Efficacy and safety of PD-1 Monoclonal antibodies in the treatment of esophageal squamous cell carcinoma: Systematic review and meta Regression.

Background: Esophageal Squamous Cell Carcinoma (ESCC) contributes to the global burden of disease. Conventional treatments such as surgical resection and chemotherapy offer limited long-term survival rates. Recently, immunotherapies targeting PD-1 have shown promise in other cancers, but their efficacy in ESCC remains unclear.

Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.

Malignant cancer cells frequently secrete significant amounts of transforming growth factor beta (TGF-β), hyaluronan (HA) and hyaluronidases to facilitate metastasizing to target organs. In a non-canonical signaling, TGF-β binds membrane hyaluronidase Hyal-2 for recruiting tumor suppressors WWOX and Smad4, and the resulting Hyal-2/WWOX/Smad4 complex is accumulated in the nucleus to enhance SMAD-promoter dependent transcriptional activity. Yeast two-hybrid analysis showed that WWOX acts as a bridge to bind both Hyal-2 and Smad4.

Lung hyaluronan levels are decreased in alpha-1 antiprotease deficiency COPD.

Introduction: Hyaluronan (HA), a long-chain polysaccharide, is currently being evaluated as a potential therapeutic agent for pulmonary emphysema, based on previous studies from this laboratory indicating its protective effect against elastic fiber breakdown. To determine whether exogenously administered HA might replace a loss of this extracellular matrix component in this disease, we measured the content of HA in lung biopsies from both healthy individuals and alpha-1 antiprotease-deficient (AAPD) COPD patients with pulmonary emphysema.

Methods: Tissue samples (9 from COPD patients, 5 from controls) were digested with papain to isolate glycosaminoglycans, and lung HA was quantified with an enzyme-linked immunoabsorbent assay.

The effect of hyaluronan on elastic fiber injury in vitro and elastase-induced airspace enlargement in vivo.

This laboratory has previously described a method of preventing air-space enlargement in experimental pulmonary emphysema using aerosolized hyaluronan (HA). Although it was found that HA preferentially binds to elastic fibers (which undergo breakdown by elastases in emphysema), it remains to be shown that such attachment actually prevents damage to the fibers. In the current study, cell-free radiolabeled extracellular matrices, derived from rat pleural mesothelial cells, were used to test the ability of low molecular weight ( approximately 100 kDa) streptococcal HA to prevent elastolysis.

The pulmonary matrix, glycosaminoglycans and pulmonary emphysema.

This paper reviews recent evidence of the effect of intratracheal hyaluronan (HA) to limit the induction of experimental emphysema in hamsters. Experimental emphysema was induced by both neutrophil and pancreatic elastase instilled intratracheally. Emphysema was quantified anatomically by measurement of alveolar mean linear intercept.

Aerosolized hyaluronic acid decreases alveolar injury induced by human neutrophil elastase.

This laboratory has previously shown that an intratracheally instilled solution of hyaluronic acid (HA) protects the lung from elastase-induced airspace enlargement. In those studies, fluorescein-labeled HA was found to bind preferentially to lung elastic fibers, suggesting a mechanism for the protective effect. The current investigation extends these findings by examining the capacity of an aerosol preparation of HA to similarly inhibit elastase-induced lung injury.

Further investigation of the use of intratracheally administered hyaluronic acid to ameliorate elastase-induced emphysema.

Previously, this laboratory has shown that intratracheally administered hyaluronic acid (HA) significantly reduces air-space enlargement in a hamster model of emphysema induced with pancreatic elastase. Whereas HA was given immediately following elastase in those initial studies, the current investigation determined the effect of instilling HA up to 2 h before or after intratracheal administration of elastase to hamsters. Both 1 and 2 mg HA, given 2 h before pancreatic elastase, significantly decreased (p < .

Synthetic polysulfated hyaluronic acid is a potent inhibitor for tumor necrosis factor production.

Based on the premise that naturally occurring glycosaminoglycans could serve as building blocks for synthesizing nontoxic drugs for suppression of tumor necrosis factor (TNF) production by inflammatory cells, we have chemically modified hyaluronic acid (HA) and tested its effects in blocking TNF-alpha and TNF-beta production in vitro. HA was chosen mainly for its structural simplicity, nonimmunogenicity, and readiness for chemical modifications. When HA was chemically polysulfated to a sulfate/hexosamine molar ratio of 3.

Pulmonary air-space enlargement induced by intratracheal instillment of hyaluronidase and concomitant exposure to 60% oxygen.

Although emphysema is generally characterized by damage to pulmonary elastic fibers, the causes of such injury appear to be complex and are not entirely explained by a singular imbalance between elastases and their inhibitors. Other factors could compromise elastic fiber integrity. To test the validity of this argument, hamsters were instilled intratracheally with a nonelastolytic enzyme, hyaluronidase (which reduces lung hexuronic acid content by 21% after 24 h), then exposed to an otherwise nontoxic concentration of oxygen (60%) for 4 days.

Conformational differences between hyaluronates of gel and liquid human vitreous: fractionation and circular dichroism studies.

Post-mortem human vitreous samples (liquid and gel) of comparable intrinsic viscosity values (n approximately equal to 3000 cc/g) were chromatographed on DEAE-Sephacel columns at 4 degrees C using a linear salt gradient ranging from 0----0.4 M NaCl. All samples examined produced numerous discrete hyaluronic acid (HA) fractions.

Hyaluronic acid-complement interactions--I. Reversible heat-induced anticomplementary activity.

The in vitro interaction of hyaluronic acid (HA) with complement (C) classical-pathway activity has been investigated. It was found that native HA, even at a high concn (greater than 3 mg/ml), has a relatively weak anticomplementary activity. However, we report here that native HA can be reversibly altered by heat treatment such that C-inhibitory properties are manifested.

A new chromatographic method for the fractionation of hyaluronic acid.

Sodium hyaluronate from rooster comb, umbilical cord, bovine vitreous and a special commercial hyaluronic acid preparation, "HealonR" have been fractionated at 4 degrees C on DEAE-Sephacel columns using salt gradients from 0 leads to 0.4M NaCl. All samples examined displayed a high degree of polydispersity.

Isolation and characterization of ichthyosan from tuna vitreous.

Ichthyosan has been prepared from tuna vitreous. Glucuronic acid was found to account for the total uronic acid content of the macromolecule, while the hexosamine content was a mixture of N-acetyl-glucosamine and N-acetyl-galactosamine. When ichthyosan was gel filtered on Sepharose 2B or Sephacryl S-300, using sodium or calcium chloride, the elution profile of the column gave only one peak indicating no separation between glucosamine and galactosamine containing fractions.

Structure-function relationships of heparin species.

We have fractionated porcine heparin species of low molecular weight, with an average specific anticoagulant activity of 96 units/mg by affinity chromotography. Highly active and relatively inactive preparations of similar size were obtained with specific anticoagulant activities of 360 and 4 units/mg, respectively. The highly active heparin fraction possesses 1.