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<em>In Vitro</em> Modeling of Cancerous Neural Invasion: The Dorsal Root Ganglion Model

One way that solid tumors disseminate is through neural invasion. This route is well-known in cancers of the head and neck, prostate, and pancreas. These ...

Rambam Medical Healthcare Campus

The common treatment of primary patients with nasopharyngeal carcinoma is chemotherapy and radiotherapy. Surgery is reserved as salvage procedure for recurrent or persistent disease. Nevertheless, information on the outcome of these patients and the role of adjuvant reirradiation treatment is scarce.

Outcome of patients undergoing salvage surgery for recurrent nasopharyngeal carcinoma: a meta-analysis.

This study aimed to create a reliable and reproducible orthotopic mouse model of laryngeal malignancy that recapitulates its biologic behavior, local invasiveness, and spread as seen in patients.

An orthotopic mouse model of laryngeal squamous cell carcinoma.

Adenoid cystic carcinoma (ACC) accounts for 3-5 % of all head and neck malignancies. Investigations of outcomes from elective neck dissection (END) for patients with ACC are sparse. This study aimed to assess the impact of END on the survival of patients with ACC.

Elective neck dissection in patients with head and neck adenoid cystic carcinoma: an international collaborative study.

Objective Chordoma is a locally aggressive tumor. The aim of this study was to assess the efficacy of different surgical approaches and adjuvant radiation modalities used to treat these patients. Design Meta-analysis. Main Outcome Measures Overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS). Results The 5-year OS and PFS rates of the whole cohort (n = 467) were 86% and 65.7%, respectively. The 5-year DSS for patients who underwent open surgery and endoscopic surgery was 45% and 49%, respectively (p = 0.8); PFS was 94% and 79%, respectively (p = 0.11). The 5-year OS of patients treated with surgery followed by adjuvant radiotherapy was 90% compared with 70% of those treated by surgery alone (p = 0.24). Patients undergoing partial resection without adjuvant radiotherapy had a 5-year OS of 41% and a DSS of 45%, significantly lower than in the total-resection group (p = 0.0002 and p = 0.01, respectively). The complication rates were similar in the open and endoscopic groups. Conclusions Patients undergoing total resection have the best outcome; adjuvant radiation therapy improves the survival of patients undergoing partial resection. In view of the advantages of minimally invasive techniques, endoscopic surgery appears an appropriate surgical approach for this disease.

Treatment and Outcome of Patients with Skull Base Chordoma: A Meta-analysis.

It was suggested that the brain microenvironment plays a role in glioma progression. Here we investigate the mechanism by which astrocytes which are abundant in glioma tumors, promote cancer cell invasion. In this study, we evaluated the effects of astrocytes on glioma biology both in vitro and in vivo and determined the downstream paracrine effect of glial-derived neurotrophic factor (GDNF) on tumor invasion. Astrocytes-conditioned media (ACM) significantly increased human and murine glioma cells migration compared to controls. This effect was inhibited when the activity of GDNF on glioma cells was blocked by RET-Fc chimera or anti-GDNF Ab and by small interfering RNA directed against GDNF expression by astrocytes. Glioma cells incubated with ACM led to time dependent phosphorylation of the GDNF receptor, RET and downstream activation of AKT. Tumor migration and GDNF-RET-AKT activation was inhibited by the RET small-molecule inhibitor pyrazolopyrimidine-1 (PP1) and by the AKT inhibitor LY294002. Finally, blocking of RET by PP1 or knockout of the RET coreceptor GFRα1 in glioma cells reduced the size of brain tumors in immunocompetent mice. We suggest a mechanism by which astrocytes attracted to the glioma tumors facilitate brain invasion by secretion of GDNF and activation of RET/GFRα1 receptors expressed by the cancer cells.

Paracrine regulation of glioma cells invasion by astrocytes is mediated by glial-derived neurotrophic factor.

A positive margin is among the most significant factors that affects the outcome in head and neck squamous cell carcinoma (SCC). The purpose of this study was to compare the negative margin rates between 2 methods of intraoperative margin assessment in patients with oral cavity SCC.

Improving the rate of negative margins after surgery for oral cavity squamous cell carcinoma: A prospective randomized controlled study.

Pancreatic ductal adenocarcinoma (PDA) ranks fourth among cancer related deaths. The disappointing 5-year survival rate of below 5% stems from drug resistance to all known therapies, as well as from disease presentation at a late stage when PDA is already metastatic. Gemcitabine has been the cornerstone of PDA treatment in all stages of the disease for the last two decades, but gemcitabine resistance develops within weeks of chemotherapy initiation. From a mechanistic perspective, gemcitabine resistance may result from alterations in drug metabolism until the point that the cytidine analog is incorporated into the DNA, or from mitigation of gemcitabine-induced apoptosis. Both of these drug resistance modalities can be either intrinsic to the cancer cell, or influenced by the cancer microenvironment. Mechanisms of intrinsic gemcitabine resistance are difficult to tackle, as many of the genes that drive the carcinogenic process itself also interfere with gemcitabine-induced apoptosis. In this regard, recent understanding of the involvement of microRNAs in gemcitabine resistance may offer new opportunities to overcome intrinsic gemcitabine resistance. The characteristically fibrotic and immune infiltrated stroma of PDA that accompanies tumor inception and expansion is a lush ground for treatments aimed at targeting tumor microenvironment-mediated drug resistance. In the last couple of years, drugs interfering with tumor microenvironment have matured to clinical trials. Although drugs inducing 'stromal depletion' have yet failed to improve survival, they have greatly increased our understanding of tumor microenvironment-mediated drug resistance. In this review we summarize the current knowledge on intrinsic and environment-mediated gemcitabine resistance, and discuss the impact of these pathways on patient screening, and on future treatments aimed to potentiate gemcitabine activity.

Gemcitabine resistance in pancreatic ductal adenocarcinoma.

Differentiated thyroid carcinoma (DTC) comprises over 90% of thyroid tumors and includes papillary and follicular carcinomas. Patients with DTC have an excellent prognosis, with a 10-year survival rate of over 90%. However, the risk of recurrent tumor ranges between 5% and 30% within 10 years of the initial diagnosis. Cervical lymph node disease accounts for the majority of recurrences and in most cases is detected during follow-up by ultrasound or elevated levels of serum thyroglobulin. Recurrent disease is accompanied by increased morbidity. The mainstay of treatment of nodal recurrence is surgical management. We provide an overview of the literature addressing surgical management of recurrent or persistent lymph node disease in patients with DTC.

Contemporary Management of Recurrent Nodal Disease in Differentiated Thyroid Carcinoma.

Objective Extramedullary plasmacytomas are rare tumors. In the current study we aim to characterize its clinical course at the skull base and define the most appropriate therapeutic protocol. Methods We conducted a meta-analysis of articles in the English language that included data on the treatment and outcome of plasmacytoma of the base of skull. Results The study cohort consisted of 47 patients. The tumor originated from the clivus and sphenoclival region in 28 patients (59.5%), the nasopharynx in 10 patients (21.2%), the petrous apex in 5 patients (10.6%), and the orbital roof in 4 patients (8.5%). The chief complaints at presentation included recurrent epistaxis and cranial nerve palsy, according to the site of tumor. Twenty-two patients (46.8%) had surgical treatment; 25 (53.2%) received radiation therapy. Adjuvant therapy was administered in 11 cases (50%) with concurrent multiple myeloma. The 2-year and 5-year overall survival rates were 78% and 59%, respectively. Clear margin resection was achieved in a similar proportion of patients who underwent endoscopic surgery and open surgery (p = 0.83). A multivariate analysis of outcome showed a similar survival rate of patients treated surgically or with radiotherapy. Conclusions The mainstay of treatment for plasmacytoma is based on radiation therapy, but when total resection is feasible, endoscopic resection is a valid option.

Shorook Na'ara

Otolaryngology,
Head and Neck Surgery Department,
The Laboratory for Applied Cancer Research,
CRIR,
Otolaryngology, Head and Neck Surgery Department, The Laboratory for Applied Cancer Research, CRIR

Rambam Medical Healthcare Campus

In Vitro Modeling of Cancerous Neural Invasion: The Dorsal Root Ganglion Model

Shorook Na'ara

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Rambam Medical Healthcare Campus

In Vitro Modeling of Cancerous Neural Invasion: The Dorsal Root Ganglion Model

Otolaryngology,
Head and Neck Surgery Department,
The Laboratory for Applied Cancer Research,
CRIR,
Otolaryngology, Head and Neck Surgery Department, The Laboratory for Applied Cancer Research, CRIR