Preoperative Hypoxyradiotherapy of Colorectal Carcinoma

AIM: The article focuses on the radioprotective effect of acute hypoxia on healthy tissues during preoperative accelerated hypoxyradiotherapy of colorectal carcinoma performed as locoregional irradiation including the common iliac lymph nodes. Analysis of early and late side effects and complications. PATIENTS AND METHODS: In this prospective study, early and late complications were assessed in 50 patients as a function of hypoxyradiotherapeutic dose increase. The preliminary treatment results of this radiotherapeutic modification were evaluated after a median follow-up of 48 months using Kaplen-Meier analysis. Between April 1991 and February 1997, 50 patients (36 men and 14 women) with colorectal carcinoma were treated preoperatively with locoregional accelerated hypofractionated hypoxyradiotherapy. The extent of disease was classified according to Dukes' criteria (A: four patients, B. 28 patients, C: 18 patients). We used a 20-MeV linear accelerator with two parallel opposed fields. Hypoxyradiotherapy was performed extending from the perineum to the L4 region. Acute hypoxia was induced during irradiation by ventilation of a hypoxic gas mixture containing 7.8-8.0% oxygen. Total doses of 24 Gy/8 days, 28 Gy/9 days, and 32 Gy/10 days were applied in five, 20, and 25 patients, respectively. Low anterior resection or abdominoperineal amputation of the rectum was performed the day after completion of preoperative hypoxyradiotherapy. The early reactions after irradiation were evaluated according to the Common Toxicity Criteria of the National Cancer Institute (CTC-NCI). RESULTS: Early postirradiation proctitis was documented in three and early radiation-induced cystitis in two patients only. Neither early nor late radiation-associated complications were observed in any of the three hypoxyradiotherapy schedules during the follow-up period of 6-105 months. Based on Kaplan-Meier analysis (median 48 months), a 5-year overall survival rate of 61.5% and a local relapse-free survival rate of 84.2% can be expected. Treatment failures were predominantly systemic. CONCLUSION: We believe it can be concluded that acute hypoxia has a radioprotective effect on normal tissues during accelerated hypoxyradiotherapy of colorectal carcinoma. Hypoxyradiotherapy permits safe administration of doses higher than those tolerated by normoxic, noncanceorus tissue, resulting in the amplification of the biological effect of radiation on tumor tissue and contributing to an improved outcome after combined radiosurgical treatment of colorectal carcinoma.     

Evaluation of the Breast Cancer Train the Trainer Program for Nurses in Turkey

The Breast Cancer Train the Trainer (TTT) program was designed to increase breast cancer awareness, improve knowledge about breast cancer among nurses, and provide quality care for breast cancer patients by trained nurses. A total of three programs were held and 82 nurses from different regions of Turkey attended this training. The educational activities employed several teaching and learning strategies. After completion, we determined that the participating nurses’ knowledge on breast cancer had increased significantly, and they were satisfied with the training received. The Breast Cancer TTT program is a unique educational endeavor for nurses in Turkey, and our results showed that the training achieved its goal. Trained nurses in Breast Cancer TTT programs can help educate women about the importance of breast health and the measures they need to take to protect themselves against breast cancer. At the same time, nurses can also increase and enhance the quality of life in patients with breast cancer. This is an example of a program that can easily be spread throughout the world as it was done from England and Australia to Turkey.     

Diagnosis of lung cancer in the general therapeutic departments of the hospital

The authors review the therapeutic aspects of lung carcinoma (LC) diagnosis based on the follow-up of 80 patients with LC referred to the hospital for different nonspecific pulmonary diseases (pneumonia, bronchitis, bronchial asthma). Point to the diagnostic significance of the therapeutic microsymptomatology (inexplicable leukocytosis, fever, alterations in the character of cough and sputum, appearance of asphyxia and so forth), measurement of the level of hormones and biologically active substances with regard to the clinico-roentgenological appearance in identification of LC in the general therapeutic departments of the hospital. Analyze the diagnostic errors in the patients' group under examination.     

Photodynamic therapy-mediated hypericin-loaded nanostructured lipid carriers against vulvovaginal candidiasis

Introduction and Aim: The indiscriminate use and adverse effects of the main conventional antifungal agents compromise the effectiveness of treating vulvovaginal candidiasis (VVC), mainly caused by the species Candida albicans. This study evaluated the effectiveness of photodynamic therapy (PDT) and the in vitro and in vivo anti-candida potential of the hypericin (HYP)-loaded nanostructured lipid carriers (NLC). Materials and Methods: Empty NLC and NLC-HYP were characterized by the dynamic light scattering technique and transmission electron microscopy to evaluate the average particle size distribution and its morphologies. The in vitro inhibition photodynamic effect of the systems was tested to reduce the planktonic viability of C. albicans. The therapeutic assay photodynamic of the systems was performed to treat VVC in mice. Results: Empty NLC and NLC-HYP presented values of average hydrodynamic diameter, polydispersity index, and ζ-potential from 136 to 133 nm, 0.16 to 0.22, and -18 to -30 mV, respectively, on day 30. Microscopically, the systems showed spherical morphologies and nanoscale particles. Furthermore, in the in vitro inhibition assay, the treatment of PDT with NLC-HYP (NLC-HYP+) showed a significant reduction of the C. albicans planktonic viability compared to YNB negative control after 5 min of LED light irradiation. In the in vivo therapeutic assay, the antifungal group (vaginal antifungal cream) and NLC-HYP+ evaluated in the dark and by PDT, respectively, had a significant log₁₀ reduction in fungal burden compared to the infected group on day 8 of the VVC treatment. Conclusion: Due to the in vitro and in vivo anti-candida potential, PDT-mediated systems can be an effective strategy in VVC therapy.     

Effects of high-voltage electrical burns and other burns on levels of serum oxidative stress and telomerase in children

Introduction

Electrical burns cause significant morbidity and mortality worldwide. Here we measured changes in levels of serum oxidative stress and telomerase in children suffering from high-voltage electrical burn (HVEB) injuries and other burns and the significance of these parameters in terms of amputation.

Fluorine-18 Labeling of the HER2-Targeting Single-Domain Antibody 2Rs15d Using a Residualizing Label and Preclinical Evaluation

Purpose

Our previous studies with F-18-labeled anti-HER2 single-domain antibodies (sdAbs) utilized 5F7, which binds to the same epitope on HER2 as trastuzumab, complicating its use for positron emission tomography (PET) imaging of patients undergoing trastuzumab therapy. On the other hand, sdAb 2Rs15d binds to a different epitope on HER2 and thus might be a preferable vector for imaging in these patients. The aim of this study was to evaluate the tumor targeting of F-18 -labeled 2Rs15d in HER2-expressing breast carcinoma cells and xenografts.

Procedures

sdAb 2Rs15d was labeled with the residualizing labels N-succinimidyl 3-((4-(4-[¹⁸F]fluorobutyl)-1H-1,2,3-triazol-1-yl)methyl)-5-(guanidinomethyl)benzoate ([¹⁸F]RL-I) and N-succinimidyl 4-guanidinomethyl-3-[¹²⁵I]iodobenzoate ([¹²⁵I]SGMIB), and the purity and HER2-specific binding affinity and immunoreactivity were assessed after labeling. The biodistribution of I-125- and F-18-labeled 2Rs15d was determined in SCID mice bearing subcutaneous BT474M1 xenografts. MicroPET/x-ray computed tomograph (CT) imaging of [¹⁸F]RL-I-2Rs15d was performed in this model and compared to that of nonspecific sdAb [¹⁸F]RL-I-R3B23. MicroPET/CT imaging was also done in an intracranial HER2-positive breast cancer brain metastasis model after administration of 2Rs15d-, 5F7-, and R3B23-[¹⁸F]RL-I conjugates.

Results

[¹⁸F]RL-I was conjugated to 2Rs15d in 40.8 ± 9.1 % yield and with a radiochemical purity of 97–100 %. Its immunoreactive fraction (IRF) and affinity for HER2-specific binding were 79.2 ± 5.4 % and 7.1 ± 0.4 nM, respectively. [¹²⁵I]SGMIB was conjugated to 2Rs15d in 58.4 ± 8.2 % yield and with a radiochemical purity of 95–99 %; its IRF and affinity for HER2-specific binding were 79.0 ± 12.9 % and 4.5 ± 0.8 nM, respectively. Internalized radioactivity in BT474M1 cells in vitro for [¹⁸F]RL-I-2Rs15d was 43.7 ± 3.6, 36.5 ± 2.6, and 21.7 ± 1.2 % of initially bound radioactivity at 1, 2, and 4 h, respectively, and was similar to that seen for [¹²⁵I]SGMIB-2Rs15d. Uptake of [¹⁸F]RL-I-2Rs15d in subcutaneous xenografts was 16–20 %ID/g over 1–3 h. Subcutaneous tumor could be clearly delineated by microPET/CT imaging with [¹⁸F]RL-I-2Rs15d but not with [¹⁸F]RL-I-R3B23. Intracranial breast cancer brain metastases could be visualized after intravenous administration of both [¹⁸F]RL-I-2Rs15d and [¹⁸F]RL-I-5F7.

Conclusions

Although radiolabeled 2Rs15d conjugates exhibited lower tumor cell retention both in vitro and in vivo than that observed previously for 5F7, given that it binds to a different epitope on HER2 from those targeted by the clinically utilized HER2-targeted therapeutic antibodies trastuzumab and pertuzumab, F-18-labeled 2Rs15d has potential for assessing HER2 status by PET imaging after trastuzumab and/or pertuzumab therapy.

     

Correlation between the combination of apparent integrated backscatter–spectral centroid shift and bone mineral density

Purpose

To introduce a new diagnostic parameter: the linear combination of apparent integrated backscatter and spectral centroid shift.

Methods

Ultrasonic backscatter measurements were performed at the calcanei of 1262 volunteers in vivo. The hip and spine bone mineral densities of the volunteers were measured using dual X-ray absorptiometry. The apparent integrated backscatter and spectral centroid shift were calculated. A new diagnostic parameter, i.e., the linear combination of apparent integrated backscatter and spectral centroid shift, was introduced and its correlation to bone mineral density was analyzed.

Results

The results show that the combination of apparent integrated backscatter and spectral centroid shift is significantly correlated to bone mineral density (R = 0.73–0.84, n = 1262, p < 0.05), and that this correlation is more significant than the correlation between the apparent integrated backscatter and bone mineral density or the correlation between spectral centroid shift and bone mineral density (R = 0.48–0.69, p < 0.05).

Conclusion

The combination of apparent integrated backscatter and spectral centroid shift can provide the complementary information of attenuation of the two parameters and predict more information about cancellous bone, and may be employed to assess cancellous bone status.