Long-term outcomes and effects of hypofractionated radiotherapy in microinvasive breast cancer: Analysis from a randomized trial.

Purpose: The natural history of microinvasive (T1mi) breast cancer is uncertain. The objective was to evaluate long-term local and distant recurrence rates following breast conserving surgery (BCS) in a prospective cohort of patients with T1mi compared to T1a-2 disease who received whole breast irradiation (WBI) in the context of a randomized trial of hypofractionation.

Methods: 1234 patients with T1-2 N0 breast cancer were randomized to receive adjuvant WBI of 42.

Management of Early-stage Hodgkin Lymphoma: A Practice Guideline.

In the past, treatment for patients with early-stage Hodgkin lymphoma consisted mainly of radiotherapy. Now, chemotherapy alone and chemoradiotherapy are treatment options. These guidelines aim to provide recommendations on the optimal management of early-stage Hodgkin lymphoma.

Regional Nodal Irradiation in Early-Stage Breast Cancer.

Background: Most women with breast cancer who undergo breast-conserving surgery receive whole-breast irradiation. We examined whether the addition of regional nodal irradiation to whole-breast irradiation improved outcomes.

Methods: We randomly assigned women with node-positive or high-risk node-negative breast cancer who were treated with breast-conserving surgery and adjuvant systemic therapy to undergo either whole-breast irradiation plus regional nodal irradiation (including internal mammary, supraclavicular, and axillary lymph nodes) (nodal-irradiation group) or whole-breast irradiation alone (control group).

Long-term results of radiation therapy oncology group 9903: a randomized phase 3 trial to assess the effect of erythropoietin on local-regional control in anemic patients treated with radiation therapy for squamous cell carcinoma of the head and neck.

Purpose: This paper reports long-term results of RTOG 9903, to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa).

Methods And Materials: The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation.

Radon.

Radon is a radioactive gas that emanates from uranium-bearing soil and porous rock. Although radon is most highly concentrated in areas of high uranium concentration, the presence of trace amounts of uranium in most ground sources means that all humans are exposed to radon to some degree. Radon migrates out of soil and rock into the surrounding air, resulting in accumulation in poorly ventilated or closed areas.

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.

The Akt isoforms are present at distinct subcellular locations.

Akt is involved in the regulation of diverse cellular functions such as cell proliferation, energy metabolism, and apoptosis. Although three Akt isoforms are known, the function of each isoform is poorly understood. To gain a better understanding of each Akt isoform, we examined the subcellular localization and expression of each isoform in transformed and nontransformed cells.

The efficacy and selectivity of tumor cell killing by Akt inhibitors are substantially increased by chloroquine.

This study was to evaluate the enhancement value of chloroquine (CQ) in cancer cell killing when used in combination with Akt inhibitors. The results showed that the combination of CQ and Akt inhibitors is much more effective than either one alone. Importantly, the CQ-mediated chemosensitization of cell killing effects by Akt inhibitors is cancer specific.

Method of detection of new contralateral primary breast cancer in younger versus older women.

Background: Surveillance for contralateral primary breast cancer after a diagnosis of unilateral breast cancer typically consists of yearly mammography and physical examinations at 3-6 month intervals. Mammography is known to be less sensitive in younger, dense breasts. It is unknown at this time how well mammography performs in young patients to detect a new contralateral primary breast cancer.

A comparative evaluation of two head and neck immobilization devices using electronic portal imaging.

A study was performed to compare the positioning reproducibility and the cost efficiency for two head and neck immobilization devices: the Uvex (Uvex Safety, Smithfield, USA) plastic mask system and the Finesse Frame with Ultraplast System (PLANET Medical, Svendborg, Denmark). 20 patients treated with 3D conformal radiation therapy for head and neck cancers were randomly selected (10 for each of the two different immobilization systems) and electronic portal images acquired during their course of treatment were saved and used in this study. The anatomical landmark coordinates and their shifts in the anteroposterior (AP) and craniocaudal (CC) directions with respect to the digitized simulator films for lateral fields were analysed using an in-house developed portal image registration system.

Scanning mutagenesis studies reveal multiple distinct regions within the human protein kinase C alpha regulatory domain important for phorbol ester-dependent activation of the enzyme.

While phorbol ester-binding sites within protein kinase C alpha (PKCalpha) have been identified and characterized utilizing fragments of the enzyme, it remains unclear whether additional regions within the enzyme may play an important role in its ability to be activated by phorbol ester. To examine this hypothesis, we generated 20 glutathione-S-transferase-tagged, V1-deficient, human PKCalpha holoenzyme constructs in which tandem six or 12 amino acid residue stretches along the full regulatory domain were changed to alanine residues. Each protein was assessed for its ability to bind phorbol ester and to induce growth repression when its catalytic activity was activated by phorbol ester upon expression in yeast cells.

High levels of Cdc7 and Dbf4 proteins can arrest cell-cycle progression.

Cdc7-Dbf4 serine/threonine kinase is essential for initiation of DNA replication. It was previously found that overexpression of certain replication proteins such as Cdc6 and Cdt1 in fission yeast resulted in multiple rounds of DNA replication in the absence of mitosis. Since this phenomenon is dependent upon the presence of wild-type Cdc7/Hsk1, we hypothesized that high levels of Cdc7 and/or Dbf4 could also cause multiple rounds of DNA replication, or could facilitate entry into S phase.

NFATc3 deficiency may contribute to the development of mammary gland adenocarcinoma in aging female mice.

The nuclear transcription factor of activated T cells (NFAT) suggested to be a tumor suppressor. Here we report that two out of three NFATc3-/- and two in four NFATc3 +/- female mice developed aggressive mammary adenocarcinoma by 12.5 and 16 mo of age, respectively, with no occurrences in age-matched wild-type littermates (N-14).

Chloroquine-mediated radiosensitization is due to the destabilization of the lysosomal membrane and subsequent induction of cell death by necrosis.

The anti-malarial drug chloroquine (CQ) is also thought to be a potential radiation sensitizer. To gain a better understanding of how the lysomotropic CQ can potentiate the effects of ionizing radiation, we investigated the effects of CQ on lysosomal and mitochondrial membrane stability, the subcellular localization of ceramide, plasma membrane permeability, and the mode of cell death in response to irradiation. We found that CQ accumulated in the lysosomes and thus lysosomal volumes increased.

Proliferating cell nuclear antigen (PCNA) may function as a double homotrimer complex in the mammalian cell.

The diverse function of proliferating cell nuclear antigen (PCNA) may be regulated by interactions with different protein partners. Interestingly, the binding sites for all known PCNA-associating proteins are on the outer surface or the C termini ("front") sides of the PCNA trimer. Using cell extracts and purified human PCNA protein, we show here that two PCNA homotrimers form a back-to-back doublet.

Quality assurance in radiotherapy: evaluation of errors and incidents recorded over a 10 year period.

Background And Purpose: To establish an incident reporting system to (1) record and classify incidents, (2) assess the impact of incidents on patients in terms of dose errors, and (3) evaluate the effectiveness of the quality assurance checking program implemented at the Radiation Treatment Program at the Northeastern Ontario Regional Cancer Centre (NEORCC).

Materials And Methods: An 'incident' is defined as an event or a series of events that has led to, or would have led to if undiscovered, dose errors to a patient undergoing radiation therapy treatment. The incidents reported between November 1992 and December 2002 were analyzed according to their source of error, stage of discovery and dose errors.

HSG cells differentiated by culture on extracellular matrix involves induction of S-adenosylmethione decarboxylase and ornithine decarboxylase.

The human salivary gland (HSG) epithelial cell line can differentiate when cultured on extracellular matrix preparations. We previously identified >30 genes upregulated by adhesion of HSG cells to extracellular matrix. In the current studies, we examined the role of one of these genes, the polyamine pathway biosynthetic enzyme S-adenosylmethionine decarboxylase (SAM-DC) and the related enzyme, ornithine decarboxylase (ODC), on HSG cell differentiation during culture on extracellular matrix.

RNA binding motif (RBM) proteins: a novel family of apoptosis modulators?

RBM5 is a known modulator of apoptosis, an RNA binding protein, and a putative tumor suppressor. Originally identified as LUCA-15, and subsequently as H37, it was designated "RBM" (for RNA Binding Motif) due to the presence of two RRM (RNA Recognition Motif) domains within the protein coding sequence. Recently, a number of proteins have been attributed with this same RBM designation, based on the presence of one or more RRM consensus sequences.

Medical history, sexual, and maturational factors and prostate cancer risk.

Purpose: Sexual, physical, and medical factors were investigated in a case-control study of prostate cancer.

Methods: This population-based study, conducted from 1995 to 1999 in northeastern Ontario, used cancer registry-identified cases (n=760), aged 45 to 84 years, diagnosed between 1995 and 1998. Age-frequency matched controls (n=1632) were obtained from telephone listings.

The Use of DNA Microarrays to Investigate the Pharmacogenomics of Drug Response in Living Systems.

With the advent of DNA microarray analysis, it is now possible to examine the response of virtually the entire human genome to cellular drug exposure and to uncover a wide variety of genes correlating with the establishment of drug resistance. This relatively new field of "pharmacogenomics" is likely to vastly increase our understanding of the mechanisms of drug action and how cells respond and adapt to drug exposure. However, DNA microarray studies typically result in the identification of hundreds of genes that may or may not be of relevance in vivo-particularly when large, genetically diverse study populations are used.

The characterization of a promising new optical source for use with a radiotherapy treatment simulator.

We report on an experimental examination of a new powerful optical source with potential application in radiotherapy treatment simulation. The illuminance, effective source position, and source size have been measured for this new source and, for comparison, for conventional sources on a simulator and a linear accelerator. This new source is considerably brighter than those in common use in radiotherapy.

Genetic instability of RBM5/LUCA-15/H37 in MCF-7 breast carcinoma sublines may affect susceptibility to apoptosis.

The MCF-7 human breast carcinoma cell line is widely used as a model system by breast cancer researchers and cell biologists investigating apoptosis. Since its establishment 30 years ago, from a patient with metastatic breast cancer, the original MCF-7 cell population has undergone genetic drift to such an extent that numerous genetically diverse sublines now exist. For instance, it has been reported that MCF-7 cells have lost the region 3p21.

LUCA-15/RBM5, a putative tumour suppressor, enhances multiple receptor-initiated death signals.

LUCA-15/RBM5 is a putative tumour suppressor. The gene encodes a number of alternative RNA splice variants with differing abilities to either enhance or suppress apoptosis, and it is likely that this ability to modulate apoptosis is central to the putative tumour suppressor activity of LUCA-15. This report demonstrates for the first time that expression from the LUCA-15 locus modulates apoptosis triggered by the death-inducing ligand TRAIL.

Evaluation of sICAM-1, sVCAM-1, and sE-Selectin levels in patients with metastatic breast cancer receiving high-dose chemotherapy.

Soluble forms of some cell adhesion molecules (CAM), sICAM-1, sVCAM-1, and sE-selectin, are elevated in the sera and plasma of patients with inflammation, arthritis, diabetes, and cancer. Increased levels of these soluble molecules in patients with cancer have been shown to correlate with disease progression and survival. This suggests that increased expression of the soluble forms of CAMs may play an important role in cancer cell growth and metastasis and may be prognostic and/or predictive of malignant disease.

Cross-resistance studies of isogenic drug-resistant breast tumor cell lines support recent clinical evidence suggesting that sensitivity to paclitaxel may be strongly compromised by prior doxorubicin exposure.

Less than half of breast cancer patients respond to second-line chemotherapy with paclitaxel after failing treatment with anthracyclines such as doxorubicin. A recent clinical trial by Paridaens et al. [J.