Doxorubicin and paclitaxel enhance the antitumor efficacy of vaccines directed against HER 2/neu in a murine mammary carcinoma model

INTRODUCTION: The purpose of the present study was to determine whether cytotoxic chemotherapeutic agents administered prior to immunotherapy with gene vaccines could augment the efficacy of the vaccines. METHODS: Mice were injected in the mammary fat pad with an aggressive breast tumor cell line that expresses HER2/neu. The mice were treated 3 days later with a noncurative dose of either doxorubicin or paclitaxel, and the following day with a gene vaccine to HER2/neu. Two more doses of vaccine were given 14 days apart. Two types of gene vaccines were tested: a plasmid vaccine encoding a self-replicating RNA (replicon) of Sindbis virus (SINCP), in which the viral structural proteins were replaced by the gene for neu; and a viral replicon particle derived from an attenuated strain of Venezuelan equine encephalitis virus, containing a replicon RNA in which the Venezuelan equine encephalitis virus structural proteins were replaced by the gene for neu. RESULTS: Neither vaccination alone nor chemotherapy alone significantly reduced the growth of the mammary carcinoma. In contrast, chemotherapy followed by vaccination reduced tumor growth by a small, but significant amount. Antigen-specific CD8(+ )T lymphocytes were induced by the combined treatment, indicating that the control of tumor growth was most probably due to an immunological mechanism. The results demonstrated that doxorubicin and paclitaxel, commonly used chemotherapeutic agents for the treatment of breast cancer, when used at immunomodulating doses augmented the antitumor efficacy of gene vaccines directed against HER2/neu. CONCLUSIONS: The combination of chemotherapeutic agents plus vaccine immunotherapy may induce a tumor-specific immune response that could be beneficial for the adjuvant treatment of patients with minimal residual disease. The regimen warrants further evaluation in a clinical setting

A Dentist-Led Oral Care System Can Prevent Stroke-Associated Pneumonia: The Effects of Early Intervention by Dental Team

Kenichiro Ozaki,1,2 Haruka Tohara,2 Mikoto Baba,1 Satoshi Teranaka,1,3 Yosuke Kawai,1,3 Satoru Komatsumoto4,5 1Department of Physical Medicine and Rehabilitation, Ashikaga Red Cross Hospital, Ashikaga, Tochigi, Japan; 2Dysphagia Rehabilitation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan; 3Gerodontology and Oral Rehabilitation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo, Tokyo, Japan; 4Ashikaga Red Cross Hospital, Ashikaga, Tochigi, Japan; 5Fujita Health University, Toyoake, Aichi, JapanCorrespondence: Kenichiro Ozaki, Department of Physical Medicine and Rehabilitation, Ashikaga Red Cross Hospital, 284-1, Yobe-cho, Ashikaga, Tochigi, 326-0843, Japan, Tel +81-284-21-0121, Fax +81-284-21-6810, Email [email protected]: Our facility’s dental team consists of a full-time dentists and dental hygienists who work exclusively in the wards to implement best practices in oral healthcare. We executed the dental care system (DCS) that includes lectures and practical training for nurses conducted by dentists and dental hygienists, the introduction to oral assessment, standardization of oral care procedures, a process for nurses to request the dental team, and early bedside oral screening conducted by the dental team. This study investigated the DCS’s effects on the incidence of stroke-associated pneumonia (SAP).Methods: This single-center retrospective cohort study included 2,771 acute stroke patients who were newly hospitalized between April 1, 2012, and March 31, 2020. The 8-year period was divided into four phases at two-year intervals as follows: Pre (N=632), Post-1 (N=642), Post-2 (N=716), and Post-3 (N=781). Pre was prior to DCS practice. Post-1 was an early introduction to DCS. Post-2 simplified dental team requests from nurses, and Post-3 added bedside oral screening within 72 hours of admission by the dental team. Statistical analysis was performed using the Cochran-Armitage trend test, followed by multivariate logistic regression.Results: A decrease in SAP rates was observed across the four groups (P< 0.0001). Logistic regression analysis revealed a significant difference for respiratory disease (odds ratio 7.74, 95% confidence interval 5.49– 10.90), hypertension (2.28, 1.39– 3.73), cardiac failure (1.72, 1.04– 2.85), and diabetes (1.59, 1.11– 2.26), 3-digit code on the Japan coma scale (3.57, 2.53– 5.05 [reference ≤ 2-digit code]), age ≥ 90 years (2.34, 1.15– 4.77 [reference 18– 59 years]), male (1.86, 1.31– 2.67), and the Post-1 (0.49, 0.31– 0.76 [reference Pre]), Post-2 (0.38, 0.25– 0.61 [reference Pre]), and Post-3 (0.24, 0.15– 0.40 [reference Pre]) periods.Conclusion: The suppression of SAP is effectively achieved through early intervention and education of nurses by dental professionals.Plain Language Summary: Pneumonia is a dangerous disease that kills millions of individuals around the world every year. Stroke patients are susceptible to developing pneumonia because their swallowing reflex is sometimes impaired. This risk may be reduced by maintaining oral hygiene through advanced oral care involving dentists and dental hygienists. For this reason, our acute care hospital has a dental team consisting of a full-time dentists and dental hygienists dedicated to the ward. In 2014, the dental team launched a program for nurses on how to provide oral care to inpatients. Additionally, we have introduced a system that enables nurses to contact the dental team immediately if oral care becomes difficult for nurses due to problems in the patient’s mouth. Furthermore, the dental team began evaluating the oral health of all stroke patients within 72 hours after hospitalization. We studied the changes in the frequency of pneumonia in stroke patients at our hospital before the application of this approach and 6 years after its introduction. The rate of pneumonia decreased steadily during this period. Overall, the pneumonia rates in stroke patients at our hospital reduced by approximately 60%, suggesting that this system is an effective way to prevent pneumonia.Keywords: hospital dental services, hospital dentistry, special care dentistry, oral health management, oral care, acute stroke, stroke-associated pneumonia, team approac

Serotonin and Neuropeptides in Blood From Episodic and Chronic Migraine and Cluster Headache Patients in Case‐Control and Case‐Crossover Settings: A Systematic Review and Meta‐Analysis

Objective: The aim of this systematic review and meta-analysis (SR-MA) was to identify signaling molecule profiles and blood-derived biomarkers in migraine and cluster headache (CH) patients. Background: Currently no migraine and CH valid biomarkers are available. Blood tests based on biomarker profiles have been used to gather information about the nervous system. Such tests have not yet been established within the primary headache field. Methods: Case-control and case-crossover studies investigating whole blood, plasma, and serum were identified worldwide. The qualitative synthesis focused on 9 signaling molecules (serotonin [5-HT], calcitonin gene-related peptide [CGRP], endothelin-1 [ET-1], neurokinin A, neurokinin B, neuropeptide Y, pituitary adenylate cyclase-activating peptide 38 [PACAP-38], substance P (SP), and vasoactive intestinal peptide) and the quantitative synthesis on 5-HT and CGRP (≥5 comparisons available). The meta-analysis was conducted using standard and 3-level random effect models. Results: Fifty-four eligible studies were identified (87.0% migraine, 9.3% CH, 3.7% migraine, and CH), and 2768 headache patients and 1165 controls included. Comparable fluctuations of 5-HT, CGRP, ET-1, PACAP-38, and SP in blood were generally observed between migraine and CH. Significant findings were observed for some subgroups and strata, for example, higher interictal and ictal 5-HT venous blood levels (ratio of means = 1.32, 95% CI: 1.08; 1.61; ratio of means = 1.23, 95% CI: 1.01; 1.49) in episodic migraine with aura with a female-dominated case group, higher interictal CGRP blood levels in episodic migraine (ratio of means = 1.63, 95% CI: 1.18; 2.26), and chronic migraine (ratio of means = 1.89, 95% CI: 1.33; 2.68), and higher ictal CGRP blood levels (ratio of means = 1.35, 95% CI: 1.09; 1.68) in episodic migraine were observed. In most subgroups, the quantitative synthesis revealed a high degree of heterogeneity between studies in part explained by the blood sampling site, specimen source, blood specimen, and sex distribution. Other potential confounders were age, aura, study quality, menstrual cycle, and methodology (eg, storage temperature). Conclusions: Potential migraine and CH signaling molecule profiles and biomarkers were revealed. Nevertheless, the high degree of heterogeneity between studies impedes identification of valid biomarkers but allowed us to assess the presence of confounders. Consideration of the potential confounders identified in this SR-MA might be of importance in the experimental planning of future studies. This consideration could be incorporated through establishment of specific guidelines