Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Laser therapy is a well-established, relatively safe, rapid, and highly effective method of palliation for the dysphagia that usually accompanies esophageal and esophagogastric cancer. It is the treatment of choice in many patients, although there remains some disagreement regarding technique and predictors of outcome. The major limitation of laser therapy is the need for repeated treatments, although the interval between treatments may be lengthened by concomitant external beam or endoluminal radiotherapy. When laser therapy is available, use of an esophageal stent should be reserved for special circumstances, such as esophagopulmonary fistulas or extrinsic compression. In addition, stent placement usually is effective when laser photoablation fails or must be performed too frequently. It remains to be seen whether or not technical improvements in esophageal stents will reduce the frequency of complications associated with these devices. Other promising modalities that may be less expensive and more readily available, such as the BICAP tumor probe or injection therapy, deserve further study. It appears that most of these methods are complementary and different modalities may be suited to different types of lesions. The results of phase III clinical trials with PDT, now underway, should help to define the role of this promising modality in the overall scheme of treatment for esophageal cancer. The concept of PDT is attractive, although refinements in photosensitive compounds and methods of light delivery may be needed. Current information suggests a moderately high complication rate for PDT, although this may decrease with technical improvements and increasing experience. Issues surrounding the palliation of esophageal cancer are complex. Whereas the tendency is to focus on technical aspects of therapy and the relief of dysphagia, broader aspects of a patient's quality of life cannot be ignored. Ultimately, the choice of therapy may depend as much on a patient's psychosocial circumstances as on the appearance of the lesion. For instance, the patient who lives at a great distance from the center where laser therapy is performed may be better served by placement of an esophageal stent despite the higher complication rate for this procedure. PDT would be inappropriate for the patient who wishes to spend the remaining few months of life outdoors in the sun. Guiding the patient to the best choice requires the skills of a physician as much as the technical ability of an endoscopist.
 ...
PMID:Palliation of esophageal carcinoma. Laser and photodynamic therapy. 751 23

A body of evidence that vascular-mediated damage occurs in murine tumours after many existing forms of anti-tumour therapy is rapidly accumulating (see Gray Conference Proceedings edited by Moore & West, 1991). Rapid conventional screens of cells in vitro or using leukaemias of lymphomas will not detect this mode of action and such screens will therefore miss effective agents. A change in the approach to experimental cancer therapy is needed to ensure that this important new avenue is fully investigated. Solid tumours will need to be studied and the importance of specific tumour cell biochemistry (e.g. on tissue factor procoagulant activity), of endothelial status and the immunocompetence of the host are all likely to be important. It is a subject of considerable debate at present whether transplanted subcutaneous mouse tumours are adequate models and whether they will reflect the response of spontaneous tumours, or even of transplants into other sites. Xenografts are not likely to be appropriate if the immuno-suppressed hosts lack the cells needed for the cytokine component of the pathway. The strategy of design and screening of new agents, for scheduling of existing agents and particularly the sequencing of adjunctive therapies are likely to be completely different for the "direct" tumor cell or "indirect" vascular-mediated approaches. It may eventually be appropriate to combine vascular manipulation with direct cytotoxicity aimed at malignant cells but the two mechanisms must be recognized as distinct entities and considered separately before attempting to coordinate them. It is important therefore to identify the "hallmarks" of vascular mediated injury and the means by which this can be distinguished from direct cell kill. These may be detectable in the tumour response but clues can also be gained from the side effects that are seen in normal tissues both with existing and with novel therapies (Figure 7). The appeal of vascular-mediated ischaemic therapy is that it is systemic and will have the potential of being effective on any tumour with a newly evoked vascular network, i.e. of about 1 mm in diameter, but it will be even more effective on large tumours than on small. Thus it should affect both large primary tumours and disseminated small metastases. The studies with many different anti-cancer agents have illustrated the potential complexity of responses that can appear to cause tumour cell death by collapse or occlusion of the blood supply. They have also focused attention on features of disparate agents, e.g. TNF, FAA, PDT, which may share similar pathways. No single feature of neovasculature can be highlighted as the sole route by which such antivascular therapy should be targeted. Rapid proliferation of the endothelial cells may prove to be a target, but it also influences differentiation characteristics, so that the immature cells will function abnormally. The permeability of these poorly formed vessels may lead to extravasation of proteins leading to increase interstitial pressures and by this means to an imbalance between intravascular and extravascular pressures and hence to collapse of the thin-walled vessels. Changes in systemic blood pressure, cardiac output, viscosity or coagulation and especially a redistribution of regional perfusion would all have differential effects in tumours and normal vessels. Clearly both vascular patho-physiology and the complexity of endothelial cell function and its imbalance in neovasculature will be important in understanding the mechanism of action of antivascular strategies. This very challenging boundary between oncology and a number of other medical and biological fields promises to lead to altered attitudes to existing therapies and the discovery of completely new classes of anti-cancer agents. The next decade should translate into clinical benefit for patients if the progress in this field continues to be as rapid as it has been in the late eighties. We must now determine what characteristics make one tumour more sensitive than another to agents such as heat, PDT, cytokines and FAA, and learn how to extrapolate from those rodent tumours to the human.
 ...
PMID:Review article: angiogenesis, neovascular proliferation and vascular pathophysiology as targets for cancer therapy. 768 69

Four Zn(II) 2,3-naphthalocyanines (unsubstituted ZnNc1, tetracetylamido substituted ZnNc2, tetramino substituted ZnNc3 and tetramethoxy substituted ZnNc4) incorporated into unilamellar liposomes of dipalmitoylphosphatidylcholine have been injected intra-peritoneally (i.p.) (0.25-0.3 mg kg-1) to male C57/Black mice bearing a transplanted Lewis lung carcinoma. The pharmacokinetic investigations show that three of the four studied ZnNcs, 1, 2 and 4, are good tumor-localizers in Lewis lung carcinoma. The highest concentration is detected after ZnNc1 administration. The lowest tumor concentration as well as the lowest phototherapeutic effect were established with ZnNc3. In previous work it was shown that this ZnNc did not differ from the other three studied ZnNcs regarding the quantum yield of 1O2-formation and the photoinduced electron transfer. Obviously not only the good photochemical properties but also the tumor drug uptake can be an important factor of effective PDT. The biodistribution investigations also show that 72 h after drug injection, the skin concentration of the studied ZnNcs returns to the original base line. Indeed, we can expect that the skin photosensitivity will last for no longer than three days after PDT. The established higher drug concentration in the tumor rather than in the liver tissue (20 h after injection) shows again the tumor targeting selectivity of the applied liposome-sensitiser delivered procedure. Evaluating the PDT effect as reflected in the dynamics of the mean tumor diameter, we obtained unambiguous data on the potential capacity of ZnNcs 1,2,4 as PDT-photosensitisers. The data obtained from the assessment of the cytotoxic effect of PDT on the basis of the degree of induced necrosis, gave an adequate characterization of the tumor tissue destruction.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hydrophobic Zn(II)-naphthalocyanines as photodynamic therapy agents for Lewis lung carcinoma. 802 49

Endoscopic thermal laser therapy of colorectal villous adenomas is associated with a high recurrence rate due to incomplete tumor ablation, as treatment over carries a risk of perforation. Photodynamic therapy has been shown to be a promising in the treatment of small malignant tumors, and may be useful for benign adenomas. Eight patients with nine colosigmoid villous adenomas measuring 1-5 cm in length were treated with photodynamic therapy using either haematoporphyrin derivative or Photofrin as photosensitizer and multiple (4-16) applications of interstitial photoirradiation with red light (630 nm, 100 mW x 500 s per application). All but one adenoma had previously been incompletely treated with Nd-YAG laser therapy. Some skin sensitivity to light was seen in one patient. Seven adenomas were eradicated (follow-up 9-56 months, median = 12) as judged by follow-up endoscopy and biopsy. No local complications were seen. Substantial necrosis was produced in the other two adenomas, but they were not completely destroyed, probably due to inadequate light. PDT holds promise in the non-surgical management of villous adenomas, particularly after initial tumour debulking with the Nd-YAG laser.
 ...
PMID:Photodynamic therapy for villous adenomas of the colon and rectum. 802 74

The potency of aluminum-chloro-tetrasulfonated phthalocyanine (AlS4Pc) as a photosensitizer in photodynamic therapy was evaluated in in vitro and in vivo studies. Compared with hematoporphyrin derivative (HpD), the following advantages of AlS4Pc were revealed: (1) AlS4Pc was less toxic than HpD in vitro without light irradiation. (2) AlS4Pc showed more photodynamic-dependent cytotoxicity and anti-tumor effect in the red area of the spectrum (> 660 nm) at which tissue penetration is high. (3) AlS4Pc appeared to be removed more rapidly from normal tissues such as muscle and skin. (4) AlS4Pc showed less photodynamic-dependent cytotoxicity in vitro and milder cutaneous phototoxicity in vivo with UVA irradiation. On the basis of these observations, AlS4Pc shows considerable promise as a photosensitizer for PDT.
 ...
PMID:Possible advantages of aluminum-chloro-tetrasulfonated phthalocyanine over hematoporphyrin derivative as a photosensitizer in photodynamic therapy. 821 18

1. The features of neoplasia which predict for drug responsiveness are rapid growth and/or inefficient repair of damage, especially to DNA. 2. PDT has the advantage of yielding responses regardless of the growth fraction of a tumor, and repair appears to play only a minor role. 3. While an entirely different spectrum of tumors can be targeted with PDT, the perhaps unavoidable accompaniment is that a new set of rules for efficacy will need to be established. 4. The selectivity of PDT is based on the need for irradiation which can be directed, along with the short tissue half-life of the cytotoxic product, singlet oxygen. Sensitizers which target specific cellular organelles could promote PDT efficacy, if in vitro data (Woodburn et al., 1992b Photochem. Photobiol. 55, 697-704) can be translated into clinical practice. 5. It remains to be established whether total drug distribution to neoplastic tissues or concentration in specific sub-cellular sites is the more important factor. 6. Questions relating to the role of biodistribution as a factor in efficacy of PDT sensitizers of photosensitizers remain to be explored. Just as the political cartographers are grappling with changes in territorial boundaries of known lands, we continue to clarify the rules relating to PDT boundaries. In this regard, it is clearly important for determinants of pharmacokinetics and biodistribution to be evaluated and understood. 7. Once clinical reports on the "second generation" agents are published, we may get a better picture, although it is not unusual for clinical reports to raise more questions than they answer.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Biodistribution of photosensitizing agents. 822 52

Endobronchial photodynamic therapy (EB-PDT) using photofrin as the photosensitizer is currently being evaluated as a new treatment modality for inoperable endobronchial tumors. One of the current problems with EB-PDT is the lack of adequate light dosimetry, which hampers proper interpretation of treatment results. In this study exploratory light dosimetry experiments were performed in plastic bronchus models using either a microlens-tipped fiber (suitable for illumination of small superficial tumors) or a cylindrical diffuser fiber (suitable for intraluminal illumination or interstitial illumination of partially obstructing tumors). It is shown that the light fluence prescriptions of current clinical protocols yield a different fluence in tissue for each illumination modality. Depending on the actual placement of the cylindrical diffuser within the lumen, the light fluence at 5 mm depth in the homogeneous tissue model may vary by a factor of 3. The results were confirmed by in vivo experiments in the trachea of a pig. There is a possibility of enhanced tissue response by accidental hyperthermia induced during EB-PDT. The temperature rise was therefore estimated in vivo using a rat tumor model to mimic clinical EB-PDT. Temperature rises of at least 5 degrees C and 10 degrees C can be expected for intraluminal and intratumoral illumination, respectively, at 3.5 +/- 1 mm depth in tissue and 400 mW/cm diffuser output. Light fluence and its distribution in the bronchus strongly depend on the geometry and the optical properties of the tissue as well as on the technique of illumination. As a result of inadequate dosimetry, significant variations in treatment response between patients may be expected.
 ...
PMID:Pilot study on light dosimetry for endobronchial photodynamic therapy. 837 37

PDT and IUdR-sensitized radiation therapy represent potential advances in the treatment of tumors of the head and neck. Light-activated photosensitizers have definite antitumor activity in both in vitro and in vivo experimental systems. Much of the early clinical work in head and neck cancer involved treatment of patients with advanced, recurrent disease who had not responded to conventional therapy. Because of the limited light penetration in tissue and infiltrative nature of most recurrent lesions, little effective palliation was seen in these advanced cases. More success has been achieved in the treatment of earlier, more superficial lesions, and active investigation continues in this area. Current research is aimed at defining the most appropriate sites and applications for the technique. HpD and DHE are currently only approved for use as investigational compounds in clinical studies. If ongoing trials of PDT in the treatment of superficial bladder cancer, obstructing esophageal cancer, and non-small cell lung cancer show encouraging results, an application will be made to the Food and Drug Administration for approval of DHE as a photosensitizer for general clinical use for these indications. Laboratory work to better understand the mechanism of action of HpD also continues, as well as investigations into alternative photosensitizers with improved tumor localization, less cutaneous photosensitivity, and absorption peaks at deeper penetrating wavelengths of light. A pilot program evaluating IUdR-sensitized radiation therapy for treatment of advanced head and neck cancer is in progress. If encouraging early results continue to be observed, a randomized trial comparing IUdR-sensitized radiation therapy with conventional radiation therapy can be conducted. Hopefully, these developments in the field will improve the therapy for patients with head and neck cancers.
 ...
PMID:Sensitizers of photoradiation and ionizing radiation in the management of head and neck cancer. 849 11

Previous studies (Biolo et al., Photochem. Photobiol. 59, 362-365, 1994) showed that liposome-delivered Si(IV)-naphthalocyanine (SiNc) photosensitizes B16 pigmented melanoma subcutaneously transplanted in C57 mice to the action of 776 nm light. However, the efficacy of the phototreatment was limited by a lack of selectivity of tumor targeting by SiNc as well as by incomplete necrosis of the neoplastic mass. The present investigations show that the use of a different delivery system (Cremophor emulsion vs liposomes of dipalmitoylphosphatidylcholine) causes no significant increase in the selectivity of tumor targeting for three injected doses of SiNc (0.5, 1, 2 mg/kg). However, upon 776 nm light irradiation (300 mW/cm2; 520 J/cm2), the delay in the rate of tumor growth was maximal (7-8 days) for the highest naphthalocyanine dose. On the other hand, a remarkable improvement in the tumor response was obtained by inducing an intratumoral temperature increase to 44 degrees C immediately after PDT. The thermal effect appeared to be due to photoexcitation of melanin by 776 nm light (550 mW/cm2; 520 J/cm2) and subsequent partial conversion of absorbed energy into heat.
 ...
PMID:Effect of photosensitizer delivery system and irradiation parameters on the efficiency of photodynamic therapy of B16 pigmented melanoma in mice. 865 36

Benzoporphyrin derivative (BPD), a sensitizer currently in clinical trials, was evaluated for the treatment of experimental Greene melanoma implanted in the rabbit iris. To improve tumor targeting, BPD was complexed with low-density lipoprotein (LDL) representing an endogenous carrier system for BPD as previously described. Twelve tumors were irradiated at a sensitizer dose of 2 mg kg-1 body weight using a dye laser at 692 nm. Tumor responses were documented by photography, angiography and light and electron microscopy. All tumors treated with 80 J cm-2 regressed irreversibly. The principal mechanism of tumor necrosis was thrombosis following disruption of endothelial membranes. Ultrastructure data suggested tumor cell damage, although evidence for this being the result of direct PDT-mediated tumor cell death was less clear. These data suggest that BPD-LDL may be used to improve the selectivity of photodynamic tumor therapy possibly by the increased uptake of lipoprotein-delivered sensitizer to neovascular endothelial cells.
 ...
PMID:Benzoporphyrin-lipoprotein-mediated photodestruction of intraocular tumors. 867 4


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>