Feasibility of electronic nose technology for discriminating between head and neck, bladder, and colon carcinomas.

Electronic nose (e-nose) technology has the potential to detect cancer at an early stage and can differentiate between cancer origins. Our objective was to compare patients who had head and neck squamous cell carcinoma (HNSCC) with patients who had colon or bladder cancer to determine the distinctive diagnostic characteristics of the e-nose. Feasibility study An e-nose device was used to collect samples of exhaled breath from patients who had HNSCC and those who had bladder or colon cancer, after which the samples were analyzed and compared. One hundred patients with HNSCC, 40 patients with bladder cancer, and 28 patients with colon cancer exhaled through an e-nose for 5 min. An artificial neural network was used for the analysis, and double cross-validation to validate the model. In differentiating HNSCC from colon cancer, a diagnostic accuracy of 81 % was found. When comparing HNSCC with bladder cancer, the diagnostic accuracy was 84 %. A diagnostic accuracy of 84 % was found between bladder cancer and colon cancer. The e-nose technique using double cross-validation is able to discriminate between HNSCC and colon cancer and between HNSCC and bladder cancer. Furthermore, the e-nose technique can distinguish colon cancer from bladder cancer.

In vitro Monocyte IL-6 Secretion Levels Following Stimulation with Autologous Spheroids Derived from Tumour or Benign Mucosa Predict Long-term Survival in Head and Neck Squamous Cell Carcinoma Patients.

MCP-1/IL-6 in vitro monocyte secretion upon coculture with autologous fragment spheroids was studied in relation to patient 5- and 10-year overall survival rates in head and neck squamous cell carcinoma (HNSCC) patients (n = 65) diagnosed between 1998 and 2005, nine of whom had an human papilloma virus (HPV) tumour infection. The spheroids were harvested from malignant or benign tissue during primary surgery. Two weeks following surgery, freshly isolated autologous monocytes and benign or malignant spheroids were cocultured 24 h in vitro. The IL-6 secretion was expressed as a fraction of the lipopolysaccharide (LPS) response from the same batch of monocytes. HPV status was obtained by employing PCR analyses of primary diagnostic blocks. IL-6/MCP-1 response levels were not found to be dependent on HPV infection status. MCP-1 secretion did not predict prognosis, nor did in vitro IL-6 monocyte background or LPS-stimulated IL-6 secretion. At 5-year observation, dichotomized IL-6 levels following monocyte coculture, with both malignant and benign spheroids, showed a strong trend towards predicting survival, that is a low monocyte malignant coculture response showed a survival of 31 ± 17 versus 58 ± 17% with a high such response (P = 0.057). When studying monocyte IL-6 coculture responses evaluating benign and malignant spheroid results statistically together, a prediction of survival up to 10 years was found (hazard ratio = 0.48; confidence interval = 0.24-0.96; P < 0.05) with double low IL-6 responses. This survival prediction was also present after an adjustment for HPV tumour infection status. In conclusion, monocyte IL-6 in vitro secretion in cocultures with autologous spheroids/serum from HNSCCs predicted 5- and 10-year survivals, both with and without tumour HPV tumour adjustment.

Honey and beehive products in otorhinolaryngology: a narrative review.

BACKGROUND: Honey and beehive products were rediscovered as an alternative treatment in wounds. The medicinal properties also raised interest of their use in Otorhinolaryngology. OBJECTIVE OF REVIEW: To give an overview of the effectiveness of beehive products in Otorhinolaryngology. TYPE OF REVIEW: Narrative. SEARCH STRATEGY AND EVALUATION: A literature search of the databases PubMed, EMBASE and Cochrane was performed from the last two decades till December 2014. The search terms 'honey', 'propolis' or 'royal jelly' were used. Articles, which evaluated the effectiveness of beehive products in Otorhinolaryngology, were included. The quality assessment of included studies was performed using the Cochrane Collaboration's risk of bias tool. DISCUSSION AND CONCLUSION: A total of 36 studies were identified and evaluated. Eighteen studies investigated their effect in oral infections, seven in infection of the respiratory tract, six in rhino-sinusal diseases, four investigated the use in tonsillectomy and head and neck surgery and one study explored the preventive effect in otitis media. Honey can be considered as effective (additional) treatment in mucositis, childhood cough, persistent post-infectious cough and after tonsillectomy. Propolis may have a role in the treatment of (aphthous) stomatitis, mouth ulcer and prevention of acute otitis media. Royal jelly showed to reduce mucositis. In the presented studies, beehive products proved to be safe, with only minor adverse reactions. Studies showed to be diverse and had some methodological limitations.

Definitive radiation therapy for treatment of laryngeal carcinoma: impact of local relapse on outcome and implications for treatment strategies.

PURPOSE: The purpose of this work was to evaluate outcome after radiotherapy (RT) for laryngeal carcinoma and investigate effects of local relapse on ultimate disease control, including surgical salvage procedures. METHODS AND MATERIALS: In all, 435 patients with laryngeal carcinoma (cT1-cT4a) treated with primary RT were retrospectively analyzed. Uni- and multivariate analyses were performed to identify prognostic factors for local relapse-free survival and overall survival. RESULTS: Median follow-up was 38 months (range 1-144 months). The cumulative frequency of local recurrence was dependent on T stage: cT1 tumors 10%, cT2 18%, cT3 23%, and cT4 36% (p<0.001). Salvage surgery for local persistent/recurrent disease was performed in 59 of 78 patients (76%). The ultimate local control rates at 5 years (including salvage therapy) were 98, 98, 87, and 68% for cT1, cT2, cT3, and cT4 tumors (p<0.001), respectively. For the patients who developed local recurrence, the 5-year ultimate local control rates were 80, 88, 55, and 26% (p<0.001), respectively. Overall survival at 5 years was 68% for patients without local relapse and 50% for patients experiencing local failure (p<0.001). In univariate analysis, cT stage, cN stage, and tumor volume were statistically significant associated with local relapse-free survival. In multivariate analysis for the cT3-4 tumors, only tumor volume remained statistically significant (HR 1.017, p=0.001) for local relapse-free survival. CONCLUSION: Local control rates for cT1-2 laryngeal carcinomas are favorable and in concordance with previous reports and most recurrences are salvaged. For cT3-4 tumors treated with RT alone, initial local control rates are moderate, and in 60% of recurring cases salvage surgery is attempted, with ultimate local control being achieved in only a subset. For voluminous, locally advanced laryngeal tumors, more aggressive treatment modalities should be considered, including upfront laryngectomy or radiochemotherapy.

Co-culture of head and neck squamous cell carcinoma spheroids with autologous monocytes predicts prognosis.

Co-culture of monocytes with autologous fragment (F) spheroids originating from malignant (M) tumour or benign (B) control mucosa of head and neck squamous cell carcinoma (HNSCC) yields interleukin (IL)-6 and monocyte chemo-attractant protein (MCP)-1 secretion. This study investigates the association between this cytokine co-culture response and prognosis. Analysis of IL-6 and MCP-1 content of supernatants from monocytes in vitro co-culture with autologous MF- or BF-spheroids was investigated in a cohort of HNSCC patients (n = 65) diagnosed between 1998 and 2005, all of whom were treated with curative intent by primary surgery. The IL-6 response was expressed as a fraction of the lipopolysaccharid response of the same batch of monocytes. Recurrence, survival and causes of death were then established following the second part of 2005. MCP-1 levels did not predict prognosis. We found that increased levels of IL-6 from autologous monocytes in co-culture with MF-spheroids predicted recurrence with a hazard ratio (HR) of 1.5 [confidence interval (CI): 1.01-2.60; P = 0.05] and co-culture with BF-spheroids and monocytes predicted recurrence (HR = 4.17; CI: 1.54-11.29; P = 0.005). The same results where obtained in addition with TNM stage of the patients. Simultaneous analysis of BF- and MF-spheroid co-culture IL-6 responses as well as adjustment for age and TNM stage of the patients allowed prediction of total survival (HR = 3.1; CI: 1.11-8.56; P = 0.03) based on BF co-culture levels. IL-6 secreted upon in vitro co-culture with monocytes and BF-spheroids predicts recurrence and prognosis, whereas co-culture with monocytes and MF-spheroids predicts recurrence.

Gene expression profile in oral squamous cell carcinomas and matching normal oral mucosal tissues from black Africans and white Caucasians: the case of the Sudan vs. Norway.

Expression profile of 588 known genes relating to tumour biology, was examined between oral squamous cell carcinomas (OSCCs) and matching normal oral mucosal tissues (NOMTs) obtained from Sudanese (n=11) and Norwegian (n=11) patients. cDNA probes were synthesised from total RNA and hybridised with the Atlas human cancer cDNA expression array membranes. RT-PCR and immunohistochemistry were applied to confirm the expression pattern of a subset of the 588 genes. Differences in expression of the genes examined were found between the OSCCs and the NOMTs on the Atlas membranes. Several of these genes were either up- or down-regulated 1.6-fold or higher in the OSCCs compared to the NOMTs in the cases from the two populations. We found that 181 (31%) and 195 (33%) genes were either up-regulated or down-regulated in the OSCCs from the Sudan and Norway, respectively. From the total number of genes (n=376) found expressed in the OSCCs investigated from the two countries, 53 genes (14%) showed common expression profile [35 (66%) were up-regulated and 18 (34%) were down-regulated] and 70 genes (19%) showed opposite regulation status. Results of the RT-PCR and immunohistochemistry confirmed the hybridisation data. These findings may provide an OSCCs-specific gene expression profile in patients from the two countries, suggesting that alterations of 123 genes are common in these OSCCs regardless of ethnic differences or other socio-cultural risk factors between the patients from the two countries. The findings might further suggest that specific genes are frequently involved in these OSCCs, which may provide novel clues as diagnostic, prognostic biomarkers and/or targets for therapy. The Atlas human cancer cDNA expression array technique can be useful to examine and describe the expression profile of known genes frequently involved in OSCCs from different populations.

Mechanisms for monocyte activation in co-culture with autologous tumor spheroids.

Biopsies from carcinoma tissue and benign control mucosa from head and neck squamous cell carcinoma patients were used to establish fragment (F)-spheroids in vitro. We have previously shown that autologous monocytes co-cultured with F-spheroids in vitro secrete interleukin (IL)-6 upon 24h in co-culture. Presently, the aim was to study the mechanisms of this monocyte secretion. Paraformaldehyde (0.1% for 2min) or actinomycin-D (1 microg/ml for 24h) pre-treatment of the F-spheroids abolished the monocyte IL-6 co-culture response. Addition of glucose (100mM) or mannose (100mM), and to some extent galactose (100mM), but not fructose (100mM) to the co-cultures, partly inhibited the monocyte IL-6 co-culture response, but such addition did not inhibit the in vitro monocyte lipopolysaccharide (LPS)-generated IL-6 secretion. When mannose was added to the co-cultures, monocyte IL-6 mRNA expression was eradicated in malignant co-cultures and reduced to a low level in benign co-cultures. Addition of mouse anti-human beta(1)-integrin (anti-CD29) antibody (2 microg/ml) diminished the IL-6 co-culture response but not the monocyte LPS-generated IL-6 response. In conclusion, the monocyte IL-6 co-culture response is dependent on live spheroids and to some extent on direct contact with the F-spheroids, possibly via lectin-like receptor(s), the mannose receptor and beta(1)-integrin.

Administration of human recombinant IL-7 to normal and irradiated mice increases the numbers of lymphocytes and some immature cells of the myeloid lineage.

In vitro experiments performed by several investigators have demonstrated that IL-7 is a growth factor for immature B lymphocytes, thymocytes, and mature T lymphocytes. To evaluate the potential therapeutic use for human rIL-7 (rhuIL-7) as a hematopoietin, we have studied the in vivo hematopoietic effects of rhuIL-7 in mice. In these experiments, sublethally irradiated and normal mice were treated with or without rhuIL-7 for up to 26 days. Administration of rhuIL-7 significantly increased the white blood cell count in the peripheral blood and spleen in both normal and irradiated mice. Treatment with rhuIL-7 also accelerated lymphocytic recovery in irradiated mice. Precursor and mature B lymphocytes showed the greatest expansion in response to rhuIL-7 administration, with smaller increases in T lymphocytes being observed. In mice recovering from high dose irradiation, rhuIL-7 treatment resulted in preferential expansion of CD8+ T lymphocytes and more rapid normalization of the CD4/CD8 ratios. Differential analysis of peripheral blood smears demonstrated that rhuIL-7 also increased the numbers of immature granulocytes in both normal and irradiated mice. Moreover, administration of rhuIL-7 to normal, irradiated, cyclophosphamide-pretreated, or 5-fluorouracil-pretreated mice increased the number of acetylcholinesterase-positive megakaryocytes in the spleen, but not the bone marrow. Therefore, although the major in vivo effects of rhuIL-7 were on cells of the lymphocytic lineage, rhuIL-7 also increased the numbers of some immature cells of the myeloid lineage.