Yi-Gan San (YGS), a traditional Chinese medicine for dementia-related symptoms, was previously fractionated. One active fraction, YGS40 exhibited a neuroprotective effect against glutamate-induced cytotoxicity. In the present study, high-performance liquid chromatography, coupled with diode-array detection and quadrupole time-of-flight mass spectrometry, was applied for the identification of its chemical constituents and for quantification studies. The chemical profile of YGS40 consisted of sixty-four identified or tentatively characterized compounds. The levels of the major marker compounds increased significantly in the mixed decoction compared with those in the single plant decoction. The results suggest the high precision of the analyses of most of the constituents in YGS40 and establish the quantitative variations of the major marker compounds between the single and mixed decoction processes.
Chromatography, Liquid ; Cytotoxins ; Drugs, Chinese Herbal ; analysis ; Glutamic Acid ; toxicity ; Mass Spectrometry ; Neuroprotective Agents ; analysis ; therapeutic use

Chemotherapy remains one of the major tools, along with surgery, radiotherapy, and more recently targeted therapy, in the war against cancer. There have appeared a plethora of highly potent cytotoxic drugs but the poor discriminability between cancerous and healthy cells of these agents limits their broader application in clinical settings. Therapeutic antibodies have emerged as an important class of biological anticancer agents, thanks to their ability in specific binding to tumor-associated antigens. While this important class of biologics can be used as single agents for the treatment of cancer through antibody-dependent cell cytotoxicity (ADCC), their therapeutical efficacy is often limited. Antitumor antibody drug conjugates (ADCs) combine the target-specificity of monoclonal antibody (mAb) and the highly active cell-killing drugs, taking advantages of the best characteristics out of both components. Thus, insufficiency of most naked mAbs in cancer therapy has been circumvented by arming the immunoglobulin with cytotoxic drugs. Here mAbs are used as vehicles to transport potent payloads to tumor cells. ADCs contain three main components: antibody, linker and cytotoxics (also frequently referred as payload). Antibodies can recognize and specifically bind to the tumor-specific antigens, leading to an antibody-assisted internalization, and payload release. While ADC has demonstrated tremendous success, a number of practical challenges limit the broader applications of this new class of anticancer therapy, including inefficient cellular uptake, low cytotoxicity, and off-target effects. This review article aims to cover recent advances in optimizing linkers with increased stability in circulation while allowing efficient payload release within tumor cells. We also attempt to provide some practical strategies in resolving the current challenges in this attractive research area, particularly to those new to the field.
Aminobenzoates ; pharmacology ; therapeutic use ; Animals ; Antibodies, Monoclonal ; pharmacology ; therapeutic use ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Cell Survival ; drug effects ; Cytotoxins ; pharmacology ; therapeutic use ; Drug Design ; Humans ; Immunoconjugates ; chemistry ; pharmacology ; therapeutic use ; Maytansine ; pharmacology ; therapeutic use ; Neoplasms ; drug therapy ; pathology ; Oligopeptides ; pharmacology ; therapeutic use

OBJECTIVETo study the immunosuppressive effect of the interleukin-2-pseudomonas exotoxin 66(IL-2-PE66) on murine corneal allograft rejection.

METHODSThirty-six recipient female BALB/c mice received corneal allografts from C57BL/6 mice and were divided randomly into treatment and control groups. The condition of the grafts was observed twice a week. On days 10, 15, 25 and 35 after the transplantation, the operated eyes were removed for pathological examinations. Peripheral blood samples were also collected for analysis of T cell subsets and T lymphocyte colony forming unit (T-CFU) assay.

RESULTSThe survival time of corneal allograft averaged 15.8-/+2.1 days in the control group and 31.2-/+2.9 days in the treatment group. The CD(4)(+)/ CD(8)(+)/ of the T cell subsets 15 days after the operation was 1.26-/+0.23 in the treatment group and 2.01-/+0.23 in the control group, with T-CFU of 201-/+18.2 and 286-/+16.8, respectively.

CONCLUSIONIL-2-PE66 can delay the development of corneal graft rejection, significantly reduce the percentage of T helper cells, and weaken the aggregation of the peripheral T cells.

Animals ; Bacterial Proteins ; therapeutic use ; Corneal Transplantation ; adverse effects ; Cytotoxins ; therapeutic use ; Exotoxins ; therapeutic use ; Female ; Graft Rejection ; drug therapy ; Graft Survival ; drug effects ; Immunosuppressive Agents ; therapeutic use ; Interleukin-2 ; therapeutic use ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Random Allocation ; Recombinant Fusion Proteins ; therapeutic use

As a newly emerged class of anticancer bioagents in the most precise and selectively targeted way, antibody-drug conjugate (ADC) combines the cancer-targeting abilities of monoclonal antibodies with the cytotoxicity potency of payload, delivering highly cytotoxic drug into tumors via 'targeted chemotherapy'. ADC has revolutionized the treatment landscape of human epidermal growth factor receptor 2 positive and triple negative subtypes in breast cancer. Three ADCs have been approved by U. S. Food and Drug Administration with breast cancer indications, including trastuzumab emtansine (T-DM1; also approved in China), trastuzumab deruxtecan (T-DXd, DS-8201) and sacituzumab govitecan (IMMU-132; also approved in China). Antibodies, cytotoxic drug, linker, and conjugation process are implicated in ADC profile, resulting in unique adverse drug reactions and toxicity heterogeneity within ADC class. For example, more attention should be paid to the management of thrombocytopenia, hepatotoxicity, and reductions in left ventricular ejection fraction (LVEF) in patients treated with trastuzumab emtansine; clinical physicians should pay attention to the risk of neutropenia, interstitial lung disease/pneumonitis, and reductions in LVEF when treated with trastuzumab deruxtecan; sacituzumab govitecan most frequently caused neutropenia, anemia and diarrhea requiring close monitor. ADC has generally favorable safety profiles, and dose modifications and/or symptomatic supporting treatment are effective in terms of toxicity management. This consensus aims at providing guidance for clinical oncologists of early detection, regular assessment, timely management and follow-up monitor of ADC-associated adverse reactions/events.
Ado-Trastuzumab Emtansine/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Antineoplastic Agents, Immunological/therapeutic use* ; Breast Neoplasms/therapy* ; Camptothecin/adverse effects* ; Consensus ; Cytotoxins/therapeutic use* ; Female ; Humans ; Immunoconjugates/therapeutic use* ; Neutropenia/etiology* ; Receptor, ErbB-2/metabolism* ; Trastuzumab/therapeutic use* ; Triple Negative Breast Neoplasms/therapy* ; Ventricular Function, Left