Selective Photokilling of Colorectal Tumors by Near-Infrared Photoimmunotherapy with a GPA33-Targeted Single-Chain Antibody Variable Fragment Conjugate.

Antibody-based near-infrared photoimmunotherapy (NIR-PIT) is an attractive strategy for cancer treatment. Tumor cells can be selectively and efficiently killed by the targeted delivery of an antibody-photoabsorber complex followed by exposure to NIR light. Glycoprotein A33 antigen (GPA33) is highly expressed in most human colorectal cancers (CRCs) and is an ideal diagnostic and therapeutic target. We previously produced a single-chain fragment of a variable antibody against GPA33 (A33scFv antibody). Here, we investigate the efficacy of NIR-PIT by combining A33scFv with the NIR photoabsorber IR700 (A33scFv-IR700). In vitro, recombinant A33scFv displayed specific binding and delivery of an NIR dye to GPA33-positive tumor cells. Furthermore, A33scFv-IR700-mediated NIR-PIT was successful in rapidly and specifically killing GPA33-positive colorectal tumor cells. NIR-PIT treatment induced the release of lactate dehydrogenase from tumor cells, followed by cell necrosis, rather than apoptosis, through the promotion of reactive oxygen species accumulation in tumor cells. In mice bearing LS174T tumor grafts, A33scFv selectively accumulated in GPA33-positive tumors. Following only a single injection of the conjugate and subsequent illumination, A33scFv-IR700-mediated NIR-PIT induced a significant increase in therapeutic response in LS174T-tumor mice compared with that in the non-NIR-PIT groups (p < 0.001). Because the GPA33 antigen is specifically expressed in CRC tumors, A33scFv-IR700 might be a promising antibody fragment-photoabsorber conjugate for NIR-PIT of CRC.

The efficacy of traditional Chinese Medicine as an adjunctive therapy in nasopharyngeal carcinoma: a systematic review and meta-analysis.

PURPOSE: The purpose of this systematic review was to assess the efficacy of traditional Chinese Medicine (TCM) as an adjunctive therapy to radiotherapy (RT) and/or chemotherapy (CT) for patients with nasopharyngeal carcinoma (NPC). METHODS: Randomized controlled trials (RCTs) with TCM to treat NPC were extensively searched in eight databases. Two researchers independently assessed the quality and validity of the included trials and extracted outcome data. Thirteen RCTs were included for analysis. RESULTS: Compared to using RT and/or CT, TCM combined with conventional cancer therapy had significantly improved Karnofsky performance status (KPS) [odds ratio (OR) 4.81, 95% confidence interval (CI) 3.06-7.56]. TCM as an adjunctive therapy significantly reduced the serious adverse effects of RT to the oral mucosa and skin so that grade I+II prevailed [OR 2.19, 95% CI 1.31-3.66; OR 8.63, 95% CI 3.28-22.70, respectively]. The combined therapy significantly enhanced immunoregulation, improving the levels of CD3, CD4 T cells (OR 10.08, 95% CI 1.38-18.78; OR 7.08, 95% CI 2.41-11.74, respectively). CONCLUSIONS: This systematic review suggests that TCM as a therapy adjunctive to RT and/or CT vs only RT and/ or CT has significant efficacy in terms of improvement of quality of life (QoL), alleviation of acute adverse effects, and enhancement of immunoregulation.

Novel method for vestibular evoked myogenic potentials: technique and reproducibility.

OBJECTIVE: A novel method was employed to control the sternocleidomastoid muscle contraction level during vestibular evoked myogenic potential (VEMP) measurement. STUDY DESIGN: A prospective study to measure the normal VEMP response. SETTINGS: A pressure feedback device composed of a firm rubber bulb and a pressure gauge was employed to monitor the muscular contraction level during measurement. METHODS: Nineteen normal-hearing subjects (12 males; mean age 34.0 ± 7.7 years) were tested. Subjects were instructed to position the chin on the rubber bulb and use the neck flexors to maintain a pressure of 120 mm Hg during the measurement. MAIN OUTCOME MEASURES: The P13 latencies, N23 latencies, and P13-N23 amplitudes were recorded. In nine subjects, the reproducibility of the technique was tested weekly for 3 consecutive weeks. RESULTS: The average (± SD) latency of P13 was 13.97 ± 1.33 ms, and the latency of N23 was 24.03 ± 1.79 ms. The average amplitude was 66.89 ± 44.1 µV. There was no significant difference between right and left ears in P13 latencies, N23 latencies, and P13-N23 amplitudes. In nine subjects, the average measured interclass correlation coefficient was 0.97 in amplitude, 0.8 in P13 latency, and 0.93 in N23 latency in three consecutive weekly measurements. CONCLUSIONS: The chin-rest pressure feedback method is easy to perform during VEMP testing. Subjects can maintain a constant level of sternocleidomastoid contraction and neck flexion to facilitate this response with a high degree of test-retest reliability. This technique provides a means to compare VEMPs across different clinical scenarios over time.

Long-term sound conditioning increases distortion product otoacoustic emission amplitudes and decreases olivocochlear efferent reflex strength.

The cochlea can be protected from acoustic trauma by moderate-level sound exposure. It is suggested that olivocochlear system may play a significant role in this protection. This study was performed to investigate distortion product otoacoustic emission (DPOAE) amplitudes changes and the efficiency of contralateral noise stimulation on DPOAE after conditioning noise exposure. Our results demonstrate that long-term conditioning can increase the DPOAE amplitudes at low frequencies (1.0-3.0 kHz) and decrease the olivocochlear efferent reflex strength at the same frequencies. The DPOAE amplitudes are partially restored to the preconditioning levels 2 weeks after conditioning; contralateral suppression also returns to the preconditioning levels. These results suggest that the enhancement of DPOAE amplitudes might be due to a decrease in olivocochlear efferent reflex strength.