Editorial: focus on waste-heat harvesting via thermoelectric conversion: materials, devices and systems for sustainable energy technologies.

The focus collection 'Waste-heat harvestingviathermoelectric conversion: Materials, devices and systems for sustainable energy technologies' collates several research articles and a Roadmap highlighting the most recent advances in the field of thermoelectricity from the viewpoint of both basic and applied research, with a special eye on the work of the Italian community.

Refractory and 17p-deleted chronic lymphocytic leukemia: improving survival with pathway inhibitors and allogeneic stem cell transplantation.

Refractory/early relapsed and 17p deletion/p53 mutation (del(17p)/TP53mut)-positive chronic lymphocytic leukemia (CLL) has been conventionally considered a high-risk disease, potentially eligible for treatment with allogeneic stem cell transplantation (alloSCT). In this multicenter retrospective analysis of 157 patients, we compared the outcomes of patients with high-risk CLL treated with alloSCT, a B-cell receptor pathway inhibitor (BCRi), and both. Seventy-one patients were treated with BCRis, 67 patients underwent reduced-intensity conditioning alloSCT, and 19 received alloSCT with a BCRi before and/or after transplantation. Inverse probability of treatment weighting analyses were performed to compare the alloSCT and no-alloSCT groups; in the 2 groups, 5-year OS, PFS, and cumulative incidence of nonrelapse mortality (NRM) and relapse were 40% versus 60% (P = .096), 34% versus 17% (P = .638), 28% versus 5% (P = .016), and 38% versus 83% (P = .005), respectively. Patients treated with alloSCT plus BCRi had a 3-year OS of 83%. The 3-year OS and NRM by year of alloSCT, including patients treated with BCRi, were 53% and 17% in 2000 to 2007, 55% and 30% in 2008 to 2012, and 72% and 18% in 2013 to 2018. In conclusion, the combination of pathway inhibitors and alloSCT is feasible and may further improve the outcome of high-risk CLL patients.

Assessing Adherence to Antihypertensive Therapy in Primary Health Care in Namibia: Findings and Implications.

INTRODUCTION: Namibia has the highest burden and incidence of hypertension in sub-Sahara Africa. Though non-adherence to antihypertensive therapy is an important cardiovascular risk factor, little is known about potential ways to improve adherence in Namibia following universal access. The objective of this study is to validate the Hill-Bone compliance scale and determine the level and predictors of adherence to antihypertensive treatment in primary health care settings in sub-urban townships of Windhoek, Namibia. METHODS: Reliability was determined by Cronbach's alpha. Principal component analysis (PCA) was used to assess construct validity. RESULTS: The PCA was consistent with the three constructs for 12 items, explaining 24.1, 16.7 and 10.8% of the variance. Cronbach's alpha was 0.695. None of the 120 patients had perfect adherence to antihypertensive therapy, and less than half had acceptable levels of adherence (≥ 80%). The mean adherence level was 76.7 ± 8.1%. Three quarters of patients ever missed their scheduled clinic appointment. Having a family support system (OR = 5.4, 95% CI 1.687-27.6, p = 0.045) and attendance of follow-up visits (OR = 3.1, 95% CI 1.1-8.7, p = 0.03) were significant predictors of adherence. Having HIV/AIDs did not lower adherence. CONCLUSIONS: The modified Namibian version of the Hill-Bone scale is reliable and valid for assessing adherence to antihypertensives in Namibia. There is sub-optimal adherence to antihypertensive therapy among primary health cares in Namibia. This needs standardized systems to strengthen adherence monitoring as well as investigation of other factors including transport to take full advantage of universal access.

Structural Texture Induced in SnSe Thermoelectric Compound via Open Die Pressing.

Outstanding ZT values registered on single crystals recently renewed the interest of thermoelectric community for SeSn compound. Owing to the strong anisotropy of the phenomenon, so far only single crystals proved to be the suitable for its application. Here we present the production and the characterization of bulk polycrystalline materials processed by open die pressing, aimed at reducing the gap with single crystal materials by taking advantage from the highly texture degree derived by the processing and by the improved phonon scattering promoted by grain boundaries. The resulting bulks display good compaction, improved mechanical properties and strong texture of the phase. Structural and morphological analyses confirmed the successful orientation according to the (400) cleavage plane. The structural transition responsible for the ultra-low thermal conductivity has been investigated and possible irreversible effects on the starting phase due to thermal cycling have been evaluated. Preliminary measurements of thermal conductivity are reported.

Emerging resistant bacteria strains in bloodstream infections of acute leukaemia patients: results of a prospective study by the Rete Ematologica Lombarda (Rel).

Multiresistant bacterial infections are a potentially life-threatening condition in acute leukaemia (AL) patients. We aimed to better define the very recent epidemiology and outcome of bloodstream infections (BSIs) in a real-life setting. We prospectively collected all consecutive febrile/infectious episodes occurring in AL patients admitted to 9 haematology units. In 293 AL patients, 433 BSIs were diagnosed. Gram-positive (GP) bacteria were isolated in 44.8 % BSI and Gram-negative (GN) in 38.3 %, while polymicrobial aetiology- or fungi-related events were identified in 15.7 and 1.1 % of the cases, respectively. GP was observed more frequently in patients not in complete remission (p = 0.04), while GN during consolidation cycles (p = 0.003). Extended spectrum ß-lactamase-producing strains accounted for 23.2 % of enterobacteria. They were associated with previous antibiotic exposure, including fluoroquinolones prophylaxis (p = 0.01). Carbapenem-resistant (CR) strains occurred in 9 % of enterobacteria. Among Pseudomonas aeruginosa strains, 21.6 % were multiresistant. Overall 30-day mortality was 8.5 %. CR GN and multiresistant P. aeruginosa BSIs were independent predictors of death (p = 0.002), as well as relapsed/resistant AL (18.3 %; p = 0.0002) and the presence of pulmonary infiltrates (26.6 %; p < 0.001). Although GP still predominate over GN BSI, the percentage of antibiotic resistant GN strains is considerable in AL patients and it is associated with poor prognosis.

Allergic reaction and metal hypersensitivity after shoulder joint replacement.

PURPOSE: Metal ion release may cause local and systemic effects and induce hypersensitivity reactions. The aim of our study is first to determine if implant-related hypersensitivity correlates to patient symptoms or not; second, to assess the rate of hypersensitivity and allergies in shoulder arthroplasty. METHODS: Forty patients with shoulder replacements performed between 2015 and 2017 were studied with minimum 2-year follow-up; no patient had prior metal implants. Each patient underwent radiographic and clinical evaluation using the Constant-Murley Score (CMS), 22 metal and cement haptens patch testing, serum and urine tests to evaluate 12 metals concentration, and a personal occupational medicine interview. RESULTS: At follow-up (average 45 ± 10.7 months), the mean CMS was 76 ± 15.9; no clinical complications or radiographic signs of loosening were detected; two nickel sulfate (5%), 1 benzoyl peroxide (2.5%) and 1 potassium dichromate (2.5%) positive findings were found, but all these patients were asymptomatic. There was an increase in serum aluminum, urinary aluminum and urinary chromium levels of 1.74, 3.40 and 1.83 times the baseline, respectively. No significant difference in metal ion concentrations were found when patients were stratified according to gender, date of surgery, type of surgery, and type of implant. CONCLUSIONS: Shoulder arthroplasty is a source of metal ion release and might act as a sensitizing exposure. However, patch test positivity does not seem to correlate to hypersensitivity cutaneous manifestations or poor clinical results. Laboratory data showed small constant ion release over time, regardless of gender, type of shoulder replacement and implant used. LEVELS OF EVIDENCE: Level II.

'Scarless reverse umbilicoplasty': A new technique of umbilical transposition in abdominoplasty.

INTRODUCTION: The navel plays a major role in the aesthetics of the abdomen. A navel that is abnormally shaped, malpositioned or has evident scarring may compromise the outcome of an otherwise well-executed full abdominoplasty. The aim of the technique in question is to recreate a navel that looks natural, with no visible scar, and that is properly positioned. MATERIALS AND METHODS: The technique was performed in 147 abdominoplasties of patients of both sexes (123 females and 24 males), with an average age of 35 years and a mean BMI of 24 kg/m2. The procedure involves the creation of a navel of reduced size, 10 × 5 mm, and its inset in the abdominal wall. Subsequently, the as-yet-not sutured abdominal flap is extended caudally to determine the point of projection of the navel. The abdominal skin is marked, the flap is reversed and an internal suture is carried out. RESULTS: The appearance of the navel is aesthetically pleasant and natural looking and with no visible scarring. In addition, the position of the umbilicus is always correct. At the two-year follow-up, the results remain stable. No major complication occurred. CONCLUSIONS: The technique allows for the attainment of an extremely natural looking navel that satisfies the aesthetic criteria of attractiveness without visible scarring. The navel is always correctly positioned, without requiring measurements during surgery. The procedure is rapid, and although it does require a short learning curve, the results are extremely aesthetically pleasing and reproducible. The patient satisfaction rate is extremely high.

Reducing rates of Clostridium difficile infection by switching to a stand-alone NAAT with clear sampling criteria.

Background: Clostridium difficile infection is an important cause of morbidity and mortality but the optimal method of diagnosis for both patient management and infection prevention remains controversial. Methods: Our hospital made a decision to switch from the use of toxin immunoassay to a stand-alone nucleic acid test. This change was accompanied by the provision of clear sampling guidance and rejection criteria and this study aimed to assess the impact of that change. We analysed sample numbers, numbers of positive results, and the proportion of cases assessed as healthcare acquired over a 6-year period during which the testing method was changed from a toxin A/B immunoassay to a stand-alone commercial nucleic acid test after the first two years. Results: Sample numbers and numbers of cases assessed as healthcare acquired fell following the introduction of the nucleic acid test and sampling guidance, while infection rates in other hospitals in the same region remained relatively stable. Conclusions: It is our opinion that the use of a highly sensitive assay together with clear sampling guidance offers the optimal approach to patient management and best use of isolation facilities.

Prolonged effect of two combined methods for Legionella disinfection in a hospital water system.

This study was conducted in our 650 bed general hospital, which is situated on the southern outskirts of Milan (Italy). After a first nosocomial case of pneumonia (caused by Legionella pneumophila serogroup 1), we first used a conventional method (heat shock) without success. To solve the problem we then tried a copper-silver ionization system combined with a chlorine dioxide device. During the four years after the installation of these two systems we recorded a significant (p < or = 0.05) reduction in Legionella colonization, and no new cases of Legionnaires' disease were observed. Our results suggest that the Cu-Ag ionization system, combined with a chlorine dioxide device, is a highly promising method for the control of Legionella pneumophila in a hospital water distribution system.

Systemic toxicity in mice induced by localized porphyrin photodynamic therapy.

An unexpected high level of acute lethality has been documented following Photofrin II-mediated photodynamic therapy (PDT) treatments which were localized to the hind leg of normal and tumor-bearing mice. Doses of PDT which induced lethality (10 mg/kg Photofrin II, 200-500 J/cm2) were in the range of doses required to obtain murine tumor cures. The percentage of lethality was proportional to the total light dose but was inversely proportional to the dose rate of delivered light. Comparable levels of acute toxicity were observed in four pigmented mouse strains (C57BL/6J, C3H/HeJ, DBA/1, and DBA/2) and in two albino mouse strains (BALB/c and Swiss Webster). Decreased sensitivity to PDT-induced lethality was observed in two pigmented mouse strains (B10D2/OSN and B10D2/NSN). The administration of warfarin, aspirin, indomethacin, or antihistamine had significant protective effects in terms of decreasing PDT-induced lethality. However, injection of cobra venom factor (to deplete C3 and C5 of the complement system) did not alter the lethality mediated by PDT. Histological profiles obtained 24 h following PDT demonstrated vascular congestion in the liver, kidney, lung, and spleen. Significant decreases in removable blood volume, core temperature, and spleen weight were also observed within 24 h of localized PDT treatment. These results indicate that PDT-induced lethality is consistent with a traumatic shock syndrome and suggest that endogenous vasoactive mediators of shock such as prostaglandins, thromboxanes, and histamine are associated with the lethality induced by localized PDT in mice.

Tissue distribution and photosensitizing properties of mono-L-aspartyl chlorin e6 in a mouse tumor model.

Mono-L-aspartyl chlorin e6 (NPe6) is a photosensitizer that possesses properties such as chemical purity and a major absorption band at 664 nm which are potentially exploitable for photodynamic therapy (PDT). The current investigation examined pharmacological and photosensitizing parameters of NPe6 in tumor and normal tissues in mice. [14C]NPe6 was used to obtain quantitative tissue distributions of the photosensitizer as a function of: (a) time following administration; (b) drug dose; (c) mode of drug administration; and (d) tumor size. The in vivo photosensitizing efficiency of NPe6 was compared directly to Photofrin II in experiments which evaluated tumor responses and induction of normal skin damage. Initial PDT experiments demonstrated that NPe6 was ineffective at inducing tumor cures when a 24-h time interval (between drug administration and light treatment) was used. However, PDT-induced tumor cures were obtained when NPe6 was administered 4-6 h prior to light exposure, and these NPe6-PDT treatment parameters were as effective as standard Photofrin II-mediated PDT. Interestingly, the level of PDT-induced normal skin damage was significantly greater for Photofrin II than for NPe6 at comparable drug and light doses. An analysis of pharmacological data and PDT time interval requirements suggests that plasma concentrations of NPe6 may be a more important predictive factor than tumor tissue levels of the photosensitizer for the production of PDT-mediated tumor cures. The results of this investigation indicate that NPe6 is an effective tumor photosensitizer with in vivo clearance properties that eliminate the side effect of prolonged normal skin photosensitization.

Metabolic properties and photosensitizing responsiveness of mono-L-aspartyl chlorin e6 in a mouse tumor model.

A mouse mammary tumor model was used to evaluate metabolic properties of the photosensitizer mono-L-aspartyl chlorin e6 (NPe6) and to determine the optimal time interval between drug administration and light treatment for effective photodynamic therapy (PDT). Photosensitizer metabolism was evaluated by comparing tissue distribution patterns of NPe6 having 14C atoms positioned on either the tetrapyrrole ring or on the aspartyl residue. High performance liquid chromatographic analysis of photosensitizer extracted from tumor tissue was also obtained as a function of time after drug administration. NPe6 distribution in tissue samples and pharmacological calculations of area under the curve were similar for both forms of [14]NPe6. Likewise, metabolic contaminants of NPe6 were not detected by high performance liquid chromatographic analysis following extraction of the photosensitizer from tumor tissue. Maximal in vivo PDT effectiveness was achieved when light treatments were started within 2 h of drug injection. PDT effectiveness was decreased by 50% when light treatments were initiated 6 h after drug injection and was abolished with a 12-h interval between NPe6 injection and light exposure. Responsiveness to NPe6-mediated PDT was correlated with photosensitizer levels in the plasma but not in tumor tissue. These results show that NPe6 was not metabolized following in vivo administration and that the responsiveness of NPe6 mediated PDT was associated with vascular clearance of the photosensitizer.

Expression of potentially lethal damage in Chinese hamster cells exposed to hematoporphyrin derivative photodynamic therapy.

Experiments were performed to determine whether the expression and/or repair of potentially lethal damage could be observed in mammalian cells exposed to hemataporphyrin derivative (HPD) photodynamic therapy (PDT). Photodynamic therapy was combined with posttreatment protocols known to inhibit the repair of potentially lethal damage in cells treated with X-rays, ultraviolet radiation, or alkylating agents. Potentiation of lethal damage from photodynamic therapy was induced by hypothermia (4 degrees C) following short (1 h) or extended (16 h) HPD incubation conditions. Caffeine potentiated the lethal effects of PDT only when cells were incubated with HPD for extended time periods. However, 3-aminobenzamide had no effect on the cytotoxic actions of PDT following either short or extended HPD incubations. Recovery from potentially lethal damage expressed by posttreatment hypothermia was complete within 1 h, while recovery from potentially lethal damage expressed by posttreatment caffeine required time periods of up to 24 h. The lack of effect of 3-aminobenzamide on expression of potentially lethal damage following photodynamic therapy may be related to direct inhibition of adenosine diphosphoribose transferase by photodynamic therapy. These results indicate that the expression and repair of potentially lethal damage can be observed in cells treated with PDT and will vary as a function of porphyrin incubation conditions.

Glucose regulated protein induction and cellular resistance to oxidative stress mediated by porphyrin photosensitization.

Photodynamic therapy (PDT) utilizes a tumor localizing porphyrin photosensitizer in the clinical treatment of cancer. At a mechanistic level, porphyrin photosensitization generates reactive oxygen species which initiate oxidative damage to a wide spectrum of biomolecules. Cellular stress proteins are also increased following oxidative stress treatments. In the current study, we examined porphyrin photosensitizing parameters associated with induction of the glucose regulated family of stress proteins. Elevated levels of mRNA encoding glucose regulated proteins (GRPs) as well as increases in GRP protein synthesis were observed for mouse radiation induced fibrosarcoma cells exposed to an extended (16-h) porphyrin incubation prior to light exposure. However, a short (1-h) porphyrin incubation prior to light treatment (designed to produce comparable phototoxicity as PDT using the 16-h porphyrin incubation protocol) was associated with only minimal increases in GRP mRNA levels or GRP protein synthesis. The relationship between GRP levels and PDT sensitivity was examined in radiation induced fibrosarcoma cells pretreated with the calcium ionophore A-23187 in order to overexpress GRPs prior to photosensitization. Resistance to PDT was observed in cells overexpressing GRPs only under photosensitizing conditions associated with the extended porphyrin incubation protocol, and this response was not due to changes in cellular porphyrin uptake. In separate experiments, a transient elevation of GRP mRNA levels was observed in transplanted mouse mammary carcinomas following in vivo PDT treatments. Our results indicate that specific targets of oxidative damage (modulated by porphyrin incubation conditions) instead of generalized cellular exposure to reactive oxygen species are correlated with PDT mediated GRP induction. In this regard, GRP induction may be a useful in vivo biochemical marker of PDT mediated injury. These results also support the hypothesis that GRPs may play a role in modulating sensitivity to cellular stresses including certain types of oxidative injury.

Decreased expression and function of alpha-2 macroglobulin receptor/low density lipoprotein receptor-related protein in photodynamic therapy-resistant mouse tumor cells.

Parental and photodynamic therapy (PDT)-resistant mouse, radiation-induced fibrosarcoma cell lines were evaluated using mRNA differential display in an attempt to identify unique transcripts. We detected one transcript that was consistently present in the parental cells but absent in PDT-resistant cells. The transcript was cloned, sequenced, and identified as alpha-2 macroglobulin receptor/low density lipoprotein receptor-related protein (alpha-2 MR/LRP). Northern and Western immunoblot analysis confirmed that receptor expression was present in the parental cell line but barely detectable in PDT-resistant cells. Functionality of the receptor was evaluated by exposing cells to Pseudomonas exotoxin A. alpha-2 MR/LRP is responsible for Pseudomonas exotoxin A internalization, and only the parental cells exhibited toxin-mediated cytotoxicity. The binding and endocytosis of activated alpha-2 macroglobulin and lipoproteins by alpha-2 MR/LRP are consistent with modulating uptake and localization of photosensitizers. Our results demonstrate that PDT-resistant murine tumor cells exhibit minimal alpha-2 MR/LRP activity and suggest that this receptor plays a role in PDT sensitivity by modulating photosensitizer uptake and/or subcellular localization.

Photodynamic therapy sensitivity is not altered in human tumor cells after abrogation of p53 function.

Photodynamic therapy (PDT) is an effective local cancer treatment that induces cytotoxicity through the intracellular generation of reactive oxygen species. The current study investigated whether abrogation of wild-type p53 expression modified the sensitivity of tumor cells to PDT-mediated oxidative stress. In these experiments, human colon (LS513) and breast (MCF-7) carcinoma cells exhibiting a wild-type p53 phenotype were directly compared to LS513 and MCF-7 cells with abrogated p53 function induced by stable integration of the human papillomavirus type 16 E6 viral oncoprotein. The effectiveness of this viral oncoprotein to target p53 for degradation was confirmed using a p53 transactivation reporter gene assay. Western analysis also confirmed attenuated expression of p53 in E6-transfected cells. Photosensitivity of PDT-treated cells was measured by a clonogenic assay and found to be equivalent for parental and p53-abrogated cells. PDT-mediated oxidative stress resulted in a rapid shift of pRb from a hyperphosphorylated form to a predominantly underphosphorylated form in parental cells that was not preceded by increases in p53 or p21 expression. Hypophosphorylated pRb was also observed in PDT-treated LS513/E6 and MCF-7/E6 cells, further indicating that p53 was not involved in this process. Delayed expression of p53 and p21 proteins was seen in parental cells 24-48 h after photosensitization. Cell cycle analysis showed that the abrogation of p53 had minimal effects on an observed PDT-induced G1 block. Rapid induction of apoptosis was documented in PDT-treated LS513 cells, whereas LS513/E6 treated cells exhibited reduced apoptosis in response to PDT. The MCF-7 cell lines exhibited a minimal apoptotic response to PDT. These results indicate that p53 expression does not directly modulate tumor cell sensitivity to PDT in either apoptosis-responsive (LS513) or nonresponsive (MCF-7) cells.

Antiangiogenic treatment enhances photodynamic therapy responsiveness in a mouse mammary carcinoma.

Photodynamic therapy (PDT) is a promising cancer treatment that induces localized tumor destruction via the photochemical generation of cytotoxic singlet oxygen. PDT-mediated oxidative stress elicits direct tumor cell damage as well as microvascular injury within exposed tumors. Reduction in vascular perfusion associated with PDT-mediated microvascular injury produces tumor tissue hypoxia. Using a transplantable BA mouse mammary carcinoma, we show that Photofrin-mediated PDT induced expression of the hypoxia-inducible factor-1alpha (HIF-1alpha) subunit of the heterodimeric HIF-1 transcription factor and also increased protein levels of the HIF-1 target gene, vascular endothelial growth factor (VEGF), within treated tumors. HIF-1alpha and VEGF expression were also observed following tumor clamping, which was used as a positive control for inducing tissue hypoxia. PDT treatment of BA tumor cells grown in culture resulted in a small increase in VEGF expression above basal levels, indicating that PDT-mediated hypoxia and oxidative stress could both be involved in the overexpression of VEGF. Tumor-bearing mice treated with combined antiangiogenic therapy (IM862 or EMAP-II) and PDT had improved tumoricidal responses compared with individual treatments. We also demonstrated that PDT-induced VEGF expression in tumors decreased when either IM862 or EMAP-II was included in the PDT treatment protocol. Our results indicate that combination procedures using antiangiogenic treatments can improve the therapeutic effectiveness of PDT.

Photodynamic therapy-mediated oxidative stress as a molecular switch for the temporal expression of genes ligated to the human heat shock promoter.

Oxidative stress associated with photodynamic therapy (PDT) is a transcriptional inducer of genes encoding stress proteins, including those belonging to the heat shock protein (hsp) family. The efficiency of PDT to function as a molecular switch by initiating expression of heterologous genes ligated to the human hsp promoter was examined in the present study. Selective and temporal reporter gene expression was documented after PDT in mouse radiation-induced fibrosarcoma cells stably transfected with recombinant vectors containing an hsp promoter ligated to either the lac-z or CAT reporter genes and in transfected radiation-induced fibrosarcoma tumors grown in C3H mice. Hyperthermia treatments were included as a positive control for all experiments. Expression vectors containing either human p53 or tumor necrosis factor (TNF)-alpha cDNA under the control of an hsp promoter were also constructed and evaluated. A p53 null and TNF-alpha-resistant human ovarian carcinoma (SKOV-3) cell line was stably transfected with either the p53 or TNF-alpha constructs. Inducible expression and function of p53 as well as inducible expression, secretion, and biological activity of TNF-alpha were documented after PDT or hyperthermia in transfected SKOV cells. These results demonstrate that PDT-mediated oxidative stress can function as a molecular switch for the selective and temporal expression of heterologous genes in tumor cells containing expression vectors under the control of an hsp promoter.

Photodynamic therapy-mediated oxidative stress can induce expression of heat shock proteins.

Photodynamic therapy (PDT) is an experimental cancer therapy inducing tumor tissue damage via photosensitizer-mediated oxidative cytotoxicity. A previous report indicates that oxidative stress induced by hydrogen peroxide or menadione activates the heat shock transcription factor in mouse cells but does not result in either increased transcription or translation of heat shock proteins (HSPs). Our study documents that photosensitizer-mediated oxidative stress can activate the heat shock factor as well as increase HSP-70 mRNA and protein levels in mouse RIF-1 cells. The cellular heat shock response after PDT varied for the different photosensitizers being examined. Treatments using either a chlorin (mono-L-aspartyl chlorin-e6)- or purpurin (tin etio-purpurin)-based sensitizer induced HSP-70 expression, whereas identical photosensitization conditions with a porphyrin (Photofrin)-based sensitizer failed to induce a cellular HSP response. These sensitizers, which generate singlet oxygen as the primary oxidant during photosensitization, were used in experiments under isoeffective treatment conditions. HSP-70 expression after photosensitization was associated with the concomitant induction of thermotolerance in PDT-treated cells. Interestingly, reverse transcription-PCR demonstrated that in vivo PDT treatments of RIF-1 tumors induce expression of HSP-70 for all photosensitizers including Photofrin. These results indicate that photosensitizer-generated singlet oxygen exposure can induce in vitro and in vivo HSP-70 expression, and that specific subcellular targets of PDT (which can differ for various sensitizers) are determinants for HSP-70 activation after oxidative stress.

Properties and applications of photodynamic therapy.

Photodynamic therapy (PDT) is the treatment of malignant lesions with visible light following the systemic administration of a tumor-localizing photosensitizer. Pharmacological and photochemical properties of the photosensitizer are combined with precise delivery of laser-generated light to produce a treatment which can offer selective tumoricidal action. Hematoporphyrin derivative (HD) and a purified component called Photofrin II are currently being used in clinical PDT. Initial patient results have been encouraging, and considerable interest has developed in the synthesis and evaluation of new photosensitizers with improved photochemical and pharmacological characteristics. In addition, there has been a gradual increase in knowledge related to in vitro and in vivo mechanisms of action of PDT. This report provides an overview of the properties and applications of PDT. Information and data related to drug development, photochemistry, subcellular targets, in vivo responses, and clinical trials of PDT are presented.