Accelerating the understanding of cancer biology through the lens of genomics.

A core mission of cancer genomics is to comprehensively chart molecular underpinnings of cancer-driving events and to provide personalized therapeutic strategies. Primarily focused on cancer cells, cancer genomics studies have successfully uncovered many drivers for major cancer types. Since the emergence of cancer immune evasion as a critical cancer hallmark, the paradigm has been elevated to the holistic tumor ecosystem, with distinct cellular components and their functional states elucidated. We highlight the milestones of cancer genomics, depict the evolving path of the field, and discuss future directions in completing the understanding of the tumor ecosystem and in advancing therapeutic strategies.

Overcoming inter-subspecific hybrid sterility in rice by developing indica-compatible japonica lines.

Rice (Oryza sativa L.) is an important staple crop. The exploitation of the great heterosis that exists in the inter-subspecific crosses between the indica and japonica rice has long been considered as a promising way to increase the yield potential. However, the male and female sterility frequently occurred in the inter-subspecific hybrids hampered the utilization of the heterosis. Here we report that the inter-subspecific hybrid sterility in rice is mainly affected by the genes at Sb, Sc, Sd and Se loci for F1 male sterility and the gene at S5 locus for F1 female sterility. The indica-compatible japonica lines (ICJLs) developed by pyramiding the indica allele (S-i) at Sb, Sc, Sd and Se loci and the neutral allele (S-n) at S5 locus in japonica genetic background through marker-assisted selection are compatible with indica rice in pollen fertility and in spikelet fertility. These results showed a great promise of overcoming the inter-subspecific hybrid sterility and exploiting the heterosis by developing ICJLs.

Hepatoprotective Effects of Grape Seed Procyanidin B2 in Rats With Carbon Tetrachloride-induced Hepatic Fibrosis.

CONTEXT: Infectious hepatitis is a serious problem affecting millions of people worldwide, particularly in China and other developing countries, and it is the major risk factor for hepatic cirrhosis. To date, the pathogenesis of hepatic cirrhosis is complex and unclear. Traditional Chinese medicine (TCM) has long been used in its treatment; however, little is known to date about the effects of grape seed procyanidin B2 (GSPB2) on liver fibrosis. OBJECTIVES: Using a rat model of carbon tetrachloride (CCl4)-induced hepatic fibrosis, the study intended to investigate the hepatoprotective effects of GSPB2 and to determine the possible pathway by which GSPB2 exerts its activities. Design • Thirty-six male, Sprague-Dawley rats were used in the study. Rats in a model (CCl4 only) group and the GSPB2 group were given CCl4 to induce hepatic fibrosis. Simultaneously, animals in the GSPB2 group were treated with GSPB2 by intragastric administration for 12 wk. In addition, the rat's Kupffer cells were cultured with CCl4 and GSPB2. SETTING: The study took place at the central laboratory of Qilu Hospital at Shandong University in Jinan, China. OUTCOME MEASURES: The following parameters were investigated: (1) hepatic function; (2) the liver fibrosis index-serum hyaluronic acid (HA), laminin (LN), type 3 procollagen (PC-3), collagen 4, and hepatic hydroxyproline; (3) the expression in the liver of transforming growth factor ß-1 (TGF-ß1); (4) inflammatory cytokines in the liver and cell culture medium-tumor necrosis factor α (TNF-α), interleukin (IL) 1-ß (IL-1ß), IL-6, and IL-17; (5) oxidative stress markers in the liver and cell culture medium-malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), total superoxide dismutase (T-SOD), and total antioxidant capacity (T-AOC); and (6) levels of angiotensin 2 (Ang 2) in the liver. RESULTS: The CCl4 induced (1) significant hepatic-function damage; (2) elevated levels of the measures of the liver fibrosis index, TGF-ß1, inflammatory cytokines, MDA, and 8-OHdG; (3) a reduction in the activities of T-SOD and T-AOC; and (4) no effect on the level of expression of hepatic Ang 2. GSPB2 treatment partially reversed the changes induced by CCl4. The cell culture also showed that CCl4 elevated the levels of inflammatory cytokines and MDA in the Kupffer cell culture medium, whereas it reduced the activities of T-SOD and T-AOC in the medium. GSPB2 treatment partially reversed the changes induced by CCl4. CONCLUSIONS: GSPB2 had hepatoprotective effects on CCl4-induced hepatic fibrosis in Sprague-Dawley rats and inhibited the inflammatory response and oxidative stress in vivo and in vitro.

Identification and fine mapping of S-d, a new locus conferring the partial pollen sterility of intersubspecific F1 hybrids in rice (Oryza sativa L.).

The partial pollen abortion of hybrids between the indica and japonica subspecies of Asian cultivated rice is one of the major barriers in utilizing intersubspecific heterosis in hybrid rice breeding. Although a single hybrid pollen sterility locus may have little impact on spikelet fertility, the cumulative effect of several loci usually leads to a serious decrease in spikelet fertility. Isolating of the genes conferring hybrid pollen sterility is necessary to understand this phenomenon and to overcome the resulting genetic barrier. In this study, a new locus for F1 pollen sterility, S-d, was identified on the short arm of chromosome 1 by analyzing the genetic effect of substituted segments of the near-isogenic line E11-5 derived from the japonica variety Taichung 65 (recurrent parent) and the indica variety Dee-geo-woo-gen (donor parent). The S-d locus was first mapped to a 0.8 cM interval between SSR markers PSM46 and PSM80 using a F2 population of 125 individuals. The flanking markers were then used to identify recombinants from a population of 2,160 plants derived from heterozygotes of the primary F2 population. Simultaneously, additional markers were developed from genomic sequence divergence in this region. Analysis of the recombinants in the region resulted in the successful mapping of the S-d locus to a 67-kb fragment, containing 17 predicted genes. Positional cloning of this gene will contribute to our understanding of the molecular basis for partial pollen sterility of intersubspecific F1 hybrids in rice.