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It is shown by experiments that replacing one-pulse sequence by RIDE (ring down elimination) pulse sequence may dramatically improve the baseline of (29)Si NMR spectra and eliminate the signal from the probe., (Copyright © 2013 John Wiley & Sons, Ltd.)

Purpose: The predictive value of topoisomerase-II alpha (topo-II) has been evaluated in advanced breast cancer patients randomly treated with single-agent doxorubicin or docetaxel., Experimental Design: Primary tumor samples from patients enrolled in a randomized, phase III clinical trial comparing single-agent doxorubicin (75 mg/m(2) q3wks) with docetaxel (100 mg/m(2) q3wks) were collected and topo-II status was evaluated by immunohistochemistry (clone KiS1)., Results: Topo-II status was evaluated in 108 samples, 55 (51%) in the doxorubicin arm and 53 (49%) in the docetaxel arm. An increment of 10% in cells expressing topo-II is associated with a statistically significant odds ratio (OR; 95% confidence interval) of 1.09 (1.03-1.15; P = 0.002) for overall response to doxorubicin versus 1.002 (0.94-1.07; P = 0.95) in the docetaxel arm. With increasing topo-II, the favorable OR for overall response to docetaxel compared with doxorubicin decreases to become not significant in patients with topo-II tumor content >10%. In a multivariate analysis, (a) HER-2 status seems positively correlated with overall response to chemotherapy (OR, 2.34; 95% confidence interval, 0.87-6.27; P = 0.09). (b) Overall response to doxorubicin is significantly lower than overall response to docetaxel (OR, 0.17; 95% confidence interval, 0.04-0.64; P = 0.009) but with a significant interaction term for doxorubicin-treated patients with topo-II tumor content >10% (OR, 8.31; 95% confidence interval, 1.86-37.03; P = 0.05)., Conclusions: (a) Topo-II overexpression confers a higher probability of response in the doxorubicin arm only. (b) Despite being a small retrospective study, this study is in line with previously reported studies and the hypotheses raised are now being tested in a prospective neoadjuvant trial.

Purpose: This phase III study compared docetaxel and doxorubicin in patients with metastatic breast cancer who had received previous alkylating agent-containing chemotherapy., Patients and Methods: Patients were randomized to receive an intravenous infusion of docetaxel 100 mg/m(2) or doxorubicin 75 mg/m(2) every 3 weeks for a maximum of seven treatment cycles., Results: A total of 326 patients were randomized, 165 to receive doxorubicin and 161 to receive docetaxel. Overall, docetaxel produced a significantly higher rate of objective response than did doxorubicin (47.8% v 33.3%; P =.008). Docetaxel was also significantly more active than doxorubicin in patients with negative prognostic factors, such as visceral metastases (objective response, 46% v 29%) and resistance to prior chemotherapy (47% v 25%). Median time to progression was longer in the docetaxel group (26 weeks v 21 weeks; difference not significant). Median overall survival was similar in the two groups (docetaxel, 15 months; doxorubicin, 14 months). There was one death due to infection in each group, and an additional four deaths due to cardiotoxicity in the doxorubicin group. Although neutropenia was similar in both groups, febrile neutropenia and severe infection occurred more frequently in the doxorubicin group. For severe nonhematologic toxicity, the incidences of cardiac toxicity, nausea, vomiting, and stomatitis were higher among patients receiving doxorubicin, whereas diarrhea, neuropathy, fluid retention, and skin and nail changes were higher among patients receiving docetaxel., Conclusion: The observed differences in activity and toxicity profiles provide a basis for therapy choice and confirms the rationale for combination studies in early breast cancer.

Background: Chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (C-TTP/HUS) is a condition involving thrombocytopenia, microangiopathic hemolytic anemia, and progressive renal dysfunction that develops in 2-10% of patients with a history of malignant neoplasms treated with certain chemotherapeutic agents. Pathogenesis of the disease may depend on the following: (1) generation of endothelial lesions in the kidney microvasculature, resulting from drug toxic effects and/or generation of small soluble circulating immune complexes (CIC), and (2) generation of autoantibodies and/or CIC that trigger aggregation and deposition of platelets around the lesions., Methods: Extracorporeal immunoadsorption treatment of plasma (PROSORBA columns, IMRE Corporation, Seattle, WA) to remove immunoglobulin G and CIC was evaluated in 55 patients for the potential to induce significant clinical benefits (increase in platelet count, decrease in hemolysis, stabilization of renal function) and longer survival., Results: Response to therapy was achieved in 25 of 55 patients examined. Response was associated with an estimated 1-year survival rate of 61%, as compared with an estimated survival rate of only 22% in those who did not respond (P = 0.0001). Patients whose malignant neoplasms were in complete or partial remission at the time of development of C-TTP/HUS had a significantly higher estimated 1-year survival rate (74%) as compared with a historic control group of patients receiving other treatments (22%, P = 0.0161). Clinical responses were correlated with normalization of serum levels of CIC and complement components C3c and C4. There were no side effects associated with 75% of treatments. Immunoadsorption therapy was associated with generally mild to moderate manageable side effects, such as fever, chills, nausea/vomiting, respiratory symptoms, pain, hypertension, and hypotension, which were reported in 25% of procedures., Conclusions: This multicenter study establishes protein A immunoadsorption as an effective and safe treatment for cancer chemotherapy-associated TTP/HUS, an otherwise fatal disease.

One hundred and one patients undergoing anticancer chemotherapy due to hematologic malignancy were retrospectively divided into two groups: 67 patients were treated with ceftriaxone plus amikacin, receiving once daily (od) 2-4 g ceftriaxone, 1-1.5 g amikacin (those without a peripheral or central venous catheter) and 34 patients with central or peripheral venous catheter (CPVC) receiving ceftizidime 2 g three times daily (tid) plus amikacin 0.5 g tid i.v. Both groups were similar as to their isolated pathogens, localization of infection, and basic diagnoses of hematologic malignancies. There was no significant difference in efficacy between ceftriaxone plus amikacin versus ceftazidime plus amikacin, but the toxicity was lower in once daily ceftriaxone plus amikacin group.

Immunodeficiency disorders have provided much information on the development and interaction of the various B and T lymphoid components in the immune system of man. As the lymphoid system becomes increasingly divided into functional subsets of cells it will be important to find immunodeficiencies affecting newly discovered cell types. Natural killer (NK) cells are a recently described but ill-defined subpopulation of lymphocytes which is thought to play an important part in surveillance against tumour development. Mice homozygous for the beige gene were found to have a selective deficiency in NK function and were more susceptible to transplantation of syngeneic tumours as predicted. We report here that patients carrying the analogous, autosomal recessive Chediak-Higashi (CH) gene have a profound defect in their ability to spontaneously lyse various tumour cells in vitro by either antibody-dependent or independent mechanisms. Since other cell-mediated cytolytic functions were relatively normal, these results suggest that the beige or Chediak-Higashi gene in both man and mouse controls NK function.

Forty patients with advanced Hodgkin's disease stage III and IV were treated with combination chemotherapy. Absolute lymphocyte count in the peripheral blood was determined before start to chemotherapy. Higher levels of lymphocytes in the peripheral blood were associated with higher chemotherapy response rates. This difference was statistically significant (P less than 0.05).

Formation of spontaneous (E--erythrocyte) and immune (EAC--erythrocyte, antibody, complement) rosettes of sheep red blood cells (SRBC) with peripheral blood T and B lymphocytes, respectively, was used for quantitative assessment of these lymphocytes populations in tumor patients and control subjects. Relative counts of T and B lymphocytes have been correlated with lymphocyte survival in short-term cultures using standard subtoxic doses of phytohemagglutinin (PHA). The mean values and SE in normal control subjects for E rosettes (T lymphocytes) were 72.8 +/- 1.2%, for EAC rosettes (B lymphocytes) 23.8 +/- 2.5% of lymphocyte population. The survival of lymphocytes in short-term cultures with PHA in control subjects was 55.3 +/- 1.1%. In tumor patients the counts of E, EAC rosettes and percentage of lymphocyte survival in short-term PHA cultures were dependent upon the clinical stage. In patients with localized tumors the values were similar to controls. In patients where dissemination of the tumorous process could be ascertained a decrease of T lymphocyte counts, an increase of B lymphocyte counts and a higher survival of peripheral blood lymphocytes in short-term cultures with PHA was found.

Seventeen patients with 52 surgically proven hepatic metastases were studied preoperatively with dynamic CT and 0.5 T magnetic resonance (MR). Dynamic CT detected 38 metastases (73%), and the combination of short echo time (T1-weighted) and T2-weighted pulse sequences detected 46 lesions (88%). Magnetic resonance was also superior at assessing potential resectability. This study suggests that MR excels in detecting and anatomically localizing individual hepatic metastases.

We have treated 11 patients having a variety of tumor types and three patients having mitomycin-C-associated thrombotic thrombocytopenic purpura (TTP) with extracorporeal plasma perfusion through filters containing immobilized protein A from Staphylococcus aureus. In performing more than 140 procedures we observed only minimal toxicity, of which fever, chills, nausea, and vomiting were the most common symptoms, occurring in 25% of the patients. Significant decrease in blood pressure and bronchospasm were rare complications. However, none of these side effects were severe enough to require therapeutic intervention. The antitumor effect of immunoperfusion was modest. In 10 adequately treated patients there was one measurable tumor reduction (40% decrease of original tumor mass). Two patients had correction of total small bowel obstruction, with return to normal food intake and restoration of normal bowel habits, lasting for 6 and 3 months; and two of the two adequately treated TTP patients had dramatic hematological improvement after four and five immunoperfusion treatments and are well at present. We found direct correlation between extent of complement activation and clinical toxicity. By temperature manipulation of the perfusion procedure we were able to control the above-mentioned side effects caused by complement activation.

Radioimmunoassays of human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) made in 49 patients with nonseminomatous testicular tumors have shown that these investigations make the diagnosis more precise, permit to follow up the dynamics of the course of the disease and the effectiveness of treatment and may help to reveal the presence of otherwise undetectable tumorous metastases. The significance of the these assays is enhanced if the two tumorous proteins are investigated in parallel. The results proved rightly positive in 43 (87.8%) and falsely negative in 6 (12.2%) of the patients. The absence of HCG and AFP production in some of the patients with an active disorder has not as yet been elucidated.