Advances in Studies on Nitrogen and Phosphorus Removal by Microalgal-Bacterial Consortia

With the development of life and industry, the nutrients in sewage increased gradually. The emerging symbiotic system of algal and bacteria has remarkable effect in removing nutrients such as nitrogen and phosphorus. In this paper, the influence of nitrogen and phosphorus on bacteria-algal consortia and the absorption mechanism of nitrogen and phosphorus by the interaction of bacteria-algal consortia were analyzed, and a variety of methods for studying bacteria-algal consortia were summarized, mainly using isotope tracer technology to study the research results of bacteria and algae absorbing nitrogen and phosphorus in water. This method is of great significance for analyzing the mechanism of the treatment of nitrogen and phosphorus by the bacterial-algal symbiosis system from the microscopic point of view

Estrogen Receptor Positive Breast Cancer with High Expression of Androgen Receptor has Less Cytolytic Activity and Worse Response to Neoadjuvant Chemotherapy but Better Survival

Estrogen receptor (ER) positive breast cancer (BC), the most abundant BC subtype, is notorious for poor response to neoadjuvant chemotherapy (NAC). The androgen receptor (AR) was reported to support estradiol-mediated ER activity in an in vitro system. Recently, ER-positive BC with fewer tumor infiltrating lymphocytes (TILs) was shown to have a better prognosis, opposite to the trend seen with ER-negative BC. We hypothesized that ER-positive BC with high expression of AR will have fewer TILs and an inferior response to NAC, but with a better prognosis. In both TCGA and METABRIC cohorts, AR expression was significantly higher in ER-positive BCs compared to ER-negatives (p < 0.001, p < 0.001, respectively) and it correlated with ER expression (R = 0.630, R = 0.509, respectively). In ER-positive tumors, AR high tumors enriched UV response down (NES = 2.01, p < 0.001), and AR low tumors enriched DNA repair (NES = −2.02, p < 0.001). AR high tumors were significantly associated with procancer regulatory T-cells, and AR low tumors were associated with anticancer immune cells, such as CD4, CD8, and Gamma-Delta T-cells and memory B-cells in ER-positive BC (p < 0.01). Further, cytolytic activity was significantly lower in AR high BC in both cohorts. Finally, AR high tumors had a significantly lower rate of attaining pathological complete response to NAC (GSE22358), but better survival. In conclusion, our results demonstrated that high AR has fewer tumor infiltrating lymphocytes as well as cytolytic activity and an inferior response to NAC, but better survival in ER-positive BC

Impact of Minimal Residual Disease on Progression-Free Survival Outcomes after Fixed-Duration Ibrutinib-Venetoclax Versus Chlorambucil-Obinutuzumab in the GLOW Study

Supported by Janssen Research & Development, LLC.PURPOSEIn GLOW, fixed-duration ibrutinib + venetoclax showed superior progression-free survival (PFS) versus chlorambucil + obinutuzumab in older/comorbid patients with previously untreated chronic lymphocytic leukemia (CLL). The current analysis describes minimal residual disease (MRD) kinetics and any potential predictive value for PFS, as it has not yet been evaluated for ibrutinib + venetoclax treatment.METHODSUndetectable MRD (uMRD) was assessed by next-generation sequencing at <1 CLL cell per 10,000 (<10-4) and <1 CLL cell per 100,000 (<10-5) leukocytes. PFS was analyzed by MRD status at 3 months after treatment (EOT+3).RESULTSIbrutinib + venetoclax achieved deeper uMRD (<10-5) rates in bone marrow (BM) and peripheral blood (PB), respectively, in 40.6% and 43.4% of patients at EOT+3 versus 7.6% and 18.1% of patients receiving chlorambucil + obinutuzumab. Of these patients, uMRD (<10-5) in PB was sustained during the first year post-treatment (EOT+12) in 80.4% of patients receiving ibrutinib + venetoclax and 26.3% receiving chlorambucil + obinutuzumab. Patients with detectable MRD (dMRD; ≥10-4) in PB at EOT+3 were more likely to sustain MRD levels through EOT+12 with ibrutinib + venetoclax versus chlorambucil + obinutuzumab. PFS rates at EOT+12 were high among patients treated with ibrutinib + venetoclax regardless of MRD status at EOT+3: 96.3% and 93.3% in patients with uMRD (<10-4) and dMRD (≥10-4) in BM, respectively, versus 83.3% and 58.7% for patients receiving chlorambucil + obinutuzumab. PFS rates at EOT+12 also remained high in patients with unmutated immunoglobulin heavy-chain variable region (IGHV) receiving ibrutinib + venetoclax, independent of MRD status in BM.CONCLUSIONMolecular and clinical relapses were less frequent during the first year post-treatment with ibrutinib + venetoclax versus chlorambucil + obinutuzumab regardless of MRD status at EOT+3 and IGHV status. Even for patients not achieving uMRD (<10-4), PFS rates remained high with ibrutinib + venetoclax; this is a novel finding and requires additional follow-up to confirm its persistence over time

CLL-106 First Prospective Data on Minimal Residual Disease Outcomes After Fixed-Duration Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for First-Line Treatment of CLL in Older Adult or Unfit Patients: The GLOW Study

Context: Minimal residual disease (MRD) is a predictive marker for progression-free survival (PFS) in chronic leukocytic leukemia (CLL) following chemoimmunotherapy and fixed-duration treatment with venetoclax and anti-CD20 antibodies. This has not been explored for ibrutinib+venetoclax (Ibr+Ven), a fixed-duration treatment with mechanisms of action that synergistically eliminate CLL subpopulations in distinct tumor compartments. Objective: Investigate MRD outcomes at primary analysis of phase 3 GLOW study (NCT03462719). Design: Randomized, open-label, active-control study. Patients: Patients aged ≥65 years or 18–64 years with a CIRS score >6 or creatinine clearance 90% for patients with uMRD<10–4 and patients with detectable MRD; however, Clb+O arm patients with detectable PB MRD relapsed more quickly than those with uMRD<10–4. Conclusions: All-oral, once-daily, fixed-duration Ibr+Ven demonstrated superior uMRD responses that were deeper and better sustained post-treatment versus Clb+O in older adult or unfit patients with previously untreated CLL

CLL-106 First Prospective Data on Minimal Residual Disease Outcomes After Fixed-Duration Ibrutinib Plus Venetoclax Versus Chlorambucil Plus Obinutuzumab for First-Line Treatment of CLL in Older Adult or Unfit Patients: The GLOW Study

Context: Minimal residual disease (MRD) is a predictive marker for progression-free survival (PFS) in chronic leukocytic leukemia (CLL) following chemoimmunotherapy and fixed-duration treatment with venetoclax and anti-CD20 antibodies. This has not been explored for ibrutinib+venetoclax (Ibr+Ven), a fixed-duration treatment with mechanisms of action that synergistically eliminate CLL subpopulations in distinct tumor compartments. Objective: Investigate MRD outcomes at primary analysis of phase 3 GLOW study (NCT03462719). Design: Randomized, open-label, active-control study. Patients: Patients aged ≥65 years or 18–64 years with a CIRS score >6 or creatinine clearance 90% for patients with uMRD<10–4 and patients with detectable MRD; however, Clb+O arm patients with detectable PB MRD relapsed more quickly than those with uMRD<10–4. Conclusions: All-oral, once-daily, fixed-duration Ibr+Ven demonstrated superior uMRD responses that were deeper and better sustained post-treatment versus Clb+O in older adult or unfit patients with previously untreated CLL