bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of low‐dose prednisone and melphalan in the treatment of poor‐risk patients with multiple myeloma
Authors: Cuttner Janet , Wasserman L. R. , Martz Georg , Sonntag Roland W. , Kyle Robert A. , Silver Richard T. , Spurr Charles , Harley John B. , Wiernik Peter M. , Cornwell Gibbons G. , Falkson Geoffrey , Glidewell Oliver , Holland James F. 
Published: February 2007

AbstractA study was designed to evaluate the effectiveness of prednisone therapy in poor‐risk patients with multiple myeloma. Patients were treated with melphalan alone or in combination with prednisone at doses of either 0.6 mg/kg or 0.3 mg/ kg. The group of patients receiving melphalan and prednisone 0.6 mg/kg had significantly improved responses in hemoglobin, lowering of the M‐protein concentration, and reduction of azotemia. Significant benefits attributable to prednisone were not demonstrated in the group receiving 0.3 mg/kg. Good responses have been shown to produce improved survival. The combination of melphalan and prednisone is effective in producing good responses, but the dose of steroids is important. A dose of prednisone of 0.6 mg/kg in gradually decreasing doses has been found to be effective in production of good responses, especially in the uremic patient.
Non‐Hodgkin's lymphoma in children
Authors: Wollner Norma , Burchenal Joseph H. , Lieberman Philip H. , Exelby Philip R. , d'Angio Giulio J. , Murphy M. Lois 
Published: February 2007

AbstractIn a study of non‐Hodgkin's lymphoma in children, 104 children were treated and followed at Memorial. Sloan‐Kettering Cancer Center from 1964 through June 1974. Forty‐three patients, previously treated and untreated, received a nonspecific group of various chemotherapeutic agents and attained an 11% disease‐free survival rate. A second group of 18 previously untreated patients, who received a chemotherapeutic regimen consisting of cyclophosphamide alone, achieved a 33% disease‐free survival rate. The last group, 43 previously untreated patients (77% of whom had far advanced disease and 86% of whom had diffuse histological types) who received a new and intensive multiple‐drug regimen (the LSA2‐L2 protocol) consisting of induction, consolidation, and maintenance phases, has maintained an 81% disease‐free survival rate after a median observation time of 21+ months. Although nervous system involvement and recurrence or metastases at any time are poor prognostic factors, initial marrow involvement and the amount of bulky disease are no longer considered negative prognosticators when intensive treatment is initiated immediately after diagnosis, is continued for 2 ‐ 3 years, and includes radiation therapy to sites of bulky disease and CNS prophylaxis. The LSA2‐L2 treatment is effective in accomplishing the dual aims of not only increasing the numbers of disease‐free patients but also prolonging their survival.
Pharmacokinetic considerations in the design of optimal chemotherapeutic regimens for the treatment of breast carcinoma: A conceptual approach
Authors: Broder Lawrence E. , Carbone Paul P. 
Published: February 2007

AbstractPharmacological data are currently available for a number of antineoplastic agents which have shown clinical activity in advanced breast carcincoma. Preclinical data reveal a relationship between therapeutic response and certain pharmacokinetic parameters such as time of effective cytotoxic exposure (Teff) and the product of concentration with time (Cxt). We have attempted to apply human pharmacologic data to get estimates of these parameters for 6 active agents in breast cancer, to relate them to response rates, and to suggest a method for estimating the role of individual drugs in a multidrug combination.The response rates for 6 single agents were obtained from literature review and related to estimates of Teff and Cxt. The Cxt‐response relations for single drugs were linear for cyclophosphamide, 5‐fluorouracil, and thiotepa; exponential for vincristine; and relatively flat for methotrexate and cytosine arabinoside. Most Teff values for the active single agents clustered about 15 hr/dose.From the graphs of response rate vs Cxt, the individual contribution of each agent in a combination study was estimated to arrive at a predicted response rate. The predicted response rates for the combination studies correlated with the actual response rates determined in the clinical study, for 6 of 6 nonrandomized studies and for 12 of 14 randomized studies analyzed. In 2 studies, deviations from the predicted response rate were attributed to differences in study design or analysis. There was no correlation between Teff and predicted response rate. Analyses of pharmacokinetic data may be useful to simulate combination chemotherapy studies to predict the effectiveness of clinical trials in breast cancer. Since the pharmacologic data were not obtained for any of the agents in the actual clinical trials done, we can only speculate on the usefulness of this method. We would encourage the prospective collection of this data in future clinical trails.
Cell kill kinetics with hydroxyurea
Authors: Yataganas Xenophon , Strife Annabel , Perez Amaury , Clarkson Bayard 
Published: February 2007

AbstractThe effects of various concentrations of hydroxyurea (HU) on a human lymphoid cell line in exponential growth phase have been studied using a combination of methods, including determination of the total and viable cell counts; the cells' relative DNA content, measured in a flow microfluorimeter after staining with a fluorescent Feulgen technique; the mitotic index; and the percentage of cells incorporating thymidine‐3 H (TdR‐3 H) during brief and continuous exposure to the isotope both in the presence and absence of colcemid.A significant redistribution of the cells in the various phases of the cell cycle occurred during the first 24 hr of continuous treatment with 10‐3 M and 10‐2 MHU as follows: (1) division of cells in G2; (2) depletion of mid and late S phase cells due to early cell death; (3) movement of most G1 cells at a normal rate into early S phase where they accumulate; and (4) arrest of the remaining cells in G1, which represented the surviving population after treatment for 96 hr or longer. After removal of the drug, the cell fraction blocked in early S phase progressed semisynchronously through S, but many of the cells were unable to complete division. Their capacity to recover depended on the drug concentration and duration of exposure, but in general the cellular injury caused by HU was more reversible than that caused by “equivalent” concentrations of arabinosylcytosine.
Mitomycin C in large infrequent doses in breast cancer
Authors: Wise Gregory R. , Kuhn Irvin N. , Godfrey Thomas E. 
Published: February 2007

AbstractSeventy‐one women with far‐advanced breast cancer resistant to standard chemotherapeutic agents were administered mitomycin C using an intermittent high dose schedule. One group consisted of 54 patients with measurable metastatic tumor; a second group consisted of 18 patients with nonmeasurable osseous metastases. Objective response rate in group 1 was 26% for an average duration of 2 1/2 months. Subjective response rate in group 2 was 44% for an average duration of 3 months. Response and toxicity data were similar to those of studies employing the less convenient protracted low‐dose schedule. Prior treatment with other alkylating agents did not adversely affect response. Further investigation into the role of mitomycin in combination chemotherapy programs is recommended.
Development of an effective treatment program for childhood acute lymphocytic leukemia: A preliminary report
Authors: Furman Lorrie , Camitta Bruce M. , Jaffe Norman , Sallan Stephen E. , Cassady J. Robert , Traggis Demetrius , Leavitt Pearl , Nathan David G. , Frei iii E. 
Published: February 2007

AbstractThe development of an effective therapeutic regimen for acute lymphocytic leukemia (ALL) of childhood is described. By careful surveillance of toxicity and efficacy, positive modifications of treatment strategy were achieved without resorting to classically randomized trials. The resultant protocol utilizes vincristine‐prednisone induction followed by asparaginase consolidation, intensive intermittent combination maintenance chemotherapy with adriamycin as a major component, and cranial radiotherapy plus intrathecal methotrexate for central nervous system prophylaxis. Preliminary analysis suggests that this regimen may result in prolonged continuous complete remission in at least 80% of children with ALL.
Sv40 dna sequences as an example of the structure of genes functioning in animal cell nuclei
Authors: Weissman Sherman M. , Subramanian K. N. , Dhar R. , Zain B. , Pan J. 
Published: February 2007

AbstractRecent studies of the structure of messenger RNA have demonstrated the existence of untranslated sequences of the 3′ and 5′ end of the messages. In addition analysis of transcription in vitro has indicated that the nucleotide sequence U6 purine may be part of a transcription termination signal in prokaryotes. Recently it has been possible to determine the sequence of extensive portions of the DNA of SV40 virus. This article reviews the analogies between certain of these sequences and sequences available from prokaryotic messengers and DNAs. Unusual structures, including blocks of AT‐rich and GC‐rich segment sections and symmetric regions in the DNA near the origin of DNA replication, have been demonstrated and the distribution of stretches of 6 or more deoxyadenylic acids in the DNA of SV40 is consistent with some rho for these sequences in animal cells, either as terminators of transcription or as sites where degradation of transcripts is initiated or sites related to the selective rejection or degradation of transcripts.
Choline antagonism of methotrexate liver toxicity in the rat
Authors: Freeman‐Narrod M. , Narrod S. A. , Yarbro J. W. 
Published: February 2007

AbstractBecause of the frequent reports of hepatic toxicity associated with long‐term administration of methotrexate, a rat model was developed utilizing daily methotrexate administration. This model revealed an incidence of fatty metamorphosis of over 80 percent, atrophy and necrosis of 30 percent, and fibrosis of 10 percent. Fatty liver changes did not differ substantially from control animals in those animals receiving long‐term hydroxyurea, an agent which, like methotrexate, inhibits DNA synthesis but unlike methotrexate, does not impair methylation reactions. Because choline has a lipotropic effect and because its synthesis requires methylation, an attempt was made to block the liver toxicity of methotrexate by simultaneous administration of choline. Animals so treated did not show the pathologic changes in the liver characteristic of methotrexate treatment alone. Furthermore, the accumulation of triglycerides in the liver which was characteristic of methotrexate administration was markedly reduced in those animals receiving choline.These data strongly suggest that, in the rat model, methotrexate produced liver toxicity by virtue of an effect other than inhibition of DNA synthesis; and that this toxicity can be blocked without impairing methotrexate effect on bone marrow by the administration of choline, a lipotropic agent requiring methylation for its synthesis. It is suggested that these results may have implications for human therapeutic situations involving long‐term administration of methotrexate.
Combination of cyclophosphamide, vincristine, and prednisone, followed by maintenance chemotherapy, with and without radiotherapy, in the management of patients with non‐Hodgkin's lymphomas
Authors: Gorin N. C. , David R. , Stachowiak J. , Najman A. , Duhamel G. 
Published: February 2007

AbstractSixty patients with non‐Hodgkin's lymphomas were treated with a cyclophosphamide, vincristine, and prednisone (CVP) induction regimen, either alone (stage IV) or in combination with radiotherapy (stages I, II, III).The response rates for lymphocytic and histocytic lymphomas were 82 and 86%. The complete remission (CR) rates were 66 and 71% with a median duration of 13 and 5.5 months respectively. Nodular types responded better than diffuse ones in both lymphocytic (CR rate 85% vs 45%; median duration 24+ months vs 2.5 months) and histiocytic lymphoma (CR rate 100% vs 0%).In lymphocytic lymphomas, survival in the responder group was 90% at 24 months vs only 20% in the nonresponder group (median survival 14.5 months). In the group with nodular lymphocytic lymphoma responding to therapy, there was a 100% survival rate at 24 months. The median survival for patients treated with chemotherapy alone (stage IV) and not responding to therapy, was 22 months vs 14.5 months in the whole nonresponder group (stages I, II, III, IV), suggesting a detrimental effect of radiotherapy in the nonresponder group.In histiocytic lymphomas, the median survivals in the responder and nonresponder groups were 19 months and 3 months respectively. These results corroborate the excellent efficacy of the CVP regimen. They also indicate that, after CVP induction, 2 major prognostic factors are the histologic type and the nature of the response to therapy.
Post‐hypophysectomy insulin response in patients with advanced breast cancer
Authors: Theologides A. , McHugh R. B. , Lindall A. W. , Hall S. M. 
Published: February 2007

AbstractSeven postmenopausal women with metastic breast cancer underwent transsphenoidal hypophysectomy. The rate of disappearance, k*, of iv glucose and insulin following iv glucose and 1‐arginine infusion was determined before and after the ablation. The k* was estimated with a linear least squares weighted regression method. The insulin secretory capacity of the pancreas before and after the ablation was evaluated with the index of insulinogenic reserve, the index representing the quantity of insulin secreted per unit of glycemic stimulus.Following iv glucose and arginine, there was no significant difference in the mean k* for glucose and insulin, before and after the ablation. The insulinogenic index before was lower than the normal. After hypophysectomy, the index decreased further for the first 30 min following iv glucose.In patients with advanced cancer the index of insulinogenic reserve is lower than normal and is suppressed further by hypophysectomy.
The action of antitumor agents: A double‐edged sword?
Authors: Sieber S. M. 
Published: February 2007

AbstractAlthough cytotoxic immunosuppressive agents play an unquestionably useful role in treating many neoplastic and non‐neoplastic disorders, there is accumulating evidence that the toxicity associated with their use is considerable. The therapeutic successes obtained with antitumor agents have led to increases in the life span of cancer patients, but have also provided the opportunity for this toxicity to become manifest. A search of the available literature was carried out, with emphasis on cases in which a malignancy developed in patients following chemotherapy for either neoplastic or non‐neoplastic (e.g., renal transplantation, psoriasis) conditions; particular focus was given to the incidence of acute myelogenous leukemia in various groups of Hodgkin's disease and multiple myeloma patients. That patients with nonmalignant conditions treated with cytotoxic immunosuppressive agents are also at increased risk of developing a malignancy raises the possibility that these agents may have oncogenic potential. Therefore, one may be faced with the paradox that the patients benefiting most from chemotherapy may be at highest risk of suffering its consequences.
Bone marrow polyamines in children with acute leukemia as related to remission status, therapy, and cellularity of specimens
Authors: Miale Thomas D. , Rennert Owen M. , Lawson Daniel L. , Shukla Jayesh B. , Frias Jaime L. 
Published: February 2007

AbstractMeasurements of polyamines have potential practicality as biochemical markers of disease activity in adult cancer patients. On this basis, similar measurements were made in children with leukemia and solid tumors. Fluctuations in blood polyamine concentration were studied in relationship to chemotherapy schematics, cellularity and composition of blood and bone marrow specimens, and remission status of patients. Our results indicate that each of these factors may influence these determinations and consequently their clinical usefulness.
Dissimilar courses of twins with leukemia
Authors: Stewart Stanford J. , Shepherd Dell A. , Steuber C. Philip , Starling Kenneth A. , Falletta John M. 
Published: February 2007

AbstractTwin girls, genetically identical, probably experienced different leukemogenic events and presented with acute lymphocytic leukemia 6 years apart. Their clinical presentations were similar, but they received significantly different therapy. The first twin died 34 months after diagnosis following multiple remissions and relapses, having received single‐drug maintenance. The second twin remains free of apparent disease 60 months after diagnosis, following vincristine and prednisone induction, 6‐mercaptopurine maintenance, methotrexate and prednisone reinforcement, and central nervous system treatment of occult disease. Their dissimilar clinical courses may have been due to different leukemogenic events and/or markedly different therapeutic programs.
False positive lymphography in Hodgkin's disease: A histologic‐lymphadenographic correlation
Authors: Abt Arthur B. , Murphy W. Linell , O'Connell Michael J. , Wiernik Peter H. 
Published: February 2007

AbstractA series of 99 consecutive patients having a staging laparotomy for Hodgkin's disease was reviewed. Negative lymph nodes removed during the laparotomy were correlated with lymphograms reported as positive or suspicious. Four patients had large nodes with a prominent hilar area or irregular cortical fat deposits. In two other patients a cluster of small lymph nodes accounted for the radiologic misinterpretation.
Combination Chemotherapy in Histiocytosis X
Authors: Komp Diane M. , Vietti Teresa J. , Berry D. H. , Starling Kenneth A. , Haggard Mary Ellen , George Stephen L. 
Published: February 2007

AbstractTwenty‐five children with generalized histiocytosis X were treated with a combination of cyclophosphamide, vinblastine, and prednisone: 8 patients experienced complete response, 8 partial response, 2 improvement, and 7 no response. Response rates for children over 1 year of age were higher than those reported for single agents.Twelve children are now off therapy with no evidence of disease for 10–50 months.Very poor response rates and high toxicity were seen in children less than 1 year of age. The two infants who eventually achieved CR did so by other therapies.Further trials in combination chemotherapy must weigh possible long‐term effects of such therapy against the prospect of more rapid disease control.
Clinical and cytokinetic aspects of remission induction of childhood acute lymphoblastic leukemia (ALL): Addition of an anthracycline to vincristine and prednisone
Authors: Sallan Stephen E. , Camitta Bruce M. , Iii Emil Frei , Furman Lorrie , Leavitt Pearl , Bishop Yvonne , Jaffe Norman 
Published: February 2007

AbstractFifty‐six untreated patients with childhood with acute lymphoblastic leukemia (ALL) were randomized to receive one of three remission induction regimens: vincristine and prednisone (VP), vincristine, prednisone and daunorubicin (VPD), or vincristine, prednisone and adriamycin (VPA).The complete remission rate was similar for all three groups. Although the anthracycline regimens caused somewhat more rapid leukemic cell reduction than the VP only group, this difference was not significant. Labeling index reduction between study days 1 and 5 was significantly greater (p < 0.001) with an anthracycline than for the VP group, but there was no difference between the two anthracyclines. Granulocytopenia during induction was significantly increased (p < 0.05) in both the VPD and VPA groups as compared with VP alone. A significantly higher rate of infectious morbidity (p < 0.01) was associated with the addition of either anthracycline, but to date no significant differences in remission duration or survival have been observed.The addition of anthracyclines to VP for remission induction in childhood ALL has theoretical advantages, but may be undesirable because of increased morbidity.
Leukemia following Reye's syndrome treated with exchange transfusions: Search for type‐C viral infection
Authors: Overturf Gary D. , Powars Darleen R. , McAllister Robert M. , Pegelow Charles , Charman Howard P. 
Published: February 2007

AbstractA 5‐year‐old child developed acute lymphoblastic leukemia during convalescence from an episode of Reye's syndrome that was treated with multiple exchange transfusions. Routine laboratory, histology, and viral serology were unable to establish a common etiology for the 2 illnesses. Cultural and immunologic methods to search for evidence of infection with type‐C viruses or viral genes in lymphoblasts from the buffy coat and bone marrow failed to reveal these agents. Although no common infectious etiology was defined for the close temporal occurrence of 2 rare diseases, the possibility of an iatrogenically induced malignancy was considered.
A study of antibiotic therapy in fever of unknown origin in neutropenic cancer patients
Authors: Björnsson Sigurdur , Preisler Harvey , Henderson Edward S. 
Published: February 2007

AbstractNeutropenic cancer patients were given carbenicillin, cephalothin, and gentamicin (CCG) during 51 evaluable episodes of fever of unknown origin. Patients in whom fever persisted despite these antibiotics and in whom infection had not been documented were randomized after 3 days either to discontinue antibiotics or to add chloramphenicol or clindamycin to CCG. During 19 episodes (37%) an infection was documented during the first 3 days, and during an additional 12 episodes (24%) there was a response in 3 days without a focus of infection or an identifiable organism. Two patients died within 3 days, and one developed renal failure. Seventeen febrile episodes (33%) were unresponsive to CCG after 3 days and were randomized. Klebsiella was cultured in 4 of 6 patients randomized to stop antibiotics within a week of cessation, and 3 of these patients died. Of 11 episodes randomized to continue antibiotics, all patients were alive at 2 weeks after randomization and 9 after 4 weeks. This study, albeit small, demonstrates no advantage to withholding treatment in unremitting fever of unknown etiology, and indeed strongly suggests that in this clinical setting, antibiotics once started should be continued until bone marrow recovery.
Phase II study of subcutaneously administered 5‐azacytidine (NSC‐102816) in patients with metastatic malignant melanoma
Authors: Bellet Robert E. , Catalano R. B. , Mastrangelo Michael J. , Berd David 
Published: February 2007

AbstractThirty (30) patients with advanced metastatic malignant melanoma refractory to DTIC (NSC‐45388) and a nitrosourea were treated with 5‐azacytidine (NSC‐102816). 5‐Azacytidine was administered subcutaneously at a dosage of 100 mg/m2/day for 10 days. Twenty‐six (26) patients were evaluable for toxicity and response. Major organ toxicities were hematologic, gastrointestinal, and cutaneous; no antitumor activity was noted.