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Byline: Jianping. Bi, Guang. Han, Xueyan. Wei, Guoliang. Pi, Yong. Zhang, Ying. Li, Mingwei. Wang, Desheng. Hu, Weining. Zhen Aims: We have previously demonstrated that brain metastases were more common [...]

Apar Kishor Ganti, MD Assistant Professor Department of Internal Medicine University of Nebraska Medical Center Department of Internal Medicine Omaha VA Medical Center Weining (Ken) Zhen, MD Associate Professor Department [...]

Stereotactic body radiation therapy (SBRT) is commonly used to treat nonsurgical patients with early-stage NSCLC. There are no prospective data on the role of adjuvant chemotherapy in this setting.

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ObjectiveEsthesioneuroblastoma is rare and the best treatment has yet to be defined. The purpose of this study is to analyze the natural history, treatment, and patterns of failure of esthesioneuroblastoma treated at one institution.

The purpose of this study was to assess heterogeneity of tumor microcirculation determined by dynamic contrast‐enhanced magnetic resonance (MR) imaging and its prognostic value for tumor radiosensitivity and long‐term tumor control using pixel‐by‐pixel analysis of the dynamic contrast enhancement. Sixteen patients with advanced cervical cancer were examined with dynamic contrast‐enhanced MR imaging at the time of radiation therapy. Pixel‐by‐pixel statistical analysis of the ratio of post‐ to precontrast relative signal intensity (RSI) values in the tumor region was performed to generate pixel RSI distributions of dynamic enhancement patterns. Histogram parameters were correlated with subsequent tumor control based on long‐term cancer follow‐up (median follow‐up 4.6 years; range 3.8–5.2 years). The RSI distribution histograms showed a wide spectrum of heterogeneity in the dynamic enhancement pattern within the tumor. The quantity of low‐enhancement regions (10th percentile RSI < 2.5) significantly predicted subsequent tumor recurrence (88% vs. 0%, P=0.0004). Discriminant analysis based on both 10th percentile RSI and pixel number (reflective of tumor size) further improved the prediction rate (100% correct prediction of subsequent tumor control vs. recurrence). These preliminary results suggest that quantification of the extent of poor vascularity regions within the tumor may be useful in predicting long‐term tumor control and treatment outcome in cervical cancer. J. Magn. Reson. Imaging 2000;12:1027–1033. © 2000 Wiley‐Liss, Inc.

Management of chondrosarcoma of the head and neck is largely based on single-institution reports with small numbers accrued over several decades. The American College of Surgeons' National Cancer Data Base included 400 cases of chondrosarcoma of the head and neck diagnosed between 1985 and 1995. Chi square analyses of selected contingency tables and Wilcoxon regression analyses of selected survival stratifications were performed. Histologic types included conventional (80.8%), myxoid (10.5%), and mesenchymal (8.8%). The mesenchymal and myxoid subtypes were rare among white patients (17.1%) and more common among African-American (31.8%) and Hispanic patients (44.9%). Treatment was most commonly surgery alone (59.5%) and surgery with irradiation (21.0%). Disease-specific survival was 87.2% at 5 years and 70.6% at 10 years. Worse 5-year survival was associated with higher grade (67.3%), regional or distant spread (71.0%), and the myxoid (45.0%) or mesenchymal (53.2%) subtypes. Chondrosarcoma of the head and neck encompasses a variety of lesions that differ substantially by demographic and tumor characteristics. Individual tumors can be classified further according to site of origin, histologic subtype, and tumor grade, which can be used to predict biologic behavior and prognosis. © 2000 John Wiley & Sons, Inc. Head Neck 22: 408–425, 2000.

Objectives:To examine the relationship of various pretreatment case‐mix characteristics and treatment modalities with medical charges incurred during diagnosis, treatment, and 2‐year follow‐up for patients with laryngeal cancer.

Cyclopentenyl cytosine (CPEC) is cytotoxic to several tumor cell lines. CPEC inhibits CTP synthesis resulting in depletion of cytidylate pools. The aim of this study was to examine CPEC's cytotoxic and antitumor activity in vitroand in vivoagainst human colon carcinoma HT-29, and to relate its action on CTP synthesis. CPEC exhibits potent cytotoxicity in vitroto HT-29 cells with an LC50(concentration that is lethal to the survival of 50% cell colonies) of 2.4 μM and 0.46 μM following 2 h and 24 h exposure, respectively. Incubation of cells with CPEC for 2 h resulted in a dose-dependent decrease in cytidylate pools. The in vivoantitumor activity of CPEC in athymic mice transplanted subcutaneously (s.c) with 3 million HT-29 cells was examined. Antitumor activity of CPEC was elucidated in early-staged tumor, wherein CPEC (1.5 mgkg, QD × 9 or 3 mgkg, QOD × 9) was administered intraperitoneally (i.p.) 24 h after tumor implantation and it resulted in a significant reduction in tumor weight to 48% of control. The effect of CPEC on established solid tumors in vivowas examined in athymic mice transplanted s.c. 14 days earlier with HT-29 cells and treated i.p. with 1.5 mgkgCPEC, QD × 5 for 4 courses, with a 10 day-interval between courses. This treatment resulted in a significant reduction in tumor weight (72%) in the treated group. HPLC analysis of HT-29 tumor obtained from mice after treatment with CPEC showed a depletion of the CTP concentration reaching a nadir at 8 h. In conclusion, the present studies demonstrate potent antitumor activity of CPEC against freshly transplanted and established human colon carcinoma which can be corroborated with the drug's biochemical actions.

Tiazofurin is an oncolytic nucleoside analog that has shown therapeutic activity in end-stage acute non-lymphocytic leukemia and in chronic granulocytic leukemia in blast crisis. Tiazofurin is anabolized to the active metabolite, TAD, which inhibits IMP dehydrogenase activity, leading to a reduction in guanylate pools and to the cessation of neoplastic cell proliferation. The drug exhibits potent cytostatic and cytotoxic activity against hepatoma 3924A cells in culture. In growth-inhibition and clonogenic assays, the 50% inhibitory concentration of tiazofurin was 3.8 and 4.2 µm, respectively. Dipyridamole, an inhibitor of nucleoside transport, curtails the salvage of nucleosides and bases for nucleotide biosynthesis. Dipyridamole exhibited cytotoxicity against hepatoma 3924A cells, with an LC50 of 24 µm and an IC50 of 29 µm being recorded. A combination of tiazofurin and dipyridamole provided synergistic cytotoxicity in hepatoma 3924A cells in culture. This synergistic activity was dependent on the order of addition of the drugs. Simultaneous addition of the two drugs produced antagonism, whereas preincubation of cells with tiazofurin or dipyridamole followed by addition of the second drug resulted in synergy. TAD concentrations were significantly higher (129% and 135%) in cells that had been pretreated with tiazofurin or dipyridamole before the addition of the second agent as compared with cells that had been treated simultaneously (113%). These studies indicate the importance of the order of the addition of drugs to obtain a synergistic response in combination chemotherapy and suggest the need for a careful selection of drug modulation in clinical trials of tiazofurin and dipyridamole.

Tiazofurin is effective in treating end-stage leukemic patients (Tricot et al., Cancer Res 49:3696-3701, 1989). In sensitive tumors, the active metabolite of tiazofurin, TAD, potently inhibits IMP dehydrogenase activity, resulting in reduced guanylate pools. To elucidate tiazofurin activity in human solid tumors, we examined its activity in human colon carcinoma HT-29. Tiazofurin exhibited an LC50 of 35 pM in cultured HT-29 cells. Incubation of HT-29 cells with 100 pM tiazofurin for 2 h resulted in TAD formation (9.3 nmollg cells) and in a 64% decrease in GTP pools. For biochemical and chemotherapy studies, athymic nude mice were transplanted s.c. with HT-29 cells. Twenty-four days later, mice were injected i.p. with tiazofurin (500 mg/kg); 6 h later, tumors were removed and analyzed. These tumors formed 17 nmollg of TAD with decreased GTP pools (56%). To study oncolytic activity, transplanted mice were treated 24 h later with tiazofurin (500 mg/kg, once a day for 10 days). To examine the effectiveness of tiazofurin in established tumors, the drug was administered to mice 14 days after tumor implantation (500 mglkg, once a day for 5 days, course repeated 4 times with a 10-day rest). Both treatment schedules resulted in significant antitumor activity. This study illustrates the potential usefulness of tiazofurin in treating human colon carcinoma.

2-β-D-Arabinofuranosylthiazole-4-carboxamide and 2-β-D-xylofuranosyl-thiazole-4-carboxamide are sugar modified analogues of tiazofurin, a C-glycosyl nucleoside which after anabolism to the dinucleotide, TAD (thiazole-4-carboxamide adenine dinucleotide), exhibits antitumor activity. However, ara-T and xylo-T did not exhibit cytotoxicity. Compared to tiazofurin, only 12.5% of the ara-T and 8.8% of the xylo-T were metabolized to TAD derivatives by human myelogenous leukemia K562 cells. This was reflected in the finding that guanylate pools were not depressed after treatment with either tiazofurin derivative. These results provide evidence that the ribose moiety is essential for the metabolism and cytotoxicity of tiazofurin. This investigation should be helpful in the design of new analogues of tiazofurin for future clinical trials.

Focuses on a study which examined the use of peracetic acid in bleaching textiles. Other chemicals used, in combination with peracetic acid, in the bleaching solution; Oxidation potential of peracetic acid; Effect of peracetic acid on additives and hydrogen-ion concentration.