Stem cells are defined as cells able to both extensively self-renew and differentiate into progenitors. Research data show that more resistant stem cells than common cancer cells exist in cancer patients.To identify unrecognized differences between cancer stem cells and cancer cells might be able to develope effective classification,diagnose and treat ment for cancer.

Stem Cells,Cancer and Cancer Stem Cells

Photosensitizers of the porphyrin and phthalocyanine series for photodynamic therapy

Delivery of molecular and cellular medicine to solid tumors

Metal Complexes as Photo- and Radiosensitizers

Extraordinary advances in molecular biology and biotechnology have led to the development of a vast number of therapeutic anti-cancer agents. To reach cancer cells in a tumor, a blood-borne therapeutic molecule, particle, or cell must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium, which it then must migrate through. Unfortunately, tumors often develop in ways that hinder these steps. The goal of research in this area is to analyze each of these steps experimentally and theoretically and integrate the resulting information into a unified theoretical framework. This paradigm of analysis and synthesis has fostered a better understanding of physiological barriers in solid tumors and aided in the development of novel strategies to exploit and/or overcome these barriers for improved cancer detection and treatment.

Transport of molecules, particles, and cells in solid tumors.

Elevated interstitial fluid pressure (IFP) of tumors may be a physiological barrier to the delivery of certain therapeutic agents. The objective of this study was to find out if IFP could be lowered using localized hyperthermia and if the reduction in IFP could predict the tumor response to treatment. Amelanotic melanoma (A-Mel-3) implanted into the dorsal skin of Syrian golden hamsters was exposed to hyperthermic treatment after 7 days of tumor growth at tumor volumes of about 100-150 mm3. Hyperthermia was induced by immersing the tumor in a water bath at 43 degrees C for 30 or 60 min. Forty-eight h later the IFP of control and treated tumors was determined by using the wick-in-needle technique. The mean IFP in control tumors was 12.6 mmHg. Hyperthermic treatment for 30 min induced a significant decrease to 2.8 mmHg (P less than 0.001 versus controls), whereas a 60-min immersion of the tumors induced a further decrease to 0.8 mmHg (P less than 0.05 versus 43 degrees C for 30 min). Separate experiments on tumor growth in corresponding groups of animals revealed a significant growth delay of 2.7 days after hyperthermia for 30 min. Enhanced growth delay and partial tumor response in 66% of the tumors were found following 60 min of hyperthermia at 43 degrees C. The thermal dose-dependent decrease in IFP presumably results from the dose-dependent damage to the tumor vasculature. In addition, the association of an enhanced biological effect with a more pronounced reduction of interstitial fluid pressure suggests that the IFP might serve as a quantitative parameter to predict the response of tumors to hyperthermic therapy.

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Interstitial fluid pressure in solid tumors following hyperthermia: possible correlation with therapeutic response.

https://journal.chestnet.org/article/S0012-3692(15)35790-1/pdf

Fiberoptic bronchoscopic balloon dilatation in malignant tracheobronchial disease: indications and results.

The hedgehog (Hh) signaling pathway has been shown to be activated in the cancer stem cells of several tumor entities. The Hh inhibitor GDC-0449 has been proven to be effective in some cancers but not yet in lung cancer. We aimed at investigating whether GDC-0449 is effective in the lung cancer cell lines HCC (adenocarcinoma) and H1339 (small-cell-lung carcinoma), whether in these cell lines stem cell-like side populations (SPs) can be identified, and whether possible effects of GDC-0449 are mediated via SPs. SPs were identified by spectrum shift and decreased fluorescence after staining with 2.5 μg/ml Hoechst 33342. Expression of proteins was quantified by immunofluorescence. GDC-0449 (25 and 50 μM) inhibited concentration-dependent cell growth in HCC and H1339 cells. Further, the inhibitory effects of cisplatin on cell growth were augmented. In HCC and H1339 cell lines, SPs of 0.57 and 0.46% could be identified, respectively. SP, but not non-SP, cells were able to repopulate the original tumor population. The Hh receptor smoothened was detectable in SP but not in non-SP cells, showing the activation of the Hh pathway only in SPs. GDC-0449 considerably reduced SPs in HCC and H1339 cells. We demonstrate for the first time that GDC-0449 effectively reduces cell growth in lung cancer cell lines. This effect is mediated by the inhibition of stem cell-like SPs.

Effects of the Hedgehog pathway inhibitor GDC-0449 on lung cancer cell lines are mediated by side populations.

High frequency jet ventilation (HFJV) is a well accepted method for securing ventilation in rigid and interventional bronchoscopy. We describe a technique of HFJV using a 14F nylon insufflation catheter placed in the trachea to support stent implantation or endobronchial balloon dilation in endobron

High frequency jet ventilation in interventional fiberoptic bronchoscopy.

Recalcitrant forms of recurrent nasal polyposis are problematic for patients as for rhinosurgeons. In aspirin-sensitive patients, aspirin desensitization is supposed to prevent recurrence by targeting the metabolism of arachidonic acid. Aspirin-sensitive patients (n = 65) following aspirin desensitization after functional endoscopic sinus surgery (FESS) for recurrent nasal polyposis under daily intake of 500-mg aspirin were compared to a post-FESS group (n = 81) of aspirin-sensitive individuals using exclusively topical mometasone. Quality of life (QoL) scores including sinonasal, pulmonal and general QoL items as well as endoscopic endonasal examination findings were evaluated during the postoperative follow-up period. After a follow-up period of minimum 18 months, a significant improvement in nasal obstruction, rhinorrhea, post nasal drip, sense of smell, facial pain, sleep quality and further general QoL items in desensitized patients was found compared to aspirin-sensitive controls. Improvement in sinonasal symptoms was evident, whereas the severity of asthmatic symptoms showed no significant changes. Although the pathophysiology of aspirin sensitivity is still not fully understood and the therapy is not sufficiently investigated, aspirin desensitization seems to have a positive effect on QoL scores concerning sinonasal symptoms and should be regarded as a possible postoperative treatment modality for recurrent nasal polyposis in aspirin-sensitive individuals.

Fernando Gamarra

Papers

Interstitial fluid pressure in solid tumors following hyperthermia: possible correlation with therapeutic response.

Fiberoptic bronchoscopic balloon dilatation in malignant tracheobronchial disease: indications and results.

Effects of the Hedgehog pathway inhibitor GDC-0449 on lung cancer cell lines are mediated by side populations.

High frequency jet ventilation in interventional fiberoptic bronchoscopy.

Sinonasal outcome under aspirin desensitization following functional endoscopic sinus surgery in patients with aspirin triad