Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PDT has been shown to be of value in inoperable basal and squamous skin cancers and in cutaneous metastases. Azone, a new investigative vehicle for HpD, is of value more for intralesional injections than for topical applications in tumors, except perhaps for superficial mucous membrane lesions. The more flexible gold head vapor is of definite value in the PDT program. For test models for PDT studies in dermatology and plastic surgery with HpD and other fluorochromes, single thickened resistant plaques of psoriasis and the common baso squamous acanthoma (seborrheic warty growth) have been used. In all these studies, adequate controls are necessary.
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PMID:Preliminary investigative studies with PDT in dermatologic and plastic surgery. 406 77

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.
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PMID:Review article: angiogenesis, neovascular proliferation and vascular pathophysiology as targets for cancer therapy. 768 69

Primary small cell carcinoma of the esophagus is a rare and aggressive disease. We report on our experience with two patients having a small cell cancer of the esophagus, being treated with photodynamic therapy combined with irradiation and induction-chemotherapy as well as a review of literature. Both patients were admitted with severe dysphagia, weight loss and a Karnovsky performance status of 90. Diagnostic work-up revealed tumor-stenosis in the proximal third in one and in the distal third in the other case. Clinical staging showed T4N2M0 and T3N2M0, pure small cell carcinoma. Due to dysphagia and lymph node enlargement, local and systemic therapy were considered as first-line treatment. Restaging after three cycles of induction-chemotherapy revealed partial response in both cases. Esophagectomy as a second-line treatment was considered. However, in the preoperative period, one patient developed motorical aphasia. The CT-scan of the brain showed multiple brain metastases. External beam irradiation and further chemotherapy was initiated. The patient died 12 months after admission. The other patient revealed anatomical inoperability at the staging laparoscopy. External beam irradiation and a second session of PDT was performed. The patient is still alive, 12 months after his first admission. The biological behavior of this aggressive disease and metastases in about 50% of patients at admission, as well as significant dysphagia makes combined systemic and local treatment necessary. Nevertheless, after reviewing the literature, esophagectomy and adjuvant chemotherapy may have an advantage pertaining to survival time when anatomical and functional operability is given.
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PMID:Local and systemic treatment in small cell carcinoma of the esophagus. 1060 16

In hilar cholangiocarcinoma, only 20-30% of the patients are candidates for curative surgical resection, leaving the majority with merely palliative treatment options. Since the natural history of hilar cholangiocarcinoma is dominated by local complications rather than metastatic disease, local palliative treatment seems a reasonable option. Here, endoluminal photodynamic therapy has emerged as a promising treatment with several prospective observational studies and 2 prospective randomised studies published which included nearly 200 patients. With low complication rate and morbidity, PDT achieves an increased median survival as well as an increased quality of life even in patients with reduced performance status. Radiotherapy is an alternative local treatment option applied as brachytherapy, external beam radiotherapy or combined modality treatment. To date, however, sufficient data from controlled clinical trials are lacking, thus palliative radiotherapy has to be considered an experimental treatment option.
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PMID:[Palliative locoregional therapy for hilar cholangiocarcinoma: photodynamic therapy and brachytherapy]. 1772 37

Head and neck metastatic tumours are uncommon. The primary tumors most likely to metastasize are those of the thyroid, breast, and lungs. The management of metastatic carcinoma in the orofacial region is variable. Palliative and symptomatic approaches are the mainstay in the management. The purpose of this case report is to highlight the feasibility of using PDT to alleviate nasal and visual symptoms and control the growth of metastatic renal cell carcinoma to the orofacial region.
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PMID:Metastatic renal cell carcinoma to the orofacial region: A novel method to alleviate symptoms and control disease progression. 2111 47

Breast cancer is the second leading cause of cancer-related death in women. Approximately 85% of patients with advanced cases will develop spinal metastases. The vertebral column is the most common site of breast cancer metastases, where overexpression of matrix metalloproteinases (MMPs) promotes the spread of cancer. Current therapies have significant limitations due to the high associated risk of damaging the spinal cord. An attractive alternative is photodynamic therapy providing noninvasive and site-selective treatment. However, current photosensitizers are limited by their nonspecific accumulation. Photodynamic molecular beacons (PP(MMP)B), activated by MMPs, offer another level of PDT selectivity and image-guidance preserving criticial tissues, specifically the spinal cord. Metastatic human breast carcinoma cells, MT-1, were used to model the metastatic behavior of spinal lesions. In vitro and in vivo evidence demonstrates MMP specific activation of PP(MMP)B in MT-1 cells. Using a clinically relevant metastatic model, fluorescent imaging establishes the specific activation of PP(MMP)B by vertebral metastases versus normal tissue (i.e., spinal cord) demonstrating the specificity of these beacons. Here, we validate that the metastasis-selective mechanism of PP(MMP)Bs can specifically image breast cancer vertebral metastases, thereby differentiating tumor and healthy tissue.
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PMID:Imaging of specific activation of photodynamic molecular beacons in breast cancer vertebral metastases. 2158 6

Although the survival of patients with osteosarcoma has improved following development of chemotherapy and surgery, the presence of pulmonary metastases indicate a poor prognosis. We developed photodynamic and radiodynamic therapies with acridine orange (AO-PDT and AO-RDT) for minimally invasive surgery to treat musculoskeletal sarcomas and reported a good clinical outcome of local control and limb function. We investigated the effect of AO-PDT using flash-wave light (FWL) on pulmonary metastasis of mouse osteosarcoma. In in vitro and in vivo studies, AO alone and AO-PDT significantly inhibited cell invasion and the growth of pulmonary metastases from primary mouse osteosarcoma. AO may have a specific metastasis-inhibitory effect, different from the effect of AO-PDT. The fluorovisualization effect on pulmonary metastases following intravenous AO administration showed that pulmonary metastases localized on the lung surface were recognized as brilliant green lesions. In conclusion, AO-PDT using FWL inhibited cell invasion and pulmonary metastases in mouse osteosarcoma; therefore, this treatment modality might be applicable for treating pulmonary metastasis from malignant musculoskeletal tumors in humans.
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PMID:Acridine orange inhibits pulmonary metastasis of mouse osteosarcoma. 2219 75

Solid tumor has unique vascular architecture, excessive production of vascular mediators, and extravasation of macromolecules from blood vessels into the tumor tissue interstitium. These features comprise the phenomenon named the EPR effect of solid tumors, described in 1986. Our investigations on the EPR revealed that many mediators, such as bradykinin, NO, and prostaglandins, are involved in the EPR effect, which is now believed to be the most important element for cancer-selective drug delivery. However, tumors in vivo manifest great diversity, and some demonstrate a poor EPR effect, for example, because of impaired vascular flow involving thrombosis, with poor drug delivery and therapeutic failure. Another important element of this effect is that it operates in metastatic cancers. Because few drugs are currently effective against metastases, the EPR effect offers a great advantage in nanomedicine therapy. The EPR effect can also be augmented two to three times via nitroglycerin, ACE inhibitors, and angiotensin II-induced hypertension. The delivery of nanomedicines to tumors can thereby be enhanced. In traditional PDT, most PSs had low MW and little tumor-selective accumulation. Our hydroxypropylmetacrylamide-polymer-conjugated-PS, zinc protoporphyrin (apparent MW >50 kDa) showed tumor-selective accumulation, as revealed by fluorescent imaging of autochthonous cancers. After one i.v. injection of polymeric PS followed by two or three xenon light irradiation/treatments, most tumors regressed. Thus, nanoprobes with the EPR effect seem to have remarkable effects. Enhancing the EPR effect by using vascular modulators will aid innovations in PDT for greater tumor-targeted drug delivery.
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PMID:A Retrospective 30 Years After Discovery of the Enhanced Permeability and Retention Effect of Solid Tumors: Next-Generation Chemotherapeutics and Photodynamic Therapy--Problems, Solutions, and Prospects. 2623 91

The metastatic spread of cancer from the primary site or organ is one of its most devastating aspects, being responsible for up to 90% of cancer-associated mortality. Bone is one of the common sites of metastatic spread, including the vertebrae. Regardless of the treatment strategy, the clinical goals for patients with vertebral metastases are to improve the quality of life by preventing neurologic decline, to achieve durable pain relief and enhance local tumor control. However, in part due to the close proximity of the spinal cord, current treatment options are limited. We propose a novel therapeutic strategy with the use of photodynamic molecular beacons (PMBs) for targeted destruction of spinal metastases, particularly to de-bulk lesions as an adjuvant to vertebroplasty or kyphoplasty in order to mechanically stabilize weak or fractured vertebrae. The PDT efficacy of a matrix metalloproteinase-specific PMB is reported in a metstatic model that recapitulates the clinical features of tumor growth within the bone. We demonstrate that not only does tumor cell destruction occur but also the killing of bone stromal cells. The potential of PMB-PDT to destroy metastatic tumors, disrupt the osteolytic cycle and better preserve critical organs with an increased therapeutic window compared with conventional photosensitizers is demonstrated.
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PMID:Matrix metalloproteinase-based photodynamic molecular beacons for targeted destruction of bone metastases in vivo. 2688 Jan 65

Actinic keratoses (AKs) represent in-situ squamous cell carcinomas that potentially invade subepidermal structures and may metastasize. Until now, it is unpredictable to determine which AK lesions show this aggressive behavior. As AKs usually occur in large sun exposed areas, field-directed treatments have become the standard treatment regimen. Among these, conventional photodynamic therapy (cPDT) with 5-aminolaevulinic acid (ALA) or methyl-aminolevulinate (MAL) using red light is particularly effective in the treatment of AKs, but acceptance of the therapy is impaired by severe pain during treatment. Daylight PDT (dPDT) has demonstrated to be an equally effective alternative treatment option which is less painful. Recent attempts to determine the risk of AKs that demonstrate particular aggressive biological behavior by implementation of clinical and histological characteristics of AKs have not lead to conclusive results. Therefore, a look at the molecular biology of AKs could serve as a useful tool to develop a risk profiling for separation of those patients that are of particular risk to develop invasive tumor and, by this, to facilitate a more effective and adapted treatment option.
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PMID:Daylight photodynamic therapy for field cancerization: lessons from molecular biology. 2968 91


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