Improved survival with lymph node sampling in Wilms tumor

We sought to determine the impact of number of lymph nodes examined on survival for Wilms tumor (WT). Data from the Surveillance, Epidemiology, and End Results and Florida Cancer Data System were queried for patients < 20 years of age with WT. Of 1805 WT patients, 1340 had lymph node (LN) data available following surgery. The mean age for the cohort was 3.3 ± 2.8 y. Most patients were White (78%), and non-Hispanic (78%). A total of 297 patients (22%) had 0 LN sampled, while 697 (52%) had 1–5 LN, 210 (16%) had 6–10 LN, and 136 (10%) had >10 LN. Overall 5-y survival was 91%. By univariate analysis, 5-y survival was significantly lower for patients with 0 LN sampled (87% versus 91% 1–5 LN; 93% 6–10 LN; 95% >10 LN, P = 0.005). Multivariate analysis confirmed a survival advantage for patients having 1–5 LN (HR 0.600, P = 0.016), 6–10 LN (HR 0.521, P = 0.048), and >10 LN (HR 0.403, P = 0.039) compared with patients with 0 LN examined. Failure to biopsy lymph nodes for WT patients not only increases the risk of local recurrence due to understaging and inadequate adjuvant therapy, but is also an independent prognostic indicator of lower survival

Lung carcinoma with hypertrophic osteoarthropathy in a teenager

Hypertrophic osteoarthropathy (HOA) characterised by arthralgia, clubbing and periosteal proliferation of long bones, is rarely encountered in children and adolescents. Whereas in adults over 80% of cases are associated with malignancy, in children the majority of cases are due to non-neoplastic causes such as cystic fibrosis, bilary atresia and congenital heart disease. Up to 5% of adults with lung cancer demonstrate signs of HOA. However, lung cancer is extremely uncommon in children and young people. Here we report a case of lung adenocarcinoma in an 18 year old male associated with HOA present both at diagnosis and at subsequent disease progression

In vitro synergistic cytoreductive effects of zoledronic acid and radiation on breast cancer cells

INTRODUCTION: Bisphosphonates are mostly used in the treatment of bone metastases. They have been shown to act synergistically with other chemotherapeutic agents. It is not known, however, whether similar synergistic effects exist with radiation on breast cancer cells. METHODS: Human MCF-7 breast cancer cells were treated with up to 100 μM zoledronic acid, were irradiated with up to 800 cGy or were exposed to combinations of both treatments to determine the antiproliferative effects of zoledronic acid and radiation. RESULTS: Zoledronic acid and radiation caused a dose-dependent and time-dependent decrease in cell viability (approximate 50% growth inhibition values were 48 μM and 20 μM for 24 hours and 72 hours, respectively, for zoledronic acid and 500 cGy for radiation). A synergistic cytotoxic effect of the combination of zoledronic acid and radiation was confirmed by isobologram analysis. CONCLUSION: These data constitute the first in vitro evidence for synergistic effects between zoledronic acid and radiation. This combination therapy might thus be expected to be more effective than either treatment alone in patients with metastatic breast carcinoma

Risks and benefits of bisphosphonates

Bone is the most common site for metastasis in cancer and is of particular clinical importance in breast and prostate cancers due to the prevalence of these diseases. Bone metastases result in considerable morbidity and complex demands on health care resources, affecting quality of life and independence over years rather than months. The bisphosphonates have been shown to reduce skeletal morbidity in multiple myeloma as well as a wide range of solid tumours affecting bone by 30–50%. Quite appropriately, these agents are increasingly used alongside anticancer treatments to prevent skeletal complications and relieve bone pain

Activation of BKCa Channels in Zoledronic Acid-Induced Apoptosis of MDA-MB-231 Breast Cancer Cells

BACKGROUND: Zoledronic acid, one of the most potent nitrogen-containing biphosphonates, has been demonstrated to have direct anti-tumor and anti-metastatic properties in breast cancer in vitro and in vivo. In particular, tumor-cell apoptosis has been recognized to play an important role in the treatment of metastatic breast cancer with zoledronic acid. However, the precise mechanisms remain less clear. In the present study, we investigated the specific role of large conductance Ca(2+)-activated potassium (BK(Ca)) channel in zoledronic acid-induced apoptosis of estrogen receptor (ER)-negative MDA-MB-231 breast cancer cells. METHODOLOGY/PRINCIPAL FINDINGS: The action of zoledronic acid on BK(Ca) channel was investigated by whole-cell and cell-attached patch clamp techniques. Cell apoptosis was assessed with immunocytochemistry, analysis of fragmented DNA by agarose gel electrophoresis, and flow cytometry assays. Cell proliferation was investigated by MTT test and immunocytochemistry. In addition, such findings were further confirmed with human embryonic kidney 293 (HEK293) cells which were transfected with functional BK(Ca) α-subunit (hSloα). Our results clearly indicated that zoledronic acid directly increased the activities of BK(Ca) channels, and then activation of BK(Ca) channel by zoledronic acid contributed to induce apoptosis in MDA-MB-231 cells. The possible mechanisms were associated with the elevated level of intracellular Ca(2+) and a concomitant depolarization of mitochondrial membrane potential (Δψm) in MDA-MB-231 cells. CONCLUSIONS: Activation of BK(Ca) channel was here shown to be a novel molecular pathway involved in zoledronic acid-induced apoptosis of MDA-MB-231 cells in vitro