Concomitant MDS with isolated 5q deletion and MGUS: case report and review of molecular aspects

Patients with monoclonal gammopathy of undetermined significance (MGUS) have a higher risk for the development of concomitant primary cancers such as multiple myeloma (MM) and myelodysplastic syndrome (MDS). We report the case of patient initially suffering from MGUS of the IgG lambda subtype for more than 10 yr, which evolved to MM and MDS with deletion (5q) with severe pancytopenia. Due to pancytopenia, he received dose‐reduced treatment with lenalidomide and dexamethasone. He achieved an ongoing transfusion independency after about 1 month of treatment. Bone marrow taken 14 months after start of treatment showed a complete cytogenetic response of the del(5q) clone and a plasma cell infiltration below 5%. In contrast to the development of MM in MGUS patients, the subsequent occurrence of MDS after diagnosis of MGUS is infrequent. Moreover, the biological association of MDS with MGUS is not sufficiently understood, but the non‐treatment‐related occurrence supports the pathogenetic role of pre‐existing alterations of stem cells. Here, we summarize data on concomitant MDS and MGUS/MM with particular emphasis on molecular aspects.     

Adoptive immunotherapy of metastatic breast cancer: present and future

Breast cancer is a systemic disease with a primarily local component. Besides surgical resection and irradiation of the locoregional tumor setting, central therapeutic aim is the elimination of disseminated micrometastatic tumor cells using cytostatic and/or hormonal treatment. Nevertheless, in the course of time a majority of patients suffer from systemic recurrence in the form of distant metastases. Intriguingly, in this connection, intratumoral cytotoxic T lymphocytes might serve as independent predictors of treatment efficacy and clinical outcome. Loss of immune balance (tumor dormancy) during intensive cross talk between T cells and tumor cells in the bone marrow microenvironment is suggested one reason for distant metastatic relapse. In this clinical context, further supportive therapies become increasingly attractive, taking immunological features of breast cancer cells into special account. The present review aims to dissect bone marrow-derived cellular antitumor immune responses and translational immunologic treatment options regarding their actual relevance to patients’ clinical benefit and their future directions in breast cancer management.     

Micro-Imaging by Interference Microscopy: A Case Study of Orientation-Dependent Guest Diffusion in MFI-Type Zeolite Host Crystals

Because of the small particle size, orientation-dependent diffusion measurements in microporous materials remains a challenging task. We highlight here the potential of micro-imaging by interference microscopy in a case study with MFI-type crystals in which, although with different accuracies, transient concentration profiles in all three directions can be observed. The measurements, which were performed with “rounded-boat” shaped crystals, reproduce the evolution patterns of the guest profiles recorded in previous studies with the more common “coffin-shaped” MFI crystals. The uptake and release patterns through the four principal faces (which in the coffin-shaped crystals extend in the longitudinal direction) are essentially coincident and there is no perceptible mass transfer in the direction of the long axis. The surface resistances of the four crystal faces through which mass transfer occurs are relatively small and have only a minor effect on the mass transfer rate. As a result of the pore structure, diffusion in the crystallographic c direction (which corresponds to the direction of the long axis) is expected to be much slower than in the transverse directions. This could explain the very low rate of mass transfer observed in the direction of the long axis, but it is also possible that the small end faces of the crystal may have high surface resistance. It is not possible to distinguish unequivocally between these two possibilities. All guest molecules studied (methyl-butane, benzene and 4-methyl-2-pentyne) show the same orientation dependence of mass transfer. The long 4-methyl-2-pentyne molecules would be expected to propagate at very different rates through the straight and sinusoidal channels. The coinciding patterns for uptake through the mutually perpendicular crystal faces therefore provide clear evidence that both the coffin shaped crystals and the rounded-boat-shaped crystals considered in this study, must be intergrowths rather than pure single crystals.     

Plant surfaces with cuticular folds and their replicas: Influence of microstructuring and surface chemistry on the attachment of a leaf beetle

Plant surfaces covered either with epicuticular wax crystals or cuticular folds have been shown to strongly reduce the ability of insects to attach to them. However, the relative impact of surface structuring vs. surface chemistry on insect attachment remains unclear. To understand the mechanisms reducing adhesion of insects on plant surfaces in more detail, we performed traction experiments (i) on plant surfaces covered with cuticular folds of different dimensions, and on their (ii) untreated and (iii) hydrophobized replicas. As a reference, measurements were performed on replicas of smooth plant surfaces and of glass. Traction forces were measured with a highly sensitive force transducer, using tethered male Colorado potato beetles (Leptinotarsa decemlineata) as a model insect species. Contact angle measurements with water and diiodomethane were also performed to examine the physicochemical properties of the test surfaces. We found that surface structuring has a strong influence on the magnitude of the attachment force. In contrast, under the chosen experimental conditions, surface chemistry had no significant influence. Our results indicate that attachment of the beetles is reduced solely by the dimensions of the folds, with cuticular folds of about 0.5 μm in both height and width being the most effective. Contrary to the attachment of beetles, the wettability of the surfaces was considerably influenced by both surface structuring and chemistry. These results contribute to a better understanding of plant–insect interactions and the function of microstructured surfaces, and may facilitate the development of biomimetic anti-adhesive surfaces.     

Immunological Deficiency Associated With Cigarette Smoke Inhalation by Mice

Inhalation of cigarette whole smoke (CWS) or its vapor phase (CVP) significantly impaired immune response capability in mice. Significant immunosuppressive effects on the humoral antibody response to a single antigenic stimulus were evident in animals exposed to smoke for seven days before or two days after administration of antigen. Impairment of the immunological response capability appeared to be temporary, with recovery about 14 days after exposure. Different lengths of exposure prior to antigenic stimulation neither produced an additive impairment of the immunological response nor rendered the experimental animals more tolerant to CWS or CVP. The immunological deficiency was specific to CWS and CVP inhalation rather than to nonspecific debilitating stress factors. The inductive phase was the period of the primary and secondary immune response most sensitive to impairment by exposure to CWS or CVP.