T cell–tumor cell: a fatal interaction?

Fas (Apo-1/CD95) is a cell-surface protein that is responsible for initiating a cascade of proteases (caspases) culminating in apoptotic cell death in a variety of cell types. The function of the Fas/FasL system in the dampening of immune responses to infectious agents through the autocrine deletion of activated T cells has been well documented. More recently, it has been proposed that tumor cells express FasL, presumably to avoid immune detection. In this review, we focus on the role of the interaction of Fas and FasL in the modulation of antitumor responses. We critically examine the evidence that FasL is expressed by tumor cells and explore alternative explanations for the observed phenomena in vitro and in vivo. By reviewing data that we have generated in our laboratory as well as reports from the literature, we will argue that the Fas/FasL system is a generalized mechanism used in an autocrine fashion to regulate cell survival and expansion in response to environmental and cellular cues. We propose that FasL expression by tumor cells, when present, is indicative of a perturbed balance in the control of proliferation while “immune privilege” is established by “suicide” of activated antitumor T cells, a form of activation-induced cell death. Received: 5 May 1998 / Accepted: 20 May 1998     

Is GIP a glucagon cell constituent?

"Gastric inhibitory peptide" or "glucose-dependent insulin-releasing peptide" (GIP) is a member of the gut hormone family. Its physiological action is thought to be related to its insulinotrophic effect. The occurrence and distribution of GIP was studied by immunohistochemistry. In all species examined including man, GIP immunoreactivity was found to reside in the glucagon cells of the pancrease and gut. Three pancreatic glucagonomas were found to contain numerous cells displaying GIP and glucagon immunoreactivity. The GIP antiserum used did not cross react with either pancreatic-type or gut-type glucagon (GLI).     

Is GIP a glucagon cell constituent?

Summary Gastric inhibitory peptide or glucose-dependent insulin-releasing peptide (GIP) is a member of the gut hormone family. Its physiological action is thought to be related to its insulinotrophic effect.The occurrence and distribution of GIP was studied by immunohistochemistry. In all species examined including man, GIP immunoreactivity was found to reside in the glucagon cells of the pancreas and gut. Three pancreatic glucagonomas were found to contain numerous cells displaying GIP and glucagon immunoreactivity.The GIP antiserum used did not cross react with either pancreatic-type or gut-type glucagon (GLI).     

What Is (Not) a Baboon?

The term “baboon” is the common name used for a subset of terrestrial Cercopithecines with large bodies and protruding snouts. Although the application of the term has changed considerably over the years, we argue that common names, such as “baboon,” should reflect the current state of phylogenetic knowledge. This practice promotes a broader understanding of taxonomic diversity that can impact decisions related to ecotourism, wildlife management, and conservation. Thus, we argue that “baboon” should be used only for members of the genus Papio.     

Is there a “dopaminergic glial cell”?

Intracellular cAMP increased 9-fold in cerebral hemisphere primary cultures after incubation with dopamine (10^–4M). The effect was dose- and time-dependent (10^–6 M-10^–4M; 2–10 minutes). It was mimicked, to some extent, by the partial agonist apomorphine (10^–5 M-10^–4 M) and antagonized by fluphenazine (10^–5 M-10^–4 M). The elevation of cAMP caused by dopamine was incompletely antagonized by propanolol (10^–5 M-10^–4 M), obviating an interaction with -adrenergic receptors. A -adrenergic effect was antagonized by propranolol but only slightly by fluphenazine. The effect of dopamine on cAMP-level was more pronounced in a subpopulation of the hemisphere culture, i.e. in astroglial cultures from the striatum, 12-fold compared with controls at 10^–4 M. No dopamine stimulated formation of cAMP was found in primary cultures from brain-stem. The results demonstrated some heterogeneity among astroglial cells. The cultures used contained mainly astroglial-like cells, as judged from immnohistochemical localization mainly astroglial-like cells, as judged from immunohistochemical localization of the glial specific proteins S 100 and GFA (-albumin). No mature neurons or oligodendroglial cells have so far been demonstrated in the cultures.     

Is there a tripeptidyl peptidase in the renal brush-border membrane?

A recent claim that the renal brush border contains a tripeptidyl peptidase [Andersen & McDonald (1987) Am. J. Physiol. 253, F649-F655] was examined. In a fluorescent assay, the hydrolysis of Gly-Pro-Met-2-naphthylamide (-NH-Nap) and Gly-Pro-Leu-NH-Nap by pig kidney microvilli was strongly inhibited by amastatin or di-isopropyl phosphorofluoridate (inhibitors of aminopeptidases and dipeptidyl peptidase IV). The products formed were shown to be Gly-Pro and Met-NH-Nap (or Leu-NH-Nap) and free 2-naphthylamine. Specific antibodies to pig and rat aminopeptidase N abolished the apparent tripeptidyl peptidase activity. We conclude that these substrates are hydrolysed by the sequential attack of dipeptidyl peptidase IV and aminopeptidase N and that pig and rat brush borders lack a detectable tripeptidyl peptidase.     

EGFR gene amplification in glioblastomas. Is there a relationship with morphology of tumor cell nuclei and proliferative activity?

OBJECTIVE: To confirm a relationship between histomorphology of glioblastomas and amplification of the gene for the epidermal growth factor receptor (EGFR) as the most important molecular biologic alteration in these tumors. STUDY DESIGN: In paraffin sections of surgical specimens from 71 primary resected glioblastomas, tumor cell nuclei in the region with the highest proliferative activity (Ki-67 immunostaining) were investigated morphometrically. Shape variables (roundness factor, Fourier amplitudes) and nuclear area were measured. Additionally, the numerical density of Ki-67-positive tumor cell nuclei was estimated. Differential polymerase chain reaction (PCR) was performed from paraffin sections of the same tumor area. The signals for the EGFR gene and IFN gamma reference gene were quantified densitometrically. RESULTS: Cases with distinct EGFR gene amplification (EGFR/IFN ratios > 5) revealed significantly lower mean values for several Fourier amplitudes, indicating a more regular nuclear shape when compared with cases without evidence of EGFR gene amplification (EGFR/IFN-ratios < or = 1). The Ki-67 index and nuclear area showed no significant differences between these groups. Although a large variation in nuclear morphology was observed for cases without evidence of EGFR gene amplification, discriminant analysis based on morphometric variables provided a good separation of these cases from cases with distinct EGFR gene amplification, with a high percentage of statistically correct reclassified cases. CONCLUSION: Our results provide evidence of a relationship between genetic alterations and histomorphology of glioblastomas.     

Wilms' tumor 1 (WT1) gene in hematopoiesis: a surrogate marker of cell proliferation as a possible mechanism of action?

BACKGROUND: Wilms' tumor 1 (WT1) gene expression is seen in a significant number of cases of human neoplasia; however, the mechanism of action remains to be clarified. We hypothesized that WT1 gene is a surrogate marker of proliferation in normal hematopoietic cells and leukemias. While we and others have recognized its value as a tool for the detection of minimal residual disease (MRD), the objective of this study was to confirm our hypothesis regarding normal. METHODS: Samples from healthy donors (n=16) and UC blood (n=9) were cultured in Methocult for 21 days. Colonies were analyzed on days 7, 14 and 21 by RT-PCR for WT1 gene expression. Our positive controls were samples from patients with leukemia (n=91). Negative controls were from normal volunteers without stimulation (n=26). RESULTS: Results showed a statistically significant difference (P<0.0001) between cultured groups, with the highest level of WT1 gene expression in the positive controls and on day 14, when cells are at their maximal proliferation. DISCUSSION: In conclusion, WT1 gene expression in the proliferating colonies was highest on day 14, although less than in leukemia samples, confirming our hypothesis that WT1 gene is a surrogate marker of proliferation, not only in leukemogenesis but also, to a lesser degree, in normal cell proliferation.     

Is Mythimna turca (Lepidoptera: Noctuidae) a migrant?

The double line moth, Mythimna turca (Linnaeus, 1761) (Lepidoptera: Noctuidae), is an important widely distributed insect species. Studies on the moth in European countries have focused on population monitoring and in China on taxonomy of Mythimna and distribution surveys of M. turca. However, whether M. turca is a migratory insect is unknown. Here, migration of the moth population was monitored using a searchlight trap from 2004 to 2020 on Beihuang island, Northern China, providing direct evidence that M. turca migrates across the Bohai Strait seasonally, in late May to early September. Population dynamics, ovarian development, wind direction and possible migration trajectories were also analyzed. Most moths migrated in June and at the end of August and the beginning of September, and a few migrated in May, July and October. The average duration of this windborne migratory period of M. turca was 93 d. Migratory trajectories demonstrated that M. turca mainly moved northward in spells of southerly winds from June to August and moved southward in spells of northerly winds during September. This new key information about the ecology of M. turca population will aid the formulation of M. turca management strategies.     

Dendritic cell–tumor cell hybrids and immunotherapy: what's next?

Dendritic cells (DC) are professional antigen-presenting cells currently being used as a cellular adjuvant in cancer immunotherapy strategies. Unfortunately, DC-based vaccines have not demonstrated spectacular clinical results. DC loading with tumor antigens and DC differentiation and activation still require optimization. An alternative technique for providing antigens to DC consists of the direct fusion of dendritic cells with tumor cells. These resulting hybrid cells may express both major histocompatibility complex (MHC) class I and II molecules associated with tumor antigens and the appropriate co-stimulatory molecules required for T-cell activation. Initially tested in animal models, this approach has now been evaluated in clinical trials, although with limited success. We summarize and discuss the results from the animal studies and first clinical trials. We also present a new approach to inducing hybrid formation by expression of viral fusogenic membrane glycoproteins.     

Is the mammalian cell plasma membrane a barrier to oxygen transport?

Oxygen transport in the Chinese hamster ovary (CHO) plasma membrane has been studied by observing the collision of molecular oxygen with nitroxide radical spin labels placed in the lipid bilayer portion of the membrane at various distances from the membrane surface using the long-pulse saturation-recovery electron spin resonance (ESR) technique. The collision rate was estimated for 5-, 12-, and 16-doxylstearic acids from spin-lattice relaxation times (T1) measured in the presence and absence of molecular oxygen. Profiles of the local oxygen transport parameters across the membrane were obtained showing that the oxygen diffusion-concentration product is lower than in water for all locations at 37 degrees C. From oxygen transport parameter profiles, the membrane oxygen permeability coefficients were estimated according to the procedure developed earlier by Subczynski et al. (Subczynski, W. K., J. S. Hyde, and A. Kusumi. 1989. Proceedings of the National Academy of Sciences, USA. 86:4474-4478). At 37 degrees C, the oxygen permeability coefficient for the plasma membrane was found to be 42 cm/s, about two times lower than for a water layer of the same thickness as the membrane. The oxygen concentration difference across the CHO plasma membrane at physiological conditions is in the nanomolar range. It is concluded that oxygen permeation across the cell plasma membrane cannot be a rate-limiting step for cellular respiration. Correlations of the form PM = cKs between membrane permeabilities PM of small nonelectrolyte solutes of mol wt less than 50, including oxygen, and their partition coefficients K into hexadecane and olive oil are reported. Hexadecane: c = 26 cm/s, s = 0.95; olive oil: c = 23 cm/s, s = 1.56. These values of c and s differ from those reported in the literature for solutes of 50 less than mol wt less than 300 (Walter, A., and J. Gutknecht. 1986. Journal of Membrane Biology. 90:207-217). It is concluded that oxygen permeability through membranes can be reliably predicted from measurement of partition coefficients.     

Is laminin-1 a guidance cue for cerebellar granule cell migration?

Laminin-1 is a glycoprotein found in the basement membrane of many tissues. In the cerebellum of rodents, it has also been localized along Bergmann glial fibers, where it is thought to be involved in promoting granule cell migration by enhancing adhesion and neurite outgrowth along these fibers. Recent reports, however, indicate that laminin-1 is not present on Bergmann fibers, but instead is associated with blood vessels and meninges. Furthermore, attempts to block granule cell migration using antibodies against laminin-1 have yielded conflicting results. In this report, we provide further evidence that laminin-1 is associated exclusively with blood vessels and meninges in the cerebellum of postnatal rats. In addition, we show that adhesion and neurite outgrowth of granule cells was impeded on laminin-coated surfaces. In fact, cerebellar cells dramatically and consistently avoided laminin-1 regions of patterned surfaces. Cells did adhere to laminin regions if it was coadsorbed with polylysine or tested in serum-containing medium. Avoidance of laminin-1 regions in culture was not, however, blocked by pretreatment with laminin-1 antibodies. By comparison, mouse neuroblastoma cells adhered preferentially to laminin-1 regions in serum-free medium, a response which was blocked by laminin-1 antibodies. These results indicate that laminin-1 is not involved in granule cell migration along Bergmann glial fibers. Instead, they suggest that laminin-1 may function as a repulsive guidance cue preventing granule cells from following inappropriate pathways during development. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 72–84, 1997     

Is parainfluenza virus a threatening virus for human cancer cell lines?

Immortalized cell lines, such as human cancer cell lines, are an indispensable experimental resource for many types of biological and medical research. However, unless the cell line has been authenticated prior to use, interpretation of experimental results may be problematic. The potential problems this may cause are illustrated by studies in which authentication of cell lines has not been carried out. For example, immortalized cell lines may unknowingly be infected with viruses that alter their characteristics. In fact, parainfluenza virus type 5 (PIV5) poses a threat to the use of immortalized cell lines in biological and medical research; PIV5 infection significantly alters cellular physiology associated with the response to interferon. If PIV5 infection is widespread in immortalized cell lines, then a very large number of published studies might have to be re-evaluated. Fortunately, analyses of a large number of immortalized cell lines indicate that PIV5 infection is not widespread.     

Is cell motility a plasmid-encoded function in the cyanobacterium Synechocystis 6803?

Abstract The unicellular facultatively heterotrophic cyanobacterium Synechocystis 6803 harbors 4 plasmids, pSY1–4, of 2.5, 5.2, 50 and 100 kb, respectively. We observed that the loss of the pSY2 plasmid and that of cell motility occurs at a high frequency. However, we showed that there is no direct correlation between these two phenomena, and that cell motility does not require a pSY2-encoded function. In addition, restriction analysis and hybridization experiments showed that pSY1 and pSY2 share no homologous DNA sequences.     

Is there a pAkt between VEGF and oral cancer cell migration?

The PI3K-Akt signalling pathway is a well-established driver of cancer progression. One key process promoted by Akt phosphorylation is tumour cell motility; however the mechanism of VEGF-induced Akt phosphorylation leading to motility remains poorly understood. Previously, we have shown that Akt phosphorylation induced by different factors causes both stimulation and inhibition of motility in different cell types. However, differential phosphorylation of Akt at T308 and S473 residues by VEGF and its role in head and neck cancer cell motility and progression is unknown. The cell lines investigated in this study exhibited a change in phosphorylation of Akt in response to VEGF. However, in terms of motility, VEGF stimulated oral cancer and its associated cell lines, but not normal keratinocytes or oral mucosal fibroblasts. The addition of a PI3 kinase and mTOR inhibitor, inhibited the phosphorylation of Akt and also effectively blocked VEGF-induced oral cancer cell motility, whereas only the PI3 kinase inhibitor blocked oral cancer associated fibroblast cell motility. This study therefore discloses that two different mechanisms of Akt phosphorylation control the motility potential of different cell lines. Akt phosphorylated at both residues controls oral cancer cell motility. Furthermore, immunohistochemical analysis of VEGF positive human head and neck tumour tissues showed a significant increase in Akt phosphorylation at the T308 residue, suggesting that pAkt T308 may be associated with tumour progression in vivo.     

The cell cycle and pluripotency: Is there a direct link?

Comment on: Edel MJ, et al. Genes Dev. 2010; 24:561-73.