Vaccinia Virus GLV-1h153 Is Effective in Treating and Preventing Metastatic Triple-Negative Breast Cancer

OBJECTIVE:: This study aimed to investigate the therapeutic impact of a new oncolytic vaccinia virus in a triple-negative breast cancer (TNBC) murine model and its potential for treating distant metastatic disease. BACKGROUND:: TNBCs are aggressive tumors associated with a high metastatic rate. Their lack of targets for hormonal/biological therapy presents significant clinical challenges and a dire need for novel therapies. METHODS:: GLV-1h153, a replication-competent vaccinia virus, was tested against multiple cell lines. Cytotoxicity and viral replication were determined. Intratumoral (IT) or intravenous (IV) injection of GLV-1h153 (1 × 10 plaque-forming units) or phosphate buffered saline was tested in an orthotopic murine model, which reliably produces systemic metastasis. Tumors, lymph nodes, and metastatic organs (lung, liver, and brain) were harvested 5 and 8 weeks after treatment and prepared for histopathological review. Demonstration of metastasis was performed using immunofluorescence and hematoxylin and eosin (H&E) staining. RESULTS:: GLV-1h153 infected, replicated in, and killed all TNBC cell lines in vitro. In vivo, mean tumor volume 2 weeks after treatment was 22 (IT), 29 (IV) versus 245 mm (control; P < 0.002). Five weeks after treatment, all harvested lymph nodes and organs showed no evidence of metastatic cells. All harvested tumors showed complete response to treatment, with only necrosis and fibrosis on H&E staining 8 weeks after treatment. CONCLUSIONS:: This is the first study to demonstrate that TNBCs are killed by a novel vaccinia virus both in vitro and in vivo. Our results suggest that GLV-1h153 is a promising therapeutic agent for preventing and treating metastatic TNBC and warrants further clinical testing in patients.     

Wallerian degeneration of the middle cerebellar peduncle after pontine infarction: MR imaging

PURPOSE: To report magnetic resonance (MR) imaging findings of wallerian degeneration of the pontocerebellar tract secondary to a pontine infarction. MATERIALS AND METHODS: We retrospectively reviewed cranial MR images obtained during the past seven years in our institution and selected those from patients with a chronic stage of pontine infarction and a hyperintense lesion at the central portion of the middle cerebellar peduncle on T2-weighted images. RESULTS: In three patients with a ventromedial pontine infarction, we found a symmetrical hyperintense lesion at the central portion of the middle cerebellar peduncle bilaterally on T2-weighted MR images in the chronic stage. In another patient with a ventrolateral pontine infarction, we found such a lesion at the ipsilateral middle cerebellar peduncle. CONCLUSION: Because the middle cerebellar peduncle carries afferent fibers from the contralateral basis pontis to the cerebellar cortex, these middle cerebellar peduncular lesions are regarded as wallerian degeneration. This secondary degeneration should not be misinterpreted as a newly developed infarction or other disease.     

Protective effect of prostaglandin E2 receptors EP2 and EP4 in alloimmune response in vivo

Prostaglandin E2 (PGE2) is produced during inflammatory responses mediating a variety of both innate and adaptive immune responses through 4 distinct receptors: EP1 to EP4. The use of gene-targeted mice and selective agonists/antagonists responsible for each receptor has gradually revealed that each receptor plays a unique and important role in various disease conditions. In addition, PGE2 is known to have some immunosuppressive properties. In this study, we investigated the role of PGE2 receptors by examining the therapeutic efficacy of highly selective receptor agonists on the alloimmune response in vivo. We used a fully major histocompatibility complex (MHC)-mismatched murine cardiac transplantation model. C57BL/6 cardiac allografts were heterotopically transplanted into BALB/c recipients. We treated mice with a highly selective agonist for each EP receptor. EP2 and EP4 agonists significantly prolonged allograft survival compared with controls. In particular, the EP4 agonist was more effective than the EP2 agonist in the inhibition of acute allograft rejection. In conclusion, PGE2 receptors merit further study as novel therapeutics for clinical transplantation.     

Association Between Anti-Helicobacter pylori Antibody Seropositive and De Novo Gallstone Formation After Laparoscopic Sleeve Gastrectomy for Japanese Patients with Severe Obesity

Purpose

Patients who have undergone bariatric surgery are at risk for gallstone formation. However, the incidence of gallstone formation after bariatric surgery has not been adequately studied in the Japanese population. We aimed to elucidate the incidence and risk factors for gallstone formation after laparoscopic sleeve gastrectomy (LSG) for Japanese patients with severe obesity.

Methods

We conducted a retrospective cohort study among patients with severe obesity treated with LSG between April 2017 and June 2020 at two institutions. Patients who had received previous cholecystectomy, had preoperative gallstones, and had received postoperative prophylactic ursodeoxycholic acid were excluded. Body weight, body mass index, and blood data were collected at each follow-up visit before and after the surgery. Follow-up abdominal ultrasonography was performed 6–12 months after surgery, and the incidence of gallstones was calculated. The association between the data and gallstone formation was evaluated.

Results

During the study period, we performed LSG for 98 patients. Of these, 61 cases remained by above conditions and were examined using abdominal ultrasonography over 6 months after surgery. The incidence of gallstones was 23.0% and that of symptomatic gallstones was 3.3%. Anti-Helicobacter pylori antibody seropositive and titer were the only factors that showed significant association with de novo gallstone formation after LSG.

Conclusions

Anti-Helicobacter pylori antibody seropositive may be associated with de novo gallstone formation after LSG for Japanese patients with severe obesity.

Graphical abstract

     

Usefulness of gradient tree boosting for predicting histological subtype and EGFR mutation status of non-small cell lung cancer on 18 F FDG-PET/CT

To develop and evaluate a radiomics approach for classifying histological subtypes and epidermal growth factor receptor (EGFR) mutation status in lung cancer on PET/CT images. PET/CT images of lung cancer patients were obtained from public databases and used to establish two datasets, respectively to classify histological subtypes (156 adenocarcinomas and 32 squamous cell carcinomas) and EGFR mutation status (38 mutant and 100 wild-type samples). Seven types of imaging features were obtained from PET/CT images of lung cancer. Two types of machine learning algorithms were used to predict histological subtypes and EGFR mutation status: random forest (RF) and gradient tree boosting (XGB). The classifiers used either a single type or multiple types of imaging features. In the latter case, the optimal combination of the seven types of imaging features was selected by Bayesian optimization. Receiver operating characteristic analysis, area under the curve (AUC), and tenfold cross validation were used to assess the performance of the approach. In the classification of histological subtypes, the AUC values of the various classifiers were as follows: RF, single type: 0.759; XGB, single type: 0.760; RF, multiple types: 0.720; XGB, multiple types: 0.843. In the classification of EGFR mutation status, the AUC values were: RF, single type: 0.625; XGB, single type: 0.617; RF, multiple types: 0.577; XGB, multiple types: 0.659. The radiomics approach to PET/CT images, together with XGB and Bayesian optimization, is useful for classifying histological subtypes and EGFR mutation status in lung cancer.     

Improved survival rate by temperature control at compression sites in rat model of crush syndrome

Background

Crush syndrome (CS) has been reported in disasters, terrorist incidents, and accidents, and the clinical and pathologic picture has gradually been clarified. Few lethal and reproducible animal models of CS with use of a quantitative load are available. A new model is needed to investigate pathologic and therapeutic aspects of this injury.

Materials and methods

Using a device built from commercially available components, both hindlimbs of anesthetized rats were respectively compressed for 6 h using 3.6-kg blocks. The effects of trunk warming alone without compressed hindlimbs (Group A), non-warming at room temperature (Group B), whole-body warming including compressed hindlimbs (Group C), or warming of compressed hindlimbs alone (Group D) during compression were examined. Survival rates were compared and hematological and histologic analyses were performed at specific time points after compression release.

Results

Limb or whole-body warming significantly worsened the survival of rats. We found a much lower survival rate of 0%–10% in animals, in which the hindlimbs were warmed during compression (Groups C and D) at 12 h after compression release, compared with 90%–100% in animals without warming of the hindlimbs (Groups A and B). Groups C and D showed significantly enhanced hyperkalemia at ≥4 h after compression release and all blood samples from dead cases showed hyperkalemia (>10 mEq/L).

Conclusions

We developed a new lethal and reproducible rat CS model with a quantitative load. This study found that warming of compressed limbs worsened the survival rate and significantly enhanced hyperkalemia, apparently leading to cardiac arrest.     

Does anatomic resection improve the postoperative outcomes of solitary hepatocellular carcinomas located on the liver surface?

Background

It is unclear whether anatomic resection achieves better outcomes than nonanatomic resection in patients with hepatocellular carcinoma. This study aimed to compare the outcomes of anatomic resection and nonanatomic resection for hepatocellular carcinoma located on the liver surface via one-to-one propensity score-matching analysis.

Differences in short-term clinical and radiological outcomes depending on timing of balloon kyphoplasty for painful osteoporotic vertebral fracture

Background

Balloon kyphoplasty or vertebroplasty is widely performed as a surgical intervention for osteoporotic vertebral fracture (OVF) and the effects have been investigated in many previous studies. However, the influence of the timing of the procedure on patient outcomes has not been studied formally. The purpose of this study was to investigate differences in the surgical outcomes of OVFs according to the timing of balloon kyphoplasty.