PROSPECTIVE SINGLE CENTER ANALYSIS OF OUTCOME STEM CELLS TRANSPLANTS IN PATIENTS WITH CEREBRAL PALSY.

OBJECTIVE: Aim: To evaluate efficacy and safety of autologous bone marrow-derived mononuclear stem cell transplantation intrathecal in children with cerebral palsy. PATIENTS AND METHODS: Materials and Methods: 35 children have levels I-V cerebral palsy aged 8-months to 8-years-old were enrolled from September (2021-2022) at Iraqi private hospital. Gross Motor Function was assessed by a pediatrician and neurologist specialist, 5 mcg/kg/day of G-CSF subcutaneous single injection daily for three consecutive days. Bone marrow harvested from posterior iliac crest under light general anesthesia. Bone marrow mononuclear cells (BMMNCs) separation was performed using density gradient centrifugation with Ficoll, the cell viability checked by propidium iodide dye in a TALI machine (Invitrogen) in average 98%. The viable BMMNCs injected intrathecal in L4-L5 over a period of 5-10 min. RESULTS: Results: Males accounted for 57.14% (20/35) while female 42.86% (15/35), and main neurological symptoms included spastic disorder spastic disorder (quadriplegia 24 (68.6), tetraplegia 2 (5.7), diplegia 5 (14.28), hemiplegia4 (11.42)). Gross Motor Function Classification System and Gross Motor Function Measure-66 (GMFM-66) showed II 10 (28.58), III 11(31.42) and IV 14 (40). On mean follow-up of 3 months post-stem cell transplant improvement was observed in 80% cases. The improvement showed in gross motor function (6/8) p=0.01, and speech (2/4) p=0.04, neck holding (5/5) p=0.0003, sitting balance (4/4) p=0.04, postural tone (5/5) p=0.0003, as well as significant reduction in seizure frequency (2/3) p=0.04 and improvement in cognition (6/7) p=0.01 were observed. CONCLUSION: Conclusion: Stem cell therapy for cerebral palsy shows a significant positive effect on the gross motor function, without long adverse effects.

Risk of Oral Squamous Cell Carcinoma in One Hundred Patients with Oral Lichen Planus: A Follow-Up Study of Umberto I University Hospital of Rome.

This study aims to retrospectively assess the potential risk of malignant transformation in patients with diagnosed oral lichen planus (OLP) between 2015 and 2022, and to evaluate the influence of different risk factors. The department's database and medical records from 2015 to 2022 were searched for patients with a confirmed diagnosis of OLP based on both clinical and histological parameters. A total of 100 patients (59 females and 41 males) were found with a mean age of 64.03 years. In the considered period, the percentage of diagnosed OLP patients was 1.6%, while the percentage of diagnosed OLP patients with transformation to oral squamous cell carcinoma (OSCC) was 0.18%. A statistically significant difference was found with age (p = 0.038), tobacco status (p = 0.022), and radiotherapy (p = 0.041). The analysis revealed the presence of significant risk in ex-smokers (>20 pack-years), with an odds ratio (OR) of 10.0000 (95% confidence interval (95% CI) 1.5793-63.3186); in alcohol-drinker patients, with an OR of 4.0519 (95% CI 1.0182-16.1253); in ex-smoker and alcohol-drinker patients, with OR of 17.6250 (95% CI 2.2464-138.2808); and in patients who had undergone radiotherapy, with OR of 6.3000 (95% CI 1.2661-31.3484). The malignant transformation of oral lichen planus was slightly higher than thought, and the results revealed a possible association with age, tobacco and alcohol status, and history of radiotherapy. An elevated risk of malignant transformation was observed in heavy ex-smoker patients, alcohol-drinker patients, and alcohol-drinker patients with a history of smoking (ex-smokers). Persuading the patient to quit tobacco and alcohol consumption and periodic follow-ups are recommended in general, but particularly in the presence of these risk factors.

The Impact of Laser Thermal Effect on Histological Evaluation of Oral Soft Tissue Biopsy: Systematic Review.

The aim of the study is to review the literature to observe studies that evaluate the extent of the thermal effect of different laser wavelengths on the histological evaluation of oral soft tissue biopsies. An electronic search for published studies was performed on the PubMed and Scopus databases between July 2020 and November 2022. After the selection process, all the included studies were subjected to quality assessment and data extraction processes. A total of 28 studies met the eligibility criteria. The most studied laser was the carbon dioxide (CO2) laser, followed by the diode laser 940 nm-980 nm. Six studies were focused on each of the Erbium-doped Yttrium Aluminium Garnet (Er:YAG), Neodymium-doped Yttrium Aluminum Garnet (Nd:YAG) lasers, and diode lasers of 808 nm and 445 nm. Three studies were for the Potassium Titanyl Phosphate (KTP) laser, and four studies were for the Erbium, Chromium-doped Yttrium, Scandium, Gallium, and Garnet (Er,Cr:YSGG) laser. The quality and bias assessment revealed that almost all the animal studies were at a low risk of bias (RoB) in the considered domains of the used assessment tool except the allocation concealment domain in the selection bias and the blinding domain in the performance bias, where these domains were awarded an unclear or high score in almost all the included animal studies. For clinical studies, the range of the total RoB score in the comparative studies was 14 to 23, while in the non-comparative studies, it was 11 to 15. Almost all the studies concluded that the thermal effect of different laser wavelengths did not hinder the histological diagnosis. This literature review showed some observations. The thermal effect occurred with different wavelengths and parameters and what should be done is to minimize it by better adjusting the laser parameters. The extension of margins during the collection of laser oral biopsies and the use of laser only in non-suspicious lesions are recommended because of the difficulty of the histopathologist to assess the extension and grade of dysplasia at the surgical margins. The comparison of the thermal effect between different studies was impossible due to the presence of methodological heterogeneity.

Liquid biopsy in the assessment of microRNAs in oral squamous cell carcinoma: A systematic review.

Background: The identification of non-invasive biomarkers from biological fluids collected by liquid biopsy provides new horizons for individualized therapeutic strategies and improves clinical decision-making in OSCC patients. Circulating microRNAs have emerged as biomarkers that may reflect not only the existence of cancer, but also the dynamic, malignant potential, and drug resistance of tumors. The aim of the systematic review is to evaluate and summarize the results of the published studies regarding the use of microRNAs as biomarkers for OSCC. Material and Methods: A literature search was conducted on PubMed, Scopus, Web of Science, and Cochrane databases till November 2020. A total of 34 studies met the inclusion criteria and were therefore subjected to quality assessment. Each study was subjected to data extraction including; patient characteristics, type of fluid sample (whole blood, plasma, serum, or saliva), molecular analysis method, specific dysregulated microRNA, and microRNA expression pattern. Results: The analysis showed that 57 microRNAs of liquid biopsy samples of four different fluids (whole blood, serum, plasma, and saliva) were analyzed. The prognostic and therapeutic significance of these microRNAs were suggested by several studies; where 41 microRNAs were upregulated while 16 were downregulated. Conclusions: Scientific evidence supports the interest in the use of microRNAs in the diagnosis and prognosis in OSCC patients; however, further studies in a larger cohort of patients are mandatory to introduce liquid biopsy in the routine clinical practice for the OSCC management. Key words:Biomarkers, liquid biopsy, microRNA, oral squamous cell carcinoma, systematic review.

Role of elastography strain ratio and TIRADS score in predicting malignant thyroid nodule.

OBJECTIVE: Ultrasonography (US) is the most accurate and cost-effective imaging method in diagnosis of thyroid nodules. A practical thyroid imaging reporting and data system (TIRADS) for thyroid nodules has been proposed to classify nodules of the thyroid gland to solve the problem of nodule selection for fine needle aspiration cytology (FNAC). Real-time elastography and strain ratio (SR) is a method used to assess the stiffness and predict the malignancy of thyroid nodules. The objective of this study was to assess the role of elastography and SR and the TIRADS scoring system in discriminating malignant from benign thyroid nodules. METHODS: From 2015 to 2018 at Cairo University Hospital, a series of 409 patients with thyroid nodules was referred to undergo thyroid ultrasound. Categorization of each nodule according to the TIRADS ranged from 1 to 5. The qualitative elastography score and semiquantitative SR of the nodules were evaluated. Final diagnosis was done by either post-thyroidectomy histopathological examination or US-guided FNAC. RESULTS: Our study included 409 patients with thyroid nodules. Their mean age was 39 ± 10 SD; 36 were males and 373 were females. There were 22 malignant nodules and 387 benign nodules. There were statistical differences between benign and malignant nodules regarding TIRADS classification, SR, anteroposterior/transverse ratio, degree of echogenicity, border, presence of calcification, and absence of halo sign (P < 0.001). The elastic properties of thyroid nodules proved to be a good discriminator between malignant and benign nodules (P- < 0.001) at a cut off value of > 2.32 with 95.2% sensitivity and 86.5% specificity. For every unit increase in SR, the risk of malignancy increased by nearly 2 times. Patients with irregular borders had nearly 17 times increased risk of malignancy than those with regular borders. CONCLUSION: Elastography and SR proved to be of high significant value in discriminating benign from malignant nodules, so we recommend adding it to the TIRADS classification.

Laser Photobiomodulation (PBM)-A Possible New Frontier for the Treatment of Oral Cancer: A Review of In Vitro and In Vivo Studies.

The treatment of oral squamous cell carcinoma (OSCC) is particularly complex due to its aggressive behavior, location, the patient's age, and its spread at diagnosis. In recent years, photobiomodulation (PBM) has been introduced in different medical fields; however, its application, in patients suffering from OSCC for palliative support or to induce analgesia, has been hotly debated due to the possibility that the cell growth stimuli induced by PBM could lead to a worsening of the lesions. The aim of this study is to review the literature to observe the available data investigating the effect of PBM on cancer cells in vitro and in vivo. A review was conducted on the PubMed and Scopus databases. A total of twelve studies met the inclusion criteria and were therefore included for quality assessment and data extraction. The analysis showed that the clinical use of PBM is still only partially understood and is, therefore, controversial. Some authors stated that it could be contraindicated for clinical use in patients suffering from SCC, while others noted that it could have beneficial effects. According to the data that emerged from this review, it is possible to hypothesize that there are possibilities for PBM to play a beneficial role in treating cancer patients, but further evidence about its clinical efficacy and the identification of protocols and correct dosages is still needed.

Ventilator associated lung injury in severe COVID-19 pneumonia patients - Case Reports: Ventilator associated lung injury in COVID-19.

Management of severe coronavirus disease 2019 requires advanced respiratory support modalities including invasive mechanical ventilation (IMV), continuous positive airway pressure (C-PAP), and non-invasive ventilation ((NIV). IMV leads to either subtle forms of lung injury (pulmonary edema, lung cysts) or more severe form of lung injury manifested as subcutaneous emphysema, pneumomediastinum, and pneumothorax (herein collectively termed barotrauma). We have described two cases showing the two end of spectrum of ventilator associated lung injury (VALI).

Role of elastography strain ratio and TIRADS score in predicting malignant thyroid nodule

ABSTRACT Objective: Ultrasonography (US) is the most accurate and cost-effective imaging method in diagnosis of thyroid nodules. A practical thyroid imaging reporting and data system (TIRADS) for thyroid nodules has been proposed to classify nodules of the thyroid gland to solve the problem of nodule selection for fine needle aspiration cytology (FNAC). Real-time elastography and strain ratio (SR) is a method used to assess the stiffness and predict the malignancy of thyroid nodules. The objective of this study was to assess the role of elastography and SR and the TIRADS scoring system in discriminating malignant from benign thyroid nodules. Materials and methods: From 2015 to 2018 at Cairo University Hospital, a series of 409 patients with thyroid nodules was referred to undergo thyroid ultrasound. Categorization of each nodule according to the TIRADS ranged from 1 to 5. The qualitative elastography score and semiquantitative SR of the nodules were evaluated. Final diagnosis was done by either post-thyroidectomy histopathological examination or US-guided FNAC. Results: Our study included 409 patients with thyroid nodules. Their mean age was 39 ± 10 SD; 36 were males and 373 were females. There were 22 malignant nodules and 387 benign nodules. There were statistical differences between benign and malignant nodules regarding TIRADS classification, SR, anteroposterior/transverse ratio, degree of echogenicity, border, presence of calcification, and absence of halo sign (P < 0.001). The elastic properties of thyroid nodules proved to be a good discriminator between malignant and benign nodules (P- < 0.001) at a cut off value of > 2.32 with 95.2% sensitivity and 86.5% specificity. For every unit increase in SR, the risk of malignancy increased by nearly 2 times. Patients with irregular borders had nearly 17 times increased risk of malignancy than those with regular borders. Conclusion: Elastography and SR proved to be of high significant value in discriminating benign from malignant nodules, so we recommend adding it to the TIRADS classification.

Management of Medication-Related Osteonecrosis of the Jaw (MRONJ) Using Leukocyte- and Platelet-Rich Fibrin (L-PRF) and Photobiomodulation: A Retrospective Study.

BACKGROUND: The aim of this study was to compare retrospectively the effect of three different treatment protocols on the healing outcome in patients with established medication-related osteonecrosis of the jaw (MRONJ). METHODS: A total of 34 MRONJ patients were recruited from the Department database and were divided according to the treatment protocols in a study group (G1) and two control groups (G2 and G3). G1 was treated with antibiotic therapy, surgery, leukocyte- and platelet-rich fibrin (L-PRF), and photobiomodulation; G2 was treated with antibiotic therapy and surgery; G3 was treated with antibiotic therapy and photobiomodulation. Various clinical variables and treatment protocols were analyzed to determine their correlation with the healing outcome at three and six months of follow-up. RESULTS: There was a significant association between the different treatment protocols and the outcomes at both three and six months follow-up (p = 0.001 and p = 0.002, respectively). No significant association was observed between the outcomes and MRONJ localization, MRONJ stage, duration of drug treatment, gender, diabetes, corticosteroid therapy, smoking habits, underlying disease, and history of chemotherapy at both three and six months follow-up. CONCLUSIONS: Our results show that the combination of antibiotic therapy, surgery, L-PRF, and photobiomodulation may effectively contribute to MRONJ management.

Klotho (rs1207568 and rs564481) gene variants and colorectal cancer risk.

BACKGROUND/AIMS: Whereas colorectal cancer (CRC) is the third most common cancer worldwide, klotho gene has been reported as a tumor suppressor gene. Therefore, the aim of this study was to investigate the association between klotho (rs1207568 and rs564481) variants and CRC in Egyptian patients. MATERIALS AND METHODS: A case-control study comprising 100 patients with CRC and 100 age- and sex-matched healthy controls was conducted. Genotyping of klotho was performed by polymerase chain reaction with confronting two-pair primers. RESULTS: The frequencies of the A allele of rs1207568 and the AC haplotype were significantly higher in patients with CRC than in the controls (p=0.019 and p=0.005, respectively). CONCLUSION: We propose that klotho (rs1207568 and rs564481) variants play a significant role in colorectal carcinogenesis and that the klotho protein could be a target for oncotherapy.

Does Medication-Related Osteonecrosis of the Jaw Influence the Quality of Life of Cancer Patients?

The aim of this study is to observe the influence of Medication-Related Osteonecrosis of the Jaw (MRONJ) on the physical and mental conditions of cancer patients using a Quality of Life (QoL) questionnaire during regular dental practice measures. Twenty cancer patients (8 males and 12 females) with established MRONJ were enrolled in the "MoMax" (Oral Medicine and Maxillofacial) project of the Department of Oral Sciences and Maxillofacial Surgery at "Sapienza" University of Rome, and were included in the study. The 12-item Short Form Survey was used to evaluate the QoL. Statistical analysis revealed a significant difference for Mental Component Summary (MCS) scores based on age (p = 0.018). The regression analysis revealed that the Physical Component Summary (PCS) scores were negatively influenced by the anti-resorptive medication duration (p = 0.031 and ß = -1.137). No significant differences were observed with the other variables considered. The QoL of cancer patients is generally deteriorated and MRONJ may cause a further negative impact. This study highlights the possible need to include psychosocial and physical evaluations in the management process of MRONJ in cancer patients.

Evaluation of adjunctive efficacy of diode laser in the treatment of peri-implant mucositis: a randomized clinical trial.

Peri-implant disease may affect survival of dental implants. The aim of the study is to analyze the effectiveness of diode laser as a supportive modality to the non-surgical conventional treatment of peri-implant mucositis (PiM) and initial peri-implantitis (PI). Twenty-three patients with single implants suffering from PiM or initial PI were selected and randomly divided into two groups; control group (CG) received non-surgical conventional treatment, and test group (TG) received non-surgical conventional treatment and diode laser application with wavelength of 980 nm. Probing pocket depth (PPD) and bleeding on probing (BOP) were recorded at baseline (T0) and at 3 months follow-up (T1). The average of PPD value for TG was 4.04 ± 0.54 mm at T0 and it was 2.98 ± 0.70 mm at T1. In the CG, PPD average was 3.8 ± 1.24 mm at T0 and was 3.54 ± 0.35 mm at T1. In TG, the BOP was positive in 44 sites at T0 and in 6 sites at T1. In CG, the BOP was positively observed in 52 sites at T0 and in 28 sites at T1. The 980-nm diode laser may be considered an adjunct to the conventional non-surgical treatments of PiM and initial PI.

Could the super-pulsed CO2 laser be used for oral excisional biopsies?

BACKGROUND: The main purpose of a biopsy is microscopic examination and diagnosis. Keeping the margins of specimens safe and readable is always fundamental to detecting marginal infiltrations or malignant transformation. Numerous options and tools have been introduced for biopsy procedures. Lasers are one of these options that provide many enhancements to clinical and surgical biopsy procedures in comparison to scalpels. OBJECTIVES: The aim of the present study is to quantify the thermal artefacts in histological specimens obtained using a CO2 laser from different oral mucosal lesions and to evaluate if the resulting thermal effect hinders the histological examination. This aim is accomplished through quantitatively and qualitatively assessing the thermal effect in both the epithelium and connective tissue. MATERIAL AND METHODS: A super-pulsed CO2 laser (10,600 nm) was used to obtain 10 excision biopsy samples. The parameters were a power of 4.2 W in focused mode and a frequency of 80 Hz in super-pulse mode. The histological analysis was performed with an optical microscope. Computerized imaging software was utilized to quantitatively evaluate the thermal effect in both the epithelium and connective tissue expressed in microns. RESULTS: The thermal effect of the CO2 laser was limited to the surgical resection margins in all the specimens and did not hinder the histological analysis. Thermal artefacts were observed in 3 specimens. The range of thermal effects in the epithelial tissue was between 184 µm and 2,292 µm, while in the connective tissue it was between 133 µm and 2,958 µm. CONCLUSIONS: The resulting thermal effects of using a CO2 laser did not hamper the histological evaluation. Utilizing a laser in biopsy procedures should be tailored. Not only should laser parameters and safety margins be taken into consideration but also the working time, clinical accessibility, and the nature and water content of the tissue.

Making an informed choice: Which breast reconstruction type has the lowest complication rate?

INTRODUCTION: The aim of this study was to investigate long-term breast reconstruction outcomes at a single institution in order to offer data-driven counseling for patients. METHODS: A retrospective review was performed of 399 patients who underwent mastectomy with 1-stage implant-based breast reconstruction (IBBR), 2-stage IBBR, or autologous tissue reconstruction (ATR) for invasive breast cancer or ductal carcinoma in situ at our institution from 2010 to 2017. Complications were classified as major for any unplanned return to the operating room (OR). RESULTS: Overall complication rates were similar among 1-stage IBBR (59%), 2-stage IBBR (60%), and ATR (52%, p = 0.54). Factors independently associated with major complications were diabetes (OR = 25.4 95% CI: 3.2-202.4; p = 0.002), and 1-stage IBBR vs. ATR (1-stage: OR = 2.0 95% CI: 1.0-4.0; p = 0.04). Bilateral procedures were also at increased risk of major complications on univariate analysis (OR = 1.59 95% CI: 1.0-2.5; p = 0.04). CONCLUSIONS: Long-term breast reconstruction complication rates are higher than previously anticipated. Patients should be counseled that IBBR is associated with higher rates of complications, including unplanned return to the OR, compared to ATR.

Gingival Reactive Lesions in Orally Rehabilitated Patients by Free Revascularized Flap.

The aim is to discuss four cases of gingival reactive hyperplastic lesions in patients with a history of excision of oral neoplastic lesions and rehabilitation by a free revascularized flap of the iliac crest. One female and 3 male patients were referred due to the presence of exophytic lesions at the rehabilitated sites. The clinical examination revealed that the poor oral hygiene was the common trigger factor in all the cases, in addition to trauma from the upper left second molar in the first case, pericoronitis related to a partially erupted lower right third molar in the third case, and poor stability of an upper removable partial denture in the fourth case. All the cases were subjected to elimination of these suspected triggering factors, exclusion of dysplasia, excisional biopsy by CO2 laser, and five follow-up visits. The histological examination of all the cases confirmed the diagnosis of pyogenic granuloma. These presented cases suggest that the limitations in oral functions and maintaining the oral hygiene measures following the free revascularized flap reconstruction surgery probably played a role in the development of gingival reactive hyperplastic lesions with presence of trigger factors such as local trauma, chronic infection, or inadequate prosthesis.

A new gallium complex inhibits tumor cell invasion and matrix metalloproteinase MMP-14 expression and activity.

In this study, we investigated the effect of [N-(5-chloro-2-hydroxyphenyl)-l-aspartato] chlorogallate (GS2), a new water soluble gallium complex, on cell invasion and on the expression and activity of matrix metalloproteinases (MMPs) in human metastatic HT-1080 fibrosarcoma and MDA-MB 231 breast carcinoma cells. The effect on cell invasion was studied using a modified Boyden chamber coated with a type-I collagen. We analyzed the effect of GS2 on MMP-2, MMP-9, and MMP-14 via zymography and enzymatic assay using high affinity fluorogenic substrates. The expression of MMP mRNA was analyzed via qRT-PCR. GS2 induced a decrease in cell invasion. A dose-dependent inhibition effect was observed on the activities of MMP-2, MMP-9, and MMP-14 with the IC50 values of 168, 82, and 20 µM, respectively. A decrease in the expression of MMP-14 mRNA was observed in both cell lines, whereas the expression of MMP-2 and MMP-9 mRNA was decreased only in the MDA-MB231 cells. Data obtained for the expression of MMP-14 mRNA were confirmed via Western blotting. In fact, MMP-14 expression was decreased in the presence of GS2. Overall, these data show that GS2 is a promising compound for anti-invasive and anticancer therapy.

Technique and outcome of autotransplanting thyroid tissue after total thyroidectomy for simple multinodular goiters.

BACKGROUND/OBJECTIVE: Limited animal and human studies have shown function, albeit inadequate, of implanted thyroid tissue in muscles. This work aimed to ascertain results in a larger number of patients, finding practical method for implantation, studying the effect of changing weight of implant and effect of passage of time on its function. METHODS: Forty patients had total thyroidectomy for simple multinodular goiters. A piece of the excised gland was finely minced, mixed with saline as emulsion, and injected in thigh muscles. Twelve patients had 5-g implants, while 28 patients had 10-g implants. Four parameters were studied at 2 months, 6 months, and 12 months: technetium isotope uptake by the implant; thyroid stimulating hormone (TSH); free T3 (FT3); and free T4 (FT4). RESULTS: All autotransplanted thyroid tissue survived and functioned. After 12 months, mean values (± standard deviation) of isotope uptake, TSH, FT3, and FT4 of the 5-g implants were 0.44 ± 0.16%, 27.74 ± 30.4 UI/mL, 3.07 ± 1.10 pg/mL, and 1.01 ± 0.3 ng/dL, repectively. Those for the 10 g implants were 0.71 ± 0.20%, 22.78 ± 19.7 UI/mL, 3.92 ± 1.2 pg/mL, and 1.05 ± 0.3 ng/dL, repectively. Ten-gram implants showed significantly higher isotope uptake than 5-g. TSH, FT3, and FT4 significantly improved over the period of 1 year. CONCLUSION: Injection of thyroid tissue suspension is a simple method for thyroid autotransplantation. TSH was elevated in the majority to maintain normal or near normal thyroid hormones. Ten-gram implants showed higher isotope uptake than 5-g, although this difference was not reflected by thyroid hormone profile. The implant seemed to function better with the passage of time from 2 months to 12 months.

Negative Impact of Total Body Irradiation on the Antitumor Activity of Rhenium-(I)-diselenoether.

It has been shown that a rhenium-(I)-diselenoether complex had significant antitumor activity in MDA-MB231 tumor-bearing mice after repeated oral or intraperitoneal administrations for 4 weeks at safe doses of 10 mg/kg/day. It has also been suggested that lower doses could be as effective as this dose. We, thus, tested two doses (5 and 10 mg/kg). The drug was orally administered daily by gavage for 4 weeks and for a further 2 weeks with or without 15 mg/kg paclitaxel treatment (intravenously, once a week). This experiment was performed in MDA-MB 231 tumor-bearing mice, as a model of resistant breast tumor. However, in contrast to previous studies, the mice were pretreated with total body irradiation to increase the tumor growth. These two doses were safe, even in combination with paclitaxel. The expected tumor regression was not observed with the rhenium-(I)-diselenoether complex, and there was even a significant increase of the tumor volume in mice treated with 10 mg/kg versus controls. No synergism was observed with paclitaxel. We comment on the possible negative impact of radiotherapy on the antitumor activity of the drug. Plasma and tumor rhenium and selenium concentrations are also reported.

Dose Effect of Rhenium (I)-diselenoether as Anticancer Drug in Resistant Breast Tumor-bearing Mice After Repeated Administrations.

Rhenium (I)-diselenoether has shown promising antiproliferative efficacy in both in vitro and in vivo models. However, the maximal tolerated dose and dose-effect relationships have not been fully addressed for this compound. Here, we evaluated the tolerance and efficacy of three dose-levels (namely 10, 40 and 100 mg/kg) intraperitoneally administered daily over 28 days in mice bearing the resistant MDA-MB231 breast cancer cell line. The upper dose was found to be toxic and was reduced to 60 mg/kg. The 10 mg/kg dose well tolerated, whereas 40 mg/kg was associated with 10% mortality (LD10). Both 10 and 40 mg/kg dosing achieved a significantly similar regression of tumor growth compared with untreated animals. This study suggests that 10 mg/kg daily is the recommended dose for rhenium (I) diselenoether.

Biological study of the effect of water soluble [N-(2-hydroxybenzyl)-L-aspartato] gallium complexes on breast carcinoma and fibrosarcoma cells.

Two water soluble gallium complexes described as [Ga(III)LCl], where L is the deprotonated form of N-2-hydroxybenzyl aspartic acid derivatives, were synthesized and characterized by (1)H NMR, (13)C NMR, FT-IR, mass spectrometry, and elemental analysis. The 2-(5-chloro-2-hydroxybenzylamino)succinic acid derivative (GS2) has been found to be a promising anticancer drug candidate. This compound was found to be more cytotoxic against human breast carcinoma MDA-MB231 and fibrosarcoma HT-1080 cell lines than the unsubstituted derivative and GaCl3. GS2 was able to induce apoptosis through downregulation of AKT phosphorylation, G2M arrest in cell cycle, and caspase 3/7 pathway. This gallium complex was found to induce an increase in mitochondrial ROS level in HT-1080 cells but not in MDA-MB231 cells. This suggests that the mechanism of action of GS2 would not be mediated by the drug-induced oxidative stress but probably by directly and indirectly inhibiting the AKT cell-signaling pathway.