Prospective pilot study of adoptive immunotherapy with autologous αβT cells for five cases of advanced and/or recurrent esophageal squamous cell carcinoma

Abstract

Background

Although several clinical trials of vaccination and cellular immunotherapy for esophageal cancer have been reported, clinical trials of anti-CD3-activated autologous αβT cell therapy for patients with esophageal squamous cell carcinoma are limited.

Method

A total of five patients with recurrent esophageal squamous cell carcinoma were enrolled in this prospective pilot study. Peripheral blood mononuclear cells from the patients were cultured with immobilized anti-CD3 antibody and interleukin-2 for approximately 14 days, and 5 × 10⁹ lymphocytes were harvested. Expanded lymphocytes were intravenously infused every 2 weeks for six courses. All patients were followed up until death. The treatment response was assessed by the number of lymphocytes, CD4/CD8 ratio, serum tumor markers, and computed tomography scan.

Results

A total of 23 courses of treatment were completed. Three of the five patients (cases 2, 3, and 4) completed six courses of cell therapy according to the protocol. However, case 1 quit treatment after three courses and case 5 quit treatment after two courses because of tumor progression. There were no adverse effects related to cell therapy. Although cases 1 and 5 did not show any treatment benefits, cases 2, 3, and 4 showed some treatment benefits. Cases 2 and 4 showed long-term survived for more than 1 year.

Conclusion

These results might suggest the safety and benefits of anti-CD3-activated autologous αβT cell therapy for the part of the patients with esophageal squamous cell carcinoma.

http://ift.tt/2pkZUIO

Assessment of Neuronal Viability Using Fluorescein Diacetate-Propidium Iodide Double Staining in Cerebellar Granule Neuron Culture

This protocol describes how to accurately measure neuronal viability using Fluorescein diacetate (FDA) and Propidium Iodide (PI) double staining in cultured cerebellar granule neurons, a primary neuronal culture used as an in vitro model in neuroscience and neuropharmacology research.

http://ift.tt/2pl3DGw

Complete response to anti-PD-1 nivolumab in massive skin metastasis from melanoma: efficacy and tolerability in an elderly patient.

The advent of immune checkpoint inhibitors anti-PD-1/PD-L1 has delivered new and effective treatment options with proven clinical benefits for patients affected by metastatic melanoma. The 30-40% of treated patients experience an objective tumour regression, with a significantly prolonged survival and an improved quality of life. Here, we report a case of a 75-year-old Caucasian woman affected by a massive cutaneous metastasis from a BRAF wild-type melanoma who experienced multiple relapses after surgery and repeated electrochemotherapy treatments. A poor response was observed after systemic therapy with ipilimumab, whereas a marked reduction in the lesion size was obtained during the treatment with nivolumab, with an objectively complete response after 6 months. Therapy was well tolerated, without immune-related side effects. During treatment, LDH levels decreased up to the standard values. Our experience confirms the good efficacy and the safety of anti-PD-1 nivolumab for the treatment of relapsed or refractory massive skin lesions, also in elderly patients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2q6S5Uo

Report of two cases of acute cardiac adverse events in patients with colorectal carcinoma receiving oral capecitabine.

Capecitabine is an oral fluoropyrimidine chemotherapeutic agent, which, after oral administration, is metabolized to its active cytotoxic compound: 5-fluorouracil (5-FU). Cardiotoxicity is a recognized side effect of 5-FU, a closely related fluorinated pyrimidine antagonist. In the present report, we report on two patients who were admitted to our department after being treated with oral capecitabine for colorectal carcinoma and developed symptoms and signs of acute myocardial infarction that resolved after appropriate treatment and monitoring. The above two cases are discussed in the context of fluoropyrimidine, 5-FU, and capecitabine-induced cardiotoxicity; in addition, a detailed literature review of relevant cases and patient series reports is presented. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2qTWTz7

Imaging of the coracoglenoid ligament: a third ligament in the rotator interval of the shoulder

Abstract

Objective

The coracoglenoid ligament (CGL) forms part of the anterosuperior capsuloligamentous complex of the shoulder. Although it has received attention in the anatomical literature, it has not been investigated on imaging. The purpose of this study is to determine the percentage value and the interobserver agreement of identification and classification of the CGL on MR and MR arthrography (MRA) imaging.

Materials and methods

Retrospectively, 280 MR and 150 MRA examinations were evaluated for detection of the CGL by two musculoskeletal radiologists. On the MRA examinations the CGL configuration in relation to the superior glenohumeral (SGHL) and coracohumeral ligament (CHL) was classified into five types. Additionally, the percentage of intra-articular appearance of the CGL and its mean thickness value were calculated. Finally, a possible correlation between pathological condition and anatomical type was evaluated on MRA.

Results

The CGL could be identified in 56%/54% of MRI and in 76%/77% of MRA examinations. On MRA, the CGL was detected as distinct structures in 37%/35% of cases and it appeared fused (partially or totally) with the SGHL and/or CHL in 39%/42%; it was absent in 12%/12% and it appears undistinguishable in the remaining cases. The interobserver agreement was excellent (κ = 0.98 for detection on MRI; p = 0.927 for classification of anterosuperior anatomy on MRA; κ = 0.873 and 0.978 for identification on sagittal and axial external rotation MRA respectively; κ = 0.943 for classification as intra- or extra-articular on MRA).

Conclusions

The CGL can be reliably identified on MRI and MRA.

http://ift.tt/2qswyZl

Transhepatic arterial infusion chemotherapy using a combination of miriplatin and CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma: a randomized controlled trial

Abstract

Background

Based on promising results from a Phase I study of hepatic arterial infusion chemotherapy using a combination of miriplatin and cisplatin powder (DDP-H) for unresectable hepatocellular carcinoma (UMIN-CTR000003541), a multicenter, open-label, randomized phase II study was conducted to evaluate the efficacy and safety of the combination therapy versus miriplatin monotherapy.

Methods

Nineteen patients, five and fourteen Barcelona-Clinic Liver Cancer staging classification A and B cases, respectively, were randomly assigned to receive either miriplatin monotherapy (n = 9) or miriplatin/DDP-H combination therapy (n = 10). DDP-H and/or miriplatin were administered through the hepatic arteries supplying the lobes of the liver containing tumors, and progression free survival was analyzed as a primary end point in addition to other secondary endpoints. The corresponding therapy was repeated unless disease progression or severe adverse events were recorded.

Results

The monotherapy or combination therapy was performed for 15 or 36 sessions in total, respectively. Although there were no significant differences between the two groups for treatment intervals (p = 0.96) or the dose of miriplatin used in each session (p = 0.99), the progression free survival and overall disease control rate were significantly better in the combination therapy group (91 vs 423 days, p = 0.025; 40.0 vs 77.8%, p = 0.0025, respectively). Consistent with these observations, a trend of a significantly slower increase in des-γ-carboxyprothrombin was observed, and the number of treatment sessions was nearly significantly larger in the combination therapy group (p < 0.0001, p = 0.057, respectively). Conversely, the median survival time did not show a significant difference (706 days, monotherapy vs 733 days, combination therapy; p = 0.40). A significant decrease in cholinesterase was observed during the course of treatment only in patients receiving combination therapy (r = −0.86, p < 0.0001). A few cases in both arms showed hematological and/or non-hematological toxicities that were categorized as grade 1 (NCI-CTCAE).

Conclusions

The higher disease control effects with the combination of miriplatin and DDP-H indicate that it is a promising alternative treatment for cases with multiple HCCs, especially for those that can tolerate the treatment without experiencing a reduction in hepatic reserve.

Trial registration

This study was registered on 1 January 2012 with the University Hospital Medical Information Network Clinical Trials Registry (http://ift.tt/1lXJedE, UMIN000004691).

http://ift.tt/2q3R1lH

The effects of video game therapy on balance and attention in chronic ambulatory traumatic brain injury: an exploratory study

Patients with traumatic brain injury often have balance and attentive disorders. Video game therapy (VGT) has been proposed as a new intervention to improve mobility and attention through a reward-learning app...

http://ift.tt/2q3VvZT