BackgroundThe efficacy of the 8-aminoquinoline (8AQ) drug primaquine (PQ) has been historically linked to CYP-mediated metabolism. Although to date no clear evidence exists in the literature that unambiguously assigns the metabolic pathway or specific metabolites necessary for activity, recent literature suggests a role for CYP 2D6 in the generation of redox active metabolites.MethodsIn the present study, the specific CYP 2D6 inhibitor paroxetine was used to assess its effects on the production of specific phenolic metabolites thought to be involved in PQ efficacy. Further, PQ causal prophylactic (developing liver stage) efficacy against Plasmodium berghei in CYP 2D knockout mice was assessed in comparison with a normal C57 background and with humanized CYP 2D6 mice to determine the direct effects of CYP 2D6 metabolism on PQ activity.ResultsPQ exhibited no activity at 20 or 40 mg/kg in CYP 2D knockout mice, compared to 5/5 cures in normal mice at 20 mg/kg. The activity against developing liver stages was partially restored in humanized CYP 2D6 mice.ConclusionsThese results unambiguously demonstrate that metabolism of PQ by CYP 2D6 is essential for anti-malarial causal prophylaxis efficacy.

Although the development of multi-disciplinary management has improved the survival of colorectal cancer (CRC), the prognosis of metastatic CRC patients remains poor. Accumulating evidence has demonstrated that immunotherapy with cancer vaccines and adoptive T cell transfusions may improve outcomes as an adjuvant to current standard CRC treatment. In this phase I/II study, 71 CRC patients who underwent radical surgery (stage I–III, n = 46) or palliative surgery (stage IV with non-resectable synchronous metastases, n = 25) were included. In the first part of this study, sentinel lymph nodes (SLNs) were intraoperatively identified in 55 patients (46 with stage I–III CRC and 9 with stage IV CRC). SLN-T lymphocytes were expanded ex vivo for a median of 28.5 days (range 23–33 days). Thereafter, a median of 153 × 106 cells (range 20.7–639.0 × 106) were transfused. No treatment-related toxicity was observed. In the second part of this study, the stage IV patients were routinely followed. The 24-month survival rate of the SLN-T lymphocyte group was significantly higher than that of the control group: 55.6 versus 17.5 % (p = 0.02). The median overall survival of the SLN-T lymphocyte and control groups was 28 and 14 months, respectively. Our study showed that adjuvant SLN-T lymphocyte immunotherapy is feasible and safe for postoperative CRC patients. Additionally, this therapy may improve the long-term survival of metastatic CRC. Further investigation of the clinical efficacy and anti-tumor immunity is warranted.

BackgroundThe presence of food-specific IgG antibodies in human serum may be useful for diagnosis of adverse food reactions. However, the clinical utility of tesing for such antibodies remains very controversial. The aim of this study was to evaluate the serum levels and population distribution of food-specific IgGs and their association with chronic symptoms in a large-scale Chinese population.Methodology/Principal FindingsA total of 21305 adult participants from different regions of China had 14 type of food-specific serum IgG antibodies that were measured by enzyme-linked immunosorbent assay. Amongthese, 5,394 participants were randomly chosen to complete follow-up questionnaire surveys on their dietary characteristics and chronic symptoms. The concentrations of food-specific IgGs against 14 foods ranged from a median (interquartile range) of 7.3 (3.8, 12.6) U/mL of pork-specfic IgG to 42.3 (28.8, 60.2) U/mL of crab-specific IgG. The concentration of food-specific IgGs was closely related to gender; after adjustment for region and age, women had higher concentrations of food-specific IgGs against all of the 14 foods except chicken (regression coefficient (95% CI): 0.01 (−0.003, 0.023); P = 0.129) and corn (0.002 (−0.013, 0.016); P = 0.825). Similar results were also found in the relationship of geographic region to the food-specific IgG concentrations for the 14 foods. Chronic symptoms were negatively associated with the concentrations of a few food-specific IgGs, and were positively associated with the concentrations of other food-specific IgGs.ConclusionsThe levels of food-specific IgGs were variable both in healthy and in symptomatic Chinese adults. These findings raise awareness that demographic factors, the type of food and specific chronic symptoms should be considered before food elimination treatment based on IgG testing in patients with chronic symptoms is used in clinical practice.

To investigate the anti-tumor efficacy and safety of adoptive cell therapy for the treatment of relapsed, refractory or chemotherapy-resistant lymphoma, we conducted a pilot clinical study using autologous anti-CD3 expanded T cells derived from patients with the diseases. A total of 12 patients, who were pathologically diagnosed with malignant lymphoma at various stages were enrolled in the study. PBMCs from the immunotherapy group were collected and expanded by anti-CD3 in the presence of IFNγ and IL2. The expanded T cells were then infused back to the patients, who were assessed for changes in lymphocyte subgroups, tumor-related biological parameters, imaging characteristics, and the condition of remission and survival. The overall response rate (ORR) to the therapy was 66.7% of the treated patients achieving the complete response (CR) and partial response (PR), with a median progression-free survival (PFS) of 43 months and median overall survival (OS) of 54 months separately. No severe toxicity or side effects were observed. Also, we found new factors influencing the clinical outcomes. The higher percentages of CD4 + T cells and CD4 + HLA