Tumor-Derived Extracellular Vesicles: Modulation of Cellular Functional Dynamics in Tumor Microenvironment and Its Clinical Implications

Cancer can be described as a dynamic disease formed by malignant and stromal cells. The cellular interaction between these components in the tumor microenvironment (TME) dictates the development of the disease and can be mediated by extracellular vesicles secreted by tumor cells (TEVs). In this review, we summarize emerging findings about how TEVs modify important aspects of the disease like continuous tumor growth, induction of angiogenesis and metastasis establishment. We also discuss how these nanostructures can educate the immune infiltrating cells to generate an immunosuppressive environment that favors tumor progression. Furthermore, we offer our perspective on the path TEVs interfere in cancer treatment response and promote tumor recurrence, highlighting the need to understand the underlying mechanisms controlling TEVs secretion and cargo sorting. In addition, we discuss the clinical potential of TEVs as markers of cell state transitions including the acquisition of a treatment-resistant phenotype, and their potential as therapeutic targets for interventions such as the use of extracellular vesicle (EV) inhibitors to block their pro-tumoral activities. Some of the technical challenges for TEVs research and clinical use are also presented.

RESPON MORFOGENESIS EKSPLAN PUCUK ANGGREK TEBU (Grammatophylum speciosum Blume) SECARA IN VITRO TERHADAP BEBERAPA KONSENTRASI KINETIN

Sugarcane orchid (Grammatophyllum speciosum Blume) are known as a type of giant orchid, adult orchids can weigh 1 ton, panicle can grow up to 2.5 – 3 meters with a diameter of about 1.5-2 cm. Each panicle has dozens, even reaching one hundred flower buds, each with a diameter of about one 10 cm. Sugarcane orchids are a type of plant that is protected because its existence is increasingly scarce so that it needs in vitro propagation techniques to support its survival. To improve the growth of Grammatophyllum speciosum Blume in vitro shoot tip was growing on MS medium with varying concentration of kinetin (0, 1, 2, 3, and 4 mg L-1) with 5 replications. Shoot tip from in vitro culture around 1 cm lengt was used as explants. Observations carried out for 8 weeks after inoculation.The results showed that shoot explants tip growth well in MS basic medium. The addition of kinetin to the medium, increases growth rate of culture. Increasing the concentration of kinetin tends to increase the growth. The best concentration for growth induction on plant height, stem diameter, leaves length and length of roots was 2 mg.L-1 kinetin, On the other hand 3 mg.L-1 kinetin gave best response on number of leaves and 4 mg.L-1 kinetin was the best concentration on leaves width and number of roots.

From Stable to Lab—Investigating Key Factors for Sudden Deaths Caused by Streptococcus suis

Swine stocks are endemically infected with the major porcine pathogen Streptococcus (S.) suis. The factors governing the transition from colonizing S. suis residing in the tonsils and the exacerbation of disease have not yet been elucidated. We analyzed the sudden death of fattening pigs kept under extensive husbandry conditions in a zoo. The animals died suddenly of septic shock and showed disseminated intravascular coagulopathy. Genotypic and phenotypic characterizations of the isolated S. suis strains, a tonsillar isolate and an invasive cps type 2 strain, were conducted. Isolated S. suis from dead pigs belonged to cps type 2 strain ST28, whereas one tonsillar S. suis isolate harvested from a healthy animal belonged to ST1173. Neither S. suis growth, induction of neutrophil extracellular traps, nor survival in blood could explain the sudden deaths. Reconstituted blood assays with serum samples from pigs of different age groups from the zoo stock suggested varying protection of individuals against pathogenic cps type 2 strains especially in younger pigs. These findings highlight the benefit of further characterization of the causative strains in each case by sequence typing before autologous vaccine candidate selection.

2-Alkyl-4-hydroxyquinolines from a Marine-Derived Streptomyces sp. Inhibit Hyphal Growth Induction in Candida albicans

Four 2-alkyl-4-hydroxyquinoline derivatives (1–4) were isolated from a semisolid rice culture of the marine-derived actinomycete Streptomyces sp. MBTG13. The structures of these compounds were elucidated by a combination of spectroscopic methods, and their data were in good agreement with previous reports. Compounds 1 and 2 exhibited weak to moderate antibacterial activity against pathogenic bacteria. Unexpectedly, we found that compound 1 acted as a potent inhibitor of hyphal growth induction in the dimorphic fungus Candida albicans, with an IC50 value of 11.4 μg/mL. Growth experiments showed that this compound did not inhibit yeast cell growth, but inhibited hyphal growth induction. Semi-quantitative reverse transcription (RT)-PCR analysis of hyphal-inducing signaling pathway components indicated that compound 1 inhibited the expression of mRNAs related to the cAMP-Efg1 pathway. The expression of HWP1 and ALS3 mRNAs (hypha-specific genes positively regulated by Efg1, an important regulator of cell wall dynamics) was significantly inhibited by the addition of compound 1. These results indicate that compound 1 acts on the Efg1-mediated cAMP pathway and regulates hyphal growth in Candida albicans.

Growth Induction of Cavendish Buds (Musa Acuminata L.) on Difference Concentration of IBA and BA in Vitro

The propagation of Cavendish (Musa acuminata L.) seedling conventionally relatively took a longer time, not uniformed in quality and possibly has a disease that is derived from unhealthy mother stock. This research aimed to find the effect of IBA and BA on difference concentrations on the growth of plantlet, also to determine the optimum concentration of IBA and BA on the growth of Cavendish bud plantlets in vitro. This research had been carried out started from April to July 2018 in Tissue Culture Laboratory, Research Institute of Horticultural Seed Development of Pasir Banteng, Sumedang, West Java. Indonesia. The method used in this research was Completely Randomized Design with two factors. The first factor was IBA (i0 = 0 mg L-1, i1= 0,75 mg L-1, dan i2= 1,5 mg L1), and the second factor was BA (b1= 1 mg L-1 b2= 3 mg L-1 b3= 5 mg L-1 b4= 7 mg L-1), replicated three times. Duncan Multiple Range Test (DMRT) was used as a further test. The result showed an interaction between IBA and BA on the parameters of shoot growth and the number of leaves at 6 WAC. IBA showed an independent effect on the number of buds. The addition of 1,5 mg L-1 IBA and 3 mg L-1 BA was optimum for the growth of Cavendish bud explants.