Lithium and preventing chemotherapy-induced peripheral neuropathy in breast cancer patients: a placebo-controlled randomized clinical trial.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of some chemotherapy regimens. Lithium has been suggested for CIPN in some animal studies. We aimed to study lithium's preventive effect on CIPN in breast cancer patients treated with taxanes and platinum-based medications. METHOD: A double-blind placebo-controlled randomized clinical trial (RCT) was implemented on 36 breast cancer patients in two equal-size groups by block randomization. Participants in both groups consumed daily tablets, either placebo or lithium (300 mg), for 5 days in each course of chemotherapy. The tablets were prescribed 1 day before the start of chemotherapy. The electromyography (EMG) and nerve-conduction-velocity (NCV) tests were achieved before the first chemotherapy, 3 and 9 months after the treatment. The changes and signs or symptoms of CIPN, such as numbness, tingling, freezing, sensitivity to touch, muscle weakness, fibrillation, and knee and elbow reflex disorders, were recorded by examination. The trend of outcome changes was compared between two groups during the 9 months of study. RESULTS: In both groups, neurologic signs and symptoms were exacerbated during the first 3 months and improved up to the ninth month of study. Results showed significant changes of all EMG-NCV variables during the 9 months of research in each group (P < 0.001), but the interaction of time and group effect was not significant in none of those indices. All symptoms changed significantly over the study time (P < 0.001) without significant statistical difference between the two groups (P=0.352). No side effect was found during the study. CONCLUSION: The study showed that 300 mg lithium prescription once daily for 5 days might not effectively prevent CIPN in breast cancer patients. Evaluation of lithium effect on CIPN on different cancers in future studies is suggested. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20160813029327N10 .  Registration date: May 16, 2018.

A 2-year multicenter, observational, prospective, cohort study on extracorporeal CO2 removal in a large metropolis area.

BACKGROUND: Extracorporeal carbon dioxide removal (ECCO2R) is a promising technique for the management of acute respiratory failure, but with a limited level of evidence to support its use outside clinical trials and/or data collection initiatives. We report a collaborative initiative in a large metropolis. METHODS: To assess on a structural basis the rate of utilization as well as efficacy and safety parameters of 2 ECCO2R devices in 10 intensive care units (ICU) during a 2-year period. RESULTS: Seventy patients were recruited in 10 voluntary and specifically trained centers. The median utilization rate was 0.19 patient/month/center (min 0.04; max 1.20). ECCO2R was started under invasive mechanical ventilation (IMV) in 59 patients and non-invasive ventilation in 11 patients. The Hemolung Respiratory Assist System (Alung) was used in 53 patients and the iLA Activve iLA kit (Xenios Novalung) in 17 patients. Main indications were ultraprotective ventilation for ARDS patients (n = 24), shortening the duration of IMV in COPD patients (n = 21), preventing intubation in COPD patients (n = 9), and controlling hypercapnia and dynamic hyperinflation in mechanically ventilated patients with severe acute asthma (n = 6). A reduction in median V T was observed in ARDS patients from 5.9 to 4.1 ml/kg (p <0.001). A reduction in PaCO2 values was observed in AE-COPD patients from 67.5 to 51 mmHg (p< 0.001). Median duration of ECCO2R was 5 days (IQR 3-8). Reasons for ECCO2R discontinuation were improvement (n = 33), ECCO2R-related complications (n = 18), limitation of life-sustaining therapies or measures decision (n = 10), and death (n = 9). Main adverse events were hemolysis (n = 21), bleeding (n = 17), and lung membrane clotting (n = 11), with different profiles between the devices. Thirty-five deaths occurred during the ICU stay, 3 of which being ECCO2R-related. CONCLUSIONS: Based on a registry, we report a low rate of ECCO2R device utilization, mainly in severe COPD and ARDS patients. Physiological efficacy was confirmed in these two populations. We confirmed safety concerns such as hemolysis, bleeding, and thrombosis, with different profiles between the devices. Such results could help to design future studies aiming to enhance safety, to demonstrate a still-lacking strong clinical benefit of ECCO2R, and to guide the choice between different devices. TRIAL REGISTRATION: ClinicalTrials.gov: Identifier: NCT02965079 retrospectively registered https://clinicaltrials.gov/ct2/show/NCT02965079.

[Evaluation of dental medical devices: Focus on the definition of needs]. / Évaluation des dispositifs médicaux dentaires pour un appel d'offres : privilégier la haute définition des besoins.

OBJECTIVES: As a university teaching hospital, the call for tender for dental medical devices (dental implants and consumables) is done with the help of a team of hospital pharmacists and users. In order to optimize the definition of needs and evaluation criteria, an exhaustive review of the products was carried out. METHODS: Dental medical devices suppliers were consulted in 2017 for reviewing their products. Their technical, clinical and economic data were compared. The products have been gathered into categories and its results had been submitted to a commission of dental experts of our university hospital for clinical opinion. RESULTS: More than 30,000 references from 30 different suppliers were analyzed (orthodontics, dental implants, membranes and bone substitutes, various dental consumables). Relating to oral implantology, the opinions converged on clinical studies. On the contrary, diverging opinions have been proffered on the systematic use of single-use drills and customized guides for surgery and on the implant's choice. The definition of needs has been specified for orthodontics and consumables. Other criteria played a great role: single packaging (unit doses), product's sterility, paediatric needs, presence of allergens, traceability of devices and supplier diversity. CONCLUSIONS: This review led to the identification of new needs in more precise terms. The complexity and diversity of dental products and techniques requires this careful review and a better collaboration with practitioners.

[Review of patient-specific instrumentation for total knee prosthesis]. / Revue des guides personnalisés à usage unique dans les prothèses totales de genou.

OBJECTIVES: Single use patient-specific instruments (PSI) for total knee prosthesis are introduced as a new alternative to conventional ancillaries and computer assisted surgery by improving implants positioning. An exhaustive review was carried out to identify their specific characteristics, with their advantages and disadvantages. METHODS: Medical devices suppliers were consulted in 2015 for reviewing their PSI. Their technical, clinical and economic data were compared. The results had been submitted to an orthopaedics expert commission of our university hospital for clinical and financial opinion. RESULTS: Ten companies have provided the documentation for the analysis. PSI are manufactured by suppliers using a three dimensional printing method based on CT scans or MRI images. PSI are produced according to the surgeon's preferences after a preliminary data check, which can be performed by the suppliers' engineers, the surgeon and automatic calculation. Five suppliers can produce sterile PSI with optional delivery of 3D bone models. According to the experts, the studies failed to demonstrate the superiority of a PSI or hospital economic gain. The prices listed remain high and operating room time is not always significantly reduced. CONCLUSIONS: With the development of personalized medicine, the role of PSI grows in importance. They facilitate the surgeon's work by fully respecting the anatomy. These systems offer an interesting perspective in their technical and pedagogical aspects. But it seems premature to take them into routine use given the low number of high-level studies that were currently done.

Intrathecal Autologous Bone Marrow-Derived Hematopoietic Stem Cell Therapy in Neurological Diseases.

BACKGROUND: Cellular transplantation is a promising treatment strategy for neurological diseases. OBJECTIVE: To report the results of intrathecal hematopoietic stem cell therapy in different neurological diseases in the past 6 years in a single center. METHODS: From October 2011 to September 2018, 220 patients with various neurological diseases were transplanted intrathecally by their bone marrow stem cells. To have a longer follow up, we only reported the first 80 patients, transplanted up to July 2015-10 patients had spinal cord injuries and paralysis, 12 had advanced Parkinson's disease, 28 had cerebral palsy, 7 had hypoxic brain damage, 2 had autism, 4 had multiple sclerosis, 5 had progressive cerebellar atrophy, and 12 had other neurological diseases. The patients were admitted to the Bone Marrow Transplant Unit. On the first day, 50-200 (median 100) mL bone marrow was aspirated from the patients' posterior iliac crests, mixed with 120 mL culture media (RPMI), and 12 mL heparin. The samples were then transferred to immunology lab in cold box. Mononuclear cells (MNCs) were separated by a Ficoll-Hypaque gradient, washed, and suspended in ringers. Cell viability was assessed with trypan blue viability test. Transplantation was performed 3-4 hours after bone marrow collection. 5-10 mL of the cerebrospinal fluids were aspirated and about 20 mL MNCs (containing stem cells) in ringers were injected intrathecally (IT). The patients were laid down on their back for 4-5 hours. The median number of MNCs was 4×107 (range 1-450×107). The median viability of the cells was 90% (range 60%-98%). The patients received intravenous ceftriaxone every 12 hours and were discharged from the hospital few days after autologous stem cell therapy. RESULTS: We noted clinical improvements in 9 of 12 patients with Parkinson's disease, 20 of 28 patients with cerebral palsy, 6 of 7 patients with hypoxic brain damage, 2 of 4 patients with multiple sclerosis, and 4 of 5 patients with cerebellar atrophy. The improvements were noted after 2-4 weeks of cell therapy. There were no improvements in patients with spinal cord injury and complete paralysis and those with autism. There were variable improvements in other patients treated. CONCLUSION: Most patients with advanced Parkinson's disease, cerebral palsy, hypoxic brain damage, progressive cerebellar atrophy, and kernicterus neuropathy reported clinical effects of this safe intervention resulting in better functioning and an increased quality of life.

[Perspective of the transition from reusable instruments to single use ancillary in orthopedic surgery]. / Ancillaires orthopédiques : évolution du matériel restérilisable vers l'usage unique, quels impacts ?

OBJECTIVES: Since 2009, single-use (SU) ancillaries for total knee arthroplasty (TKA) and total hip arthroplasty (THA) have been marketed to replace reusable ancillaries. The concept is not innovative but their use in orthopedics is still uncommon. An assessment has been done for the use of SU ancillary in Assistance publique-hôpitaux de Paris with the consequences for the patient, the surgeon and the hospital. METHODS: A technical and a clinical review has been done with those devices in 2015. The economic and organizational impacts were identified and submitted for opinion to committee experts in orthopedics. RESULTS: Three SU ancillaries are commercialized. No clinical studies are currently available. There is no reimbursement for SU ancillaries whereas reusable ancillaries are included in prosthesis reimbursement price. Although SU ancillaries (TKA and THA) saving costs for sterilization, the annual additional budget estimated for their purchase would approximately be 2.5 times higher. Nevertheless, indirect savings could be also considered in the long-term period (global costs for sterilization, volume effect…). For the same quality, according to the experts, organizational impacts are low for the patient and the surgeon but potentially important for the hospital, the nursing and pharmaceutical staff, and logistical activities. CONCLUSIONS: On logistic, clinical and financial aspects, SU ancillaries need more evaluation. The switch to SU ancillaries allows saving sterilization costs and time, and provided an immediate mobilization of the equipment but their interest must be demonstrated by clinical and economic data.

Predictive factors of response to phase I complete decongestive therapy in upper extremity lymphedema following breast carcinoma in Iran.

Post-mastectomy chronic lymphedema as a complication of breast cancer treatment is primarily managed with Complete Decongestive Therapy (CDT). We examined various factors for correlating with results of Phase I CDT treatment in controlling the upper extremity lymphedema. Study population consisted of patients with lymphedema referred to the Lymphedema Clinic of the Iranian Breast Cancer Research Center for control of arm edema. After obtaining the demographic and clinical data, patients were treated with CDT for 2 - 3 weeks. One hundred and thirty seven patients (mean age +/- SD; 53.5 +/- 10 years) were studied. In 48.7% of patients, the affected arm was the dominant limb. Fifty percent of patients experienced lymphedema during the first year after surgery, and mean duration of lymphedema was 35 +/- 43 months. Mean volume reduction was 43% +/- 14.87% (p = 0.03). There was a significant relationship between the percent of volume reduction and initial lymphedema volume (p=0.003) as well as duration of lymphedema (p=0.002). Our results demonstrate that Phase I CDT treatment is very effective for post mastectomy lymphedema, and particularly if it is provided in earlier stages of disease. In addition, CDT also has an important role in reducing clinical symptoms and improving limb function. In the appropriate setting, Phase I CDT has been an effective method of controlling post mastectomy lymphedema in this Iranian population.

Standardized breast cancer mortality rate compared to the general female population of Iran.

INTRODUCTION: Breast cancer is the most common cancer in women. Improvements of early diagnosis modalities have led to longer survival rates. This study aimed to determine the 5, 10 and 15 year mortality rates of breast cancer patients compared to the normal female population. MATERIALS AND METHODS: The follow up data of a cohort of 615 breast cancer patients referred to Iranian Breast Cancer Research Center (BCRC) from 1986 to 1996 was considered as reference breast cancer dataset. The dataset was divided into 5 year age groups and the 5, 10 and 15 year probability of death for each group was estimated. The annual mortality rate of Iranian women was obtained from the Death Registry system. Standardized mortality ratios (SMRs) of breast cancer patients were calculated using the ratio of the mortality rate in breast cancer patients over the general female population. RESULTS: The mean age of breast cancer patients at diagnosis time was 45.9 (±10.5) years ranging from 24-74. A total of 73, 32 and 2 deaths were recorded at 5, 10 and 15 years, respectively, after diagnosis. The SMRs for breast cancer patients at 5, 10 and 15 year intervals after diagnosis were 6.74 (95% CI, 5.5- 8.2), 6.55 (95%CI, 5-8.1) and 1.26 (95%CI, 0.65-2.9), respectively. CONCLUSION: Results showed that the observed mortality rate of breast cancer patients after 15 years from diagnosis was very similar to expected rates in general female population. This finding would be useful for clinicians and health policy makers to adopt a beneficial strategy to improve breast cancer survival. Further follow-up time with larger sample size and a pooled analysis of survival rates of different centres may shed more light on mortality patterns of breast cancer.

Comparing two treatment methods for post mastectomy lymphedema: complex decongestive therapy alone and in combination with intermittent pneumatic compression.

There is no cure for breast cancer related lymphedema. This study was conducted to compare two treatment methods for postmastectomy lymphedema: Complex Decongestive Therapy (CDT) and Modified CDT (MCDT) combined with Intermittent Pneumatic Compression (IPC). One hundred and twelve patients referred to the Lymphedema Clinic of the Iranian Center for Breast Cancer in 2008, were included in a randomized clinical trial. They were randomly allocated into two equal groups receiving daily CDT alone or in combination with IPC. The volume reduction of the upper limb was measured by water displacement volumetry. No statistically significant differences in demographic and clinical variables between the two groups were observed. During the intensive phase (phase I) of treatment, CDT alone yielded a significantly higher mean volume reduction than the combination modality (43.1% vs. 37.5%; p = 0.036). Limb volume measured three months following treatment, showed 16.9% volume reduction by CDT alone, and 7.5% reduction by MCDT plus IPC. This study demonstrated that the use of CDT alone, or in combination with IPC significantly reduced limb volume in patients with post mastectomy lymphedema. CDT alone provided better results in both treatment phases. Further studies will help to define the role of multidisciplinary approaches in the management of postmastectomy lymphedema.

[An update on the use of tissue adhesives in ophthalmology]. / Mise au point sur l'utilisation des colles tissulaires en ophtalmologie.

Tissue adhesives have a long history of use in almost all surgical disciplines, both as an alternative and a complement to sutures. Nevertheless, ophthalmologists have restricted knowledge of their potential applications; consequently, tissue adhesives have been underutilized so far. This review discusses the most relevant clinical and experimental advances in the use of tissue adhesives in ophthalmology and details the characteristics and properties of the glues. Among the currently available adhesives, synthetic glues are mainly represented by cyanoacrylates and biologic glues by fibrin-based adhesives. Cyanoacrylate-based glues are especially useful for treating perforated or preperforated corneal ulcers and performing temporary tarsorrhaphy. Fibrin-based glues have the largest field of application, as they can be used in corneal perforations and are being widely used in pterygium surgery and conjunctival surgery. We also reviewed other anecdotic applications of these adhesives. Novel biomaterials such as biodendrimers, polyethylene glycols, modified chondroitin sulfates, and acrylic copolymers show promising results in the experimental field, and one product has been on the market for a short period of time.

Factors predicting the use of complementary and alternative therapies among cancer patients in Iran.

This study was carried out to examine the factors that predicting the use of complementary and alternative medicine (CAM) among cancer patients in Tehran, Iran. Predicting factors included were patients' demographic characteristics, type of cancer, the knowledge of diagnosis, time since diagnosis, satisfaction with their care physician, fear of recurrence and measures of anxiety, depression and global quality of life. In total, 625 cancer patients were studied, and 35% (n=219) reported that they used or were using CAM. The most commonly used CAM was prayer and spiritual healing (n=178, 75.7% of responses). The results of logistic regression analysis indicated that the use of CAM among cancer patients was associated with the fear of cancer recurrence (OR=2.03, 95% CI=1.45-2.85, P<0.0001) and dissatisfaction with their care physician (OR=1.98, 95% CI=1.36-2.89, P<0.0001). The results indicate that apart from the prayer and spiritual healing, the use of the other common methods of CAM among Iranian cancer patients is unpopular. However, the findings suggest that the use of CAM is more common among cancer patients who suffer from fears, uncertainties and dissatisfaction, and these might be a marker of greater psychological distress in users as compared with non-users.

Surgical hand rubbing compared with surgical hand scrubbing: comparison of efficacy and costs.

The aim of this study was to compare the efficacy of surgical hand rubbing (SHR) with the efficacy of surgical hand scrubbing (SHS), and to determine the costs of both techniques for surgical hand disinfection. A review of studies reported in the literature that compared the efficacy of SHS and SHR was performed using MEDLINE. The costs of SHR and SHS were estimated based on standard hospital costs. The literature showed that SHR had immediate efficacy that was similar to that of SHS, but SHR had a more lasting effect. SHR reduced costs by 67%. In conclusion, SHR is a cost-effective alternative to SHS.

Anxiety and depression in breast cancer patients before and after participation in a cancer support group.

A prospective study was conducted to assess the long-term impact of attending a support group on the prevalence of psychological morbidity in patients with breast cancer before and after 1-year participation in the Iranian breast cancer support group. Psychological morbidity was measured using the hospital anxiety and depression scale (HADS). In addition, qualitative data were collected to throw some lights on the topic. All current members of the three Iranian breast cancer support groups (n=56) were interviewed. The mean age of patients was 45.4 (S.D.=9.2) years, most were married (n=46, 82%), and 54% of patients (n=30) were diagnosed as having breast cancer from 1 to 5 years ago. While at baseline 16 patients (29%) scored high on the anxiety sub-scale and eight patients (14%) scored high on the depression sub-scale, at follow-up only two patients (2%) were likely experiencing severe anxiety symptoms and there were no patients with probable severely depressed mood. Comparing anxiety and depression at baseline and follow-up, there was a statistically significant difference between baseline and follow-up anxiety (P=0.03) and depression (P=0.008) scores. Analysis of the qualitative data indicated that the group involvement was the most important factor that contributed to the patients' improved psychological well-being. The findings of this prospective study suggest that participation in cancer support groups could have a long-term effect in reducing anxiety and depression in breast cancer survivors.

Evaluation of a national breast cancer information service: the Iranian experience.

This descriptive study evaluates a newly established national breast cancer information service in Iran and reports data on the impact of contacting the service. Two instruments were used to collect data: a "call record form" and a "user survey" questionnaire. The call record was filled in after each inquiry, and during 1 year 1,000 forms were completed. The questionnaire was filled in 1 week after each inquiry and was completed for a random sample of 400 callers. Thus, the results are presented in two parts. Analysis of the call record forms (part one) showed that 95% of the callers were female, mostly married (82%) and with secondary or higher education (80%). Most callers reported that they had heard about the service through the mass media (69%). Benign breast diseases, mastalgia and breast masses were the most common subjects of the inquiries (28%, 27%, and 18%, respectively). The majority of callers (77%) said that the main reason for contacting the service was that they wanted more information about breast diseases. Examination of the questionnaires (part two) revealed that 97% of respondents described the service as "useful" or "very useful". The vast majority (80%) perceived the information given as "easy" or "very easy" to understand. When respondents were asked to compare their feelings before and after contacting the service, 86% said that they felt "much more" or "a little more cheerful" and 81% said that they felt "much less" or "a little less worried". Practically all (99%) were satisfied with the overall service provided. The findings indicate that the service is effective in providing information and support for patients, relatives and the general public. The real challenge is how to make the service more widely available, especially to breast cancer patients.

Dose response of human tumor cells to rhodamine 123 and laser phototherapy.

Previous studies have shown that Rhodamine 123 (Rh123) is an efficient tumor targeting agent for argon laser photodynamic therapy in vitro. Effectiveness of this approach for cancer treatment in vivo will depend on Rh123 tumor uptake kinetics and laser energy delivery via fiberoptics to the tumor site. In the present study, tumor and normal cells were exposed in vitro to 1 micrograms/mL Rh123 until 10%, 50%, and 100% of maximum uptake was achieved. Laser treatment response was monitored by trypan blue exclusion for tumor cell viability and by MTT tetrazolium assays to measure mitochondrial dehydrogenase activity. TE671 fibrosarcoma cells were highly sensitive to argon laser phototherapy (514 nm, 5 W, 1 minute, Tmax = 8 degrees C), with mitochondrial inhibition seen after Rh123 uptake of 12, 50, and 100 ng/million cells. P3 squamous cell carcinoma cells were inhibited 20% and 75% by the laser after Rh123 uptake of 13 or 30 ng/million cells, respectively. M26 melanoma cells were not sensitive to the laser after 15 ng/million cells Rh123 uptake but were inhibited 45% and 75% after Rh123 uptake of 80 and 160 ng/million cells. Micro2 fibroblast mitochondrial activity was reduced less than 25% by the laser after Rh123 uptake of 50 ng/million cells. Cell viability after maximum Rh123 uptake and laser treatment was decreased to 30%, 15%, and 2% for M26 melanoma, P3 squamous cell carcinoma, and TE671 fibrosarcoma cells, but remained over 80% for Micro2 fibroblasts. The results suggest that Rh123 laser treatment response depends on tumor type and drug uptake level, with normal cells being much less sensitive to phototherapy.

The synergistic effects of rhodamine-123 and merocyanine-540 laser dyes on human tumor cell lines: a new approach to laser phototherapy.

Many new photosensitizers and laser wavelengths are being tested to improve photodynamic therapy by enhancing specific tumor uptake and/or retention, lowering systemic toxicity, and increasing laser tissue penetration. In this study the potential synergistic effects of rhodamine-123 (Rh-123) and merocyanine-540 (MC-540) sensitization of human tumor cell lines after laser exposure were explored. In a first series of experiments, the kinetics of uptake of Rh-123 and M-540 were tested on three human leukemia cell lines (K562, RAJI, 729HF2), P3 squamous carcinoma, and M26 melanoma. Our results demonstrate a clear difference in the rate and amount of uptake of MC-540 (K562 > P3 > RAJI > 729HF2 > M26) and Rh-123 (P3 > RAJI > 729HF2 > K562 > M26) by these cell lines. In a second series of experiments, M26 tumor cells were sensitized with either Rh-123 (1 microgram/ml) or with MC-540 (20 micrograms/ml) alone or with a combination of the two dyes for 60 minutes, then exposed to the argon (514.5 nm) laser at nonthermal energy levels. Our results demonstrate a significant enhancement of the tumoricidal effects of the laser on M26 carcinoma cells after sensitization with both dyes together (MC-540 and Rh-123) when compared to each dye alone. As with combination antibiotherapy, the synergistic effects of two laser dyes that have different intracellular targeting sites appear to enhance tumoricidal effects significantly after exposure to a matching laser wavelength. The data provide evidence for effective laser phototherapy by dye synergy.

Biodistribution of rhodamine-123 in nude mice heterotransplanted with human squamous cell carcinomas.

Rhodamine-123 uptake and release was determined in nu/nu mice heterotransplanted with P3 human squamous carcinomas to assess its value as an in vivo laser photosensitizer for treatment of solid tumors. Following intraperitoneal injection of Rh-123 (1 micrograms/g of body weight), mice were killed at 2, 4, 6 and 24 hours, and 3 and 7 days postinjection. The peak concentrations of Rh-123 per milligram of tissue measured by fluorescence spectrophotometry was distributed as follows: kidneys greater than spleen greater than intestine greater than stomach greater than liver greater than tumor greater than skin greater than skeletal muscles greater than lung greater than heart greater than blood greater than brain. No preferential uptake or retention of Rh-123 by tumors was observed. However, a longer retention with higher concentrations of the dye was seen in normal skin as opposed to P3 tumors from 4 hours to 7 days postinjection with Rh-123. The elimination of Rh-123 was rapid, with the dye falling to less than 2% of peak concentration at 7 days postinjection. Knowledge of Rh-123 biodistribution in tumors and other tissues suggests that optimal timing after injection of this dye may allow selective photodiagnosis and photodynamic therapy of tumors with the argon laser.

Laser dyes for experimental phototherapy of human cancer: comparison of three rhodamines.

The mitochondrial dye Rhodamine 123 (Rh-123) has been shown to be an effective photosensitizer for argon-laser irradiation of some types of human cancer cells in vitro. We reported that 514.5-nm laser illumination of Rh-123 sensitized human melanoma, and squamous carcinoma cells strongly inhibited tumor-cell proliferation as measured by decreased 3H-thymidine (3H-T) uptake in vitro and may eradicate some tumors when grown as transplants in nude mice. However, several other human tumors were resistant to Rh-123 laser therapy in vitro and in vivo. In the current study, it was possible to obtain 100- to 1000-fold increased sensitivity to 514.5-nm laser illumination by replacement of Rh-123 with the cationic rhodamine dyes Rh-3G and Rh-6G. Cell viability was decreased over 95% and 3H-T incorporation reduced at least 80% by laser phototherapy after sensitizing tumor cells with 1 micrograms/mL Rh-123, 0.01 microgram/mL Rh-3G, or 0.001 microgram/mL Rh-6G. However, Rh-123 alone did not decrease 3H-T uptake significantly unless present at over 10- to 100-fold higher levels than Rh-3G, respectively. The tumor cell dye uptake level was measured by N-butanol extraction and absorption scans at 400 to 600 nm. The results revealed that dye uptake was more rapid, and retention of Rh-3G and Rh-6G was 5- to 10-fold higher than for Rh-123 in the human tumor cells. The data suggest that Rh-3G and Rh-6G may be highly sensitive chromophores for laser phototherapy of human cancer cells.