NK Cells Stimulate Recruitment of cDC1 into the Tumor Microenvironment Promoting Cancer Immune Control

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Semi-quantitative analysis of soft-tissue reactions in fine needle aspirates from tissue cysticercosis

Fine needle aspiration cytology (FNA) has a well-documented role in the diagnosis of cysticercosis. However, little is discussed about the associated inflammatory response in the host tissues. Aspirates from 182 cases of subcutaneous cysticercosis were semiquantitated for the type and degree of inflammatory response, and the amount and preservation of the parasite. Tissue sections were reviewed where available. In the FNA where no parasite was observed but a confirmatory tissue diagnosis was available, it was found that eosinophils (52%), epithelioid cell granulomas (30%), palisading histiocytes (33%) and giant cells (28%) were seen less frequently than in those where larval fragments were identified in the aspirated material in varying quantities, the response being 88-92% eosinophils, 50-70% palisading histiocytes, 68-80% epithelioid cell granulomas and 46-74% giant cells. Repair cells were maximally seen when readily identifiable larval fragments were seen in the aspirate. Bizarre cells were equally distributed in these aspirates. The tissue response in FNA from subcutaneous cysticercosis can be varied and eosinophils are found to increase with the presence of the degenerating parasite. In soft-tissue aspirates, palisading histiocytes with epithelioid cell granulomas with or without giant cells and an inflammatory exudate with predominantly eosinophils alerts one to search diligently for a parasite.     

Extrinsic factors can mediate resistance to BRAF inhibition in central nervous system melanoma metastases

Here, we retrospectively review imaging of 68 consecutive unselected patients with BRAF V600‐mutant metastatic melanoma for organ‐specific response and progression on vemurafenib. Complete or partial responses were less often seen in the central nervous system (CNS) (36%) and bone (16%) compared to lung (89%), subcutaneous (83%), spleen (71%), liver (85%) and lymph nodes/soft tissue (83%), P < 0.001. CNS was also the most common site of progression. Based on this, we tested in vitro the efficacy of the BRAF inhibitors PLX4720 and dabrafenib in the presence of cerebrospinal fluid (CSF). Exogenous CSF dramatically reduced cell death in response to both BRAF inhibitors. Effective cell killing was restored by co‐administration of a PI‐3 kinase inhibitor. We conclude that the efficacy of vemurafenib is variable in different organs with CNS being particularly prone to resistance. Extrinsic factors, such as ERK‐ and PI3K‐activating factors in CSF, may mediate BRAF inhibitor resistance in the CNS.     

Melanoma invasion – current knowledge and future directions

The acquisition of invasive behaviour is the key transition in the progression of benign melanocyte hyperplasia to life threatening melanoma. Understanding this transition and the mechanisms of invasion are the key to understanding why malignant melanoma is such a devastating disease and will aid treatment strategies. Underlying the invasive behaviour is increased cell motility caused by changes in cytoskeletal organization and altered contacts with the extra‐cellular matrix (ECM). In addition, changes in the interactions of melanoma cells with keratinocytes and fibroblasts enable them to survive and proliferate outside their normal epidermal location. Proteomic and genomic initiatives are greatly increasing our knowledge of which gene products are deregulated in invasive and metastatic melanoma; however, the next challenge is to understand how these genes promote the invasion of melanoma cells. In recent years new models have been developed that more closely recapitulate the conditions of melanoma invasion in vivo. It is hoped that these models will give us a better understanding of how the genes implicated in melanoma progression affect the motility of melanoma cells and their interactions with the ECM, stromal cells and blood vessels. This review will summarise our current understanding of melanoma invasion and focus on the new model systems that can be used to study melanoma.     

Cytological and histochemical observations on the cortical zone of oocytes of a teleost fish, Nandus nandus (Ham)

The cortical zone of oocyte of Nandus nandus has been studied by cytological and histochemical techniques. In an early stage of oocyte development some granular substances appear in the juxtanuclear region which during oocyte growth move to the peripheral ooplasm and forms a thick cortical granular layer. Cytochemically, this cortical granular layer consists of proteins and carbohydrates along with RNA positive material, lipids, mitochondria and Golgi bodies. This cortical granular layer, later on, converts into the cortical vacuolar layer and ultimately forms the cortical alveolar structures in the vitellogenic oocyte of Nandus nandus. The results suggest that the cortical zone plays an important role in the storage of substances transported from the follicular epithelium to the oocyte. Further, the cortical granular substances which are rich in proteins, carbohydrates and lipoidal material, also help in the formation of jelly layers of the developing oocytes.     

Genesis and systematization of cardiovascular anomalies and analysis of skeletal malformations in murine trisomy 16 and 19

Summary On account of genetic homologies, trisomy 16 in the mouse is generally regarded as a direct animal model of Down's syndrome. Mouse trisomy 19, on the other hand, can be seen as a general model of human trisomies. A detailed evaluation of the cardiovascular system and skeleton in 109 fetuses with trisomy 16 and 422 balanced siblings was carried out in order to systematize the cardiovascular anomalies and the pathogenetic mechanisms responsible for their formation according to (1) general retardation, (2) genetically determined impairment of neural-crest cell migration, and (3) direct gene action on organogenesis. Skeletal malformations in the form of a rib-vertebra syndrome encountered in Ts 16 are described here for the first time. In 108 fetuses and 219 neonates resulting from cross-breeding to induce trisomy 19, we found no significant increase in the frequency of the foregoing anomalies. These results are discussed with regard to a chromosome-specific genetic influence as opposed to a general effect of chromosome imbalance. The specificity of the Ts16 syndrome is compared with that of individual organ anomalies as can be induced by teratogenic agents. Our investigation shows that specific malformation patterns of a particular type can be produced by a variety of methods. However, the overall patterns of the two syndromes are highly chromosome-specific. On detailed examination, the malformation pattern of mouse trisomy 16 shows significant similarities with that of human trisomy 21.     

Enhanced apoptosis in transformed human lung fibroblasts after exposure to sodium butyrate

Summary Simian virus-transformed human cells, WI-38 VA13A, showed a dose-dependent induction of apoptosis and reduction in cell numbers after exposure to sodium butyrate. Apoptosis was confirmed by ApopTag staining, isolation of apoptotic envelopes, and immunofluorescent staining with an antibody specific for apoptotic envelopes. Examination of the cell cultures by phase contrast and fluorescent microscopy revealed the presence of enlarged cells that displayed a more flattened morphology and morphological changes in the nucleus of cells exposed to sodium butyrate. Cell proliferation assays showed control and sodium butyrate cultures were synthesizing DNA and excluded any cytotoxic effects of sodium butyrate. Flow cytometry results indicated an increase in the number of aneuploid cells following sodium butyrate treatment. There was a decrease in the percentage of cells in G2/M in the diploid populations, but an increase in the percentage of cells in G2/M in aneuploid populations. This humanin vitro model system suggests a mode of action for the therapeutic effects of sodium butyrate, which have been observed in the topical treatment of neoplastic cells and reversal of symptoms in ulcerative colitis: namely, the induction of apoptosis.     

The Changes in Soluble Protein of Excised Barley Leaves during Senescence and Kinetin Treatment

Sterile detached barley leaves were floated on water or kinetin (10 mg/1)and supernatant extracts (30,000 x g for 30 min) were prepared from these leaves over an 8 day incubation period. Changes in selected total enzyme levels and in individual soluble protein components wore compared. Ribonuclease, deoxyribonuclease and peptidase activities rose in senescing leaves, even as total protein levels fell. Kinetin to some extent depressed these activities. Evidence of considerable loss of ribonuclease and to a lesser extent of deoxyribonuclease into the surrounding medium was obtained. Soluble supernatant ant extracts were resolved on DEAE-Sephadex (A-50) columns into about 15 components. While most components were degraded during senescence they did so at different rates. Kinetin lowered the rate of degradation of all components. Since no conclusive evidence of a new protein(s) was obtained in water and kinetin treated leaves, it was considered that any protein changes may have been of a quantitative rather than qualitative nature.     

Studies on the chromatin of barley leaves during senescence

1. The activity of soluble ribonuclease and deoxyribonuclease first declined during senescence, but later increased during advanced stages of senescence. 2. Young leaves had very low ribonuclease or deoxyribonuclease activity associated with the chromatin, but the activity of these enzymes increased progressively during senescence until the leaves died. 3. No significant changes in the composition of chromatin from first seedling leaves of barley plants during aging (from 7 to 25 days) were noted. 4. The amount of RNA synthesized by chromatin in vitro declined as the leaf aged. However, if the loss of RNA due to chromatin-associated ribonuclease was taken into account, the RNA-synthesizing activity of chromatin from senescing (15-16-day-old) leaves appeared to be somewhat higher than that of chromatin from young (7-8-day-old) leaves. In leaves at the terminal stages of senescence (23 days old) the estimates of RNA synthesis by chromatin could not be made owing to complications created by high nuclease activities. 5. It is suggested that senescence may be triggered by a decline in some hormonal factor in leaves, and that the resulting production of chromatin-associated deoxyribonuclease and ribonuclease in increasing proportions may progressively cause increased degradation of DNA and newly synthesized RNA, so that ultimately the cellular functions are impaired and the cells die.     

Effect of Kinetin on Ribosomes of Excised Barley Leaves

The changes in the amount and the composition of ribosomes in excised barley leaves floated on water or on 10 mg/l kinetin solution in the dark were examined. The rapid loss of polyribosomes and ribosomes in leaves floated on water was greatly retarded by kinetin. The ribosomes-polyribosomes which originally contained 49 per cent protein showed substantial decline in protein content in leaves floated on water but only slight decline in leaves floated on kinetin solution. It is suggested that kinetin by stimulating RNA synthesis and by suppressing the activities of rihonuclease and peplidase may preserve the ribosomes in excised leaves.