Molecular pharmacology of cancer therapy in human colorectal cancer by gene expression profiling.

Global gene expression profiling has potential for elucidating the complex cellular effects and mechanisms of action of novel targeted anticancer agents or existing chemotherapeutics for which the precise molecular mechanism of action may be unclear. In this study, decreased expression of genes required for RNA and protein synthesis, and for metabolism were detected in rectal cancer biopsies taken from patients during a 5-fluorouracil infusion. Our observations demonstrate that this approach is feasible and can detect responses that may have otherwise been missed by conventional methods.

Adnexal masses and pregnancy: a 12-year experience.

Objective: Our purpose was to describe pregnancy-associated adnexal masses in eastern North Carolina.

Study Design: A retrospective study was performed of 60 adnexal masses resected during pregnancy at a regional referral hospital from January 1990 to March 2002.

Results: Adnexal masses occurred in 0.

Twelve weeks of protracted venous infusion of fluorouracil (5-FU) is as effective as 6 months of bolus 5-FU and folinic acid as adjuvant treatment in colorectal cancer.

We performed a multicentre randomised trial to compare the efficacy and toxicity of 12 weeks of 5-fluorouracil (5-FU) delivered by protracted intravenous infusion (PVI 5-FU) against the standard bolus regimen of 5-FU and folinic acid (5-FU/FA) given for 6 months as adjuvant treatment in colorectal cancer. A total of 716 patients with curatively resected Dukes' B or C colorectal cancer were randomised to 5-FU/FA (5-FU 425 mg m(-2) i.v.

Adjuvant therapy in pancreatic cancer: historical and current perspectives.

The results from pancreatic ductal adenocarcinoma appear to be improving with increased resection rates and reduced postoperative mortality reported by specialist pancreatic cancer teams. Developments with medical oncological treatments have been difficult, however, due to the fundamentally aggressive biological nature of pancreatic cancer and its resistance to chemotherapy coupled with a relative dearth of randomised controlled trials. The European Study Group for Pancreatic Cancer (ESPAC)-1 trial recruited nearly 600 patients and is the largest trial in pancreatic cancer.

Results of a randomized study of preradiation chemotherapy versus radiotherapy alone for nonmetastatic medulloblastoma: The International Society of Paediatric Oncology/United Kingdom Children's Cancer Study Group PNET-3 Study.

Purpose: To determine whether preradiotherapy (RT) chemotherapy would improve outcome for Chang stage M0-1 medulloblastoma when compared with RT alone. Chemotherapy comprised vincristine 1.5 mg/m2 weekly for 10 weeks and four cycles of etoposide 100 mg/m2 daily for 3 days, and carboplatin 500 mg/m2 daily for 2 days alternating with cyclophosphamide 1.

Neoadjuvant systemic fluorouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer.

This study was designed to evaluate the benefits of neoadjuvant chemotherapy prior to chemoradiation and surgery in patients with locally advanced rectal cancer. Patients with previously untreated primary rectal cancer, reviewed in a multidisciplinary meeting and considered to have locally advanced disease on the basis of physical examination and imaging (MRI+CT n=30, CT alone n=6), were recruited. Patients received protracted venous infusion 5-FU (300 mg m(-2) day(-1) for 12 weeks) with mitomycin C (MMC) (7 mg m(-2) i.

Intestinal complications after chemotherapy for patients with unresected primary colorectal cancer and synchronous metastases.

Background: The role of palliative resection of the primary tumour in patients who present with metastatic colorectal cancer is unclear.

Aims: This study compared the incidence of major intestinal complications in such patients who received chemotherapy treatment with or without prior palliative resection of the primary tumour.

Patients: The incidence of intestinal obstruction, perforation, fistula formation, and gastrointestinal haemorrhage, and the requirement for abdominal radiotherapy in patients with metastatic colorectal cancer treated at a single institution over a 10 year period was determined.

A multicentre phase II trial of primary chemotherapy with cisplatin and protracted venous infusion 5-fluorouracil followed by chemoradiation in patients with carcinoma of the oesophagus.

Background: We undertook a multicentre phase II trial to evaluate the safety and efficacy of primary chemotherapy followed by chemoradiation for localised adenocarcinoma or squamous carcinoma of the oesophagus.

Patients And Methods: Chemotherapy comprised five 3-weekly cycles of cisplatin and protracted continuous infusion 5-fluorouracil, with conformally planned radiotherapy commencing at the start of the fifth cycle.

Results: The planned treatment programme was completed by 39 of 72 patients (54%), and a further 13% completed chemotherapy and proceeded to surgical oesophagectomy.

The role of posttransplantation maintenance chemotherapy in improving the outcome of autotransplantation in adult acute lymphoblastic leukemia.

Extending the principle of conventional acute lymphoblastic leukemia (ALL) therapy to transplantation, 77 adult patients receiving autografts in first remission after melphalan with or without total body irradiation were scheduled to receive 6-mercaptopurine (6MP), methotrexate (MTX), and vincristine-prednisone (VP) for 2 years after transplantation to reduce relapse. Seventy-one percent of patients received 6MP, 57% received MTX, and 38% received VP. Thirty patients had a relapse at 1.

Does donor-recipient ABO incompatibility protect against relapse after allogeneic bone marrow transplantation in first remission acute myeloid leukemia?

It is not known if donor-recipient ABO blood group incompatibility contributes to graft-versus-leukemia after allogeneic BMT. One hundred and nineteen patients with acute myeloid leukemia in first remission underwent non-T cell-depleted marrow allografts from HLA-identical siblings after TBI and cyclophosphamide (n = 72) or melphalan (n = 47). GVHD prophylaxis comprised cyclosporine alone or cyclosporine-methotrexate.

Effectiveness of installing overhead ceiling lifts. Reducing musculoskeletal injuries in an extended care hospital unit.

The effectiveness of replacing floor lifts with mechanical ceiling lifts was evaluated in the extended care unit of a British Columbia hospital. Sixty-five ceiling lifts were installed between April and August 1998. Injury data were abstracted from injury reports for all staff musculoskeletal injuries (MSI) occurring in the unit during a 3 year period prior to installation and a 1.

Accuracy of set-up of thoracic radiotherapy: prospective analysis of 24 patients treated with radiotherapy for lung cancer.

In thoracic radiotherapy, a number of factors hinder the use of portal films and electronic portal imaging devices for measuring field placement errors (FPEs). The aim of this study was to assess the accuracy of treatment set-up using simulator check films (SCFs) in radiotherapy for lung cancer. Prospective evaluation was performed on 24 patients.

Non-invasive methods of assessing angiogenesis and their value in predicting response to treatment in colorectal cancer.

Background: Tumour neoangiogenesis can be assessed non-invasively by measuring angiogenic cytokine concentrations in peripheral circulation and by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The aim of this study was to assess whether these methods can predict and monitor response to treatment in patients with rectal cancer treated with preoperative chemoradiotherapy.

Methods: Serum and plasma vascular endothelial growth factor levels were measured in 31 patients with T3/T4 rectal cancers before quantitating tumour permeability (ln Ktrans) by DCE-MRI.

A comparison of conformal and intensity-modulated techniques for oesophageal radiotherapy.

Background And Purpose: To investigate the potential of intensity-modulated radiotherapy (IMRT) to reduce lung irradiation in the treatment of oesophageal carcinoma with radical radiotherapy.

Materials And Methods: A treatment planning study was performed to compare two-phase conformal radiotherapy (CFRT) with IMRT in five patients. The CFRT plans consisted of anterior, posterior and bilateral posterior oblique fields, while the IMRT plans consisted of either nine equispaced fields (9F), or four fields (4F) with orientations equal to the CFRT plans.

Prognosis for papillary serous carcinoma of the endometrium after surgical staging.

Background: To investigate the pattern of failure and the prognosis following pathological staging for uterine papillary serous carcinoma (UPSC).

Patients And Methods: A retrospective review was conducted of 22 patients with UPSC, treated between 1989 and 1998 at a single institution. All patients were surgically staged.

What is the prevalence of symptomatic or asymptomatic femoral head osteonecrosis in patients previously treated with chemoradiation? A magnetic resonance study of anal cancer patients.

It is generally assumed that femoral head osteonecrosis (FHO) is a serious but rare complication of pelvic radiotherapy. A review of the literature carried out by the authors indicates a prevalence of 4/763 (95% confidence interval 0.1%-1.

Influence of a vac-fix immobilization device on the accuracy of patient positioning during routine breast radiotherapy.

Continued use of basic planning and treatment techniques, in contrast to the improved methods implemented at many other anatomical sites, has emphasized the need for improved breast dosimetry. Any future technique delivering a superior three-dimensional dose distribution will be of maximum benefit if set-up errors are minimized. To determine the influence of vacuum moulded bag (vac-fix) immobilization on routine breast radiotherapy, 17 patients received half their radiotherapy fractions using our standard breast board technique and half using a vac-fix device positioned on the breast board.

A patient with 17 primary tumours and a germ line mutation in TP53: tumour induction by adjuvant therapy?

We report the case history of a woman with a germ line mutation in the TP53 gene who developed 17 separate primary tumours. The incidence of new tumours rose steeply after adjuvant tamoxifen treatment for breast cancer and adjuvant vaginal vault radiotherapy for endometrial cancer. This increase could be due to cumulative genetic damage from environmental agents and the fact that the patient lived to the relatively late age of 60 years, or to a high inherent deleterious somatic mutation rate, which could represent the inability of cells from patients with TP53 mutations to repair therapy-induced genetic damage.

Gene therapy for carcinoma of the breast: Therapeutic genetic correction strategies.

Gene therapy is a therapeutic approach that is designed to correct specific molecular defects that contribute to the cause or progression of cancer. Genes that are mutated or deleted in cancers include the cancer susceptibility genes p53 and BRCA1. Because mutational inactivation of gene function is specific to tumor cells in these settings, cancer gene correction strategies may provide an opportunity for selective targeting without significant toxicity for normal nontumor cells.

Variation in size and position of the planning target volume in the transverse plane owing to respiratory movement during radiotherapy to the lung.

Movement of thoracic tumours with respiration poses a real dilemma in terms of the accuracy of delivering radical radiotherapy in patients with carcinoma of the lung. Movements in the craniocaudal direction have previously been described. This technical note describes ten patients planned for radical lung radiotherapy using CT.

Preclinical studies of a new generation retroviral vector for ovarian cancer BRCA1 gene therapy.

Objective: The aim of this study was to determine the preclinical stability, toxicity, and efficacy of a second-generation complement-resistant retroviral BRCA1 vector, MFG-BRCA1, for ovarian cancer gene therapy.

Methods: MFG-BRCA1 was packaged in human 293 renal cells and manufactured and tested under cGMP conditions and is allowed for use in humans by the Food and Drug Administration. Vector stability studies were performed in mice and human serum by PCR analysis.

A quantitative treatment planning study evaluating the potential of dose escalation in conformal radiotherapy of the oesophagus.

Background And Purpose: This study aims to evaluate the reduction in radiation dose to normal thoracic structures through the use of conformal radiotherapy techniques in the treatment of oesophageal cancer, and to quantify the resultant potential for dose escalation.

Materials And Methods: Three different CT-derived treatment plans were created and compared for each of ten patients. A two-phase treatment with conventional straight-edged fields and standard blocks (CV2), a two-phase conformal plan (CF2), and a three-phase conformal plan where the third phase was delivered to the gross tumour only (CF3), were considered for each patient.