Potential therapeutic and diagnostic applications of the growth of testicular cancer in soft agar

Sixteen histologically documented testicular cancer specimens obtained at diagnostic procedures following induction chemotherapy with cis-platinum containing regimens were cloned in soft agar. Seven (44%) of the specimens cultured formed colonies with a mean cloning efficiency of .021%. Colony formation was observed with all the common histologic subtypes of testicular cancer (seminoma, embryonal carcinoma, choriocarcinoma and mixed tumors). In vitro drug sensitivity tests were performed using cis-platinum, vinblastine and VP-16. Three of four specimens demonstrated a decrease in colony formation to less than 50% of controls after a 1 h exposure to VP-16 at 300 micrograms/ml. Two of these patients had a response to treatment with a VP-16 based salvage regimen. Immunoperoxidase staining of the colonies for alpha feto protein and human chorionic gonadotropin were correlated with the serum levels of these tumor markers determined at the time the specimen was obtained. In three instances the same markers were elevated in the serum as detected within cells which formed the colonies; however, in two other cases the marker(s) that was elevated in the serum was not expressed in the colonies. In one case a biopsy of a residual retroperitoneal mass following chemotherapy histologically was a teratoma, but it formed colonies in the assay which stained positive for alpha feto protein. This patient subsequently developed an elevated serum alpha feto protein. These studies have demonstrated that (a) testicular cancer can be cloned directly in soft agar; (b) a heterogeneous tumor cell population exists in metastatic testicular cancer specimens; and (c) a dose response exists for VP-16 in relapsed testicular cancer which suggests that increasing the dose of VP-16 may be clinically beneficial.     

Studies of in vitro γ-interferon production in coeliac disease as a response to gliadin peptides

The effects of certain fractions of a peptic-tryptic-pancreatinic (PTP) digest of wheat gliadin of synthetic peptides on the production of gamma interferon (γ-IFN) in cultures of whole blood from adult patients with coeliac disease (CD) have been studied using a sandwich enzyme immunoassay. The most active peptides were fraction 9, its two principal sub-fractions (sub-fractions 1 and 2) and a synthetic peptide of sequence RPQQPYPQPQPQ (peptide V) corresponding to the principal peptide obtained from reversed-phase HPLC of fraction 9. Results with blood from the control group of subjects also indicated some response to these antigens, in most cases at similar levels to those observed with the coeliacs. Fraction 1 of the PTP digest and the other nine synthetic peptides tested were inactive with both coeliacs and controls. These results are in agreement with the results of in vivo and in vitro toxicity tests. They provide evidence of a link between toxicity and cell-mediated immune response in CD, and suggest that peptide V represents one of the active parts of the gliadin molecule.     

Exploiting the Oxygen Inhibitory Effect on UV Curing in Microfabrication: A Modified Lithography Technique

Rapid prototyping (RP) of microfluidic channels in liquid photopolymers using standard lithography (SL) involves multiple deposition steps and curing by ultraviolet (UV) light for the construction of a microstructure layer. In this work, the conflicting effect of oxygen diffusion and UV curing of liquid polyurethane methacrylate (PUMA) is investigated in microfabrication and utilized to reduce the deposition steps and to obtain a monolithic product. The conventional fabrication process is altered to control for the best use of the oxygen presence in polymerization. A novel and modified lithography technique is introduced in which a single step of PUMA coating and two steps of UV exposure are used to create a microchannel. The first exposure is maskless and incorporates oxygen diffusion into PUMA for inhibition of the polymerization of a thin layer from the top surface while the UV rays penetrate the photopolymer. The second exposure is for transferring the patterns of the microfluidic channels from the contact photomask onto the uncured material. The UV curing of PUMA as the main substrate in the presence of oxygen is characterized analytically and experimentally. A few typical elastomeric microstructures are manufactured. It is demonstrated that the obtained heights of the fabricated structures in PUMA are associated with the oxygen concentration and the UV dose. The proposed technique is promising for the RP of molds and microfluidic channels in terms of shorter processing time, fewer fabrication steps and creation of microstructure layers with higher integrity.     

Breast cancer-derived exosomes: Tumor progression and therapeutic agents

Tumor cells secrete extracellular vesicles (EVs) for intercellular communication. EVs by transporting different proteins, nucleic acids, and lipids contribute to affect target cell function and fate. ‎EVs which originate directly from multivesicular bodies so-called exosomes have dramatically fascinated the attention of researchers owing to their ‎pivotal roles in the tumorigenesis. Breast cancer, arising from milk-producing cells, is the most identified cancer among women and has become the leading cause of cancer-related death in women globally. Although different therapies are applied to eliminate breast tumor cells, however, the efficient therapy and survival rate of patients remain challenges. Growing evidence ‎shows exosomes from breast cancer cells contribute to proliferation, metastasis, angiogenesis, chemoresistance, and also radioresistance and, thus carcinogenesis. Additionally, these exosomes may serve as a cancer treatment tool because they are a good candidate for cancer diagnosis (as biomarker) and therapy (as drug-carrier). Despite recent development in the biology of tumor-derived exosomes, the detailed mechanism of tumorigenesis, and exosome-based cancer-therapy remain still indefinable. Here, we discuss the key function of breast cancer-derived exosomes in tumorgenesis and shed light on the possible clinical application of these exosomes in breast cancer treatment.