in NSHL than in reactive LNs. The resting CD4 þ CD26À T cells in NSHL showed higher mRNA levels of CD25, CTLA4, OX40 and CCR4 compared with in LNs, supporting a regulatory T-cell (Treg) type, and this was validated by immunohistochemistry. Moreover, these cells showed low or no expression of the Th1-or Th2-related cytokines IL-2, IFN-g, IL-13, IL-12B, IL-4, and IL-5, and the chemoattractant receptor CRTH2. Besides Tregs, Th17 cells may exist in NSHL based on the significantly higher IL-17 mRNA level for both T-cell populations in NSHL. Upon stimulation in vitro, lack of upregulation of mRNA levels of most cytokine genes indicated an anergic character for the CD4 þ CD26À T-cell subset. Anergy fits with the Treg profile of these cells, probably explaining the immunosuppressive mechanism involved in NSHL.

Ovarian cancer has the highest mortality of all of the gynecological malignancies. There are several distinct histotypes of this malignancy characterized by specific molecular events and clinical behavior. These histotypes have differing responses to platinum-based drugs that have been the mainstay of therapy for ovarian cancer for decades. For histotypes that initially respond to a chemotherapeutic regime of carboplatin and paclitaxel such as high-grade serous ovarian cancer, the development of chemoresistance is common and underpins incurable disease. Recent discoveries have led to the clinical use of PARP (poly ADP ribose polymerase) inhibitors for ovarian cancers defective in homologous recombination repair, as well as the anti-angiogenic bevacizumab. While predictive molecular testing involving identification of a genomic scar and/or the presence of germline or somatic BRCA1 or BRCA2 mutation are in clinical use to inform the likely success of a PARP inhibitor, no similar tests are available to identify women likely to respond to bevacizumab. Functional tests to predict patient response to any drug are, in fact, essentially absent from clinical care. New drugs are needed to treat ovarian cancer. In this review, we discuss applications to address the currently unmet need of developing physiologically relevant in vitro and ex vivo models of ovarian cancer for fundamental discovery science, and personalized medicine approaches. Traditional two-dimensional (2D) in vitro cell culture of ovarian cancer lacks critical cell-to-cell interactions afforded by culture in three-dimensions. Additionally, modelling interactions with the tumor microenvironment, including the surface of organs in the peritoneal cavity that support metastatic growth of ovarian cancer, will improve the power of these models. Being able to reliably grow primary tumoroid cultures of ovarian cancer will improve the ability to recapitulate tumor heterogeneity. Three-dimensional (3D) modelling systems, from cell lines to organoid or tumoroid cultures, represent enhanced starting points from which improved translational outcomes for women with ovarian cancer will emerge.

As an ancient Gram-negative bacterium, <i>Helicobacter pylori</i> has settled in human stomach. Eradicating <i>H. pylori</i> increases the morbidities of asthma and other allergic diseases. Therefore, <i>H. pylori</i> might play a protective role against asthma. The “disappearing microbiota” hypothesis suggests that the absence of certain types of the ancestral microbiota could change the development of immunology, metabolism, and cognitive ability in our early life, contributing to the development of some diseases. And the Hygiene Hypothesis links early environmental and microbial exposure to the prevalence of atopic allergies and asthma. Exposure to the environment and microbes can influence the growing immune system and protect subsequent immune-mediated diseases. <i>H. pylori</i> can inhibit allergic asthma by regulating the ratio of helper T cells 1/2 (Th1/Th2), Th17/regulatory T cells (Tregs), etc. <i>H. pylori</i> can also target dendritic cells to promote immune tolerance and enhance the protective effect on allergic asthma, and this effect relies on highly suppressed Tregs. The remote regulation of lung immune function by <i>H. pylori</i> is consistent with the gut-lung axis theory. Perhaps, <i>H. pylori</i> also protects against asthma by altering levels of stomach hormones, affecting the autonomic nervous system and lowering the expression of heat shock protein 70. Therapeutic products from <i>H. pylori</i> may be used to prevent and treat asthma. This paper reviews the possible protective influence of <i>H. pylori</i> on allergic asthma and the possible application of <i>H. pylori</i> in treating asthma.