germanium and Colonic-Neoplasms

A new large-area germanium ATR crystal is utilised with an FTIR microscope to improve the acquired images of de-paraffinized colon biopsy sections, without recourse to a synchrotron source. The large crystal (⌀ = 28 mm) offers significant improvements compared to slide-on small germanium crystal (⌀ = 3.5 mm); for example, it facilitates more uniform distribution of higher signal intensity within the field of view and more rapid acquisition time. Mapping of a larger sample area up to ca. 350 × 350 μm

Topics: Biomarkers, Tumor; Biopsy; Cluster Analysis; Colon; Colonic Neoplasms; Crystallization; Germanium; Humans; Least-Squares Analysis; Principal Component Analysis; Signal Processing, Computer-Assisted; Signal-To-Noise Ratio; Spectroscopy, Fourier Transform Infrared; Vibration

Accumulating evidence indicates the crucial contribution of chronic inflammation to various types of carcinogenesis, including colon carcinoma associated with ulcerative colitis and asbestosis-induced malignant mesothelioma. Ulcerative colitis-associated colon carcinogenesis can be recapitulated in mice by azoxymethane administration followed by repetitive dextran sulfate sodium ingestion. In the course of this carcinogenesis process, the expression of a macrophage-tropic chemokine, CCL2, was enhanced together with intracolonic massive infiltration of macrophages, which were a major source of cyclooxygenase (COX)-2, a crucial mediator of colon carcinogenesis. Mice deficient in CCL2-specific receptor, CCR2, exhibited less macrophage infiltration and lower tumor numbers with attenuated COX-2 expression. Moreover, CCL2 antagonists decreased intracolonic macrophage infiltration and COX-2 expression, attenuated neovascularization, and eventually reduced the numbers and size of colon tumors, even when given after multiple colon tumors have developed. These observations identify CCL2 as a crucial mediator of the initiation and progression of chronic colitis-associated colon carcinogenesis and suggest that targeting CCL2 may be useful in treating colon cancers, particularly those associated with chronic inflammation.

Topics: Animals; Azoxymethane; Chemokine CCL2; Colitis, Ulcerative; Colonic Neoplasms; Cyclooxygenase 2; Dextran Sulfate; Female; Germanium; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Transgenic; Organometallic Compounds; Propionates; Receptors, CCR2; RNA, Messenger

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

We studied DMH induced colon cancer in 120 wistar rats, which were divided into 8 groups based on different diets. They were killed and autopsied on 4 weeks after the last injection of DMH. The tumors in various organs including its characteristics, number, site, histological types and ultrastructural changes were observed. The results showed that high fat diet has a significant effect on DMH induced colon cancer. Selenium and calcium can inhibit the effect of DMH and decrease the incidence of colon cancer. Selenium can also interfere the effect of high fat diet but germanium has no effect on colon carcinogenesis.

Topics: Animals; Antineoplastic Agents; Calcium; Carcinogens; Carcinoma, Papillary; Colonic Neoplasms; Dietary Fats; Dimethylhydrazines; Germanium; Male; Organometallic Compounds; Propionates; Rats; Rats, Wistar; Selenium

The natural killer (NK) activity of peripheral blood lymphocytes from 18 cancer patients was studied prior to and after multiple administration of organo-germanium compound (Ge-132). In successive oral administration of Ge-132 at a dose of 1000 mg/day for 10 days, NK-activity of patients was augmented at 3 days, but by 10 days, depression of NK activity was observed in all cases. In intermittent oral administration of Ge-132, however, more than half of the patients with augmented NK activity at day 3 maintained the high activity level at day 10. This result suggests the superiority of intermittent administration of Ge-132 for clinical use.

Topics: Colonic Neoplasms; Cytotoxicity, Immunologic; Germanium; Humans; Killer Cells, Natural; Lung Neoplasms; Organometallic Compounds; Propionates; Stomach Neoplasms

Spirogermanium, an azaspirane compound, has recently had limited clinical trials using a schedule of intravenous injection one to three times every week. The observation of clinical antitumor activity and lack of myelosuppression prompted us to investigate further the clinical effects of spirogermanium administered on various schedules. A total of 52 patients with advanced metastatic tumors refractory to standard therapy were treated with spirogermanium. Three different schedules of drug administration were evaluated. Initially, a short daily IV infusion for 5 days every week was evaluated, starting with a dose of 30 mg/m2/day. A total of 22 patients received 69 courses with a dose range of 30-120 mg/m2/day for 5 days every week. The maximum tolerated dose was 100 mg/m2/day IV over 1 hr and 120 mg/m2 over 2-3 hr. In the second phase of the study, 12 patients received 41 courses of spirogermanium as a 24-hr continuous infusion for 5 days/wk at a dose of 150-375 mg/m2/day. The maximum tolerated dose was 200 mg/m2/day for 5 days. In the third phase of the study, 18 patients received spirogermanium as a continuous infusion daily for a median of 30 days (range 6-77 days) in a dose range of 100-200 mg/m2/day. The maximum tolerated dose was 150 mg/m2/day. Of the 44 assessable patients, 3 demonstrated a partial response and 3 had minor tumor regression; all responses occurred in lymphoma patients. The dose-limiting toxicity of spirogermanium was neurologic; other side effects consisted of mild anorexia, nausea and vomiting, and possible lung toxicity. There was no clear evidence of cumulative toxicity despite daily administration of spirogermanium. Our data suggest that spirogermanium can be administered daily by several different schedules, and the optimum dose depends on the infusion time and the duration of therapy. The delivery of drug by continuous infusion permitted administration of twofold higher dose levels compared to the standard IV schedules used in previous studies.

Topics: Adult; Aged; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation; Female; Germanium; Humans; Infusions, Parenteral; Lymphoma; Male; Middle Aged; Nausea; Nervous System Diseases; Organometallic Compounds; Ovarian Neoplasms; Spiro Compounds

The effect of chemotherapy on bony metastases from adenocarcinoma of the colon was investigated by quantitative skeletal imaging over a two-month interval. The quantitative skeletal imaging results correlated with conventional blood chemistry results over this time period. While chemical assay techniques furnish an average value of lesion response, the quantitative bone scan represents a method for individual lesion analysis. This methodology has the potential to provide a better understanding of metastatic bone disease therapy.

Topics: Adenocarcinoma; Antineoplastic Agents; Bone and Bones; Bone Neoplasms; Colonic Neoplasms; Diphosphonates; Fluorouracil; Germanium; Humans; Male; Middle Aged; Organometallic Compounds; Radionuclide Imaging; Spiro Compounds; Technetium; Technetium Compounds; Time Factors

Lethal and other biological effects of 2-aza-8-germanspiro[4,5]decane-2-propanamine-8,8-diethyl-N,N-dimethyl dichloride (NSC 192965; spirogermanium), representing a new chemical class of compound exhibiting antitumor activity, have been studied in vitro. Survival curves for NIL 8 hamster cells were exponential with greater kill occurring with increasing drug concentrations and longer exposure times. Cytotoxicity was temperature dependent. "Quiescent" cultures were significantly less sensitive to spirogermanium than were logarithmically growing cells. These lethal effects showed no phase specificity. There was no evidence of progression delay through the cycle following spirogermanium treatment. When spirogermanium was tested against a range of human cell lines, the consistency of the values for the drug concentration required to reduce survival by 50% on the exponential part of the survival curve, derived from colony-forming assays, was most marked. The survival curves, characterized by an initial shoulder, were steep and exponential with measurements possible over only a narrow concentration range since complete cell lysis occurred at levels causing a greater than 2-log kill. Cell membrane damage by spirogermanium, as judged by dye exclusion, was progressive with time and increasing drug concentrations. Protein synthesis proved most susceptible to the drug. Spirogermanium concentrations cytotoxic to tumor cells were also toxic to cultured rat neurons, confirming the clinical neurological toxicity encountered. The precise mode of action of spirogermanium remains to be established, and these data further illustrate its apparent lack of specificity.

Topics: Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Cell Cycle; Cell Line; Cell Survival; Cells, Cultured; Colonic Neoplasms; Cricetinae; Female; Germanium; Humans; Mesocricetus; Neuroblastoma; Neurons; Organometallic Compounds; Ovary; Rats; Spiro Compounds