Metastatic TNBC is closely associated with a fused mitochondrial morphology and a glycolytic and lipogenic metabolism.

Mitochondria modify their function and morphology to satisfy the bioenergetic demand of the cells. Cancer cells take advantage of these features to sustain their metabolic, proliferative, metastatic, and survival necessities. Understanding the morphological changes to mitochondria in the different grades of triple-negative breast cancer (TNBC) could help to design new treatments. Consequently, this research explored mitochondrial morphology and the gene expression of some proteins related to mitochondrial dynamics, as well as proteins associated with oxidative and non-oxidative metabolism in metastatic and non-metastatic TNBC. We found that mitochondrial morphology and metabolism are different in metastatic and non-metastatic TNBC. In metastatic TNBC, there is overexpression of genes related to mitochondrial dynamics, fatty-acid metabolism, and glycolysis. These features are accompanied by a fused mitochondrial morphology. By comparison, in non-metastatic TNBC, there is a stress-associated mitochondrial morphology with hyperfragmented mitochondria, accompanied by the upregulated expression of genes associated with the biogenesis of mitochondria; both of which are characteristics related to the higher production of reactive oxygen species observed in this cell line. These differences between metastatic and non-metastatic TNBC should provide a better understanding of metastasis and contribute to the development of improved specific and personalized therapies for TNBC.

3,7-Dimethylpentadecane: a Novel Sex Pheromone Component from Leucoptera sinuella (Lepidoptera: Lyonetiidae).

Leucoptera sinuella is a leaf-miner moth present in several regions in the world, which has been recently introduced into Chile. The larvae feed exclusively on the leaves of poplar and willow trees, and the damage caused by the feeding behavior poses a threat to the wood-producing industry. Besides, L. sinuella larvae invade nearby orchards for pupation, causing rejections in Chilean fresh fruit for export. Here we report the identification of the female-produced sex pheromone of L. sinuella as a first step towards the development of pheromone-based methods for pest management of this species. First, we analyzed hexane extracts of the abdominal glands of virgin females by gas chromatography coupled with mass spectrometry and identified the major compound in these extracts to be 3,7-dimethylpentadecane, while minor compounds in the extracts proved to be 3,7-dimethyltetradecane and 7-methylpentadecane. Structure assignments were carried out by comparison of retention times and mass spectra of the natural products with those of authentic reference samples. Second, we conducted field tests, which showed that traps baited with synthetic 3,7-dimethylpentadecane were significantly attractive to males in a dose-dependent response. Our results also showed that a mixture of 3,7-dimethylpentadecane, 3,7-dimethyltetradecane, and 7-methylpentadecane in proportions similar to those found in gland extracts was the most attractive lure.

CyberKnife Stereotactic Radiosurgery in brain metastases: A report from Latin America with literature review.

BACKGROUND AND AIM: Stereotactic radiosurgery is increasingly being employed for the treatment of brain metastases, both as an adjuvant to surgical resection, and also as a primary treatment modality. The aim of this study is to evaluate overall survival and local control in patients with brain metastases treated with CyberKnife Stereotactic Radiosurgery (CKRS), due to the lack of evidence reported in Latin America. MATERIALS AND METHODS: We performed a retrospective chart review from October 2011 to January 2017 of 49 patients with 152 brain metastases. Clinical and prognostic factors were further analyzed by independent analysis. Kaplan-Meier curves were constructed for overall survival and local control. The median follow-up period was 12 months (range, 1-37 months). RESULTS: The median age was 61 years (range, 27-85 years) and Karnofsky performance status >70 in 96% of the patients. The median overall survival rate was 15.5 months (95% confidence interval [CI], 10.23-24.3 months). Overall 3-month, 6-month and 1-year local control rates were 98% (95% CI, 85-99%), 96% (95% CI, 82-99%), and 90% (94% IC, 76-96%), respectively. Local failure (LF) was observed in 6 patients (18 lesions). No late complications, such as radiation necrosis, were observed during the follow-up period. CONCLUSIONS: CKRS achieves excellent overall survival and local control rates with low toxicity in patients with brain metastases.

Cyberknife stereotactic radiosurgery and denosumab for giant cell tumour of the skull base: Case report.

Giant cell tumours (GCT) of the skull is a rare entity with only small number of cases reported in literature and optimal treatment is yet to be determined. These tumours have shown high recurrence rates after incomplete surgery, usually occurring during the first year. Even with new surgical techniques a complete resection in skull base tumours is not always possible without functional compromise. Therefore, adjuvant therapy is essential to enhance local control and quality of life. We report a rare case of a 34-year-old male with giant cell tumour (GCT) of the skull base involving the petrous bone, clivus and sphenoid body. The patient received Cyberknife stereotactic radiosurgery (CK SRS) and denosumab after surgery. This combined therapy allowed local control and tumour reduction with secondary neurological improvement during a 4-year follow up.

Glucolipotoxicity-induced Oxidative Stress is Related to Mitochondrial Dysfunction and Apoptosis of Pancreatic ß-cell.

Glucolipotoxicity-induced oxidative stress and mitochondrial dysfunction of pancreatic ß-cells are some of the mechanisms that have been related to the low insulin secretion and cell death during diabetes development. In early or non-chronic stages, the pancreatic ß-cells respond to hyperglycemia or hyperlipidemia, stimulating insulin secretion. However, the chronic effect of both leads to glucolipotoxicity, which induces constant overstimulation of pancreatic ß-cells, a condition that leads to cell death by apoptosis. The mechanism described, at this moment, is the accelerated mitochondrial dysfunction triggered by the high production of reactive oxygen species (ROS) due to excess nutrients. At first, mitochondria respond to over-nutrition accelerating oxygen consumption and consequently increasing the ATP synthesis. A permanent increase of ATP/ADP ratio leads to a constant inhibition of K+ ATP-channel and, therefore, a continuous insulin secretion accompanied by an increase in ROS. Finally, ROS accumulation compromises mitochondrial function due to the uncontrolled oxidation of proteins, lipids, and DNA generating functional alterations such as a drop of membrane potential, deregulation of mitochondrial dynamics, low rate of ATP synthesis and consequently the cell death. This review aims to describe the effect of glucolipotoxicity- induced oxidative stress and its relationship with mitochondrial dysfunction in ß-cell during type 2 diabetes development.

A single session of physical activity restores the mitochondrial organization disrupted by obesity in skeletal muscle fibers.

BACKGROUND: Several studies have proved that physical activity (PA) regulates energetic metabolism associated with mitochondrial dynamics through AMPK activation in healthy subjects. Obesity, a condition that induces oxidative stress, mitochondrial dysfunction, and low AMPK activity leads to mitochondrial fragmentation. However, few studies describe the effect of PA on mitochondrial dynamics regulation in obesity. AIM: The present study aimed to evaluate the effect of a single session of PA on mitochondrial dynamics regulation as well as its effect on mitochondrial function and organization in skeletal muscles of obese rats (Zucker fa/fa). MAIN METHODS: Male Zucker lean and Zucker fa/fa rats aged 12 to 13 weeks were divided into sedentary and subjected-to-PA (single session swimming) groups. Gastrocnemius muscle was dissected into isolated fibers, mitochondria, mRNA, and total proteins for their evaluation. KEY FINDINGS: The results showed that PA increased the Mfn-2 protein level in the lean and obese groups, whereas Drp1 levels decreased in the obese group. OMA1 protease levels increased in the lean group and decreased in the obese group. Additionally, AMPK analysis parameters (expression, protein level, and activity) did not increase in the obese group. These findings correlated with the partial restoration of mitochondrial function in the obese group, increasing the capacity to maintain the membrane potential after adding calcium as a stressor, and increasing the transversal organization level of the mitochondria analyzed in isolated fibers. SIGNIFICANCE: These results support the notion that obese rats subjected to PA maintain mitochondrial function through mitochondrial fusion activation by an AMPK-independent mechanism.

The 8-oxo-deoxyguanosine glycosylase increases its migration to mitochondria in compensated cardiac hypertrophy.

Cardiac hypertrophy is a compensatory mechanism maladapted because it presents an increase in the oxidative stress which could be associated with the development of the heart failure. A mechanism proposed is by mitochondrial DNA (mtDNA) oxidation, which evolved to a vicious cycle because of the synthesis of proteins encoded in the genome is committed. Therefore, the aim of the present work was to evaluate the mtDNA damage and enzyme repairing the 8-oxo-deoxyguanosine glycosylase mitochondrial isoform 1-2a (OGG1-2a) in the early stage of compensated cardiac hypertrophy induced by abdominal aortic constriction (AAC). Results showed that after 6 weeks of AAC, hearts presented a compensated hypertrophy (22%), with an increase in the cell volume (35%), mitochondrial mass (12%), and mitochondrial membrane potential (94%). However, the increase of oxidative stress did not affect mtDNA most probably because OGG1-2a was found to increase 3.2 times in the mitochondrial fraction. Besides, mitochondrial function was not altered by the cardiac hypertrophy condition but in vitro mitochondria from AAC heart showed an increased sensibility to stress induced by the high Ca2+ concentration. The increase in the oxidative stress in compensated cardiac hypertrophy induced the OGG1-2a migration to mitochondria to repair mtDNA oxidation, as a mechanism that allows maintaining the cardiac function in the compensatory stage.

Clinical benefits of femoroplasty: a nonsurgical alternative for the management of femoral metastases.

BACKGROUND: Bone metastases occur frequently in advanced cancer. The spine, pelvis, ribs, skull and femur are the most affected sites. It is reported that up to 83% of the patients develop pain at some point of the disease. The patient can also develop fractures and disability, particularly in the femur.. OBJECTIVES: To evaluate the effectiveness of percutaneous femoroplasty in patients with metastatic osseous disease located in the proximal femur (trochanter, neck, and femoral head). STUDY DESIGN: A retrospective clinical review, comparing pain status "before vs after" intervention. SETTING: National Cancer Institute in Mexico. METHODS: We included patients over 18 years old, with mild to severe pain due to metastasis in the proximal femur (trochanter, neck, or head), or with a high risk of fracture according to Mirels scale (> 8 points) or severe osteoporosis according to the World Health Organization (a Karnofsky score more than 50%). Exclusion criteria were femoral fracture. We recorded the following variables age, sex, type of neoplasm, concomitant therapy, We used the Karnofsky functionality scale, the VAS pain intensity assessment, the "Mayo Clinic" scale to measure improved functionality, and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative (EORTC QLQ-C15-PAL) (Spanish version) questionnaires. Follow-up was performed at 7 days, one month after femoroplasty, and during the individual outpatient that lasted one year on average. RESULTS: Eighty subjects were enrolled. Seventy-three percent were women. The most frequent tumors were breast (46.3%), followed by multiple myeloma (18.7%). All patients had a decrease in the intensity of pain, analgesic consumption, and improved quality of life, at 7 and 30 days after the intervention. There were no complications with serious consequences. Two participants experienced polymethylmetacrylate (PMMA) leakage, without clinical or functional impact. In 4 patients, the needle was occluded during the filling process and we had to place another biopsy needle through the same entry site to finish the injection process. LIMITATIONS: The sample was a single group of patients evaluated before and after the femoroplasty. We did not include a control group. CONCLUSION: The results of the current report suggest that femoroplasty, a percutaneous cement placement analogous to a vertebroplasty, might be a therapeutic option for patients with metastatic bone disease of the proximal femur, providing the patient an analgesic reduction and a better quality of life.