Noninvasive assessment of oral lesions using elastic light single-scattering spectroscopy: a pilot study.

PURPOSE: In the present study, we investigated the potential application of elastic light single-scattering spectroscopy (ELSSS) as a noninvasive, adjunctive tool to differentiate between malignant and benign oral lesions in vivo. METHODS: ELSSS spectra were acquired from 52 oral lesions of 47 patients prior to surgical biopsy using a single optical fiber probe. The sign of the spectral slope was used as a diagnostic parameter and was compared to the histopathology findings to obtain sensitivity and specificity of the ELSSS system in differentiating between benign and malignant tissues. RESULTS: The sign of the spectral slope was positive for the benign tissues and negative for the malignant tissues. Nine malignant lesions and one high-grade dysplasia were correctly classified as cancerous. Six out of the ten low-grade dysplasia were correctly classified as cancerous, and four of them were misclassified as benign. Thirty benign lesions were correctly classified as benign, and two were misclassified as malignant. Our results indicate that the sign of the spectral slope enables the differentiation between malignant and benign oral lesions with a sensitivity of 80% and specificity of 94%. CONCLUSIONS: ELSSS has the potential to be developed as an adjunctive screening tool in the noninvasive evaluation of oral lesions in vivo. This new diagnostic system may reduce the number of unnecessary biopsies.

Identification of novel mutations of Insulin Receptor Substrate 1 (IRS1) in tumor samples of non-small cell lung cancer (NSCLC): Implications for aberrant insulin signaling in development of cancer.

Lung cancer is the leading cause of cancer-related death, and NSCLC constitutes nearly 85%-90% of all cases. The IRS proteins function as adaptors and transmit signals from multiple receptors. Upon binding of insulin to the insulin receptor (IR), IRS1 is phosphorylated at several YXXM motifs creating docking sites for the binding of PI3Kp85, which activates AKT kinase. Therefore, we thought that gain of function mutantions of IRS1 could be related to development of lung cancer. In line with this, we wanted determine whether the IRS1 gene was mutated in the coding regions surrounding YXXM motifs. We sequenced the coding regions surrounding YXXM motifs of IRS1 using tumor samples of 42 NSCLC patients and 40 matching controls and found heterozygote p.S668T mutation in nine of 42 samples and four of nine also had the p.D674H mutation. We generated IRS1 expression vectors harboring p.S668T, p.D674H and double mutants. Expression of the mutants differentially affected insulin-induced phosphorylation of IRS1, AKT, ERK, and STAT3. Also, our mutants induced proliferation, glucose uptake, inhibited the migration of 293T cells and affected the responsiveness of the cells to cisplatin and radiation. Our results suggest that these novel mutations play a role in the phenotype of lung cancer.

Perinatal Diagnostic Approach to Fetal Skeletal Dysplasias: Six Years Experience of a Tertiary Center.

Skeletal dysplasias (SDs) constitute a group of heterogeneous disorders affecting growth morphology of the chondro-osseous tissues. Prenatal diagnosis of SD is a considerable clinical challenge due to phenotypic variability. We performed a retrospective analysis of the fetal autopsies series conducted between January 2006 and December 2012 at our center. SD was detected in 54 (10%) out of 542 fetal autopsy cases which included; 11.1% thanatophoric dysplasia (n = 6), 7.4% achondroplasia (n = 4), 3.7% osteogenesis imperfect (n = 2), 1.9% Jarcho-Levin Syndrome (n = 1), 1.9% arthrogryposis (n = 1), 1.9% Dyggve-Melchior-Clausen syndrome (n = 1), 72.1% of dysostosis cases (n = 39). All SD cases were diagnosed by ultrasonography. In 20 of the cases, amniocentesis was performed, 4 cases underwent molecular genetic analyses. Antenatal identification of dysplasia is important in the management of pregnancy and in genetic counseling. Our data analysis showed that SD is usually detected clinically after the 20th gestational week. Genetic analyses for SD may provide early diagnosis and management.

Differential expression and activation of epidermal growth factor receptor 1 (EGFR1), ERK, AKT, STAT3, and TWIST1 in nonsmall cell lung cancer (NSCLC).

Lung cancer is the leading cause of death of both men and women across the world. Overexpression and activating mutations of the epidermal growth factor receptor-1 (EGFR1) are frequently observed and associated with poor prognosis. To inhibit the function of EGFR1, multiple antibodies and small-molecule tyrosine kinase inhibitors (TKI) that target EGFR1 have been developed. Even though some patients respond to these TKI, subsequent studies reveal that this is not the case for all nonsmall cell lung cancer (NSCLC) patients. In this study, we determine whether activation and expression levels of EGFR1, ERK, AKT, STAT3, and TWIST1 are dependent on the activating mutations of EGFR1. Protein lysates and DNA have been isolated from tumor and corresponding normal tissues of 16 NSCLC patients. Genomic-DNA is used to sequence the exons 18, 19, and 21 of EGFR1, and exon 2 of k-RAS. Protein lysates were used to determine the expression or phosphorylation levels of EGFR, STAT3, ERK, AKT, and TWIST1. Our results revealed that 16 tumor samples of NSCLC patients showed no mutation in any of the indicated exons of EGFR1 and k-RAS albeit significant levels of activation or expression of the above-mentined oncogenes. In NSCLC patients, the tumor micro-environment can be as important as the activating mutations of EGFR1. TK therapy may also be considered for patients who show high levels of activation of EGFR1 even in the absence of activating mutations.

A rare phenomenon, primary pulmonary smooth muscle tumor and its management.

Smooth muscle tumors of uncertain malignant potential, the borderline tumors arising from the smooth muscle cells, usually grow slowly and do not fulfill the diagnostic criteria of leiomyosarcoma and its variants, but may behave in a malignant manner. A 15-year-old female patient with an endobronchial mass in the left main bronchus on thoracic computed tomography underwent thoracotomy and tracheobronchoplasty with a wide and safe margin. Histopathological evaluation revealed a smooth muscle tumor of uncertain malignant potential. There were no complications related to the operation during the hospital stay. At six months of surgery, there were no symptoms or signs suggesting any recurrence in her follow-up. In conclusion, In conclusion, pulmonary leiomyomas may rarely present as an endobronchial mass and may mimic asthma by causing respiratory symptoms developing as attacks due to displacement of the mass within the lumen.

Tbx3 represses PTEN and is over-expressed in head and neck squamous cell carcinoma.

BACKGROUND: Despite advances in diagnostic and treatment strategies, head and neck squamous cell cancer (HNSCC) constitutes one of the worst cancer types in terms of prognosis. PTEN is one of the tumour suppressors whose expression and/or activity have been found to be reduced in HNSCC, with rather low rates of mutations within the PTEN gene (6-8%). We reasoned that low expression levels of PTEN might be due to a transcriptional repression governed by an oncogene. Tbx2 and Tbx3, both of which are transcriptional repressors, have been found to be amplified or over-expressed in various cancer types. Thus, we hypothesize that Tbx3 may be over expressed in HNSCC and may repress PTEN, thus leading to cancer formation and/or progression. METHODS: Using immunohistochemistry and quantitative PCR (qPCR), protein and mRNA levels of PTEN and Tbx3 were identified in samples excised from cancerous and adjacent normal tissues from 33 patients who were diagnosed with HNSCC. In addition, HeLa and HEK cell lines were transfected with a Tbx3 expressing plasmid and endogenous PTEN mRNA and protein levels were determined via qPCR and flow cytometry. Transcription assays were performed to demonstrate effects of Tbx3 on PTEN promoter activity. Mann-Whitney, Spearman's Correlation and Wilcoxon signed-rank tests were used to analyze the data. RESULTS: We demonstrate that in HNSCC samples, Tbx3 mRNA levels are increased with respect to their normal tissue counterparts (p<0.001), whereas PTEN mRNA levels are significantly reduced in cancer tissues. Moreover, Tbx3 protein is also increased in HNSCC tissue sections. Over-expression of Tbx3 in HeLa and HEK cell lines causes reduction in endogenous PTEN mRNA and protein levels. In addition, transcription activity assays reveal that Tbx3 is capable of repressing both the basal and induced promoter activity of PTEN. CONCLUSIONS: We show that Tbx3 is up-regulated in tissue samples of HNSCC patients and that Tbx3 represses PTEN transcription. Thus, our data not only reveals a new mechanism that may be important in cancer formation, but also suggests that Tbx3 can be used as a potential biomarker in cancer.

Acute effects of vardenafil on pulmonary artery responsiveness in pulmonary hypertension.

Phosphodiesterase type-5 (PDE-5) inhibitors are novel and important options for the treatment of pulmonary arterial hypertension (PAH). Therefore, we aimed to examine effects of vardenafil, a PDE-5 inhibitor, on the pulmonary arteries isolated from rats with monocrotaline- (MCT-) induced pulmonary hypertension. MCT (60 mg/kg) or its vehicle was administered by a single intraperitoneal injection to 6-week-old male Sprague Dawley rats. Rats were sacrificed 21 days after MCT injection, and the main pulmonary arteries were isolated and then mounted in 20 mL organ baths. Concentration-response curves for vardenafil (10(-10)-10(-5) M) were constructed in phenylephrine- (Phe-) precontracted rings. PAH caused marked rightward shift in the curves to vardenafil whereas maximal responses were not affected. Inhibition of NO synthase (L-NAME, 10(-4) M) or guanylyl cyclase (ODQ, 10(-5) M) caused similar attenuation in responses evoked by vardenafil. Moreover, contraction responses induced by CaCl(2) (3 × 10(-5)-3 × 10(-2) M) were significantly reduced in concentration-dependent manner by vardenafil. In conclusion, vardenafil induced pulmonary vasodilatation via inhibition of extracellular calcium entry in addition to NO-cGMP pathway activation. These results provide evidence that impaired arterial relaxation in PAH can be prevented by vardenafil. Thus, vardenafil represents a valuable therapeutic approach in PAH besides other PDE-5 inhibitors.

Comparative evaluation of the efficacy of ozone therapy and low level laser therapy on oral mucosal wound healing in rat experimental model.

OBJECTIVE: The aim of the present study was to evaluate and compare the effectiveness of ozone therapy and low-level laser therapy (LLLT) on healing of oral mucosal wounds in rats through histological assessment. METHODS: Thirty male Wistar rats were employed in this study. Following a 5-mm surgical wound created on the buccal mucosa, the rats were randomly distributed into 3 groups of 10: (1) ozone group (treated with topical gaseous ozone), (2) laser group (treated with LLLT), and (3) control group (received no treatment). Following the sacrifice of rats on day 21, samples were taken from rats' buccal mucosa for histological assay and scoring. The data were analyzed using Mann-Whitney test. RESULTS: Ozone and laser groups demonstrated reduced acute inflammation scores compared to control group (p=.01), while no significant differences were observed between the ozone and laser groups (p = 1.00). Similarly, ozone and laser groups showed higher histological tissue repair scores than the control group (p=.00), and no difference was found between ozone and laser groups (p=.76). On the other hand, no significant difference in expression of TNF-α (p=.33) and TGF-ß1 (p=.13) was identified between ozone, laser and control samples. CONCLUSION: The present study demonstrated that both adjunctive ozone therapy and LLLT with a 940 nm diode laser provided significant improvement in parameters of acute inflammation and tissue repair in surgical oral mucosal wounds in rats.

Lung involvement in patients with primary Sjögren's syndrome: what are the predictors?

The aim of this study was to investigate the prevalence, predictors and radiological findings of primary Sjögren's syndrome (pSS)-associated lung involvement. This retrospective cohort study included 123 patients with demographic, clinical, laboratory and radiological data who were diagnosed with pSS. Lung involvement was defined based on the presence of pulmonary signs/symptoms and/or impaired pulmonary function tests along with alterations in high-resolution computerized tomography (HRCT). Thirty patients (24.4%) had pulmonary signs/symptoms at the initial presentation and/or during the follow-up period. Based on the criteria, 14 patients (11.4%) were defined as having pSS with lung involvement. The smoking rate, male/female ratio and the mean ages were found to be higher in patients with lung involvement (P < 0.05). Positive IgM-rheumatoid factor (RF), anti-La and anti-Ro results, the presence of hypergammaglobulinemia and lymphopenia had high specificity despite the low sensitivity rates to detect pSS-associated lung disease. A significant difference was found in forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV(1)) results between the patients with and without lung involvement. Impaired FEV(1) had high specificity and positive predictive value compared to impaired FVC, particularly in non-smoker patients. The most frequent HRCT finding was ground-glass attenuation (64.3%). Other common findings were bronchiectasis, reticular pattern and honeycombing. The lesions involved predominantly the lower lobes. In conclusion, the presence of hypergammaglobulinemia and lymphopenia, positivity for RF, anti-La and anti-Ro, and impaired (FVC) and/or FEV(1) values could be the predictive parameters with a high specificity despite the low sensitivity rates. Smoking history, male gender and age are also risk factors. These parameters may be helpful to distinguish pSS-associated lung involvement from lung disorders unrelated to pSS.

A case of primary Sjögren's syndrome with pulmonary-limited Wegener's granulomatosis.

A 60-year-old woman had a history of dyspnea for 5-6 weeks. The chest radiograph and computed tomography scans revealed bilateral patchy reticulonodular pattern. The patient had positive test results for antineutrophil cytoplasmic antibody against proteinase-3 (c-ANCA), antinuclear antibody and anti-Ro antibody. According to European Study Group on Classification Criteria for Sjögren's Syndrome, the patient was diagnosed as primary Sjögren's syndrome based on the presence of clinical features, positive findings on Schirmer's test and parotis scintigraphy. Lung biopsy obtained by wedge resection showed granulomatous inflammation with extensive multinuclear giant cells involving the lung parenchyma and vascular structures. There was neither upper airway nor renal involvement. Thus, the patient was simultaneously diagnosed as pulmonary-limited Wegener's granulomatosis. With this unique case, we would like to emphasize that the awareness of ANCA-associated vasculitis as a diagnostic possibility in primary Sjögren's syndrome is important during the work-up of lung lesions.

Pediatric Tonsillar Synovial Sarcoma- Very Rare Localization: A Case Report and Review of the Literature.

Tonsillar synovial sarcoma is an extremely rare entity and only 9 adult patients have been reported up to now. Here, we describe the first pediatric tonsillar synovial sarcoma of the literature in a patient who presented with a 2-month history of dysphagia and snoring. Clinical and radiological examinations showed that the tumor arose from the right palatine tonsil and narrowed the parapharyngeal space. An incisional biopsy from the palatine tonsil revealed the diagnosis of synovial sarcoma. The patient has underwent total tonsillectomy and received radiotherapy and chemotherapy because of the positive surgical margins. The patient is clinically in good condition and free of tumor 30 months after the initial diagnosis. We achieved a long-term complete remission with a combination of surgery, radiotherapy and chemotherapy in our case. Tonsillar synovial sarcoma should be kept in mind while dealing with tonsillar masses. We can conclude that a multidisciplinary approach is warranted while treating synovial sarcoma with this localization.

Vascular endothelial growth factor expression and neovascularization in non--small cell lung carcinoma.

The prognostic significance of microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression were investigated in 15 patients with adenocarcinoma (AC) and 15 patients with squamous cell carcinoma (SCC). Immunohistochemically, VEGF and factor VIII were applied. The average microvessel counts were given as MVD, and VEGF expression was given as VEGF percentage area and VEGF staining degree. Higher values of MVD were obtained in patients with AC (11.47 +/- 3.48) when compared with patients with SCC (7.47 +/- 2.50; P = .001) and also in patients at early stages of disease (10.77 +/- 3.24) when compared with patients at advanced stages (8.47 +/- 3.64; P = .050). A significant correlation was shown between MVD and VEGF percentage area (P = .006) and between VEGF percentage area and VEGF staining degree (P = .000). No significant difference was found in VEGF percentage area between patients with SCC and AC and between patients at early and advanced stages. In conclusion, VEGF or MVD should not be regarded as a solitary prognostic factor but should be supported by other prognostic factors.

Hyalinizing Clear Cell Carcinoma of the Maxilla.

Hyalinizing clear cell carcinoma (HCCC) is a rare low-grade salivary gland tumor with distinctive clear cell morphology, accounting for < 1% of all salivary gland tumors. In the majority of cases, the tumor originates typically from the minor salivary glands in the oral cavity. A total of 155 cases of HCCCs from head and neck region have been reported in the literature until 2017, of which only 16 are of maxillary origin. Due to its low incidence, there is no clear consensus on prognostic factors and optimal treatment strategies yet. In this paper, a new case of HCCC of the maxilla is presented and its clinical and histopathological features are discussed.

Synchronous occurrence of multiple distinct jaw lesions in Simpson-Golabi-Behmel Syndrome: A case report.

Simpson-Golabi-Behmel Syndrome (SGBS) is an X-linked overgrowth syndrome characterized by pre- and post-natal overgrowth, typical facial appearance and multiple visceral, skeletal, and neurological anomalies. There is only few information in the current literature, on clinical and particularly dentofacial findings due to recent identification of the syndrome and its clinical overlap with other overgrowth syndromes. The aim of this case report is to present dentofacial findings in a 16-year-old boy who had been diagnosed with SGBS. Following comprehensive clinical, radiographic and histopathological examinations, six pathologically distinct lesions including odontogenic keratocyst, ameloblastoma, lateral periodontal cyst, dentigerous cyst and mucous retention cyst in both mandible and maxilla were identified. The clinical report is followed by a discussion aimed to clarify unique features of this condition and how practitioners should consider similar cases.

Neoangiogenesis and expression of hypoxia-inducible factor 1alpha, vascular endothelial growth factor, and glucose transporter-1 in endometrioid type endometrium adenocarcinomas.

OBJECTIVE: Hypoxia Inducible Factor-1alpha (HIF-1alpha) is a transcriptional factor that activates multiple genes including Vascular Endothelial Growth Factor (VEGF) and glucose transporter-1 (GLUT-1) in response to hypoxia and promotes neoangiogenesis. METHODS: Expression of HIF-1alpha VEGF, and GLUT-1 were analyzed by immunohistochemistry and microvessel density (MVD) was determined by CD 34 immunostaining in 100 endometrioid type endometrial adenocarcinoma, FIGO Stages I-IV. RESULTS: High expression of HIF-1alpha, VEGF and GLUT-1 were significantly more prevalent in advanced stages than early stages (p<0.001). High expression of HIF-1alpha was found in 100% of Stage III-IV patients, whereas 50% of Stage II and 9% of Stage I patients had high HIF-1alpha expression. Similarly, high VEGF expression was determined in 4% of Stage I and 30% of Stage II patients, however 90% of Stage III-IV patients had high expression of VEGF. Comparing the GLUT-1 scores, it was found that increasing stages correlated with high GLUT-1 expression. Additionally, a statistically significant difference was also noted in MVD between stages (p<0.001). The average MVD of Stage I patients was 31.87+/-7.73. It was found 49.24+/-7.60 in Stage II, and 78.74+/-14.48 in Stage III-IV patients. On analyzing expression of HIF-1alpha, VEGF and GLUT-1 and MVD in pairs, statistically significant correlations were found between each other (p<0.001). CONCLUSION: HIF-1alpha was increasingly expressed from early stages through advance stages of endometrioid adenocarcinoma, paralleled by activation of its downstream genes such as GLUT-1, VEGF and increased angiogenesis. These results highlight the importance of hypoxia and related pathways in progression of endometrial carcinoma.

Coexisting sublingual dermoid cyst and heterotopic gastrointestinal cyst: Case report.

A heterotopic oral gastrointestinal cyst coexisting with a lingual dermoid cyst is a rare condition, with only 3 reported cases in the English-language literature. Clinically, both gastrointestinal and dermoid cysts tend to manifest as an asymptomatic swelling. Cysts above the mylohyoid often present with sublingual swelling, whereas those below the mylohyoid present with submental swelling. Increased salivation, altered speech, dyspnea and difficulties in eating, swallowing and respiration may be present, depending on the size of the cyst. This paper describes the case of a 4-year-old girl presenting with swelling of the tongue and floor of the mouth that interfered with normal speech. Two cystic lesions were surgically excised using an intraoral approach, and recovery was uneventful. Histopathological examination of the specimens taken during surgery revealed the first, anterior cyst to be a dermoid cyst and the second, posterior cyst to be a heterotopic oral gastrointestinal cyst (HGIC). Although this situation is very rare, it should be included in the differential diagnosis of swellings in the submandibular region in the pediatric population. Key words:Dermoid cyst, heterotopic gastrointestinal cyst, children, tongue.

Changes in expressions of ADAM9, 10, and 17 as well as α-secretase activity in renal cell carcinoma.

BACKGROUND: ADAM9, 10, and 17 are a class of disintegrins and metallproteinases with α-secretase activity. There are conflicting results regarding the role(s) of ADAM9, 10, and 17 in carcinogenesis, and only a few studies have examined their levels and cellular localization in renal cell carcinoma (RCC). Studies examining changes in α-secretase activity in RCC compared to enzymatic activity of the uninvolved kidney are lacking. METHOD: A cross-sectional study was conducted in 56 patients undergoing radical nephrectomy after the diagnosis of RCC. α-Secretase activity was determined using flourogenic substrate in freshly frozen tumor tissues as well as similarly treated tissues from the neighboring kidney. Immunohistochemical analyses of ADAM9, 10, and 17 were also performed. RESULTS: α-Secretase activity decreased markedly in all types of RCC as compared to neighboring uninvolved kidney tissue having 5 to 10 times higher levels of α-secretase activity. Although type-dependent variations were observed, tumoral expressions of ADAMs, except for ADAM17, were lower in the tumors compared to that of neighboring tissues, but the changes in α-secretase activity were greater. In RCC tissue, ADAM9 expressions were localized in nuclear and cytoplasmic compartments, whereas ADAM10 and 17 were present predominately in the cytoplasm potentially explaining the markedly decreased enzyme activity. Membranous localization of ADAMs was noted in uninvolved kidney tissue. CONCLUSIONS: The loss of α-secretase activity observed here in conjunction with previous findings argue against tumorigenic effects of ADAM9, 10, and 17 supporting that increased nuclear and cytoplasmic expression may be an attempt to compensate for loss of function.

Langerhans Cell Histiocytosis: A Diagnostic Challenge in the Oral Cavity.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder of the reticuloendothelial system with unknown etiology. This report aims to present a case of LCH with diffuse involvement of the oral cavity and to raise awareness of the distinguishing features of this diagnostically challenging entity. CASE REPORT: A 26-year-old male patient presented with complaints of teeth mobility, intense pain, and difficulty in chewing. Intraoral and radiological examinations revealed generalized gingival hyperplasia and severe teeth mobility with widespread alveolar bone loss. Periodontal therapy was performed with no significant improvement. An incisional biopsy revealed Langerhans cells and positive reaction to S-100 and CD1, and the patient was diagnosed with LCH. The patient underwent systemic chemotherapy with vinca alkaloids and corticosteroids. Regression of gingival lesions, as well as significant decrease in mobility of the remaining teeth and severity of pain, was achieved during 12 months of follow-up. CONCLUSION: The rarity and variable system involvement of LCH necessitate a multidisciplinary approach be carried out for accurate diagnosis, effective treatment, and an uneventful follow-up. Awareness of oral manifestations of LCH may aid clinicians greatly in reducing morbidity and mortality associated with this debilitating condition.

Chronic Invasive Nongranulomatous Fungal Rhinosinusitis in Immunocompetent Individuals.

Chronic invasive nongranulomatous fungal rhinosinusitis is a well-described but uncommon type of fungal rhinosinusitis (FRS). While the prevalence of chronic FRS is 0.11% in healthy individuals, only 1.3% of them are in nongranulomatous invasive nature. The majority of the cases in the literature have been reported from developing countries mostly located in the tropical regions, as typically occurring in the background of diabetes mellitus or corticosteroid treatment. The current paper reports four consecutive cases, who were diagnosed within a short period of six months at a single center of a country located outside the tropical climate zone. None of the patients had a comorbid disease that may cause immune suppression or a history of drug use. The only risk factor that may have a role in development of chronic invasive nongranulomatous FRS was that all of our patients were people working in greenhouse farming. Three cases underwent endoscopic sinus surgery, and one case underwent surgery with both endoscopic and external approaches. Systemic antifungal therapy was initiated in all cases in the postoperative period with voriconazole 200 mg orally twice a day. All patients achieved a complete clinical remission. Chronic invasive nongranulomatous FRS should be kept in mind in the presence of long-standing nonspecific sinonasal symptoms in immunocompetent individuals, particularly with a history of working in greenhouse farming.

Neuropeptide Levels as well as Neprilysin Activity Decrease in Renal Cell Carcinoma.

Calcitonin Gene-related Peptide (CGRP), Vasoactive Intestinal Peptide (VIP) and Substance P (SP) are sensory neuropeptides which may alter cancer growth through modulation of chronic inflammation. We recently reported that SP suppresses breast cancer growth and metastasis through neuroimmune modulation. These neuropeptides are hydrolyzed by Neprilysin (NEP) to bioactive fragments. Decreased activity of NEP was reported in clear cell and chromophobe type renal cell carcinoma (RCC). It is however not known how the levels of neuropeptides hydrolyzed with NEP changes in RCC. Decrease activity of SP and CGRP containing sensory nerve endings was previously reported to increase cancer metastasis in animal models. It is however not known how peptidergic nerve endings are altered in RCC. Hence we here evaluated the levels of neuronal and non-neuronal neuropeptides and NEP activity in RCC including papillary type as well as neighboring uninvolved kidney. A cross-sectional study was conducted in 57 patients undergoing radical nephrectomy and diagnosed with RCC. NEP activity, levels and expression were determined using flourogenic substrate, western blot and qPCR respectively in freshly-frozen tissues. Immunohistochemical analyses were also performed. Neuronal and non-neuronal levels of CGRP, SP and VIP levels were determined using two-step acetic acid extraction. Levels and activity of NEP were markedly decreased in RCC regardless of subtype. Similar levels of VIP were detected in first and second extractions. VIP levels were higher in clear cell and papillary RCC compared to nearby kidney tissue. VIP levels of neighboring kidney tissue of papillary type RCC was significantly lower compared to kidney samples from clear cell RCC. CGRP levels were higher in second extraction. Similar to VIP levels, CGRP levels of neighboring kidney tissue from clear cell and chromophobe type RCC was significantly lower compared to corresponding tumor samples, an effect observed in the second extraction. VIP and CGRP levels of nearby kidney tissue varied subtype dependently demonstrating that different subtypes of RCC alter their local environment differently. Furthermore NEP-induce hydrolysis of VIP creates selective VPAC-1 receptor agonist which has anti-proliferative and anti-inflammatory effects. Hence loss of NEP activity may prevent anti-tumoral effects of VIP on RCC.