Characteristics of development and variations in ecdysteroid levels in Clitumnus embryos deprived of their cephalic endocrine glands

Microsurgical suppression of presumptive endocrine areas in very young embryos of Clitumnus resulted in an arrest in development, which occurred at different stages according to the operation. In most cases however. the duration of embryonic life was not reduced significanly. The repercussions of each operation type on the ecdysteroid content of the embryos were determined using a radioimmunoassay technique.Consideration of the experimental results provides some indication on the part played by each endocrine formation during the last part of embryonic development that is between dorsal closure and hatching time. Our experiments offer original evidence that the corpora allata of the embyro are of utmost importance at the stage VII_3t, in initiating the normal expression of larval characteristics.     

Long cytoplasmic processes in pancreatic polypeptide cells

Pancreatic polypeptide (PP) cells were studied in human endocrine pancreatic tumours and in normal human pancreata by immunohistochemical techniques and electron miscroscopy. The existence of long cytoplasmic processes was demonstrated both in tumours and normal tissue. These processes are in close contact with other endocrine cells or with acinar cells. This particular morphological aspect suggests that PP cells may control the function of other cells via paracrine secretion.     

A proteomic and phosphoproteomic landscape of KRAS mutant cancers identifies combination therapies

1. Download : Download high-res image (203KB)
2. Download : Download full-size image

     

NK cells: An attractive candidate for cancer therapy

Natural killer (NK) cells have significant capability in tumor immune-surveillance. The ability of lyse transformed cells immediately in an antigen-independent manner make them an attractive candidate for cancer cell therapy. Despite employment of NK cells in cancer immunotherapy, clinical trials are faced with serious limitations such as trouble with the penetration of NK cells in tumor sites, limited in vivo persistence, and tumor microenvironment interference. Taken together, the NK-cell cancer therapy is still infant scenario that has a long way to be translated in clinic. Current article first reviews characteristic features of NK lymphocytes. Then, it discusses about important disruptive barriers and motivator in the developmental stages of NK cells like as tumor microenvironment. Finally, some revolutionary approaches are highlighted utilizing of NK cells in cancer therapy.     

Development of a human three-dimensional organotypic skin-melanoma spheroid model for in vitro drug testing

Despite remarkable efforts, metastatic melanoma (MM) still presents with significant mortality. Recently, mono-chemotherapies are increasingly replenished by more cancer-specific combination therapies involving death ligands and drugs interfering with cell signaling. Still, MM remains a fatal disease because tumors rapidly develop resistance to novel therapies thereby regaining tumorigenic capacity. Although genetically engineered mouse models for MM have been developed, at present no model is available that reliably mimics the human disease and is suitable for studying mechanisms of therapeutic obstacles including cell death resistance. To improve the increasing requests on new therapeutic alternatives, reliable human screening models are demanded that translate the findings from basic cellular research into clinical applications. By developing an organotypic full skin equivalent, harboring melanoma tumor spheroids of defined sizes we have invented a cell-based model that recapitulates both the 3D organization and multicellular complexity of an organ/tumor in vivo but at the same time accommodates systematic experimental intervention. By extending our previous findings on melanoma cell sensitization toward TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) by co-application of sublethal doses of ultraviolet-B radiation (UVB) or cisplatin, we show significant differences in the therapeutical outcome to exist between regular two-dimensional (2D) and complex in vivo-like 3D models. Of note, while both treatment combinations killed the same cancer cell lines in 2D culture, skin equivalent-embedded melanoma spheroids are potently killed by TRAIL+cisplatin treatment but remain almost unaffected by the TRAIL+UVB combination. Consequently, we have established an organotypic human skin-melanoma model that will facilitate efforts to improve therapeutic outcomes for malignant melanoma by providing a platform for the investigation of cytotoxic treatments and tailored therapies in a more physiological setting.     

Cell sheet technology: a promising strategy in regenerative medicine

Regenerative medicine is a burgeoning field that is important to combat challenging diseases and functional impairments. Compared with traditional cell therapies with evident shortcomings (e.g., cell suspension injection or tissue engineering with scaffolds), scaffold-free cell sheet technology enables transplanted cells to be grafted and fully maintain their viability on target sites. Clinical and experimental studies have advanced the application of cell sheet technology to numerous tissues and organs (e.g., liver, cornea and bone). However, previous reviews have failed to discuss vital aspects of this rapidly developing technology, and many new challenges are gradually emerging. This review aims to provide a comprehensive introduction to cell sheet technology from cell selection to the ultimate applications of cell sheets, and challenges and future visions are also described.     

PD-1/PD-L1 pathway: Basic biology and role in cancer immunotherapy

Over the course of past few years, cancer immunotherapy has been accompanied with promising results. However, preliminary investigations with respect to immunotherapy concentrated mostly on targeting the immune checkpoints, nowadays, emerge as the most efficient strategy to raise beneficial antitumor immune responses. Programmed cell death protein 1 (PD-1) plays an important role in subsiding immune responses and promoting self-tolerance through suppressing the activity of T cells and promoting differentiation of regulatory T cells. PD-1 is considered as an immune checkpoint and protects against autoimmune responses through both induction of apoptosis in antigen-specific T cells and inhibiting apoptosis in regulatory T cells. Several clinical trials exerting PD-1 monoclonal antibodies as well as other immune-checkpoint blockades have had prosperous outcomes and opened new horizons in tumor immunotherapy. Nonetheless, a bulk of patients have failed to respond to these newly emerging immune-based approach and the survival rate was not satisfying. Additional strategies, especially combination therapies, has been initiated and been further promising. Attempts to identify novel and well-suited predictive biomarkers are also sensed. In this review, the promotion of cancer immunotherapy targeting PD-1 immunoinhibitory pathway is discussed.     

Plasma netrin-1 is a diagnostic biomarker of human cancers

Context:?The axon guidance cues netrin-1 is a secreted protein overexpressed in many different cancer tissues.

Objectives:?To determine whether plasma netrin-1 can be used as a diagnostic biomarker of human cancer.

Materials and Methods:?A total of 300 cancer plasma samples from breast, renal, prostate, liver, meningioma, pituitary adenoma, glioblastoma, lung, pancreatic and colon cancer patients were compared against 138 control plasma samples. Netrin-1 levels were quantified by ELISA and immunohistochemistry.

Results:?Plasma netrin-1 levels were significantly increased in breast, renal, prostate, liver, meningioma, pituitary adenoma, and glioblastoma cancers as compared to control samples.

Discussion and Conclusion:?Our results suggest that plasma netrin-1 can be used as a diagnostic biomarker for many human cancers.