Twist1 Is an Independent Prognostic Factor of Esophageal Squamous Cell Carcinoma and Associated with Its Epithelial–Mesenchymal Transition

Background  

Twist1 is known to be involved in epithelial–mesenchymal transition (EMT) and tumor progression. However, its specific role is different depending on the type of cancer. The functional role and clinical significance of Twist1 in esophageal squamous cell carcinoma (ESCC) have been rarely studied.     

Expression of Hepatocyte Growth Factor Activator Inhibitor Type 1 in Human Hepatocellular Carcinoma and Postoperative Outcomes

Background  

Hepatocyte growth factor activator inhibitor type 1 (HAI-1), one of the Kunitz-type serine protease inhibitors, has an important role in cancer progression through regulation of the activity of hepatocyte growth factor. HAI-1 is expressed in hepatocellular carcinoma (HCC) to various degrees. Investigation of the relationship between HAI-1 expression and clinicopathological features of HCC may contribute to improved treatment outcomes for HCC through understanding the mechanism of tumor progression or improvement in the prediction of tumor malignancy.     

Surgery of the alimentary tract for benign and malignant disease with the novel robotic platform HUGOTM RAS. A first world report of safety and feasibility

Introduction

As robotic surgery increases its reach, novel platforms are being released. We present the first 17 consecutive cases of alimentary tract surgery performed with the Hugo^TM RAS (Medtronic).

Methods

patients were selected to undergo surgery from February through April 2023. Exclusion criteria were age <16 years, BMI>60, ASA IV.

Results

17 patients underwent ileocaecal resection for Chrons disease (2 M and 1 F) and pseudo-obstruction of the terminal ileum (1 M), cholecystectomy (3 M and 5 F), subtotal gastrectomy with D2 lymphadenectomy (1 F), sleeve gastrectomy (1 F), hiatal hernia repair with Nissen fundoplication (1 M), right hemicolectomy (1 M) and sigmoidectomy (1 M). No conversion to an open approach or any arm collisions requiring corrective actions were reported.

Conclusions

Our preliminary experience with the Hugo^TM RAS point to safety and feasibility for a rather wide spectrum of surgical procedures of the alimentary tract.     

Overexpression of Endothelial Cell Specific Molecule-1 (ESM-1) in Gastric Cancer

Background  

The endothelial cell-specific molecule-1 (ESM-1) gene is involved in various biological events. This study was designed to clarify its clinical significance and explore its biological behavior in gastric cancer (GC).     

Adenoviral-mediated gene transfer of insulin-like growth factor 1 enhances wound healing and induces angiogenesis

Background

Chronic wounds are characterized by a wound healing and neovascularization deficit. Strategies to increase neovascularization can significantly improve chronic wound healing. Insulin-like growth factor (IGF)-1 is reported to be a keratinocyte mitogen and is believed to induce angiogenesis via a vascular endothelial growth factor (VEGF)-dependent pathway. Using a novel ex vivo human dermal wound model and a diabetic-impaired wound healing murine model, we hypothesized that adenoviral overexpression of IGF-1 (Ad-IGF-1) will enhance wound healing and induce angiogenesis through a VEGF-dependent pathway.

Methods

Ex vivo: 6-mm full-thickness punch biopsies were obtained from normal human skin, and 3-mm full-thickness wounds were created at the center. Skin explants were maintained at air liquid interface. Db/db murine model: 8-mm full-thickness dorsal wounds in diabetic (db/db) mice were created. Treatment groups in both human ex vivo and in vivo db/db wound models include 1 × 10⁸ particle forming units of Ad-IGF-1 or Ad-LacZ, and phosphate buffered saline (n = 4–5/group). Cytotoxicity (lactate dehydrogenase) was quantified at days 3, 5, and 7 for the human ex vivo wound model. Epithelial gap closure (hematoxylin and eosin; Trichrome), VEGF expression (enzyme-linked immunosorbent assay), and capillary density (CD 31 + CAPS/HPF) were analyzed at day 7.

Results

In the human ex vivo organ culture, the adenoviral vectors did not demonstrate any significant difference in cytotoxicity compared with phosphate buffered saline. Ad-IGF-1 overexpression significantly increases basal keratinocyte migration, with no significant effect on epithelial gap closure. There was a significant increase in capillary density in the Ad-IGF-1 wounds. However, there was no effect on VEGF levels in Ad-IGF-1 samples compared with controls. In db/db wounds, Ad-IGF-1 overexpression significantly improves epithelial gap closure and granulation tissue with a dense cellular infiltrate compared with controls. Ad-IGF-1 also increases capillary density, again with no significant difference in VEGF levels in the wounds compared with control treatments.

Conclusions

In two different models, our data demonstrate that adenoviral-mediated gene transfer of IGF-1 results in enhanced wound healing and induces angiogenesis via a VEGF-independent pathway. Understanding the underlying mechanisms of IGF-1 effects on angiogenesis may help produce novel therapeutics for chronic wounds or diseases characterized by a deficit in neovascularization.     

FAME‐04: A Phase 1 trial to assess the safety,acceptability, pharmacokinetics and pharmacodynamics of film and gel formulations of tenofovir

Introduction

Fast‐dissolving vaginal film formulations release antiretroviral drugs directly into vaginal fluid and may be as efficient at drug delivery yet more acceptable to women than gels. In this Phase 1 vaginal film study, the safety, acceptability, pharmacokinetics and pharmacodynamics of two doses of tenofovir (TFV) film and TFV 1% gel were compared to corresponding placebo formulations.

Methods

Seventy‐eight healthy HIV negative women were randomized to self‐insert daily vaginal film (10 mg TFV, 40 mg TFV or placebo) or 4 mL of vaginal gel (TFV 1% [40 mg] or placebo) for seven days. Grade 2 and higher adverse events (AEs) related to study product were compared across study arms using Fisher's exact test. Plasma TFV concentrations were measured before and 2 hours after last product use. Paired cervical and vaginal tissue biopsies obtained 2 hours after the last dose were measured to determine tenofovir diphosphate (TFV‐DP) concentrations and exposed to HIV in an ex vivo challenge assay. Acceptability was assessed through questionnaire.

Results

There was only one grade 2 or higher related AE, the primary endpoint; it occurred in the placebo gel arm. AEs occurred in 90% of participants; the majority (91%) were grade 1. AEs were similar across study arms. TFV concentrations in plasma and TFV‐DP concentrations in cervical and vaginal tissues were comparable between 40 mg TFV film and the TFV gel groups. There was a significant relationship between reduced viral replication and TFV‐DP concentrations in cervical tissues. Film users were less likely to report product leakage than gel users (66% vs. 100%, p < 0.001).

Conclusions

Films were safe and well tolerated. Furthermore, films delivered TFV to mucosal tissues at concentrations similar to gel and were sufficient to block HIV infection of genital tissue ex vivo.