Photodynamic therapy: A promising new modality for the treatment of cancer

The first reports on photodynamic therapy (PDT) date back to the 1970s. Since then, several thousands of patients, both with early stage and advanced stage solid tumours, have been treated with PDT and many claims have been made regarding its efficacy. Nevertheless, the therapy has not yet found general acceptance by oncologists. Therefore it seems legitimate to ask whether PDT can still be described as "a promising new therapy in the treatment of cancer". Clinically, PDT has been mainly used for bladder cancer, lung cancer and in malignant diseases of the skin and upper aerodigestive tract. The sensitizer used in the photodynamic treatment of most patients is Photofrin, (Photofrin, the commercial name of dihematoporphyrin ether/ester, containing > 80% of the active porphyrin dimers/oligomers (A.M.R. Fisher, A.L. Murphee and C.J. Gomer, Clinical and preclinical photodynamictherapy, Review Series Article, Lasers Surg. Med., 17 (1995) 2-31). It is a complex mixture of porphyrins derived from hematoporphyrin. Although this sensitizer is effective, it is not the most suitable photosensitizer for PDT. Prolonged skin photosensitivity and the relatively low absorbance at 630 nm, a wavelength where tissue penetration of light is not optimal, have been frequently cited as negative aspects hindering general acceptance. A multitude of new sensitizers is currently under evaluation. Most of these "second generation photosensitizers" are chemically pure, absorb light at around 650 nm or greater and induce no or less general skin photosensitivity. Another novel approach is the photosensitization of neoplasms by the induction of endogenous photosensitizers through the application of 5-aminolevulinic acid (ALA). This article addresses the use of PDT in the disciplines mentioned above and attempts to indicate developments of PDT which could be necessary for this therapy to gain a wider acceptance in the various field

Haemolysis during Sample Preparation Alters microRNA Content of Plasma

The presence of cell-free microRNAs (miRNAs) has been detected in a range of body fluids. The miRNA content of plasma/serum in particular has been proposed as a potential source of novel biomarkers for a number of diseases. Nevertheless, the quantification of miRNAs from plasma or serum is made difficult due to inefficient isolation and lack of consensus regarding the optimal reference miRNA. The effect of haemolysis on the quantification and normalisation of miRNAs in plasma has not been investigated in great detail. We found that levels of miR-16, a commonly used reference gene, showed little variation when measured in plasma samples from healthy volunteers or patients with malignant mesothelioma or coronary artery disease. Including samples with evidence of haemolysis led to variation in miR-16 levels and consequently decreased its ability to serve as a reference. The levels of miR-16 and miR-451, both present in significant levels in red blood cells, were proportional to the degree of haemolysis. Measurements of the level of these miRNAs in whole blood, plasma, red blood cells and peripheral blood mononuclear cells revealed that the miRNA content of red blood cells represents the major source of variation in miR-16 and miR-451 levels measured in plasma. Adding lysed red blood cells to non-haemolysed plasma allowed a cut-off level of free haemoglobin to be determined, below which miR-16 and miR-451 levels displayed little variation between individuals. In conclusion, increases in plasma miR-16 and miR-451 are caused by haemolysis. In the absence of haemolysis the levels of both miR-16 and miR-451 are sufficiently constant to serve as normalisers

EUROSCAN, a randomized trial of vitamin A and N-Acetylcysteine in patients with head and neck cancer or lung cancer

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Cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma or pleural metastases of thymoma

STUDY OBJECTIVES: No established curative treatment is available for pleural thymoma metastases and malignant pleural mesothelioma (MPM). Recently, peritoneal malignancies have been treated by cytoreductive surgery and intraoperative hyperthermic intracavitary perfusion chemotherapy (HIPEC). We investigated the feasibility and safety of this multimodality treatment in the thoracic cavity. DESIGN: Patients with pleural thymoma metastases or early-stage MPM were enrolled in a feasibility study. Morbidity, recurrence, and survival rates were recorded. SETTING: The Netherlands Cancer Institute. PATIENTS: Three patients with pleural thymoma metastases and 11 patients with pleural mesothelioma were treated. INTERVENTIONS: Cytoreductive surgery and intraoperative hyperthermic intrathoracic perfusion chemotherapy (HITHOC) with cisplatin and adriamycin were performed. The mesothelioma patients received adjuvant radiotherapy on the thoracotomy wound and drainage tracts. MEASUREMENTS AND RESULTS: Morbidity and mortality rates were 47% and 0%, respectively. Reoperation was necessary in four cases. Severe chemotherapy-related complications were not observed. A solitary mediastinal and a contralateral pleural thymoma recurrence were successfully treated by radiotherapy and a contralateral HITHOC procedure. All thymoma patients were alive and free of disease after a mean follow-up period of 18 months. After a mean follow-up period of 7.4 months, nine mesothelioma patients are alive. Two mesothelioma patients died of contralateral pleural and peritoneal recurrent disease, while one patient is alive with locoregional recurrence. CONCLUSIONS: Cytoreductive surgery and HITHOC with cisplatin and adriamycin is feasible in patients with pleural thymoma metastases and early-stage MPM, and is associated with acceptable morbidity rates. Early data on locoregional disease control are encouraging, and a phase II study will be conducte

The value of chest computer tomography and cervical mediastinoscopy in the preoperative assessment of patients with malignant pleural mesothelioma

BACKGROUND: Patients with localized malignant pleural mesothelioma (MPM) can be considered for surgical resection with or without additional treatment. For this approach it is imperative to select patients without mediastinal lymph node involvement. In this study cervical mediastinoscopy (CM) is compared with computer tomography (CT) scanning for its diagnostic accuracy in assessing mediastinal lymph nodes during preoperative workup. METHODS: Computer tomography scans of the chest and CM were performed in 43 patients with proven unilateral MPM. The CT scans were reviewed by one radiologist and two chest physicians. At CM the lymph node samples were taken from stations Naruke 2, 3, 4, and 7. Computer tomography and CM results were compared with final histopathologic findings obtained at thoracotomy or, if this was not performed, at CM. RESULTS: Computer tomography scanning revealed pathologic enlarged lymph nodes with a shortest diameter of at least 10 mm in 17 of 43 patients (39%). There was histopathologic evidence of lymph node metastases at CM in 11 of these patients (26%). This resulted in a sensitivity of 60% and 80%, a specificity of 71% and 100%, and a diagnostic accuracy of 67% and 93% for CT and CM, respectively. CONCLUSIONS: Cervical mediastinoscopy is a valuable diagnostic procedure for patients with MPM who are considered candidates for surgical-based therapy. Results of CM are more reliable than those obtained by CT scanning. Our data confirm results of previous studies reporting that mediastinal lymph node involvement is a frequent event in MP

A proteomics-based approach identifies secreted protein acidic and rich in cysteine as a prognostic biomarker in malignant pleural mesothelioma

Background: We aimed to identify prognostic blood biomarkers using proteomics-based approaches in malignant pleural mesothelioma (MPM). Methods: Plasma samples from 12 MPM patients were used for exploratory mass spectrometry and ELISA analyses. The significance of secreted protein acidic and rich in cysteine (SPARC) was examined in sera from a Dutch series (n¼97). To determine the source of the circulating SPARC, we investigated SPARC expression in MPM tumours and healthy controls, as well as the expression and secretion from cell lines and xenografts. Results: Secreted protein acidic and rich in cysteine was identified as a putative prognostic marker in plasma. Validation in the Dutch series showed that the median survival was higher in patients with low SPARC compared with those with high SPARC (19.0 vs 8.8 months; P¼0.01). In multivariate analyses, serum SPARC remained as an independent predictor (HR 1.55; P¼0.05). In MPM tumour samples, SPARC was present in the tumour cells and stromal fibroblasts. Cellular SPARC expression was higher in 5 out of 7 cell lines compared with two immortalized mesothelial lines. Neither cell lines nor xenograft tumours secreted detectable SPARC. Conclusions: Low circulating SPARC was associated with favourable prognosis. Secreted protein acidic and rich in cysteine was present in both tumour cells and stromal fibroblasts; and our in vitro and in vivo experiments suggest that stromal fibroblasts are a potential source of circulating SPARC