A phase I trial of autologous RAK cell immunotherapy in metastatic renal cell carcinoma.

BACKGROUND: Treatment of metastatic renal cell carcinoma (mRCC) remains a challenge worldwide. Here, we introduced a phase I trial of autologous RAK cell therapy in patients with mRCC whose cancers progressed after prior systemic therapy. Although RAK cells have been used in clinic for many years, there has been no dose-escalation study to demonstrate its safety and efficacy. METHODS: We conducted a phase I trial with a 3 + 3 dose-escalation design to investigate the dose-related safety and efficacy of RAK cells in patients with mRCC whose cancers have failed to response to systemic therapy (ChiCTR1900021334). RESULTS: Autologous RAK cells, primarily composed of CD8+ T and NKT cells, were infused intravenously to patients at a dose of 5 × 109, 1 × 1010 or 1.5 × 1010 cells every 28 days per cycle. Our study demonstrated general safety of RAK cells in a total of 12 patients. Four patients (33.3%) showed tumor shrinkage, two of them achieved durable partial responses. Peripheral blood analysis showed a significant increase in absolute counts of CD3+ and CD8+ T cells after infusion, with a greater fold change observed in naive CD8+ T cells (CD8+CD45RA+). Higher peak values of IL-2 and IFN-γ were observed in responders after RAK infusion. CONCLUSION: This study suggests that autologous RAK cell immunotherapy is safe and has clinical activity in previously treated mRCC patients. The improvement in peripheral blood immune profiling after RAK cell infusion highlights its potential as a cancer treatment. Further investigation is necessary to understand its clinical utility.

Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment.

Macrophages and tumour stroma cells account for the main cellular components in the tumour microenvironment (TME). Current advancements in single-cell analysis have revolutionized our understanding of macrophage diversity and macrophage-stroma interactions. Accordingly, this review describes new insight into tumour-associated macrophage (TAM) heterogeneity in terms of tumour type, phenotype, metabolism, and spatial distribution and presents the association between these factors and TAM functional states. Meanwhile, we focus on the immunomodulatory feature of TAMs and highlight the tumour-promoting effect of macrophage-tumour stroma interactions in the immunosuppressive TME. Finally, we summarize recent studies investigating macrophage-targeted therapy and discuss their therapeutic potential in improving immunotherapy by alleviating immunosuppression.

A review: potential application and outlook of photothermal therapy in oral cancer treatment.

As one of the most common malignant tumors, oral cancer threatens people's health worldwide. However, traditional therapies, including surgery, radiotherapy, and chemotherapy cannot meet the requirement of cancer cure. Photothermal therapy (PTT) has attracted widespread attentions for its advantages of the noninvasive process, few side effects, and promising tumor ablation. Up to now, three types of photothermal agents (PTAs) have been widely employed in oral cancer therapies, which involve metallic materials, carbon-based materials, and organic materials. Previous research mainly introduced hybrid materials due to benefits from the synergistic effect of multiple functions. In this review, we present the advancement of each type PTAs for oral cancer treatment in recent years. In each part, we introduce the properties and synthesis of each PTA, summarize the current studies, and analyze their potential applications. Furthermore, we discuss the status quo and the deficiencies hindering the clinical application of PTT, based on which gives the perspective of its future developing directions.

The Role of Metacognitive Components in Creative Thinking.

Metacognition refers to the knowledge and regulation of one's own cognitive processes, which has been regarded as a critical component of creative thinking. However, the current literature on the association between metacognition and creative thinking remains controversial, and the underlying role of metacognition in the creative process appears to be insufficiently explored and explained. This review focuses on the roles of three aspects of metacognition (i.e., metacognitive knowledge, metacognitive experience, and metacognitive monitoring and control) in creative thinking and offers a primary summary of the neurocognitive mechanisms that support metacognition during creative thinking. Future research is needed to explore the interactive effects of the metacognitive components on creative thinking and to elucidate the function of metacognition during different stages of the creative process.

Effect of individual thinking styles on item selection during study time allocation.

The influence of individual differences on learners' study time allocation has been emphasised in recent studies; however, little is known about the role of individual thinking styles (analytical versus intuitive). In the present study, we explored the influence of individual thinking styles on learners' application of agenda-based and habitual processes when selecting the first item during a study-time allocation task. A 3-item cognitive reflection test (CRT) was used to determine individuals' degree of cognitive reliance on intuitive versus analytical cognitive processing. Significant correlations between CRT scores and the choices of first item selection were observed in both Experiment 1a (study time was 5 seconds per triplet) and Experiment 1b (study time was 20 seconds per triplet). Furthermore, analytical decision makers constructed a value-based agenda (prioritised high-reward items), whereas intuitive decision makers relied more upon habitual responding (selected items from the leftmost of the array). The findings of Experiment 1a were replicated in Experiment 2 notwithstanding ruling out the possible effects from individual intelligence and working memory capacity. Overall, the individual thinking style plays an important role on learners' study time allocation and the predictive ability of CRT is reliable in learners' item selection strategy.

The Effect of Word Frequency on Judgments of Learning: Contributions of Beliefs and Processing Fluency.

Previous research has shown that word frequency affects judgments of learning (JOLs). Specifically, people give higher JOLs for high-frequency (HF) words than for low-frequency (LF) words. However, the exact mechanism underlying this effect is largely unknown. The present study replicated and extended previous work by exploring the contributions of processing fluency and beliefs to the word frequency effect. In Experiment 1, participants studied HF and LF words and made immediate JOLs. The findings showed that participants gave higher JOLs for HF words than for LF ones, reflecting the word frequency effect. In Experiment 2a (measuring the encoding fluency by using self-paced study time) and Experiment 2b (disrupting perceptual fluency by presenting words in an easy or difficult font style), we evaluated the contribution of processing fluency. The findings of Experiment 2a revealed no significant difference in self-paced study time between HF and LF words. The findings of Experiment 2b showed that the size of word frequency effect did not decrease or disappear even when presenting words in a difficult font style. In Experiment 3a (a questionnaire-based study) and Experiment 3b (making pre-study JOLs), we evaluated the role of beliefs in this word frequency effect. The results of Experiment 3a showed that participants gave higher estimates for HF as compared to LF words. That is, they estimated that hypothetical participants would better remember the HF words. The results of Experiment 3b showed that participants gave higher pre-study JOLs for HF than for LF words. These results across experiments suggested that people's beliefs, not processing fluency, contribute substantially to the word frequency effect on JOLs. However, considering the validation of the indexes reflecting the processing fluency in the current study, we cannot entirely rule out the possible contribution of processing fluency. The relative contribution of processing fluency and beliefs to word frequency effect and the theoretical implications were discussed.

Chain length dependence of the interactions of bisquaternary ligands with the Torpedo nicotinic acetylcholine receptor.

The interactions of a series of bisholine esters [(CH3)3N+CH(2)CH2OCO-(CH2)n-COOCH2CH2N+(CH3)3] with the Torpedo nicotinic acetylcholine receptor have been investigated. In equilibrium binding studies, [3H]-suberyldicholine (n=6) binds to an equivalent number of sites as [3H]-acetylcholine and with similar affinity (KD approximately 15 nM). In competition studies, all bischoline esters examined displaced both radioligands in an apparently simple competitive manner. Estimated dissociation constants (KI) showed clear chain length dependence. Short chain molecules (n6) had high affinity similar to suberyldicholine. Functional responses were measured by either rapid flux techniques using Torpedo membrane vesicles or voltage-clamp analyses of recombinant receptors expressed in Xenopus oocytes. Both approaches revealed that suberyldicholine (EC50 approximately 3.4 microM) is 14-25-fold more potent than acetylcholine. However, suberyldicholine elicited only about 45% of the maximum response of the natural ligand, i.e., it is a partial agonist. The potency of this bischoline series increased with chain length. Whereas the shorter ligands (nor=4) had similar (or higher) potency to suberyldicholine. Ligand efficacy had an approximately bell-shaped dependence on chain length and compounds where nor=8 were very poor partial agonists. Based on estimates of interonium distances, we suggest that bisquaternary ligands can interact with multiple binding sites on the nAChR and, depending on the conformational state of the receptor, these sites are 15-20A apart.

A study on sampling strategies in the figure cognitive process.

This study was aimed at investigating the sampling strategies for 2 types of figures: 3-D cubes and human faces. The research was focused on: (a) from where the sampling process started; (b) in what order the figures' features were sampled. The study consisted of 2 experiments: (a) sampling strategies for 3-D cubes; (b) sampling strategies for human faces. The results showed that: (a), for 3-D cubes, the first sampling was mostly located at the outline parts, rarely at the center part; while for human faces, the first sampling was mostly located at the hair and outline parts, rarely at the mouth or cheek parts, in most cases, the first sampling-position had no significant effects on cognitive performance and that (b), the sampling order, both for 3-D cubes and for human faces, was determined by the degree of difference among the sampled-features.

Characterization and evaluation of a novel anti-MUC-1 monoclonal antibody: induction of the idiotypic network in experimental mice.

OBJECTIVE: To investigate the anti-idiotypic effect induced by a monoclonal antibody. METHODS: A conventional fusion method was used to obtain hybridoma cells producing monoclonal antibody, which were detected by flow cytometry. ELISA were used to detect the humoral response induced by the antibody in mice. Cytotoxic and proliferation experiments were used to detect the cellular response induced by the antibody in mice. RESULTS: CS20 is a MUC-1 specific monoclonal antibody that strongly reacts with MUC-1 antigen expressed on the cell surface of breast cancer cells. The antibody could not kill tumor cells directly through complement-dependent cytotoxicity or antibody-dependent cell-mediated cytotoxicity. However, after 6 administrations of mAb CS20-KLH (keyhole limpet hemocyanin) conjugated to BALB/c mice (n = 5) at a dose of 50 micro g/mouse, anti-idiotypic antibodies and anti-anti-idiotypic antibodies were induced. T cells derived from CS20-KLH-immunized mice responded to mAb CS20, indicating the existence of idiotype-specific T cells. CONCLUSION: These data indicated the possibility of using MUC-1 specific antibody for active immunotherapy of breast cancer.

[Anti-CD19-liposomes encapsulated domain III of pseudomonas exotoxin in the targeting of human B lymphoma].

OBJECTIVE: To evaluate the targeting ability and cytotoxicity of domain III of pseudomonas exotoxin encapsulated in anti-CD19-immunoliposomes to lymphoma cells in vitro and in vivo. METHODS: Binding ability of anti-CD19 immunoliposomes to B lymphoma cells was detected by binding assay. MTT assay was used to detect the cytotoxicity of free domain III and domain III encapsulated in anti-CD19-immunoliposomes against B lymphoma cells. An in vivo therapeutic study of domain III formulated in immunoliposomes on human B lymphoma was detected in a murine model. RESULTS: The cytotoxicity of free domain III disappeared when domain I and II were deleted. When domain III was encapsulated into anti-CD19-immunoliposomes, the cytotoxicity of immunoliposomes against tumor cells were significantly increased. Treatment, using this formulation, of mice inoculated with B lymphoma could enhance the survival time. CONCLUSION: Anti-CD19-immunoliposomes, as drug carriers, can specifically recognize B lymphoma cells and deliver non-toxic domain III into the tumor cells. This formulation of domain III might be an effective anti-tumor agent.