Yorkshire Cancer Research

About: Yorkshire Cancer Research is a nonprofit organization based out in Harrogate, United Kingdom. It is known for research contribution in the topics: Cancer & Bone disease. The organization has 131 authors who have published 122 publications receiving 11945 citations.

Prospective Identification of Tumorigenic Prostate Cancer Stem Cells

Abstract: Existing therapies for prostate cancer eradicates the bulk of cells within a tumor. However, most patients go on to develop androgen-independent disease that remains incurable by current treatment strategies. There is now increasing evidence in some malignancies that the tumor cells are organized as a hierarchy originating from rare stem cells that are responsible for maintaining the tumor. We report here the identification and characterization of a cancer stem cell population from human prostate tumors, which possess a significant capacity for self-renewal. These cells are also able to regenerate the phenotypically mixed populations of nonclonogenic cells, which express differentiated cell products, such as androgen receptor and prostatic acid phosphatase. The cancer stem cells have a CD44+/α2β1hi/CD133+ phenotype, and we have exploited these markers to isolate cells from a series of prostate tumors with differing Gleason grade and metastatic states. Approximately 0.1% of cells in any tumor expressed this phenotype, and there was no correlation between the number of CD44+/α2β1hi/CD133+ cells and tumor grade. The identification of a prostate cancer stem cell provides a powerful tool to investigate the tumorigenic process and to develop therapies targeted to the stem cell.

Skeletal complications of malignancy

Abstract: The skeleton is the most common organ to be affected by metastatic cancer, and tumors arising from the breast, prostate, thyroid, lung, and kidney possess a special propensity to spread to bone. Breast carcinoma, the most prevalent malignancy, causes the greatest morbidity. Of great clinical importance is the observation that metastatic bone disease may remain confined to the skeleton. In these patients, the decline in quality of life and eventual death is due almost entirely to skeletal complications and their subsequent treatment. Bone pain is the most common complication of metastatic bone disease, resulting from structural damage, periosteal irritation, and nerve entrapment. Recent evidence suggests that pain caused by bone metastasis may also be related to the rate of bone resorption. Hypercalcemia occurs in 5-10% of all patients with advanced cancer but is most common in patients with breast carcinoma, multiple myeloma, and squamous carcinomas of the lung and other primary sites. Pathologic fractures are a relatively late complication of bone involvement. The clinical courses of breast and prostate carcinoma are relatively long, with a median survival of 2-3 years. For patients with breast carcinoma, good prognostic factors for survival after the development of bone metastases are good histologic grade, positive estrogen receptor status, bone disease at initial presentation, a long disease free interval, and increasing age. In addition, patients with disease that remains confined to the skeleton have a better prognosis than those with subsequent visceral involvement. For patients with prostate carcinoma, adverse prognostic features include poor performance status, involvement of the appendicular skeleton and visceral involvement, whereas for patients with multiple myeloma, the levels of serum beta2-microglobulin and lactate dehydrogenase and the immunologic phenotype are the most important factors. These prognostic factors may be useful in planning the rational use of bisphosphonates in the treatment of advanced cancer.

Zoledronic acid reduces skeletal-related events in patients with osteolytic metastases: A double-blind, randomized dose-response study

Abstract: BACKGROUND This study evaluated the dose–response relation for zoledronic acid, a new generation high potency bisphosphonate, given as a 5-minute infusion in patients with malignant osteolytic disease. METHODS Two-hundred eighty patients with osteolytic lesions due to metastatic breast carcinoma or multiple myeloma were randomized to double-blind treatment with either 0.4, 2.0, or 4.0 mg of zoledronic acid or 90 mg pamidronate. The primary efficacy endpoint was the proportion of patients receiving radiation to bone. Other skeletal-related events, bone mineral density (BMD), bone markers, Eastern Cooperative Oncology Group performance status, pain and analgesic scores, and safety also were evaluated. RESULTS Zoledronic acid at doses of 2.0 and 4.0 mg and pamidronate at a dose of 90 mg each significantly reduced the need for radiation therapy to bone (P < 0.05) in contrast with 0.4 mg zoledronic acid, which did not. Skeletal-related events of any kind, pathologic fractures, and hypercalcemia also occurred less frequently in patients treated with 2.0 or 4.0 mg zoledronic acid or pamidronate than with 0.4 mg zoledronic acid. Increases in lumbar spine BMD (6.2–9.6%) and decreases in the bone resorption marker N-telopeptide (range, −37.1 to −60.8%) were observed for all treatment groups. Skeletal pain, fatigue, nausea, vomiting, and headache were the most commonly reported adverse events. Adverse events were similar in nature and frequency with zoledronic acid and pamidronate. CONCLUSIONS A 5-minute infusion of 2.0–4.0 mg zoledronic acid was at least as effective as a 2-hour 90-mg pamidronate infusion in treatment of osteolytic metastases. A 0.4-mg dose of zoledronic acid was significantly less effective. Both zoledronic acid and pamidronate were well tolerated. Cancer 2001;91:1191–200. © 2001 American Cancer Society.

Predictive Value of Bone Resorption and Formation Markers in Cancer Patients With Bone Metastases Receiving the Bisphosphonate Zoledronic Acid

Abstract: Purpose Three large, randomized trials of patients with bone metastases recently demonstrated that zoledronic acid reduces the risk of skeletal-related events. These trials provide an opportunity for investigating the correlation between bone metabolism and clinical outcome during bisphosphonate therapy. Patients and Methods Urinary measurements of N-telopeptide (Ntx) and serum bone alkaline phosphatase (BAP) were obtained in 1,824 bisphosphonate-treated patients—1,462 with zoledronic acid (breast, 490; prostate, 411; myeloma, 210; non–small-cell lung, 183; other, 168) and 362 with pamidronate (breast, 254; myeloma, 108). This exploratory cohort analysis grouped patients by baseline and most recent levels of Ntx as low (< 50 nmol/mmol creatinine), moderate (50 to 99 nmol/mmol creatinine), or high (≥ 100 nmol/mmol creatinine), and BAP as low (< 146 U/L) or high (≥ 146 U/L). The relative risks for negative clinical outcomes were estimated for each group using multiple-event and Cox regression models with ti...