Ca2+-induced reactive oxygen species production promotes cytochrome c release from rat liver mitochondria via mitochondrial permeability transition (MPT)-dependent and MPT-independent mechanisms: role of cardiolipin.

Release of cytochrome c from mitochondria is considered a critical, early event in the induction of an apoptosis cascade that ultimately leads to programmed cell death. Mitochondrial Ca(2+) loading is a trigger for the release of cytochrome c, although the molecular mechanism underlying this effect is not fully clarified. This study tested the hypothesis that distinct Ca(2+) thresholds may induce cytochrome c release from rat liver mitochondria by membrane permeability transition (MPT)-dependent and independent mechanisms. The involvement of reactive oxygen species (ROS) and cardiolipin in the Ca(2+)-induced cytochrome c release was also investigated. Cytochrome c was quantitated by a new, very sensitive, and rapid reverse-phase high performance liquid chromatography method with a detection limit of 0.1 pmol/sample. We found that a low extramitochondrial Ca(2+) level (2 microM) promoted the release of approximately 13% of the total alamethicin releasable pool of cytochrome c from mitochondria. This release was not depending of MPT; it was mediated by Ca(2+)-induced ROS production and cardiolipin peroxidation and appears to involve the voltage-dependent anion channel. High extramitochondrial Ca(2+) level (20 microM) promoted approximately 45% of the total releasable pool of cytochrome c. This process was MPT-dependent and was also mediated by ROS and cardiolipin. It is suggested that distinct Ca(2+) levels may determine the mode and the amount of cytochrome c release from rat liver mitochondria. The data may help to clarify the molecular mechanism underlying the Ca(2+)-induced release of cytochrome c from rat liver mitochondria and the role played by ROS and cardiolipin in this process

Decrease in Mitochondrial Complex I Activity in Ischemic/Reperfused Rat Heart

Reactive oxygen species (ROS) are considered an important factor in ischemia/reperfusion injury to cardiac myocytes. Mitochondrial respiration is an important source of ROS production and hence a potential contributor to cardiac reperfusion injury. In this study, we have examined the effect of ischemia and ischemia followed by reperfusion of rat hearts on various parameters related to mitochondrial function, such as complex I activity, oxygen consumption, ROS production, and cardiolipin content. The activity of complex I was reduced by 25% and 48% in mitochondria isolated from ischemic and reperfused rat heart, respectively, compared with the controls. These changes in complex I activity were associated with parallel changes in state 3 respiration. The capacity of mitochondria to produce H 2 O 2 increased on reperfusion. The mitochondrial content of cardiolipin, which is required for optimal activity of complex I, decreased by 28% and 50% as function of ischemia and reperfusion, respectively. The lower complex I activity in mitochondria from reperfused rat heart could be completely restored to the level of normal heart by exogenous added cardiolipin. This effect of cardiolipin could not be replaced by other phospholipids nor by peroxidized cardiolipin. It is proposed that the defect in complex I activity in ischemic/reperfused rat heart could be ascribed to a ROS-induced cardiolipin damage. These findings may provide an explanation for some of the factors responsible for myocardial reperfusion injury

FEM analysis of RF breast ablation: Multiprobe versus cool-tip electrode

Background: Radio-frequency ablation (RFA) has recently received much attention as an effective minimally invasive strategy for the local treatment of tumors. The purpose of this study was to evaluate the efficacy of single-needle cool-tip RF breast ablation in terms of temperature distribution and duration of the procedure as compared to multiprobe RF breast ablation. Materials and Methods: Two different commercially available radiofrequency ablation needle electrodes were compared. Finite-element method (FEM) models were developed to simulate the thermoablation procedures. A series of ex vivo radiofrequency thermal lesions were induced to check the response of the FEM calculations. Results: Data obtained from FEM models and from ex vivo procedures showed that cool-tip RF breast ablation assures better performances than multiprobe RF breast ablation in terms of temperature distribution and duration of the procedure. Histopathological analysis of the cool-tip RF thermoablated specimens showed successful induction of coagulation necrosis in the thermoablated specimens. Conclusion: Data obtained from FEM models and from ex vivo procedures suggest that the proposed cool-tip RF breast ablation may kill more tumor cells in vivo with a single application than the multiprobe RF breast ablation

3–5 BI-RADs Microcalcifications: Correlation between MRI and Histological Findings

Purpose. To evaluate the correlation between MRI and histopathological findings in patients with mammographically detected 3–5 BI-RAD (Breast Imaging Reporting And Data Systems) microcalcifications and to allow a better surgical planning. Materials and Method. 62 female Patients (age 50 ± 12) with screening detected 3–5 BI-RAD microcalcifications underwent dynamic 3 T contrast-enhanced breast MRI. After 30-day (range 24–36 days) period, 55 Patients underwent biopsy using stereotactic vacuum-assisted biopsy (VAB), 5 Patients underwent stereotactic mammographically guided biopsy, and 2 Patients underwent MRI-guided VAB. Results. Microhistology examination demonstrated 36 malignant lesions and 26 benign lesions. The analysis of MRI findings identified 8 cases of MRI BI-RADS 5, 23 cases of MRI BI-RADS 4, 11 cases of MRI BI-RADS 3, 4 cases type A and 7 cases type B, and 20 cases of MRI BI-RADS 1-2. MRI sensitivity, specificity, positive predictive value, and negative predictive value were 88.8%, 76.9%, 84.2%, and 83.3%, respectively

The Combination of Immune Checkpoint Blockade with Tumor Vessel Normalization as a Promising Therapeutic Strategy for Breast Cancer: An Overview of Preclinical and Clinical Studies

Immune checkpoint inhibitors (ICIs) have a modest clinical activity when administered as monotherapy against breast cancer (BC), the most common malignancy in women. Novel combinatorial strategies are currently being investigated to overcome resistance to ICIs and promote antitumor immune responses in a greater proportion of BC patients. Recent studies have shown that the BC abnormal vasculature is associated with immune suppression in patients, and hampers both drug delivery and immune effector cell trafficking to tumor nests. Thus, strategies directed at normalizing (i.e., at remodeling and stabilizing) the immature, abnormal tumor vessels are receiving much attention. In particular, the combination of ICIs with tumor vessel normalizing agents is thought to hold great promise for the treatment of BC patients. Indeed, a compelling body of evidence indicates that the addition of low doses of antiangiogenic drugs to ICIs substantially improves antitumor immunity. In this review, we outline the impact that the reciprocal interactions occurring between tumor angiogenesis and immune cells have on the immune evasion and clinical progression of BC. In addition, we overview preclinical and clinical studies that are presently evaluating the therapeutic effectiveness of combining ICIs with antiangiogenic drugs in BC patients

Ultrasound-guided laser ablation after excisional vacuum-assisted breast biopsy for small malignant breast lesions: Preliminary results

Background: The purpose of this preliminary study is to evaluate the feasibility of the excisional ultrasound (US) guided vacuum-assisted breast biopsy (VAE), followed by US-guided Laser Interstitial Thermal Therapy (LITT) in the treatment of unifocal ductal breast carcinomas ≤ 1 cm and estimate the ablation rate analyzing the final histopathological results after subsequent surgical excision. Methods: In a single session 11 female patients with unifocal less than a centimeter breast cancer underwent 2 different minimally invasive percutaneous US-guided techniques: a VAE breast biopsy with an 8 G needle to remove the lesion and, immediately after, a LITT ablation in the biopsy site. Four weeks later, all patients underwent radiological follow-up. Afterward, a systematic surgery was performed, the ablation rate was calculated, and iconographic and histological features were correlated. Results: Average maximum diameter of the lesions was 7.6 mm (5-10 mm). No patient reported pain or discomfort during procedure. 1/11 patient (9.1%) reported an early minor complication (a small superficial skin burn). After surgical excision, the histopathological evaluation reported in 10/11 cases (90.9%) complete ablation of the target lesion. In only one case (9.1%) residual cancer was detected. The necrotic-hemorrhagic cavities showed a mean maximum diameter of 27.3 mm (20-35 mm). Conclusions: Laser ablation performed after excisional biopsy could be considered a valid alternative to surgical excision for the treatment of lesions ≤ 1 cm, if carried out by expert radiologists. The association of these minimally invasive percutaneous methods has proven to be reliable, fast, and safe with an ablation rate of 90.9% and excellent aesthetic results. RM and CESM are potentially able to quantifying treatment results and to follow-up the ablation effects

The Effect of coronavirus (COVID-19) on breast cancer teamwork: A multicentric survey

Background/Aim: Despite the large amount of clinical data available of Coronavirus-19 (COVID-19), not many studies have been conducted about the psychological toll on Health Care Workers (HCWs). Patients and Methods: In this multicentric descriptive study, surveys were distributed among 4 different Breast Cancer Centers (BCC). BCCs were distinguished according to COVID-19 tertiary care hospital (COVID/No-COVID) and district prevalence (DP) (High vs. Low). DASS-21 score, PSS score and demographic data (age, sex, work) were evaluated. Results: A total of 51 HCWs were analyzed in the study. Age, work and sex did not demonstrate statistically significant values. Statistically significant distribution was found between DASS-21-stress score and COVID/No-COVID (p=0.043). No difference was found in the remaining DASS-21 and PSS scores, dividing the HCWs according to COVID-19-hospital and DP. Conclusion: Working in a COVID-19-hospital represents a factor that negatively affects psychosocial wellbeing. However, DP seems not to affect the psychosocial well-being of BCC HCWs. During the outbreak, psychological support for low risk HCWs should be provided regardless DP

Possible adverse events in children treated by manual therapy: a review

BACKGROUND: Pediatric manual therapy is controversial within the medical community particularly with respect to adverse events. Pediatric manual therapy (Ped MT) is commonly used by a number of professions such as chiropractors, osteopaths and naturopaths for a variety of treatments in children. Ped MT interventions range from advice, light touch, massage, through to mobilisation and high velocity spinal manipulation. However, current evidence related to adverse events associated with Ped MT is not well understood. OBJECTIVE: To update the clinical research literature from the 2007 report by Vohra, Johnston, Cramer and Humphreys on possible adverse events in children treated by spinal manipulation. METHODS: A review of the clinical research literature from June 2004 until January 2010 as reported in MEDLINE, PubMed and PubMed Central for adverse events specifically related to the treatment of pediatric cases by manual therapy. RESULTS: Only three new clinical studies, one systematic review with meta-analysis and one evidence report were identified. Two clinical studies reported on chiropractic care and one on osteopathic spinal manipulation in children. The systematic review investigated all studies of adverse events and manual therapy and was not specific for pediatric patients. The evidence review focused on effectiveness of spinal manipulation in a variety of musculoskeletal conditions. No serious or catastrophic adverse events were reported in the clinical studies or systematic review. However for adults, it has been estimated that between 0.003% and 0.13% of manual therapy treatments may result in a serious adverse event. Although mild to moderate adverse events are common in adults, an accurate estimate from high quality pediatric studies is currently not available. CONCLUSIONS: There is currently insufficient research evidence related to adverse events and manual therapy. However, clinical studies and systematic reviews from adult patients undergoing manual therapy, particularly spinal manipulation report that mild to moderate adverse events are common and self limiting. However serious adverse events are rare and much less than for medication commonly prescribed for these problems. More high quality research specifically addressing adverse events and pediatric manual therapy is needed