The risk of central nervous system metastases after trastuzumab therapy in patients with breast carcinoma.

Background: Trastuzumab, which is a large monoclonal antibody that is efficacious in the treatment of patients with HER-2/neu-overexpressing, metastatic breast carcinoma, does not penetrate the blood-brain barrier and, thus, may allow the brain to become a sanctuary site for micrometastases. Few studies have compared the risk of central nervous system (CNS) metastases in patients treated with or without trastuzumab.

Methods: The authors conducted a retrospective cohort study that compared 264 patients who did not receive trastuzumab therapy with 79 patients who received trastuzumab therapy.

Radiation induced mucositis: co-ordinating a research agenda.

Aims: A one-day workshop was hosted by the Symptom Control Committee of the National Cancer Institute of Canada, Clinical Trials Group (NCIC-CTG), in conjunction with the October 2002 annual meeting of the Canadian Association of Radiation Oncologists in Toronto, Ontario. The primary intention of the workshop was to direct the future research agenda of the Symptom Control Committee. Large group presentations were held initially to review the contemporary research issues of four selected areas of interest: fatigue, brain metastasis, bone metastasis and radiation-induced mucositis.

The role of integrin-linked kinase (ILK) in cancer progression.

Integrin-linked kinase (ILK) is an intracellular protein, which interacts with the cytoplasmic domains of integrin beta and beta3 subunits. ILK is a 59 kDa protein containing a phosphoinositide phospholipid-binding domain flanked by an N-terminal ankyrin repeat domain and a C-terminal serine/threonine protein kinase domain. Genetic and biochemical evidence have established an essential role of ILK in connecting integrins to the actin cytoskeleton.

Flavopiridol in untreated or relapsed mantle-cell lymphoma: results of a phase II study of the National Cancer Institute of Canada Clinical Trials Group.

Purpose: To determine the response rate and toxicity of flavopiridol in patients with previously untreated or relapsed mantle-cell lymphoma.

Patients And Methods: Adult patients with previously untreated or in first or second relapse of previously responsive mantle-cell lymphoma were given flavopiridol 50 mg/m2/d by intravenous bolus for 3 consecutive days every 21 days with antidiarrheal prophylaxis. Flavopiridol was continued until disease progression, unacceptable toxicity, or stable disease for four cycles.

Efficacy of bisphosphonates in the management of skeletal complications of bone metastases and selection of clinical endpoints.

Bisphosphonates are the current standard of palliative care for patients with bone lesions from breast cancer and multiple myeloma. This article discusses the selection of endpoints and statistical methods used to assess clinical efficacy of bisphosphonate therapies in patients with bone metastases. Recent studies of pamidronate and zoledronic acid have set the standards for the design and conduct of multicenter, randomized, placebo-controlled trials to assess the clinical benefit of bisphosphonates in patients with bone metastases.

Nuclear localization of cyclin B1 regulates DNA damage-induced apoptosis.

Some cells undergo apoptosis in response to DNA damage, whereas others do not. To understand the biochemical pathways controlling this differential response, we have studied the intracellular localization of cyclin B1 in cell types sensitive or resistant to apoptosis induced by DNA damage. We found that cyclin B1 protein accumulates in the nucleus of cells that are sensitive to gamma radiation-induced apoptosis (thymocytes, lymphoid cell lines), but remains cytoplasmic in apoptosis-resistant cells (primary and transformed fibroblasts).

CCI-779 Wyeth.

Wyeth Research (formerly Wyeth-Ayerst Research) is developing the sirolimus (rapamycin) analog CCI-779 as a potential treatment for various cancers [320924]. By November 2001, phase III trials had been initiated [428972], [429576]. In October 2001, Raymond James predicted filing in 2003, with a potential launch in 2005 [426718].

Informing breast cancer patients about clinical trials: a randomized clinical trial of an educational booklet.

Background: To evaluate the impact of an educational booklet on women's knowledge of and willingness to participate in a randomized clinical trial of treatment for breast cancer.

Materials And Methods: Women undergoing surgery for newly diagnosed early stage breast cancer were randomized to receive, or not, an information booklet explaining the need for and manner in which randomized trials are conducted.

Results: Eighty-three women with newly diagnosed early stage breast cancer completed a questionnaire assessing attitudes to random clinical trials (RCTs) and were randomized to receive usual information treatment options provided from their oncologist, or the educational booklet in addition to usual information from their oncologist (42 usual information, 41 booklet).

Central venous catheters for infusion therapy in gastrointestinal cancer. A comparative study of tunnelled centrally placed catheters and peripherally inserted central catheters.

Protracted venous infusion of 5-fluorouracil (5-FU) is a common treatment for patients with gastrointestinal malignancy. A central venous access device is required for safe and effective drug delivery. This study uses a survival analysis to compare the useful life and treatment completion success of tunelled centrally placed catheters (TCPCs) and peripherally inserted central catheters (PICCs).

Chemical conjugation of a novel antibody-interleukin 2 immunoconjugate against c-erbB-2 product.

Objective: To develop a new chemical method to produce a monoclonal antibody (MoAb) 520C9/recombinant human interleukin 2 (rhIL-2) conjugate.

Methods: MoAb 520C9 reactive with the protooncogene c-erbB-2 product P185 was chemically conjugated with rhIL-2 by using a simple two-step method. First, the rhIL-2 was activated by Sulfosuccinimidyl 4-[N-maleimidomethyl] cyclohexane-1-carboxylate, a heterobifunctional linker, and N-succinimidyl s-acetylthioacetate was introduced onto 520C9.

Experimental verification of the effect of refractive index mismatch on the light fluence in a turbid medium.

Diffusion theory is often used to model the transport of light within tissue. It can be used to calculate the light fluence rate in tissue, for example, during photodynamic therapy, or to measure the absorption and scattering properties of tissue. For both of these applications, the influence of the interface between the tissue and the exterior medium on the fluence rate inside the tissue must be known in order to make accurate calculations.

alpha-, beta-, and gamma-Tubulin polymerization in response to DNA damage.

Microtubules provide structural support for a cell and play key roles in cell motility, mitosis, and meiosis. They are also the targets of several anticancer agents, indicating their importance in maintaining cell viability. We have investigated the possibility that alterations in microtubule structure and tubulin polymerization may be part of the cellular response to DNA damage.

In vitro induction of PDT resistance in HT29, HT1376 and SK-N-MC cells by various photosensitizers.

Our approach to examine the mechanism(s) of action for photodynamic therapy (PDT) has been via the generation of PDT-resistant cell lines. In this study we used three human cell lines, namely, human colon adenocarcinoma (HT29), human bladder carcinoma and human neuroblastoma. The three photosensitizers used were Photofrin, Nile Blue A and aluminum phthalocyanine tetrasulfonate.

Abundance of cyclin B1 regulates gamma-radiation-induced apoptosis.

gamma-Radiation is a potent inducer of apoptosis. There are multiple pathways regulating DNA damage-induced apoptosis, and we set out to identify novel mechanisms regulating gamma-radiation-induced apoptosis in hematopoietic cells. In this report, we present data implicating the cyclin B1 protein as a regulator of apoptotic fate following DNA damage.

Oral bisphosphonates: A review of clinical use in patients with bone metastases.

Background: This study was conducted to review the efficacy and safety of oral bisphosphonates for the treatment of bone metastases in cancer patients.

Methods: Available published clinical studies of oral bisphosphonates in bone metastases from 1980 to the present were identified through a MEDLINE search and from literature references. Data were reviewed for efficacy and safety, with an emphasis on double blind, placebo-controlled studies; clinically relevant endpoints; and appropriate study methodology.

p53 regulates a G2 checkpoint through cyclin B1.

The p53 tumor suppressor controls multiple cell cycle checkpoints regulating the mammalian response to DNA damage. To identify the mechanism by which p53 regulates G2, we have derived a human ovarian cell that undergoes p53-dependent G2 arrest at 32 degrees C. We have found that p53 prevents G2/M transition by decreasing intracellular levels of cyclin B1 protein and attenuating the activity of the cyclin B1 promoter.

Effect of recombinant human interleukin 2 on neutrophil adherence to endothelial cells in vitro.

Human neutrophils were demonstrated to possess interleukin-2 receptor (IL-2R) beta and gamma chains, not alpha chain and the binding of IL-2 to the IL-2R beta chain on neutrophils plays an important regulatory role in neutrophil functions. We have investigated in this study the hypothesis that recombinant human IL-2 (rhIL-2) can directly activate human neutrophils and increase their adherence to human umbilical vein endothelial cells (HUVEC). In an in vitro microtiter adherence assay, rhIL-2 significantly stimulated neutrophil adherence to HUVEC in a dose- and time-dependent manner, rhILI-2 concentration at 2000 u/ml and 2 hour incubation gave the best neutrophil stimulation.

Bone cell matrix promotes the adhesion of human prostatic carcinoma cells via the alpha 2 beta 1 integrin.

Prostatic carcinoma cells have a propensity to metastasize to bone, and we propose that this phenomenon may be promoted by the adhesion of metastatic cells to bone matrix. Bone matrix is produced by osteoblasts, and we have developed an in vitro model of bone matrix by isolating the substratum deposited by human osteoblast-like U2OS cells. The collagenous nature of this matrix was demonstrated by the incorporation of [3H]proline and its subsequent release by purified collagenase.

Good outcome associated with a standardized treatment protocol using selective postoperative radiation in patients with clinical stage I adenocarcinoma of the endometrium.

In 1982, a treatment protocol was instituted for the management of patients with clinical stage I adenocarcinoma of the endometrium. All pertinent historical, operative, and pathologic findings were reviewed by a multidisciplinary committee and 384 patients were prospectively assigned to either high- or low-risk categories. Patients were excluded from the study if they had clinically apparent extrauterine disease, clear cell or serous histologies, or microscopic ovarian metastasis.

Breast irradiation postlumpectomy: development and evaluation of a decision instrument.

Purpose: To develop an instrument to help clinicians inform patients about the benefits and risks of breast irradiation following lumpectomy and to help an informed patient decide whether she prefers this treatment.

Methods: A Decision Board consisting of written material and visual aids was developed. It provides the patient with detailed information about her choices (breast irradiation or not), outcomes (breast recurrence and survival), probability of those outcomes, and quality of life associated with treatment and outcome.

The value of endorectal ultrasonography in the follow-up of intracavitary radiation treated early rectal cancer.

In selected patients with early rectal cancer, intracavitary radiation is a successful treatment. Endorectal ultrasound has proved an accurate method for staging and selecting such cancers for treatment. The value of endorectal ultrasound in the follow-up of patients with intracavitary radiation has not been previously assessed.

Investigations of large vessel cooling during interstitial laser heating.

Interstitial laser heating of tissues is influenced by blood flow in the treatment region. Temperature gradients around large blood vessels may result in local underheating of tissues. A three-dimensional, time-dependent finite difference model of interstitial laser heating around large vessels is presented.