Endemism and rarity have long intrigued scientists. We focused on a rare endemic and critically-endangered species in a global biodiversity hotspot, Grevillea thelemanniana (Proteaceae). We carried out plant and soil analyses of four Proteaceae, including G. thelemanniana, and combined these with glasshouse studies. The analyses related to hydrology and plant water relations as well as soil nutrient concentrations and plant nutrition, with an emphasis on sodium (Na) and calcium (Ca). The local hydrology and matching plant traits related to water relations partially accounted for the distribution of the four Proteaceae. What determined the rarity of G. thelemanniana, however, was its accumulation of Ca. Despite much higher total Ca concentrations in the leaves of the rare G. thelemanniana than in the common Proteaceae, very few Ca crystals were detected in epidermal or mesophyll cells. Instead of crystals, G. thelemanniana epidermal cell vacuoles contained exceptionally high concentrations of noncrystalline Ca. Calcium ameliorated the negative effects of Na on the very salt-sensitive G. thelemanniana. Most importantly, G. thelemanniana required high concentrations of Ca to balance a massively accumulated feeding-deterrent carboxylate, trans-aconitate. This is the first example of a calcicole species accumulating and using Ca to balance accumulation of an antimetabolite.

OBJECTIVE: To evaluate safety of TAS-102 administered twice daily (bid) on days 1-5 and 8-12 of a 4-week cycle, confirm feasibility of the Japanese recommended dose (RD), 35 mg/m(2), in Western patients with metastatic colorectal cancer (mCRC) refractory to standard chemotherapies, and describe preliminary antitumor activity.
METHODS: This open-label, dose-escalation phase 1 study was conducted at four US centers. Patients were enrolled into two sequential cohorts [30 (cohort 1) or 35 mg/m(2)/dose bid (cohort 2)]; dose-limiting toxicities (DLT) were evaluated during cycle 1 in dose-escalation cohorts. At RD, 15 additional patients were enrolled in an expansion cohort.
RESULTS: Patients (N = 27) with refractory mCRC received TAS-102; 74 % had received ≥4 prior regimens. DLT was not observed in three patients in cohort 1, and was in one out of nine patients in cohort 2 (grade 3 febrile neutropenia). Therefore, RD was identified as 35 mg/m(2) bid. At RD, fatigue (63 %), gastrointestinal disturbances and nausea (46 %), vomiting (46 %), and diarrhea (42 %) were common but rarely grade 3/4. Grade 3/4 nausea, vomiting, and diarrhea occurred at 4 % each. Grade 3/4 toxicity was predominantly hematologic [neutropenia (71 %), anemia (25 %)]; febrile neutropenia was observed in two patients. Stable disease lasting ≥6 weeks was achieved by 16 evaluable patients (70 %); median progression-free survival and overall survival were 5.3 and 7.5 months, respectively.
CONCLUSIONS: TAS-102 has an acceptable safety profile and preliminary evidence of disease stabilization in Western patients with refractory mCRC. Results from a randomized phase 3 study have shown survival benefit with disease stabilization evidence in this population.

OBJECTIVE: The aim of this study is to investigate whether CS-g-MMCs conjugate (CSM) could be a new agent to prevent the post-operative fibrosis in a rabbit model of experimental glaucoma filtration surgery.
METHODS: In a randomized, controlled, masked-observer study, 40 New Zealand White rabbits underwent trabeculectomy in the right eyes and randomly received subconjunctival injection of phosphate buffered saline, chitosan (CS), CSM (100 µg/ml), CSM (200 µg/ml) or Mitomycin C (100 µg/ml). Bleb characteristics and anterior chamber depth were evaluated by slit-lamp examination. The animals were killed on day 14 and 28. Histopathology and immunohistochemistry were performed to determine the amount of the scarring and fibrosis. Ocular toxicity was assessed by histopathology and electron microscope.
RESULTS: We found that the five groups were similar with respect to intraocular pressure and anterior chamber depth. The medians for survival days were: 5.5, 8, 17.5, 28 and 16 in the PBS, CS, CSM100, CSM200 and MMC groups, respectively. Both the CSM200 and the MMC group showed a significantly larger bleb area than the CSM100, CS and the PBS group. Less scarring was seen on day 14 and 28 in CSM200 and MMC group than in the PBS, CS and CSM100 group by histology and immunohistochemistry assessment. No damages were found in the rabbit eyes in each group.
CONCLUSIONS: Subconjunctival injection of CSM postoperatively can improve the filtration bleb survival in the rabbit model. It can be a safe and effective antimetabolite in glaucoma surgery.