Objective To investigate the security and efficacy in the elderly patients with acute myeloid leukemia (AML) treated by decitabine based regimen. Methods A retrospective analysis was carried out on 12 elderly patients with AML who were treated by decitabine alone or with low-dose chemotherapy in Beijing Luhe Hospital, Capital Medical University from June 2014 to December 2015. Results There were 6 patients of complete remission (CR), 5 patients of partial remission (PR), 1 patient of none remission (NR) after one course of chemotherapy. 1 case of 6 CR patients relapsed after 6 cycles of chemotherapy , others remained CR during the follow-up . Among 5 PR patients , 2 cases achieved CR , 1 patient relapsed after 2 cycles of chemotherapy and 2 patients relapsed after 3 cycles of chemotherapy. 1 patient remained NR after 2 cycles of chemotherapy and died of severe pulmonary infection. 3 of 4 complex karyotype patients had poor efficiency, and only 1 patient achieved CR but relapsed eventually. 7 patients achieved CR in patients with +8, -X or normal karyotype in the near future. The main adverse effects were bone marrow suppression and infection. All patients could tolerate. Conclusion Elderly patients with primary AML treated by decitabine alone or with low-dose chemotherapy show good effects, well tolerance and high safety, which could serve as the front-line treatment.

Objective To explore the efficacy and safety of high-dose methotrexate (MTX) and L-asparaginase (L-Asp) for the treatment of adult patients with high risk Ph acute lymphoblastic leukemia (ALL).Methods Five adult patients with high risk Ph-ALL were treated with several courses of MTX (3-5 g/m2 by continually intravenous drip for 24 h) and L-Asp (8 000-10 000 U/time, once a day, 10 times for one cycle).Results Five patients were disease-free survival, their survival time was 60-96 months and the median survival time was 73 months.The chemotherapy-related bone marrow depression was mild.No obvious liver and kidney damage, severe allergic reaction and pancreatitis were observed.Conclusion Highdose MTX and L-Asp are effective and well tolerated, and may contribute to long-term survival of adult patients with high risk Ph-ALL.

Forty eight patients with IgG-related disease (IgG-RD) were treated in Beijing Luhe Hospital, Capital Medical University between January 2014 and January 2017. The clinical features, organ involvement, laboratory findings and treatment of patients were analyzed. The median age of patients was 59 (29-78) years old. The most common symptoms were submandibular gland enlargement (20.8%), abdominal pain (18.8%), eyelid mass or edema (18.8%) and jaundice (16.7%). The involved organs mainly were submandibular glands (62.5%), lymph nodes (54.2%), lacrimal glands (45.8%), parotid glands (41.7%) and pancreas (31.3%). PET/CT was performed in 9 cases (18.8%), the SUVmax value was not correlated with the number of affected organs (r=0.511, P=0.160) and IgG4 (r=0.385, P=0.306). Histopathology showed increased lymphocytes and plasma cells in 46 cases (95.8%), eosinophilia in 15 cases (31.3%), and fibrous hyperplasia in 26 cases (54.2%). Twenty-three patients (47.9%) were treated with single glucocorticoid, 20 patients (41.6%) were treated with glucocorticoid combined immunosuppressants, 3 patients (6.3%) received surgical treatment, and 2 (4.2%) were observed with watch and wait regimen. Forty (97.9%) patients responded well to the initial treatment. Ten out of 23 cases (43.5%) in corticosteroid monotherapy group relapsed, while 6 out of 20 cases (30.0%) in corticosteroids plus immunosuppressive group relapsed, for whom the full dose of corticosteroid and immunosuppressive agents were still effective. IgG4-RD is a chronic inflammatory and fibrous sclerotic disease with multiple organ involvement, increase serum IgG4 level and tissue infiltration with large number of IgG4+cells. Hormone and immunosuppressive therapy is effective, and the overall prognosis is good.

HDA9, a member of the deacetylase family, plays a vital role in regulating plant flowering time through flowering integrator SOC1 and AGL24. However, it remains elusive how HDA9 interacts with SOC1 and AGL24 in flowering time control. Here, HDA9 was cloned in Brassica juncea and then its three active sites were separately replaced with Ala via overlap extension PCR. Thus, mutants of HDA9(D172A), HDA9(H174A) and HDA9(D261A) were constructed and fused into the pGADT7 vector. The yeast one-hybrid assays indicated that HDA9 mutants remained the interactions with the promoters of SOC1 and AGL24. Furthermore, the aforementioned results were confirmed in the dual luciferase assays. Interestingly, the DNA-protein interactions were weakened significantly due to the mutation in the three active sites of HDA9. It suggested that flowering signal integrator SOC1 and AGL24 were regulated by the key amino acid residues of 172th, 174th and 261th in HDA9. Our results provide valuable information for the in-depth study of the biological function and molecular regulation of HDA9 in Brassica juncea flowering time control.
Flowers ; genetics ; Gene Expression Regulation, Plant ; genetics ; Mustard Plant ; enzymology ; genetics ; Mutation ; Plant Proteins ; genetics ; metabolism ; Promoter Regions, Genetic ; genetics

Objective: To evaluate the feasibility and potential value of comprehensive geriatric assessment (CGA) in elderly (≥60 years) patients with newly diagnosed acute myeloid leukemia (AML) in China. Methods: The CGA results of 83 newly diagnosed AML (non-APL) patients from 16 hospitals in Beijing and Tianjin between March 2016 and December 2017 were prospectively collected and analyzed. The clinical data, treatment and follow-up information were also collected. Results: Of 83 newly diagnosed elderly AML patients, 81 patients (97.6%) completed all designated CGA assessment. The median number of impaired scales of the CGA assessment in the studied population was 2(0-6). Sixteen patients (19.3%) showed no impairments according to the geriatric assessment scales implem ented by this study. The distributions of impaired scales were as follows: impairment in ADL, 55.4%; IADL impairment, 42.2%; MNA-SF impairment, 48.2%; cognitive impairment, 15.7%; GDS impairment, 31.7%; HCT-CI impairment, 19.5%, respectively. In patients with "good" ECOG (n=46), the proportion of impairment for each CGA scale ranged from 6.5% to 37.0% and 32 patients (68.9%) had at least one impaired CGA scale. Survival analysis showed that the number of impaired scales of the CGA was significantly correlated with median overall survival (P=0.050). Conclusions CGA was a tool with feasibility for the comprehensive evaluation in elderly AML patients in China. Combined with age and ECOG, CGA may be more comprehensive in assessing patients’ physical condition.

Endocrine-resistance remains a major challenge in estrogen receptor α positive (ERα⁺) breast cancer (BC) treatment and constitutively active somatic mutations in ERα are a common mechanism. There is an urgent need to develop novel drugs with new mode of mechanism to fight endocrine-resistance. Given aberrant ERα activity, we herein report the identification of novel covalent selective estrogen receptor degraders (cSERDs) possessing the advantages of both covalent and degradation strategies. A highly potent cSERD 29c was identified with superior anti-proliferative activity than fulvestrant against a panel of ERα⁺ breast cancer cell lines including mutant ERα. Crystal structure of ERα‒ 29c complex alongside intact mass spectrometry revealed that 29c disrupted ERα protein homeostasis through covalent targeting C530 and strong hydrophobic interaction collied on H11, thus enforcing a unique antagonist conformation and driving the ERα degradation. These significant effects of the cSERD on ERα homeostasis, unlike typical ERα degraders that occur directly via long side chains perturbing the morphology of H12, demonstrating a distinct mechanism of action (MoA). In vivo, 29c showed potent antitumor activity in MCF-7 tumor xenograft models and low toxicity. This proof-of-principle study verifies that novel cSERDs offering new opportunities for the development of innovative therapies for endocrine-resistant BC.