Author: Lee, Chi-Sing ; Qu, Zhao ; Tai, William Chi-Shing ; Chen, Sibao ; Huang, Junrong ; Lee, Magnolia Muk-Lan ; Chan, Brandon Dow ; Leung, Tsz-Wing ; Zhu, Lizhi ; Wong, Wing-Yan

Cancer is the second leading cause of death globally, responsible for an estimated 9.6 million deaths in 2018, and this burden continues to increase. Therefore, there is a clear and urgent need for novel drugs with increased efficacy for the treatment of different cancers. Previous research has demonstrated that brevilin A (BA) exerts anticancer activity in various cancers, including human multiple myeloma, breast cancer, lung cancer, and colon carcinoma, suggesting the anticancer potential present in the chemical scaffold of BA. Here, we designed and synthesized a small library of 12 novel BA derivatives and evaluated the biological anticancer effects of the compounds in various cancer cell lines. The results of this structure-activity relationship study demonstrated that BA derivatives BA-9 and BA-10 possessed significantly improved anticancer activity toward lung, colon, and breast cancer cell lines. BA-9 and BA-10 could more effectively reduce cancer cell viability and induce DNA damage, cell-cycle arrest, and apoptosis when compared with BA. Our findings represent a significant step forward in the development of novel anticancer entities.

01 Jan 2005·Developmental NeuroscienceQ4 · MEDICINE

Regional Dendritic Variation in Neonatal Human Cortex: A Quantitative Golgi Study

Q4 · MEDICINE

Article

Author: Travis, Katie ; Jacobs, Bob ; Ford, Kevin

The present study quantitatively compared the basilar dendritic/spine systems of lamina V pyramidal neurons across four hierarchically arranged regions of neonatal human neocortex. Tissue blocks were removed from four Brodmann’s areas (BAs) in the left hemisphere of four neurologically normal neonates (mean age = 41 ± 40 days): primary (BA4 and BA3-1-2), unimodal (BA18), and supramodal cortices (BA10). Tissue was stained with a modified rapid Golgi technique. Ten cells per region (N = 160) were quantified. Despite the small sample size, significant differences in dendritic/spine extent obtained across cortical regions. Most apparent were substantial differences between BA4 and BA10: total dendritic length was 52% greater in BA4 than BA10, and dendritic spine number was 67% greater in BA4 than BA10. Neonatal patterns were compared to adult patterns, revealing that the relative regional pattern of dendritic complexity in the neonate was roughly the inverse of that established in the adult, with BA10 rather than BA4 being the most complex area in the adult. Overall, regional dendritic patterns suggest that the developmental time course of basilar dendritic systems is heterochronous and is more protracted for supramodal BA10 than for primary or unimodal regions (BA4, BA3-1-2, BA18).

01 Jan 1992·Infection and ImmunityQ2 · MEDICINE

Decreased metabolism and viability of Mycoplasma hominis induced by monoclonal antibody-mediated agglutination

Q2 · MEDICINE

Article

Author: Hadding, U ; Kolb-Bachofen, V ; Henrich, B ; Feldmann, R C

Monoclonal antibodies (MAbs) were generated against lysates of clinical Mycoplasma hominis isolates. Three of these, designated BG2, BA10, and FE6, recognized an integral membrane protein of M. hominis with an apparent molecular weight of 50,000 (p50). Electron microscopy studies demonstrated that this protein is distributed evenly over the cell surface. These anti-p50 MAbs were species specific for M. hominis; they reacted with 42% of 126 tested clinical M. hominis isolates and showed no reactivity to heterologous mycoplasma species. Immunoblot analysis after limited proteolysis of purified p50 demonstrated that the three MAbs reacted with different epitopes of the protein. Unlike BA10 and FE6, MAb BG2 induced a decrease in arginine metabolism and a reduction of CFU in metabolic inhibition tests. F(ab)2 fragments of MAb BG2 showed the same inhibitory effect as the intact MAb molecule, while Fab and Fc fragments had no influence on vital functions. Preincubation of the mycoplasmas with MAb BG2 followed by trypsin treatment yielded the same amount of CFU as the control without antibodies. In conclusion, the cell aggregates were resolved by the trypsin treatment. These experiments and tests with the antibody fragments led to the conclusion that only the intact MAb structure or the F(ab)2 structure had metabolic inhibition potential and that the observed metabolism inhibition as well as the apparent decrease in viability were a result of agglutination by MAb BG2.

100 Deals associated with BA-10

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Indication	Highest Phase	Country/Location	Organization	Date
Neuralgia	Phase 2	EE	Genecode Health Pvt Ltd.	-

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