OBJECTIVE:Rhinitis medicamentosa poses a therapeutic challenge for both patients and physicians. Treatment strategies vary, starting with avoidance of decongestants, followed by medications or surgical intervention. This study aimed to compare two treatment strategies for this condition.METHODS:A review was conducted of patients diagnosed with rhinitis medicamentosa from 2013 to 2021, who were managed conservatively with medications or surgically by inferior turbinate reduction.RESULTS:Forty-seven patients were included: 21 patients were treated conservatively and 26 underwent turbinate reduction. Following surgical therapy, the frequency of using decongestants was significantly reduced (p < 0.001), with a significant improvement in Sino-Nasal Outcome Test-22 scores (p < 0.001). The conservative treatment group was significantly older with more co-morbidities. Following medical therapy, the conservative treatment group had a significant decrease in the frequency of decongestant use, but there was no significant improvement in their Sino-Nasal Outcome Test-22 scores.CONCLUSION:Compared to conservative treatment, inferior turbinate reduction for rhinitis medicamentosa resulted in reduced decongestant use and improved quality of life.

Supplementary Figure 1 from Structure-Function Approach Identifies a COOH-Terminal Domain That Mediates Heparanase Signaling

Supplementary Figure 2 from Structure-Function Approach Identifies a COOH-Terminal Domain That Mediates Heparanase Signaling

Supplementary Figure Legends 1-2 from Structure-Function Approach Identifies a COOH-Terminal Domain That Mediates Heparanase Signaling

Squamous cell carcinoma of head and neck (SCCHN) is the most common cancer in the head and neck and is the sixth most common neoplasm worldwide. SCCHN has a high propensity to lymph node metastases, especially cancer of the pharynx. Prognosis of patients with SCCHN is severely influenced by the status of metastatic cervical lymph nodes and survival rates drop down to half when patients are presented with a metastatic node. The clinical relevance of heparanase as a prognostic marker in SCCHN was reported in several publications. Low levels of heparanase in SCCHN tumor cells was correlated with prolonged disease-free and overall survival. Furthermore, nuclear localization of heparanase predicts a favorable outcome compared to cytoplasmic localization. Heparanase staining was positively correlated with lymphatic vessel density and lymph node metastasis associated with the elevation of vascular endothelial growth factor C (VEGF-C). Heparanase ability to enhance phosphorylation of epidermal growth factor receptor (EGFR), and signal transducer and activator of transcription 3 (STAT3) were postulated to serve as critical molecular mechanisms by which heparanase facilitates tumor growth. Heparanase-2 (HPA2) is a close homolog of heparanase that lacks intrinsic HS-degrading activity but retains the capacity to bind HS with high affinity. HPA2 expression was markedly elevated in SCCHN patients, correlating with prolonged follow-up time to recurrence and inversely correlating with patients’ N-stage. HPA2 appears to inhibit tumor dissemination, suggesting that HPA2 functions as a tumor suppressor. Thus, Heparanase and Heparanase-2 seem to exert opposing effects on SCCHN.

INTRODUCTION Head and neck cancer is the sixth most common malignancy worldwide. Along with other "classical" risk factors such as tobacco and alcohol use, the human papillomavirus (HPV) is well established to play a pivotal role in the development of head and neck cancers, particularly in oropharyngeal cancer (OPC). While head and neck cancer incidence decline worldwide, OPC is on the rise. The incidence of HPV-positive oropharyngeal carcinoma predominantly increased in younger, married male patients with higher socioeconomic status and with high-risk sexual practices. This OPC subtype is characterized by limited local tumor with a substantially larger regional nodal disease. However, HPV-positive OPC patients exhibited a significantly better prognosis than patients with HPV-negative OPC, leading to a recent change in the clinical guidelines. The current non-surgical standard of care for OPC results in excellent disease control, though associated with substantial toxicity. Numerous studies now focus on less intensive (i.e., deintensified) treatment for the improvement of patient safety while maintaining excellent disease control. Furthermore, the recent development of more advanced surgical techniques with promising outcomes may shift the therapeutic paradigm back to the operating room. During the past decade, there is widespread use of HPV vaccination, and lately, it was also approved for boys. However, the preventive effects of the HPV vaccine on head and neck cancers, particularly on OPC is yet to be determined.

Molecular and chemical chaperones are key components of the two main mechanisms that ensure structural stability and activity under environmental stresses. Yet, chemical chaperones are often regarded only as osmolytes and their role beyond osmotic regulation is not fully understood. Here, we systematically studied a large group of chemical chaperones, representatives of diverse chemical families, for their protective influence under either thermal or chemical stresses. Consistent with previous studies, we observed that in spite of the structural similarity between sugars and sugar alcohols, they have an apparent difference in their protective potential. Our results support the notion that the protective activity is mediated by the solvent and the presence of water is essential. In the current work we revealed that i) polyols and sugars have a completely different profile of protective activity toward trifluoroethanol and thermal stress; ii) minor changes in solvent composition that do not affect enzyme activity, yet have a great effect on the ability of osmolytes to act as protectants and iii) increasing the number of active groups of carbohydrates makes them better protectants while increasing the number of active groups of methylamines does not, as revealed by attempts to synthesize de novo designed methylamines with multiple functional groups.

Abstract Heparanase is an endo-β-d-glucuronidase capable of cleaving heparan sulfate, activity that is strongly implicated in cellular invasion associated with tumor metastasis, angiogenesis, and inflammation. In addition, heparanase was noted to exert biological functions apparently independent of its enzymatic activity, enhancing the phosphorylation of selected protein kinases and inducing gene transcription. A predicted three-dimensional structure of constitutively active heparanase clearly delineates a TIM-barrel fold previously anticipated for the enzyme. Interestingly, the model also revealed the existence of a COOH-terminal domain (C-domain) that apparently is not an integral part of the TIM-barrel fold. We provide evidence that the C-domain is critical for heparanase enzymatic activity and secretion. Moreover, the C-domain was found to mediate nonenzymatic functions of heparanase, facilitating Akt phosphorylation, cell proliferation, and tumor xenograft progression. These findings support the notion that heparanase exerts enzymatic activity-independent functions, and identify, for the first time, a protein domain responsible for heparanase-mediated signaling. Inhibitors directed against the C-domain, combined with inhibitors of heparanase enzymatic activity, are expected to neutralize heparanase functions and to profoundly affect tumor growth, angiogenesis, and metastasis. [Cancer Res 2009;69(5):1758–67]