Molecular Targeting of the Phosphoinositide-3-Protein Kinase (PI3K) Pathway across Various Cancers.

The dysregulation of the phosphatidylinositol-3-kinase (PI3K) pathway can lead to uncontrolled cellular growth and tumorigenesis. Targeting PI3K and its downstream substrates has been shown to be effective in preclinical studies and phase III trials with the approval of several PI3K pathway inhibitors by the Food and Drug Administration (FDA) over the past decade. However, the limited clinical efficacy of these inhibitors, intolerable toxicities, and acquired resistances limit the clinical application of PI3K inhibitors.

A Perspective on Hormonal Contraception Usage in Central Nervous System Injury.

Naturally occurring life stages in women are associated with changes in the milieu of endogenous ovarian hormones. Women of childbearing age may be exposed to exogenous ovarian hormone(s) because of their use of varying combinations of estrogen and progesterone hormones-containing oral contraceptives (OC; also known as "the pill"). If women have central nervous system (CNS) injury such as spinal cord injury (SCI) and traumatic brain injury (TBI) during their childbearing age, they are likely to retain their reproductive capabilities and may use OC.

Multimodal magnetic resonance imaging after experimental moderate and severe traumatic brain injury: A longitudinal correlative assessment of structural and cerebral blood flow changes.

Traumatic brain injury (TBI) is a worldwide problem that results in death or disability for millions of people every year. Progressive neurological complications and long-term impairment can significantly disrupt quality of life. We demonstrated the feasibility of multiple magnetic resonance imaging (MRI) modalities to investigate and predict aberrant changes and progressive atrophy of gray and white matter tissue at several acute and chronic time points after moderate and severe parasagittal fluid percussion TBI.

Traumatic brain injury in women across lifespan.

Traumatic brain injury (TBI) is a leading cause of death and disability and a global public health challenge. Every year more than 50 million people suffer a TBI, and it is estimated that 50% of the global population will experience at least one TBI in their lifetime. TBI affects both men and women of all ages, however there is a male bias in TBI research as women have frequently been left out of the literature despite irrefutable evidence of male and female dimorphism in several posttraumatic measures.

BRE12-158: A Postneoadjuvant, Randomized Phase II Trial of Personalized Therapy Versus Treatment of Physician's Choice for Patients With Residual Triple-Negative Breast Cancer.

Purpose: Patients with triple-negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence with prior data suggesting improved outcomes with capecitabine. Targeted agents have demonstrated activity across multiple cancer types. BRE12-158 was a phase II, multicenter trial that randomly allocated patients with TNBC with residual disease after NAC to genomically directed therapy versus treatment of physician choice (TPC).

Determinants of pain interference and headache impact in patients who have chronic migraine with medication overuse: Results from the MOTS trial.

Objective: "Pain interference" and "headache impact" refer to negative consequences that pain and headache have on one's life. This study investigated determinants of these negative impacts in a large patient cohort who have chronic migraine with medication overuse.

Methods: Six hundred and eleven adults were enrolled from 34 headache, neurology, and primary care clinics.

Association of Circulating Tumor DNA and Circulating Tumor Cells After Neoadjuvant Chemotherapy With Disease Recurrence in Patients With Triple-Negative Breast Cancer: Preplanned Secondary Analysis of the BRE12-158 Randomized Clinical Trial.

Importance: A significant proportion of patients with early-stage triple-negative breast cancer (TNBC) are treated with neoadjuvant chemotherapy. Sequencing of circulating tumor DNA (ctDNA) after surgery, along with enumeration of circulating tumor cells (CTCs), may be used to detect minimal residual disease and assess which patients may experience disease recurrence.

Objective: To determine whether the presence of ctDNA and CTCs after neoadjuvant chemotherapy in patients with early-stage TNBC is independently associated with recurrence and clinical outcomes.

Mild Hyperthermia Aggravates Glucose Metabolic Consequences in Repetitive Concussion.

Traumatic brain injury (TBI) is one of the leading causes of mortality and disability around the world. Mild TBI (mTBI) makes up approximately 80% of reported cases and often results in transient psychological abnormalities and cognitive disruption. At-risk populations for mTBI include athletes and other active individuals who may sustain repetitive concussive injury during periods of exercise and exertion when core temperatures are elevated.

Neurotherapeutic capacity of P7C3 agents for the treatment of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a significant public health problem around the world. A promising area of research is the characterization of small, drug-like molecules that have potent clinical properties. One pharmacotherapeutic agent in particular, an aminopropyl carbazole called P7C3, was discovered using an in vivo screen to identify new agents that augmented the net magnitude of adult hippocampal neurogenesis.

No Decision Is Final: Career Planning and Career Transitions.

Several factors play a role in job selection after completion of a hematology/oncology training program, such as a fellows' overall career goals, expected income potential, and limitations imposed by visa status, among many others. Training programs play an integral role in mentoring trainees in career selection. For many, the first job is often not career-long.

Evaluation of weekly paclitaxel plus carboplatin followed by anthracycline chemotherapy on the neoadjuvant treatment of patients with triple-negative breast cancer.

Objective: To evaluate the effectiveness and tolerability of neoadjuvant chemotherapy with weekly paclitaxel in combination with weekly carboplatin area under curve 2 followed by anthracycline chemotherapy.

Patients And Methods: This is a retrospective review of electronic medical records of patients (N = 32) with stage 1c-III triple-negative breast cancer. Patients received neoadjuvant chemotherapy with paclitaxel 80 mg/m once per week for 12 weeks in combination with carboplatin area under curve 2 once per week for 12 weeks (wP + wCb), followed by a standard anthracycline regimen including either doxorubicin 60 mg/m and cyclophosphamide 600 mg/m every 2 or 3 weeks, or epirubicin 90 mg/m and cyclophosphamide 600 mg/m every 3 weeks for four cycles with myeloid growth factor support.

Synthesis and luminescence modulation of pyrazine-based gold(III) pincer complexes.

The first examples of pyrazine-based gold(III) pincer complexes are reported; their intense photoemissions can be modified by protonation, N-alkylation or metal ions, without the need for altering the ligand framework. Emissions shift from red (77 K) to blue (298 K) due to thermally activated delayed fluorescence (TADF).

Influence of the local application of sodium alendronate gel on osseointegration of titanium implants.

The aim of this study was to perform a comparative analysis of aspects of the osseointegration of titanium implants placed with and without the local application of a bisphosphonate agent, after 28 days in vivo. The study involved the placement of 50 commercially pure titanium implants in the middle third of the tibia of 10 rabbits, with the right tibia used as the control and the left as the test site. Sodium alendronate gel was applied locally in the test group and sterile saline solution in the control group.

Neural progenitor cell transplantation promotes neuroprotection, enhances hippocampal neurogenesis, and improves cognitive outcomes after traumatic brain injury.

Transplantation of neural progenitor cells (NPCs) may be a potential treatment strategy for traumatic brain injury (TBI) due to their intrinsic advantages, including the secretion of neurotrophins. Neurotrophins are critical for neuronal survival and repair, but their clinical use is limited. In this study, we hypothesized that pericontusional transplantation of NPCs genetically modified to secrete a synthetic, human multineurotrophin (MNTS1) would overcome some of the limitations of traditional neurotrophin therapy.

A phase II study of capecitabine plus docetaxel in gemcitabine-pretreated metastatic pancreatic cancer patients: CapTere.

Purpose: Docetaxel and capecitabine combination is synergistic in preclinical models. We investigated the efficacy and toxicity of this combination as second-line chemotherapy in patients with metastatic pancreatic adenocarcinoma (mPC), pretreated with gemcitabine-based chemotherapy.

Methods: Eligible patients were treated with capecitabine 800 mg/m(2) orally PO bid on days 1-14 in combination with intravenous docetaxel 30 mg/m(2) on days 1 and 8 of each 21-day cycle.

Neuroprotective efficacy of a proneurogenic compound after traumatic brain injury.

Traumatic brain injury (TBI) is characterized by histopathological damage and long-term sensorimotor and cognitive dysfunction. Recent studies have reported the discovery of the P7C3 class of aminopropyl carbazole agents with potent neuroprotective properties for both newborn neural precursor cells in the adult hippocampus and mature neurons in other regions of the central nervous system. This study tested, for the first time, whether the highly active P7C3-A20 compound would be neuroprotective, promote hippocampal neurogenesis, and improve functional outcomes after experimental TBI.

Diphosphonate immobilization on hydroxyapatite-coated titanium--method description.

Purpose: The aim of this study was to promote the immobilization of a bone activity biomodulator (diphosphonate) on titanium, commonly used in implant dentistry, to provide a local method of delivering this drug during the osseointegration process.

Methods: The implant material used in this study was commercially wrought titanium (Ticp), 99.9 mass%, grade II.

Planning cancer control in Latin America and the Caribbean.

Non-communicable diseases, including cancer, are overtaking infectious disease as the leading health-care threat in middle-income and low-income countries. Latin American and Caribbean countries are struggling to respond to increasing morbidity and death from advanced disease. Health ministries and health-care systems in these countries face many challenges caring for patients with advanced cancer: inadequate funding; inequitable distribution of resources and services; inadequate numbers, training, and distribution of health-care personnel and equipment; lack of adequate care for many populations based on socioeconomic, geographic, ethnic, and other factors; and current systems geared toward the needs of wealthy, urban minorities at a cost to the entire population.

Stiff person syndrome.

Recognizing stiff person syndrome is clinically important. It is uncommon, characterized by body stiffness associated with painful muscle spasms, and varies in location and severity. It is subdivided into stiff trunk versus stiff limb presentation, and as a progressive encephalomyelitis.

Midbrain raphe stimulation improves behavioral and anatomical recovery from fluid-percussion brain injury.

The midbrain median raphe (MR) and dorsal raphe (DR) nuclei were tested for their capacity to regulate recovery from traumatic brain injury (TBI). An implanted, wireless self-powered stimulator delivered intermittent 8-Hz pulse trains for 7 days to the rat's MR or DR, beginning 4-6 h after a moderate parasagittal (right) fluid-percussion injury. MR stimulation was also examined with a higher frequency (24 Hz) or a delayed start (7 days after injury).

Accelerated second-line or maintenance chemotherapy versus treatment at disease progression in NSCLC.

For many decades, the use of chemotherapy as second-line therapy in non-small-cell lung cancer relied upon disease progression. Several studies have shown that four to six cycles of chemotherapy administered as front-line therapy treatment offers a survival advantage to patients; however, further chemotherapy beyond this initial treatment was more associated with side effects and no benefit in survival. Until 2009, second-line treatment for lung cancer was well established for three therapeutic agents: docetaxel, pemetrexed and erlotinib.

Evaluation of tensile strength of different configurations of orthodontic retraction loops for obtaining optimized forces.

The aim of this study was to analyze the mechanical behavior of different orthodontic retraction loops. Two designs of orthodontic loops for closing space were analyzed: teardrop-shaped (T) and circle-shaped loop (C), of two different heights (6 and 8 mm), and two types of orthodontic wires (stainless steel - 0.19' x 0.

Gene expression profiling and non-small-cell lung cancer: where are we now?

Despite new developments in molecular techniques and better knowledge on lung cancer tumor biology, many genetic alterations associated with the development and progression of lung carcinogenesis still remain unclear. Although the development of targeted agents has improved response rates and survival, lung cancer has a very high mortality rate, even for early stages. Thus, there is a greater need for other mechanisms or technologies that may help us diagnose, predict, and treat patients with lung cancer in a more effective way.