A Cancer Care Ontario Consensus-Based Organizational Guideline for the Planning and Delivery of Spine Stereotactic Body Radiation Therapy Treatment in Ontario.

The proposed recommendations are primarily based on the consensus opinion and in-field experience of the Ontario Health/Cancer Care Ontario stereotactic body radiation therapy (SBRT) for Spine Metastasis Guideline Development Group and published literature when available. Primary consideration was given to the perceived benefits for patients and the small likelihood of harm arising from recommendation implementation. Apart from the magnetic resonance imaging (MRI) follow-up strategy, all evidence was considered indirect and was provided by the working group in conjunction with their collective expertise in the field of SBRT.

Performance of the eHealth decision support tool, MIPOGG, for recognising children with Li-Fraumeni, DICER1, Constitutional mismatch repair deficiency and Gorlin syndromes.

Background: Cancer predisposition syndromes (CPSs) are responsible for at least 10% of cancer diagnoses in children and adolescents, most of which are not clinically recognised prior to cancer diagnosis. A variety of clinical screening guidelines are used in healthcare settings to help clinicians detect patients who have a higher likelihood of having a CPS. The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) is an electronic health decision support tool that uses algorithms to help clinicians determine if a child/adolescent diagnosed with cancer should be referred to genetics for a CPS evaluation.

Sensitivity of docetaxel-resistant MCF-7 breast cancer cells to microtubule-destabilizing agents including vinca alkaloids and colchicine-site binding agents.

Introduction: One of the main reasons for disease recurrence in the curative breast cancer treatment setting is the development of drug resistance. Microtubule targeted agents (MTAs) are among the most commonly used drugs for the treatment of breaset cancer and therefore overcoming taxane resistance is of primary clinical importance. Our group has previously demonstrated that the microtubule dynamics of docetaxel-resistant MCF-7TXT cells are insensitivity to docetaxel due to the distinct expression profiles of β-tubulin isotypes in addition to the high expression of p-glycoprotein (ABCB1).

Omitting radiation therapy after lumpectomy for pure DCIS does not reduce the risk of salvage mastectomy.

Purpose: Radiation therapy (RT) after breast-conserving surgery (BCS) for Ductal Carcinoma in Situ (DCIS) halves the risk of local recurrence (LR). The omission of RT is often supported by the paradigm that patients who develop LR can be salvaged with further breast-conserving therapy leading to higher rates of breast preservation and improved quality of life. However, population-based, long-term rates of breast preservation in women treated by upfront BCS ± RT are unknown.

Point-of-Care Ultrasound for Jugular Venous Pressure Assessment: Live and Online Learning Compared.

Introduction: Point-of-care ultrasound (POCUS) is a novel technique for the assessment of jugular venous pressure. Distance education may allow for efficient dissemination of this technique. We compared online learning to a live course for teaching ultrasonography jugular venous pressure (u-JVP) to determine if these teaching methods yielded different levels of comfort with and use of u-JVP.

The effects of electromagnetic fields on B16-BL6 cells are dependent on their spatial and temporal character.

Exposure to low intensity, low frequency electromagnetic fields (EMF) has effects on several biological systems. Spatiotemporal characteristics of these EMFs are critical. The effect of several complex EMF patterns on the proliferation of B16-BL6 mouse melanoma cells was tested.

PANCREOX: A Randomized Phase III Study of Fluorouracil/Leucovorin With or Without Oxaliplatin for Second-Line Advanced Pancreatic Cancer in Patients Who Have Received Gemcitabine-Based Chemotherapy.

Purpose The standard of care for second-line therapy in patients with advanced pancreatic cancer after gemcitabine-based therapy is not clearly defined. The CONKO-003 phase III study reported a survival benefit with second-line fluorouracil (FU) and oxaliplatin using the oxaliplatin, folinic acid, and FU (OFF) regimen. PANCREOX was a phase III multicenter trial to evaluate the benefit of FU and oxaliplatin administered as modified FOLFOX6 (mFOLFOX6; infusional fluorouracil, leucovorin, and oxaliplatin) versus infusional FU/leucovorin (LV) in this setting.

Close or positive resection margins are not associated with an increased risk of chest wall recurrence in women with DCIS treated by mastectomy: a population-based analysis.

Mastectomy is effective treatment for ductal carcinoma in situ (DCIS) but some women will develop chest wall recurrence. Most chest wall recurrences that develop after mastectomy are invasive cancer and are associated with poorer prognosis. Past studies have been unable to identify factors predictive of chest wall recurrence.

Long-term outcomes of hypofractionation versus conventional radiation therapy after breast-conserving surgery for ductal carcinoma in situ of the breast.

Purpose: Whole-breast radiation therapy (XRT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) may decrease the risk of local recurrence, but the optimal dose regimen remains unclear. Past studies administered 50 Gy in 25 fractions (conventional); however, treatment pattern studies report that hypofractionated (HF) regimens (42.4 Gy in 16 fractions) are frequently used.

Effect of orbital decompression on diplopia in thyroid-related orbitopathy.

Purpose: To determine the incidence of new-onset diplopia and evolution of preexisting diplopia in patients with thyroid-related orbitopathy undergoing orbital decompression surgery.

Methods: A retrospective chart review was conducted of patients who had undergone orbital decompression for thyroid-related orbitopathy between 1999 and 2008 in one of the authors' practice (D.J.

Incorporating CanMEDS and subspecialty training into paediatric residency programs: Why are we still deficient?

Background: The Royal College of Physician and Surgeons of Canada mandates that paediatric training programs in Canada incorporate subspecialty training and the teaching and evaluation of the seven CanMEDS roles into their curriculum. The literature suggests that newly practicing paediatricians feel inadequately prepared in many subspecialties and CanMEDS roles.

Hypothesis: That either current training programs underestimate the importance of these areas for future practice, or that residents themselves feel that these areas are less important.

Concise review: immunomodulatory properties of mesenchymal stem cells in cellular transplantation: update, controversies, and unknowns.

Stem cell transplantation is a promising approach for improving cardiac function after severe myocardial damage, for which the use of autologous donor cells has been preferred to avoid immune rejection. Recently, however, rodent as well as human mesenchymal stem cells have been reported to be uniquely immune-tolerant, in both in vitro and in vivo transplant models. In this review, we explore in detail the current understanding of the underlying immunologic mechanisms, which can facilitate the use of such cells as "universal donor cells" with fascinating clinical implications.

Downregulating activated epidermal growth factor receptor has no effect on RBM5 expression.

Background: We were interested in determining how the tumor suppressor gene RBM5 is regulated in lung cancers. Previous studies suggested that the gene expression is related to histological subtype and smoking exposure, since in small cell lung cancers the RBM5 gene is deleted whereas in non-small cell lung carcinomas (NSCLC) RBM5 expression is reduced. Of particular interest was the recent finding that in lung adenocarcinomas, a histological subtype of NSCLC, smoking exposure correlated with mutational activity in the transforming growth factor alpha (TGF-a) signaling pathway.

Phase ii trial of a metronomic schedule of docetaxel and capecitabine with concurrent celecoxib in patients with prior anthracycline exposure for metastatic breast cancer.

Background: This phase ii clinical trial examined the activity of a metronomic dosing schedule of docetaxel and capecitabine chemotherapy in patients with advanced breast cancer. Patients also received daily oral celecoxib in an effort to improve outcome measures and to ameliorate some of the common side effects of chemotherapy.

Methods: Patients received docetaxel at a starting dose of 15 mg/m² weekly, oral capecitabine 1250 mg/m² once daily, and oral celecoxib 200 mg twice daily.

Alterations in tumor necrosis factor signaling pathways are associated with cytotoxicity and resistance to taxanes: a study in isogenic resistant tumor cells.

Introduction: The taxanes paclitaxel and docetaxel are widely used in the treatment of breast, ovarian, and other cancers. Although their cytotoxicity has been attributed to cell-cycle arrest through stabilization of microtubules, the mechanisms by which tumor cells die remains unclear. Paclitaxel has been shown to induce soluble tumor necrosis factor alpha (sTNF-α) production in macrophages, but the involvement of TNF production in taxane cytotoxicity or resistance in tumor cells has not been established.

The effect of ABCB1 genetic variants on chemotherapy response in HIV and cancer treatment.

Despite their clearly distinct pathophysiologies, HIV and cancer are diseases whose response to chemotherapy treatment varies substantially amongst patients, in particular for those with prior drug exposure. This has been attributed, in part, to elevated expression of the ABCB1 drug transporter in some patients, which results in reduced drug accumulation in target tissues. Many mechanisms have been identified for this elevated expression of ABCB1, including variations in the sequence of the gene coding for the transporter (ABCB1).

Single nucleotide polymorphisms in CHRNA5 rs16969968, CHRNA3 rs578776, and LOC123688 rs8034191 are associated with heaviness of smoking in women in Northeastern Ontario, Canada.

Introduction: The development of nicotine dependence (ND) is an important final step in the development of nicotine addiction, is associated with substantial morbidity and mortality, and makes long-term smoking cessation difficult.

Methods: We used questionnaire data and DNA from buccal swabs previously collected from a population-based case-control study in Northeastern Ontario, Canada; an area with high smoking and smoking-related disease rates. Women smokers were classified into heavy and light phenotypes, a proxy for ND, and we assessed the association between phenotype and single nucleotide polymorphisms (SNPs) that have been associated with increased or decreased risk of ND.

A nutrition referral priority rating system in an outpatient oncology centre.

Purpose: An oncology nutrition referral priority rating system (NRPRS) was developed and evaluated as a tool to classify patients into nutrition risk categories and allocate reasonable wait times.

Methods: A retrospective chart audit (n=112), patient focus groups (n=14), and a prospective chart audit (n=179) were conducted to refine the tool. Using the NRPRS, the dietitians assigned a priority rating from the information on the referral and then compared it with a second rating after the first visit.

Quinoline as a privileged scaffold in cancer drug discovery.

Quinoline (1-azanaphthalene) is a heterocyclic aromatic nitrogen compound characterized by a double-ring structure that contains a benzene ring fused to pyridine at two adjacent carbon atoms. Quinoline compounds are widely used as "parental" compounds to synthesize molecules with medical benefits, especially with anti-malarial and anti-microbial activities. Certain quinoline-based compounds also show effective anticancer activity.

Ablation of Akt2 induces autophagy through cell cycle arrest, the downregulation of p70S6K, and the deregulation of mitochondria in MDA-MB231 cells.

Background: Akt/PKB is a promising anticancer therapeutic target, since abnormally elevated Akt activity is directly correlated to tumor development, progression, poor prognosis and resistance to cancer therapies. Currently, the unique role of each Akt isoform and their relevance to human breast cancer are poorly understood.

Methodology/principal Findings: We previously found that Akt1, 2 and 3 are localized at specific subcellular compartments (the cytoplasm, mitochondria and nucleus, respectively), raising the possibility that each isoform may have unique functions and employ different regulation mechanisms.

Same partners, different dance: involvement of DNA replication proteins in centrosome regulation.

Genome replication is the most fundamental element of the continuity of life. In eukaryotes, DNA replication is regulated by an elegant network of many different protein factors to ensure the timely and accurate copying of their entire genome once per cell cycle. The replication factors include the maintenance (MCM) proteins, Cdt1, Cdc6, Cdc7, Cdc45, and geminin.

Proliferating cell nuclear antigen in the cytoplasm interacts with components of glycolysis and cancer.

Proliferating cell nuclear antigen (PCNA) is involved in a wide range of functions in the nucleus. However, a substantial amount of PCNA is also present in the cytoplasm, although their function is unknown. Here we show, through Far-Western blotting and mass spectrometry, that PCNA is associated with several cytoplasmic oncoproteins, including elongation factor, malate dehydrogenase, and peptidyl-prolyl isomerase.

Defining normal jugular venous pressure with ultrasonography.

Objective: Determination of jugular venous pressure (JVP) by physical examination (E-JVP) is unreliable. Measurement of JVP with ultrasonography (U-JVP) is easy to perform, but the normal range is unknown. The objective of this study was to determine the normal range for U-JVP.

Design and synthesis of chloroquine analogs with anti-breast cancer property.

A series of chloroquine (CQ) analogs were designed and synthesized in a repositioning approach to develop compounds with high anti-breast cancer property. The compounds were then examined for their antiproliferative effects on two human breast tumor cell lines and a matching non-cancer cell line. Although many of them showed substantial antiproliferative effects on breast cancer cells examined, two compounds, 7-chloro-N-(3-(4-(7-(trifluoromethyl)quinolin-4-yl)piperazin-1-yl)propyl)quinolin-4-amine (14) and {3-[4-(7-chloro-quinolin-4-yl)-piperazin-1-yl]-propyl}-(7-trifluoromethyl-quinolin-4-yl)-amine (26), emerged as the most active among this series.

Nucleotide excision repair polymorphisms and survival outcome for patients with metastatic breast cancer.

Purpose: Inter-individual variations in treatment efficacy may be influenced by polymorphisms in DNA repair genes. We investigated the association of 3 functional polymorphisms in the nucleotide excision repair (NER) pathway with survival outcome of 95 patients with metastatic breast cancer (MBC) treated with DNA-damaging chemotherapy.

Methods: ERCC1 8092 C/A, ERCC2 Asp312Asn and ERCC2 Lys751Gln were determined using Taqman-based genotyping assays.