germanium and Breast-Neoplasms

The formation of premetastatic niches creates a fertile environment for the seeding of disseminated cancer cells in selected secondary organs. This is crucial for the development of metastasis in various malignancies, including breast cancer (BC). We previously reported that the loss of FBXW7 in bone marrow-derived stromal cells promoted cancer metastasis by increasing the production of the chemokine CCL2, which attracts myeloid-derived suppressor cells and macrophages to the premetastatic niche. Furthermore, treatment with the CCL2 inhibitor propagermanium (PG), which has been used in Japan as a therapeutic agent against chronic hepatitis B, was shown to block the enhancement of metastasis in FBXW7-deficient mice through inhibiting the formation of premetastatic niches. Here, we describe a phase I dose-escalation study of PG used as an antimetastatic drug for perioperative patients with primary BC. The primary end-point was the percentage of patients who experience dose-limiting toxicity. Twelve patients were enrolled in the study. Dose-limiting toxicity was not observed, and the maximum dose was determined to be 90 mg/body/day. The serum concentrations of PG were nearly within the normal range in all observation days. We observed an inverse correlation between FBXW7 mRNA levels in blood and the serum concentrations of CCL2 and interleukin (IL)-6, in agreement with our previous mouse model. Also, IL-6 was downregulated in a PG dose-dependent manner, as observed in mice. Thus, PG was given safely and it is expected to have antimetastatic potential in BC. This trial is registered in the UMIN Clinical Trials Registry as UMIN000022494.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Chemokine CCL2; F-Box-WD Repeat-Containing Protein 7; Female; Germanium; Humans; Interleukin-6; Japan; Macrophages; Middle Aged; Myeloid-Derived Suppressor Cells; Organometallic Compounds; Propionates; RNA, Messenger; Signal Transduction; Young Adult

Estrogen receptor is an attractive target for the diagnosis and treatment of breast cancer. This article reports for the first time a dual-modality imaging agent targeting estrogen receptor that can use PET imaging to diagnose breast cancer and utilize fluorescence imaging to achieve intraoperative navigation. Fluorescence experiments show that [

Topics: Breast Neoplasms; Female; Germanium; Humans; Isotope Labeling; MCF-7 Cells; Molecular Conformation; Optical Imaging; Positron-Emission Tomography; Radiopharmaceuticals; Receptors, Estrogen

This study evaluated lesion mislocalization between PET and CT on PET/CT studies when CT instead of germanium is used for attenuation correction (AC).. PET/CT scans were obtained for 300 clinical patients. Both CT and germanium scans were used to correct PET emission data. Cases were noted of suspected inaccurate localization of lesions on any of the 5 sets of images (PET using germanium AC [GeAC] fused and not fused with CT, PET using CT AC fused and not fused with CT, and PET with no AC [NAC]). Independent CT or MRI was used to determine true lesion locations.. Six of 300 patients (2%) had lesion mislocalization when CT was used for AC or fusion. True liver dome lesions were mislocalized to the right lung base on PET/CT, likely because of a respiratory motion difference between PET and CT. No mislocalization was present on NAC PET or non-CT-fused GeAC PET images.. Serious lesion mislocalization on PET/CT studies may occur, albeit very infrequently, when CT is used for either AC or fusion.

Topics: Adult; Aged; Breast Neoplasms; Colonic Neoplasms; Diagnostic Errors; False Negative Reactions; False Positive Reactions; Female; Fluorodeoxyglucose F18; Germanium; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasms; Radioisotopes; Radiopharmaceuticals; Rectal Neoplasms; Reproducibility of Results; Retrospective Studies; Sensitivity and Specificity; Subtraction Technique; Tomography, Emission-Computed; Tomography, X-Ray Computed

Compton (incoherently) scattered photons which are directly proportional to the electron density of the scatterer, have been employed in characterising human breast tissues. Gamma ray photons scattered incoherently from normal and pathological breast tissue samples of nine breast cancer patients were measured using a high purity germanium detector and an americium (Am-241) source. The breast tissue samples were obtained from female patients undergoing mastectomy. The samples were examined in freeze dried form and the results were corrected for the reduction in the water content of each tissue type by use of the Mixture Rule. This study is aimed at providing electron density information in support of the introduction of new tissue substitute materials for mammography phantoms.

Topics: Americium; Breast; Breast Neoplasms; Electrons; Female; Gamma Rays; Germanium; Humans; Mastectomy; Photons; Radiography; Reproducibility of Results; Scattering, Radiation

The case history is described of a woman aged 57 years with renal, hepatic and muscular damage attributed to intake of germanium lactate-citrate (a cumulative dose of 32.1 g germanium) over at least one year, as alternative treatment of metastatic breast cancer. Histological examination of biopsies showed highly vacuolated cytoplasm of the epithelial cells of the distal renal tubules and micro- and macrovesicular steatosis of centrilobular hepatocytes. After discontinuation of the germanium, serum aminotransferases and creatine kinase values returned to normal, but moderately severe renal impairment persisted.

Topics: Breast Neoplasms; Chemical and Drug Induced Liver Injury; Citrates; Complementary Therapies; Female; Germanium; Humans; Kidney; Lactates; Liver; Middle Aged; Muscles

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Central Nervous System Diseases; Drug Evaluation; Female; Germanium; Humans; Infusions, Parenteral; Middle Aged; Organometallic Compounds; Spiro Compounds

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Drug Evaluation; Female; Germanium; Humans; Middle Aged; Neoplasm Metastasis; Organometallic Compounds; Receptors, Estrogen; Spiro Compounds

Cooperative oncology groups usually run pilot studies of new agents or combinations concurrently with their major randomized clinical trials. A primary objective of these studies is to determine whether the new regimen should be tested further in a group-wide clinical trial. The accrual goals of such pilot studies are typically fixed in advance at between 30 and 40 patients, on the grounds that this number provides a reasonably tight confidence interval on the true response rate. Nevertheless early termination of pilot studies is often desirable either because the regimen appears inactive or because early results indicate extreme activity and justify immediate testing in a randomized study. Statistical charts are provided for early termination in both these situations. The charts are read by specifying the number of evaluable patients already accrued, the number of responses observed and the minimum true response rate, theta 0, at which the regimen would be considered active. The charts provide the posterior probability that the true response rate exceeds theta 0, that is, that the regimen is active. An additional chart that computes a 90% probability interval for the true response rate, based on the observed rate and sample size, is also provided. The use of the chart is illustrated with two examples from the Eastern Cooperative Oncology Group.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials as Topic; Esophageal Neoplasms; False Negative Reactions; Female; Germanium; Humans; Male; Models, Biological; Organometallic Compounds; Pilot Projects; Probability; Sampling Studies; Spiro Compounds; Time Factors

Topics: Adult; Aged; Antineoplastic Agents; Bone Neoplasms; Breast Neoplasms; Drug Evaluation; Female; Germanium; Humans; Middle Aged; Organometallic Compounds; Spiro Compounds

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Drug Evaluation; Female; Germanium; Humans; Middle Aged; Organometallic Compounds; Spiro Compounds