Novel human lymph node-derived matrix supports the adhesion of metastatic oral carcinoma cells.

BACKGROUND: 3D culture is increasingly used in cancer research, as it allows the growth of cells in an environment that mimics in vivo conditions. Metastases are the primary cause of morbidity and mortality in cancer patients, and solid tumour metastases are mostly located in lymph nodes. Currently, there are no techniques that model the pre-metastatic lymph node microenvironment in vitro. In this study, we prepared a novel extracellular matrix, Lymphogel, which is derived from lymph nodes, mimicking the tumour microenvironment (TME) of metastatic carcinoma cells. We tested the suitability of the new matrix in various functional experiments and compared the results with those obtained using existing matrices. METHODS: We used both commercial and patient-derived primary and metastatic oral tongue squamous cell carcinoma (OTSCC) cell lines. We characterized the functional differences of these cells using three different matrices (human uterine leiomyoma-derived Myogel, human pre-metastatic neck lymph node-derived Lymphogel (h-LG), porcine normal neck lymph node-derived Lymphogel (p-LG) in proliferation, adhesion, migration and invasion assays. We also performed proteomic analyses to compare the different matrices in relation to their functional properties. RESULTS: OTSCC cells exhibited different adhesion and invasion patterns depending on the matrix. Metastatic cell lines showed improved ability to adhere to h-LG, but the effects of the matrices on cell invasion fluctuated non-significantly between the cell lines. Proteomic analyses showed that the protein composition between matrices was highly variable; Myogel contained 618, p-LG 1823 and h-LG 1520 different proteins. The comparison of all three matrices revealed only 120 common proteins. Analysis of cellular pathways and processes associated with proteomes of each matrix revealed similarities of Myogel with h-LG but less with p-LG. Similarly, p-LG contained the least adhesion-related proteins compared with Myogel and h-LG. The highest number of unique adhesion-related proteins was present in h-LG. CONCLUSIONS: We demonstrated that human pre-metastatic neck lymph node-derived matrix is suitable for studying metastatic OTSCC cells. As a whole-protein extract, h-LG provides new opportunities for in vitro carcinoma cell culture experiments.

Cause-specific mortality in patients with head and neck cancer: Long-term follow-up of a population-based cohort from 1986 to 2012 accounting for competing risks.

OBJECTIVES: Recent recommendations for treating head and neck cancer (HNC) patients favor an individualized approach. Expected long-term survival - together with short-term survival - after diagnosis is the primary focus in assessing the treatment modality and follow-up scheme. "Disease-specific" survival up to five years is often used for measuring the prognosis and for assessing treatment methods. However, especially long-term survival is strongly affected by competing causes of death among HNC patients. MATERIALS AND METHODS: The long-term prognosis of patients with HNC in terms of mortality from both cancer and competing causes was analyzed according to recent methodological guidelines by examining cumulative incidence functions and models for cause-specific hazards and sub-distribution hazards in a population based cohort of 220 patients treated in a tertiary care center in Northern Finland. RESULTS: In addition to well-known tumor-related factors, mortality from HNC was associated with older age. The mortality from other causes of death was strongly dependent on age and Charlson's Comorbidity Index, but less on gender. When demonstrating the importance of individualized approach in simulated patients, the mortality was highly variable across patients with similar cancer status, but with different comorbidities or age. CONCLUSION: The overall survival pattern of HNC patients depends not only on their cancer characteristics, but also varies greatly according to their age and comorbidities. Our findings support the need for individualized treatment and follow-up protocols, and active management of comorbid diseases. Appropriate methods for analyzing competing risks should be used when presenting survival estimates of cancer patients.

Predictive factors and treatment outcome of laryngeal carcinoma recurrence.

BACKGROUND: Up to 30% of patients with laryngeal squamous cell carcinoma (SCC) present with recurrence after treatment. We analyzed factors associated with the risk of cancer recurrence and prognosis after recurrence. METHODS: A nationwide laryngeal SCC cohort from Finnish university hospitals during 2001 to 2005 with initial successful therapy (n = 316) was analyzed. RESULTS: Laryngeal SCC recurred in 22% of patients. The median time to recurrence was 9 months, with 90% occurring within 36 months after treatment. The World Health Organization (WHO) performance status >0, neck metastasis at presentation, and nonsurgical treatment were independent prognostic factors for recurrence. Patients with local recurrence had a 5-year overall survival (OS) of 53% compared with 5% in patients with regional/distant recurrences. OS for glottic and nonglottic laryngeal SCC recurrence was 45% and 0%, respectively. CONCLUSION: The type of treatment affected the risk of recurrence in this retrospective series. Local recurrences carried a chance for successful salvage treatment. Routine follow-up beyond 36 months remains controversial. © 2016 Wiley Periodicals, Inc. Head Neck 39: 555-563, 2017.

Characteristics and medical-care-seeking of head and neck cancer patients: a population-based cross-sectional survey.

OBJECTIVES: Well-known risk factors, such as smoking and alcohol consumption, easily denounce head and neck cancer patients as smokers, alcohol abusers, and persons who are socially excluded and have low socioeconomic status. To diagnose these patients as early as possible, we should not have a prejudiced assumption of their characteristics. MATERIALS AND METHODS: We collected detailed data on patient characteristics and health behavior and explored whether these traits had any effect on seeking medical advice in a population-based cross-sectional study involving 85 patients with head and neck cancer diagnosed between January 2003 and December 2007, residing in two health care districts (population 1,600,000) in Finland. The data were gathered from patient charts and questionnaires. The questionnaire data were compared with the general population in Finland. RESULTS: We found these patients to be ordinary elderly people whose demographic and social features resembled those of the general population. They smoked more often, but otherwise had a rather healthy lifestyle. Only half were aware that smoking and alcohol consumption were risk factors of head and neck cancer. In a multivariate analysis, fear of physicians (adjusted odds ratio 11.0; 95% confidence interval 1.2-103), medical-care-seeking for symptoms other than pain (18.5; 2.2-156), and not suspecting cancer (11.2; 1.7-75.1) were independent risk factors for delayed consultation (combined appraisal and help-seeking interval over 3 months). CONCLUSION: Head and neck cancer patients deviated from the same-aged general population only in excessive smoking. Fear of doctors, having no pain, and no suspicion of cancer resulted in delayed medical-care-seeking.