bluuebunny/crossref_metadata_2025 huggingface dataset:
The combination 5‐fluorouracil/levamisole induces enhanced rat kupffer cell‐mediated cytotoxicity in vitro against the syngeneic colon adenocarcinoma cell line CC531
Authors: Schuurman Bart , Sirovich Igor , Heuff Gijsbert , Van Wilt Clasina L. Der , Peters Godefrinus J. , Beelen Robert H. J. , Meyer Sybren
Published: February 2007

The mode of action of the combination treatment 5‐fluorouracil (5‐FU) and levamisole in colorectal cancer patients is unknown. It is postulated that the beneficial effect may be explained by an immunomodulatory effect on Kupffer cell (KC) cytotoxicity. We evaluated the effect of levamisole (200 (μg/ml) and 5‐FU (10 μM) on rat KC cytotoxicity against syngeneic CC531 tumor cells. Viability of KCs was unaffected by 5‐FU and/or levamisole. The combination did not enhance growth inhibition of CC531 compared to 5‐FU alone. A significant increase in KC cytotoxicity was observed after 24‐hr incubation with 5‐FU/levamisole especially at an effector/target ratio of 10 (P < 0.05). 5‐FU alone had no effect on KC cytotoxicity, while levamisole induced only a slight increase. Our in vitro data suggest that the additive effect of the combination 5‐FU/levamisole on KC cytotoxicity may attribute to the beneficial effect of the adjuvant treatment in colorectal cancer patients. © 1995 Wiley‐Liss, Inc.
Prognostic evaluation of lymphadenectomy for epithelial ovarian cancer
Authors: Kikkawa Fumitaka , Ishikawa Hisatake , Tamakoshi Koji , Sucanuma Nobuhiko , Mizuno Kimio , Kawai Michiyasu , Arm Yoshitaro , Tamakoshi Akiko , Kuzuya Kazuo , Tomoda Yutaka
Published: February 2007

Between 1989 and 1991, 150 patients with ovarian cancer were treated with chemotherapy, including cisplatin, in the Tokai Ovarian Tumor Study Group. Of these patients, 25 underwent cytoreductive surgery with lymphadenectomy, including removal of either pelvic or para‐aortic lymph nodes, and 36 underwent both lymphadenectomies. A significant difference was observed between survival curves of the groups with positive and negative lymph nodes, respectively (P = 0.0049). The overall survival was longer in the lymphadenectomy group than in the nonlymphadenectomy group (P = 0.0842), and a significantly longer survival time was noted for stage III patients who underwent lymphadenectomy compared to those who did not (P = 0.0185). Multivariate analysis demonstrated that lymphadenectomy is a positive prognostic factor. The authors conclude that both pelvic and para‐aortic lymph nodes should be resected to improve survival as well as to assess exact staging in patients with ovarian cancer. © 1995 Wiley‐Liss, Inc.
Treatment of radiation‐induced dermatitis with light‐emitting diode (LED) photomodulation
Authors: DeLand M. Maitland , Weiss Robert A. , McDaniel David H. , Geronemus Roy G.
Published: February 2007

Background and Objective

Light‐emitting diode (LED) photomodulation increases dermal collagen and reduces inflammation. This study evaluated the use of LED photomodulation in the prevention of radiation‐induced dermatitis in breast cancer.

Materials and Methods

Patients (n = 19) were treated with LED photomodulation (Gentlewaves™, Light BioScience, LLC, Virginia Beach, VA) after each of a series of intensity‐modulated radiation treatments (IMRT). Skin reactions were monitored weekly with National Cancer Institute (NCI) criteria. Age‐matched controls (n = 28) received IMRT without LED photomodulation.

Results

In LED‐treated patients, 18 (94.7%) had grade 0 or 1 reaction and 1 (5.3%) had grade 2 reaction. Among controls, 4 (14.3%) had a grade 1 reaction, 24 (85.7%) had a grade 2 or 3 reaction. One LED‐treated patient (5.3%) and 19 controls (67.9%) had to interrupt treatment.

Conclusion

LED photomodulation treatments immediately after IMRT reduces the incidence of NCI grades 1, 2, and 3 skin reactions in patients with breast cancer treated by radiation therapy (RT) postlumpectomy. Lasers Surg. Med. 39:164–168, 2007. © 2007 Wiley‐Liss, Inc.
Effects of femtosecond laser irradiation on osseous tissues
Authors: Girard B. , Yu D. , Armstrong M.R. , Wilson B.C. , Clokie C.M.L. , Miller R.J. Dwayne
Published: February 2007

Background and Objective

Few studies have investigated femtosecond (fs) lasers for cutting bone tissue.

Study Design/Materials and Methods

A 775 nm, 1 kHz, 200 femtosecond, up to 400 µJ laser system was used to irradiate in vitro calcified cortical bone samples and bone tissue culture samples.

Results

The ablation threshold in cortical bone was 0.69±0.08 J/cm2 at 775 nm and 0.19±0.05 J/cm2 at 387 nm. Plasma shielding experiments determined that the ablation plume and the plasma significantly affect material removal at high repetition rates and appear to generate thermal transients in calcified tissue. Confocal analysis revealed intact enzymatic activity on the surface of cells immediately adjacent to cells removed by fs laser irradiation.

Conclusions

These experiments demonstrate that fs lasers used for bone tissue cutting do not appear to generate significant temperature transients to inactivate proteins and that cellular membrane integrity is disrupted for only a few cell layers. Lasers Surg. Med. 39:273–285, 2007. © 2007 Wiley‐Liss, Inc.
Declining mortality and improving survival from Wilms' tumor
Authors: Everson Richard B. , Fraumeni Joseph F.
Published: February 2007

Mortality from kidney cancer in the United States declined dramatically over the period 1940–1969. This trend was nearly proportional to the increases in survival for 644 U.S. children reported to the End Results Group, National Cancer Institute. The improvements in survival occurred for all stages of disease and appeared to result from therapeutic advances rather than earlier detection. Total incidence trends showed no consistent change, but a shift toward female preponderance resembled that seen in the mortality statistics and suggests sex differences in etiology.
Indium‐111 bleomycin tumor scanning in lymphoma
Authors: Jones Stephen E. , Lilien David L. , O'Mara Robert E. , Durie Brian G. M. , Salmon Sydney E.
Published: February 2007

A new radiopharmaceutical, indium‐111 labeled bleomycin (IB), was evaluated as a tumor‐imaging agent in 55 patients with lymphoma. Overall disease activity was correctly identified in 79% of 75 whole‐body scans obtained 48 hours after intravenous administration of IB. Serial scans in 19 patients accurately reflected changes in their disease status. Lymphatic and soft tissue sites of involvement both above and below the diaphragm were most readily identified by scanning. Bone marrow and hepatic involvements were more difficult to detect because of normal tissue background in the considered organs. Five patients manifested diffuse pulmonary uptake of IB and only in one case was it explained.

To determine the accuracy of scanning with IB, we evaluated 731 individual sites of potential tumor involvement with these results: true positives 90%, false negatives 10%, false positives 4%, and true negatives 96%. Thus, tumor scanning with indium‐111 bleomycin is an important new technique for the initial staging and serial evaluation of patients with lymphoma.
Clinical and morphological correlations in acute promyelocytic leukemia
Authors: Valdivieso Manuel , Rodriguez Victorio , Drewinko Benjamin , Bodey Gerald P. , Ahearn Michael J. , McCredie Kenneth , Freireich Emil J
Published: February 2007

Thirty adults with acute leukemia and greater than 20% bone marrow infiltrate by promyelocytes were studied. Eighteen patients had acute promyelocytic leukemia (APML) as defined by the presence of malignant promyelocytes, and the remaining 12 patients had acute myelocytic leukemia (AML) with an elevated percentage of normal promyelocytes. Malignant promyelocytes were characterized by abundant, abnormal, cytoplasmic granules, by Auer rods in meshwork pattern, and by splinter cytoplasmic granulations and dilatation of the cisternae of endoplasmic reticulum. Patients with APML had, in general, greater than 35% bone marrow infiltrate by promyelocytes. The degree of bone marrow infiltrate by these cells correlated with the clinical status of the patients. Diffuse intravascular coagulation with bleeding occurred in 61% of patients with APML, and the bone marrows of these patients had greater than 50% promyelocytes. No coagulation abnormalities were seen among patients with elevated bone marrow promyelocytes infiltrate and without APML. Coagulation abnormalities in patients with APML were only corrected by controlling the leukemia itself. When this occurred, patients with APML had an excellent rate of complete remission, and the duration of remission and survival were comparable to the results obtained in adults with AML.
Response of 65 measurable epidermoid bronchogenic tumors of known spontaneous doubling time to four different chemotherapeutic regimens — strategic deductions
Authors: Israel Lucien , Chahinian Philippe , Depierre Alain
Published: February 2007

Variations in the dimensions of 65 bronchogenic epidermoid tumors of known spontaneous doubling time were studied under the influence of four chemotherapeutic regimens: cyclophosphamide, 19 cases; Mitomycin C, 20 cases; CCNU, 9 cases; and a five‐drug combination, 17 cases. Several parameters were measured, and escape was defined as the moment in time when the growth curve during treatment became parallel to the spontaneous growth curve. The parameters measured were nature and distribution of responses (unchanged progression, slowing‐down, plateau, regression), duration of response, time required to achieve maximum response, and time lapse between maximum response and escape. Regarding application to lung cancer, we have concluded from our results that Mitomycin C should replace cyclophosphamide in combination chemotherapeutic regimens. With regard to general strategy, our results suggest that the drug regimen should be changed as soon as maximum response is reached or immediately following the first course if progression continues unchanged. Moreover, in all of the 27 patients whose tumors regressed, escape occurred within less than three months from the onset of the treatment. In view of this fact and insofar as chemotherapy is considered for adjuvant therapy aiming at complete eradication, sequential combinations would be preferable to prolonged administration of a single agent or combination.
Antibody response to poliovirus immunization in childhood leukemia
Authors: Bosu S. K. , Ciudad Hernan , Sinks Lucius F. , Ogra Pearay I.
Published: February 2007

Polio antibody titers were determined in 29 children with ALL in various clinical stages, including a group of five patients in continuous remission for over five years and who, at the time of study, were off all therapy for at least six months. Regardless of the stage of disease, no detectable YM response was elicited. The five children described above displayed the same depressed response as did the other children with ALL. This strongly suggests an inherent defect in the immune system of these children with ALL unrelated to therapy.
Three dose regimens of adriamycin for induction of remission in acute leukemia in children: A Southwest oncology group study
Authors: Starling K. A. , Berry D. H. , Britton H. A. , Humphrey G. B. , Vats T. , Ragab A. H.
Published: February 2007

Three therapeutic regimens (6‐hr intervals for 6 doses daily for 3 days, and a single infusion) utilizing the same total dose of adriamycin for the induction of remission in children with late‐stage acute leukemia were evaluated in 150 patients. Complete remission rates were 15%, 28%, and 25%, respectively. Twenty‐five children who achieved complete bone marrow remissions with adriamycin therapy were treated a second time after subsequent relapses. Of these children 20% achieved second bone marrow remissions.
Active specific immunization in malignant melanoma
Authors: Gercovich Felipe G. , Gutterman Jordan U. , Maviigit Giora M. , Hersh Evan M.
Published: February 2007

The effects of active specific immunization with nonirradiated autologous and irradiated cultured allogeneic melanoma tumor cells (TC) on cell‐associated immunity was studied in 11 patients with widespread malignant melanoma receiving chemoimmunotherapy. Immunization with 1 × 106‐8 × 107 TC was done in the draining area of a BCG scarification on day 7 of the study. The in vitro lymphocyte blastogenic response (BR) to autologous TC was studied in terms of the stimulation index on day 1, 7, 14, and 21. The stimulation index (SI) was the counts per min (cpm) in the TC stimulated culture minus the cpm among the TC alone divided by the cpm in the unstimulated controls. A positive BR was considered as a SI equal to or greater than 3. Six out of 11 patients had a significant increase in BR lasting 7‐14 days after immunization. The pre‐ to post‐immunization changes in the SI of the 6 patients were 2.5 to 7.5; 0.7 to 3.2; 0 to 5.2; 0 to 16; 0.1 to 6.6; and 6.5 to 30.0. Nine out of 11 patients showed a delayed local inflammatory reaction at the immunization site. Five out of 11 patients mounted a cutaneous delayed hyper sensitivity reaction to autologous tumor cells at a separate test site following immunization. There were no side effects. Active specific immunization in the drainage of a BCG reaction appears to be safe. Since a positive BR to autologous TC correlates with a good prognosis in patients with solid tumors, studies of the immunotherapeutic efficacy of this approach may be warranted.
The influence of sequential chemotherapy and radiotherapy on mitogen‐induced lymphocyte transformation in patients with acute lymphoblastic leukemia
Authors: Humphrey G. Bennett , Parker Donald E. , Nesbit Mark , Krivit William
Published: February 2007

Although these studies do not allow a definitive differentiation between the relative influence of chemotherapy and radiotherapy on mitogen‐induced lymphocyte transformation, the data suggested both radiotherapy and chemotherapy can cause depression; however, radiotherapy may have a more pronounced effect. The relationship between the absolute peripheral blood lymphocyte count and phytohemagglutin and pokeweed mitogen‐induced lymphocyte transformation was also analyzed. These data revealed that patients who are receiving or who have received intensive therapy may have normal peripheral absolute lymphocyte counts with impaired lymphocyte transformation. Serial studies of lymphocyte transformation were evaluated in 10 children with acute lymphoblastic leukemia who received both chemotherapy and radiotherapy.
The disparity of the size of the liver as determined by physical examination and by hepatic gammascanning in 504 patients
Authors: Ariel Irving M. , Briceno Melchor
Published: February 2007

The liver extended a minimum of 5 cm inferior to the right costal margin in 51% of the 504 patients studied. In 53% of these patients, experienced, mature physicians declared that the liver was not palpable on physical examination. In 3% of the cases, a mass was palpated which was believed to be liver by the examining physician but was found to be extrahepatic upon scanning and laparotomy.

The unreliability of physical examination in determining whether or not the liver extends inferior to the costal margin in many instances is demonstrated.
Clinically significant cardiac infiltration in acute leukemia, lymphocytic lymphoma, and plasma cell myeloma
Authors: Wiernik Peter H. , Sutherland John C. , Stechmiller Bruce K. , Wolff John
Published: February 2007

Cardiac infiltration by hematologic neoplasms leading to clinically significant cardiovascular disease is rare. Three such cases are described in this report, and it is suggested that rare manifestations of hematologic neoplasms may become more common in the future since these diseases are more amenable to therapy than heretofore. Cardiac involvement with hematologic neoplasms is of more than academic interest since this complication is likely to respond to radiotherapy.
A controlled clinical trial of fluorouracil plus imidazole carboxamide dimethyl triazeno plus vincristine plus bis‐chloroethyl nitrosourea plus radiotherapy in stomach cancer
Authors: Falkson Geoffrey , van Eden Errol B. , Sandison A. G.
Published: February 2007

The aim of this study was to seek a better treatment for patients with inoperable or recurrent stomach cancer. Seventy patients were randomly allocated to receive courses of treatment with either A (5‐Fluorouracil plus radiotherapy) or B (5‐Fluorouracil plus Imidazole Carboxamide Dimethyl Triazeno plus Vincristine plus Bis‐Chloroethyl Nitrosourea plus radiotherapy). Only 59 of these patients were evaluable. The median survival time of patients allocated to Group A was 220 days and Group B was 199 days. Seventeen of 31 patients in Group A and 10 of 28 patients in Group B had objectively documented remission. The median survival time of responders was 222 days for Group A and 410 for Group B. While it would appear that those patients who respond to the more intensive treatment do better, a larger percentage of patients responded to the simpler treatment regimen of 5‐Fluorouracil plus radiotherapy.
Neutrophil leukocyte reserves in lymphoreticular malignancies
Authors: Fortuny Ignacio E. , Theologides Athanasios , Hadlock Daniel C. , Kennedy B. J. , Deinard Amos
Published: February 2007

The marginal neutrophil leukocyte pool and the bone marrow neutrophil reserves were assessed in 43 patients with lymphoreticular malignancies, using epinephrine and steroid stimulation. Thirty‐three patients were studied before staging, following splenectomy, before and after nodal irradiation and during remission induction chemotherapy. Ten patients in partial remission were studied after 12 months or more of chemotherapy. A neutrophil count of 1,500–2,500 cells/mm3 is not a sufficient guide for modifying the chemotherapy. The response to steroid stimulation may be a more dependable guide to evaluate the patient's potential risk for infection.
Remission induction with L‐asparaginase, vincristine, and prednisone in children with acute nonl ymphoblastic leukemia
Authors: Land Vita J. , Sutow Wataru W. , Dyment Paul G. , Falletta John M. , Morgan Samuel K. , Bryan J. Hugh
Published: February 2007

Forty‐five children with acute nonlymphoblastic leukemia in relapse received a total of 56 courses of L‐asparaginase combined with vincristine and prednisone. The complete remission rate of 40% (12 of 30 trials) in patients resistant to vincristine and prednisone was almost identical to that in children still sensitive to vincristine and prednisone (42%, 11 of 26 trials). The complete remission rate of 38% (14 of 37 exposures) in those children who had not received L‐asparaginase previously compared favorably with the complete remission rate in those children who had received prior L‐asparaginase (47%, 9 of 19 exposures). Forty‐seven of the 56 induction trials were in children with 1 or more remissions and 14 of these were in children with 3 or more prior remissions. Toxicity was minimal.
Inhibition of uridine‐cytidine kinase by 5‐azacytidine 5′‐triphosphate
Authors: Lee Thomas T. , Momparler Richard L.
Published: February 2007

5‐Azacytidine 5′‐triphosphate (5‐aza‐CTP) inhibited the phosphorylation of uridine, cytidine, and 5‐azacytidine (5‐aza‐C) in a reaction catalyzed by uridine‐cytidine kinase. The inhibition appeared to be competitive with respect to the adenosine 5′‐triphosphate and noncompetitive with respect to nucleoside substrates. 5‐aza‐CTP was a potent inhibitor of 5‐aza‐C phosphorylation but a weak inhibitor of uridine and cytidine phosphorylation. These results suggest that the feedback inhibition of uridine‐cytidine kinase by 5‐aza‐CTP may limit the amount of intracellular nucleotide analog formed in drug‐treated cells.
A new hamster fibrosarcoma model for in vitro/in vivo evaluation of cancer chemotherapeutic agents
Authors: Benedict William F. , Khwaja Tasneem A.
Published: February 2007

A hamster fetal cell clone has been developed for in vitro chemotherapeutic studies as well as in an in vivo fibrosarcoma model system. Highly reproducible quantitative in vitro chemotherapeutic data can be obtained with this cell line within 5 days, and as few as 102 cells produce rapidly growing fibrosarcomas when injected subcutaneously into adult hamsters. We found using these cells in vitro that 1‐β‐D‐arabinofuranosylcytosine (ara‐C) can antagonize the effect of 5‐azacytidine (aza‐C) if given simultaneously or if aza‐C treatment is preceded by a 2‐hr exposure to ara‐c. Using the same cell line as in vivo model for chemotherapy it was also shown that ara‐C and cyclocytidine significantly inhibited tumor growth. This hamster cell line may be quite useful as an in vitro/in vivo model system for the study of cancer chemotherapeutic agents.
Uptake of 1‐β‐D‐arabinofuranosylcytosine and prednisolone by synchronized human lymphoma cells
Authors: Persohn Linda K. , Drewinko Benjamin , Loo Ti Li
Published: February 2007

The cytotoxicity of many antitumor agents exhibits cell‐cycle phase specificity. Using a human lymphoma cell line synchronized by thymidine block, we have investigated the differential uptake of radioactive 1‐β‐D‐arabinofuranosylcytosine (ara‐C) and prednisolone in various phases of the cycle. Uptake of ara‐C is highest during early S and declines steadily throughout the rest of the cycle. In comparison, prednisolone demonstrates no significant age‐dependent difference in uptake although its cytotoxicity is cell cycle sensitive.
L‐asparaginase reinduction and maintenance therapy in previously treated acute lymphocytic leukemia
Authors: Sieger Lance , Higgins Gussie , Ortega Jorge , Shore Nomie , Williams Kenneth
Published: February 2007

Four patients with acute lymphocytic leukemia previously treated with conventional chemotherapy received intramuscular L‐asparaginase in combination with other chemotherapy for reinduction and maintenance therapy. These patients received the L‐asparaginase for 8, 14, 27, and 34+ months without demonstrating any significant adverse effects. Only 1 of the 4 was clearly resistant to the other chemotherapy, and 3 of 4 had recurrence of their disease while receiving L‐asparaginase. L‐asparaginase can be added to reinduction and maintenance regimens of patients resistant to other chemotherapy and is well tolerated for long periods when given intramuscularly weekly with other immunosuppressant agents.
Overview of early and investigational chemotherapeutic agents in solid tumors
Authors: Rozencweig Marcel , Slavik Milan , Muggia Franco M. , Carter Stephen K.
Published: February 2007

A tentative evaluation is proposed for the clinical status of 15 early and investigational drugs in human solid tumors.
Emphysematous gastritis in A leukemic child
Authors: Rowen Marshall , Myers Marilyn , Williamson Robin A.
Published: February 2007

Emphysematous gastritis associated with gram‐negative sepsis is described in a leukemic child on chemotherapy and steroids. Bubbly‐appearing air and thickening of the gastric wall were radiographically demonstrated. This is analogous to the demonstration of air within the thickened bowel wall in necrotizing enterocolitis, which is not unusual in seriously ill leukemic children. Gastric involvement has not been previously reported.
Breast cancer: Lack of prognostic value of adrenal pathology at adrenalectomy
Authors: Boasberg Peter D. , Warner Nancy E. , Hall Thomas C. , Helsper James T. , Donovan Arthur J.
Published: February 2007

The adrenal glands of 58 patients undergoing adrenalectomy for advanced breast cancer were reviewed and correlated with the subsequent course of the patients' disease. Three patients had thecomatous metaplasia in the adrenal cortex, six patients had myelolipomatous changes, and 13 patients had metastatic breast cancer in their adrenal glands at the time of adrenalectomy. Neither the presence of metastases nor myelolipomatous changes were associated with a long disease‐free interval, a long period from mastectomy to adrenalectomy, or a prolonged postadrenalectomy survival The patients with metastatic breast cancer in the adrenal glands had more widespread disease than patients without adrenal metastases. The presence of breast cancer metastases in the adrenal glands at the time of adrenalectomy identifies patients further advanced in the course of their disease, but is not related prognostically to the effect of adrenalectomy.
Cyclophosphamide, vincristine, and prednisone (CVP) versus adriamycin, bleomycin, and prednisone (ABP) in stage IV non‐Hodgkin's lymphomas
Authors: Monfardini Silvio , Tancini Gabriele , Delena Mario , Villa Eugenio , Valagussa Pinuccia , Bonadonna Gianni
Published: February 2007

In stage IV non‐Hodgkin's lymphomas, CVP (cyclophosphamide, vincristine, and prednisone) was randomly compared to ABP (adriamycin, bleomycin, and prednisone). Of 62 patients entered into the study, 57 (CVP 27, ABP 30) were considered evaluable for comparison. In patients with liver and/or marrow involvement a second biopsy was performed to define complete remission (CR). CR occurred in 48% of patients treated with CVP and in 50% of those given ABP. The median duration of CR was 10.5 and 20.5 months, respectively. The difference is not statistically significant. Also the survival of complete responders was not significantly different between the two treatment groups. After cross‐over, secondary treatment with CVP produced an overall response rate of 40% (six of 15), compared to 50% (six of 12) obtained with ABP. In the ABP group, four patients developed a reversible interstitial penumonia. In two other patients, cardiomyopathy (fatal in one) was observed. In conclusion, although complete remission was similar in both groups, cumulative toxicity occurred in few patients given ABP. However, this combination could represent in effective alternative treatment to be used either in CVP failures or in sequence with CVP.
Neurotoxicity Due to CNS Therapy for Leukemia
Authors: Pochedly Carl
Published: February 2007

CNS symptoms ranging from mild to lethal have occurred following CNS radiotherapy and intrathecal chemotherapy. Cranial radiotherapy often produces signs of mild encephalopathy, with predominance of somnolence. In rare cases, it appears that CNS radiotherapy may be followed by progressive encephalopathy. Intrathecal methotrexate frequently causes symptoms of meningeal irritation. Occasionally cases of weakness and paralysis, and rare instances of severe encephalopathy, may occur. However, in leukemic children treated with intensive chemotherapy and CNS radiotherapy who develop neurological complications, it is often difficult to determine which of many possible factors may be causing the CNS symptoms. The pathogenesis of the various forms of methotrexate neurotoxicity is poorly understood. The best‐established cause for these symptoms is high concentrations of methotrexate in the CSF or prolonged exposure of the brain to low CSF concentrations of methotrexate. These elevated concentrations of the drug may in turn be due to impaired elimination of the drug from the cerebrospinal fluid (usually due to overt CNS leukemia) or to increased dosage in relation to cerebrospinal fluid volume (due to adolescent age). Leukoencephalopathy is occasionally found at autopsy in children given intensive therapy with CNS radiotherapy and intrathecal methotrexate, together with intensive systemic chemotherapy. It was proposed that alteration of the blood‐brain barrier by cranial radiotherapy allows systemically administered anti‐leukemic drugs to enter the brain and to cause necrotic changes in the CNS white matter. Leukoencephalopathy also occurs following intraventricular administration of methotrexate. CNS‐toxicity due to intrathecal cytosine arabinoside is clinically similar to the symptoms seen following intrathecal methotrexate.
Social and Ethical Implications of Claims for Cancer Hazards
Authors: Weisburger John H.
Published: February 2007

Current data show that about 80% of human cancers can be traced to environmental causes. The majority of human cancers are associated with two main etiologic factors: smoking of cigarettes and diet, which account for most of the cancers in the respiratory tract, in the digestive tract, and in the endocrine sensitive and reproductive organs. The evidence for these multifactorial causes is both epidemiologic and experimental. In recent years a number of lay and professional groups have expressed concern that the microcontaminants in our environment are responsible for cancer in man. Agitation, press releases, and statements before legislative and executive government departments have made claims for cancer hazards which do not appear to rest on sound epidemiologic or experimental bases, yet these claims have alarmed and indeed scared the public. Government agencies and industry have spent funds to investigate such claims. It appears that such actions not only divert valuable research funds and efforts into lines which do not seem to be fruitful in leading to a reduction in cancer risk for the main human cancers, but by falsely alarming the public, dilute serious efforts of cancer prevention with respect to the experimentally and epidemiologically established cancer risks.
Releasing carcinogenesis test results: Timing and extent of reporting
Authors: Saffiotti Umberto , Page Norbert P.
Published: February 2007

A carcinogenic response in an animal bioassay is usually characterized by gradual accumulation of a tumor incidence significantly in excess in the treated versus the control animals. In some cases, a definite response is realized relatively early, prior to planned sacrifice. In others, positive results are found at termination. In both cases, a long delay may occur before the information is ready to reach the public due to the time needed to complete pathology, data analysis, and publication of a report. Since the finding that a chemical is carcinogenic may have serious implications for public health and technology, reports of carcinogenesis bioassays should be thoroughly and critically reviewed before being issued. A delicate ethical dilemma confronts scientists in selecting the proper timing and extent for the release of carcinogenesis test results. Early findings may not be confirmed and may cause technological and economic problems and unnecessary anxiety. On the other hand, delaying public notification of highly suspicious findings until a final, detailed report is published, may delay preventive actions that could protect exposed populations from unnecessary risks. To meet differing requirements in regard to timing and extent of reporting, procedures were developed to issue reports on National Cancer Institute (NCI) carcinogenesis bioassays when the findings are clearly identified and well documented in the following forms: a) reports of preliminary findings, when the evidence is strongly suggestive; b) summary reports of completed bioassays; and c) detailed technical reports. Availability of such reports, particularly for preliminary findings, will be announced in the Federal Register and in a press release. The reports will be submitted for publication in the scientific literature.
Estimation of risks due to environmental carcinogenesis
Authors: Cranmer Morris F.
Published: February 2007

Several Federal agencies share responsibility for enforcing laws designed to control human exposures to carcinogens. This enforcement activity often has immense effects on other factors of our environment. Absolute safety is not possible, but increased protection is obtainable. Improvements are urgently needed in our ability not only to detect but also to quantify relative risk. Resources should be directed for maximum overall effect. Relative risk must be quantified if we are to reasonably compare risk and benefit. Examples of the inexactness of current toxicological epidemiological, and mathematical models for estimating risk due to exposures to DDT, aflatoxinb1, DES, and benzidine are presented. The impact of different laws and regulations applicable to the control of these agents is compared. Reference is made to major programs in toxicological methods for risk estimation.
A phase II evaluation of bacillus calmette‐guerin plus megestrol acetate in patients with metastatic renal adenocarcinoma
Authors: Laucius J. Frederick , Patel Yogish A. , Lusch Charles J. , Koons Lawrence S. , Bellet Robert E. , Mastrangelo Michael J.
Published: February 2007

The case is reported of a patient with pulmonary metastases from a renal adenocarcinoma who experienced subjective improvement and objective tumor regression on Bacillus Calmette‐Guerin (BCG) and megestrol acetate therapy. In a subsequent Phase II trial, no objective responses were noted among 15 patients treated with megestrol acetate (160 mg/day × 56 days) and BCG (five immunizing doses intradermally, every 2 weeks × 5). It is concluded that this treatment regimen is not clinically useful in patients with metastatic renal adenocarcinoma.
Adriamycin in combination chemotherapy of adult acute lymphoblastic leukemia: A southwest oncology group study
Authors: Shaw Michael T. , Raab Spencer O.
Published: February 2007

Eighteen (72%) of 25 evaluable and previously untreated patients with adult acute lymphoblastic leukemia entered complete remission (CR) following induction therapy with Adriamycin, vincristine, and prednisone in a Southwest Oncology Group study. Remission maintenance therapy with methotrexate and 6‐mercaptopurine resulted in a median duration of CR of 10.2 months. The addition of Adriamycin to prednisone and vincristine may be beneficial in slow responders or nonresponders to these two drugs and in patients with initially high peripheral blood blast counts.
Lymphocyte function in the blood of patients with untreated non‐hodgkin lymphoma: Influence of stage and pathology
Authors: Thatcher Nick , Gasiunas Nijole , Crowther Derek , Potter Michael R.
Published: February 2007

Lymphocytotoxicity of T, non‐T and K cells was found to be diminished in a proprotion of 30 patients with untreated non‐Hodgkin lymphoma; T cell number as enumerated by E sheep cell rosettes was also reduced. The reduction was greatest in patients with disease of unfavorable pathology; the effect of stage on these tests was not marked. Decreased skin reactivity was found in the same group of patients with unfavorable pathology. The reduction of direct and antibody dependent lymphocytotoxicity was not related to an obvious reduction in non‐T cell numbers, as assessed by rosetting tests. There was, however, a decrease in phytohemagglutinin cytotoxicity in those groups with reduced T cell number. The influence of unfavorable pathology on lymphocyte effector function is emphasized by this study.
Chemotherapy with cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP) in childhood acute lymphoblastic leukemia (ALL)
Authors: Sallan Stephen E. , Camitta Bruce M. , Chan David M. , Traggis Demitrius , Jaffe Norman
Published: February 2007

Three groups of children with acute lymphoblastic leukemia (ALL) were treated with intermittent cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP). Group A (no prior relapse) and Group B (prior single‐agent relapse) received COAP after 12 months on another chemotherapy regimen. Children in Group C (prior relapse on multiagent regimens) received COAP following A‐COAP (asparaginase plus COAP) reinduction. Median disease‐free survival after beginning COAP was not reached for Group A, but was only 7 months for Groups B and C. As of November 1976, there were 8 of 15 Group A patients, 1 of 12 Group B patients, and 1 of 28 Group C patients who had remained disease‐free from 38 to 60 (median 54.5) months and were off chemotherapy. COAP has activity in childhood ALL. However, effectiveness in markedly diminished in patients with prior bone marrow relapse.
Lack of correlation between blast cell size and length of first remission in acute lymphocytic leukemia in childhood
Authors: Wagner Virginia M. , Baehner Robert L.
Published: February 2007

The bone marrow from 55 children with acute lymphocytic leukemia diagnosed from April 1969 to June 1973 were evaluated for blast cell morphology and size. Sixteen marrows contained a predominance of macrolymphoblasts (> 12 μ), while the remainder contained mainly microlymphoblasts. There was no correlation between blast cell size and the known front‐end prognostic indicators of age and initial white blood count, nor could blast cell size be used to predict the length of initial bone marrow remission.
Hexamethylmelamine treatment of sarcomas and lymphomas
Authors: Borden Ernest C. , Larson Paula , Ansfield Fred J. , Bryan George T. , Johnson Robert O. , Ramirez Guillermo , Wilson William L.
Published: February 2007

An evaluation of the effectiveness of hexamethylmelamine (HMM) in the treatment of tumors of mesenchymal origin was undertaken in 75 patients. To determine the efficacy of HMM for treatment of sarcomas, records of 61 patients treated with this drug were reviewed. One patient with metastatic osteosarcoma obtained a complete response of greater than 8 years duration. Shorter partial responses were observed in individual patients with a leiomyosarcoma, a fibrosarcoma, and a lymphangiosarcoma. Stabilization of disease process for intervals up to 5 years occurred in 20 patients with sarcomas. The records of 14 Hodgkin and non‐Hodgkin lymphomas treated with HMM were also reviewed. Two of these patients had complete responses while partial responses were noted in 10 others. Although a variety of dosages were used, all responses were at doses of 8 mg/kg and almost all occurred within 30 days of initiation of therapy. Responses were observed in 5 lymphoma patients who had had prior alkylating‐agent therapy. At the doses used (up to 12 mg/kg), only 17% of the patients had white blood counts less than 3,000, and only 4% had platelet counts below 50,000. Moderate to severe gastrointestinal toxicity limited therapy in 48% of patients.
Effective combination chemotherapy of adult malignant histiocytosis (histiocytic medullary reticulosis)
Authors: Cabanillas Fernando , Rodriguez Victorio , Valdivieso Manuel , Butler James J. , Burke Jerome S.
Published: February 2007

Adult malignant histiocytosis, also known as histiocytic medullary reticulosis, has been, in the past, considered a very aggressive disorder usually resistant to chemotherapy. Management in the past has included either single agent therapy or splenectomy. Recently, several cases have been reported that have responded favorably to combination chemotherapy. This paper reports on our experience with combination chemotherapy for this disorder. Of three patients treated, all three responded with a complete remission and two remain alive and free of disease at the present time. The outlook for patients with this diagnosis appears to be changing favorably with the advent of new treatment regimens.
Mitomycin‐C alone and in combination with infused 5‐fluorouracil in the treatment of disseminated gastrointestinal carcinomas
Authors: Buroker Thomas R. , Kim Paik N. , Baker Laurence H. , Ratanatharathorn Voravit , Wojtaszak Bonnie , Vaitkevicius Vainutis K.
Published: February 2007

One hundred and thirty‐two previously untreated patients with metastatic adenocarcinoma of the gastrointestinal (GI) tract were randomized to receive either a 120‐hr infusion of 5‐fluorouracil (5FU) with mitomycin‐C or mitomycin‐C alone. Superiority of the combination treatment was demonstrated with remissions in 30 out of 82 (37%) patients versus 9 out of 50 (18%) with the single drug treatment (P = 0.02). The median survival with 5FU—mitomycin‐C was 29 weeks, as opposed to 20 weeks with mitomycin‐C alone (P = 0.03). The combination produced significantly more severe myelotoxicity than the single drug, and jaundiced patients experienced more myelosuppression than non‐jaundiced patients with both treatments.
Calcinosis in nonparathyroid malignant disease: An unusual case report and clinicopathologic review of 17 cases
Authors: Hall Stephen W. , Luna Mario A. , Bedrossian Doctorcarlos , Rodriguez Victorio
Published: February 2007

An unusual finding of systemic calcinosis in a patient with a nonparathyroid malignant neoplasm stimulated us to do a clinicopathologic review of similar cases at our institution in the past seven years. Of 3,268 autopsies performed from 1968 to 1975, a total of 17 cases of calcinosis were found, 11 with solid tumors and 6 with hematopoietic neoplasms. Calcinosis was most prominent in the lung, kidney, heart, and stomach and was rarely discovered prior to death. Eighty‐two percent of the patients had hypercalcemia and 53% had associated bony metastatic disease. Corticosteroid or phosphate treatment for the hypercalcemia may have contributed to the tissue deposition of calcium. Significant hepatic, renal, metabolic, and pulmonary dysfunctions were also associated with this disorder. Thirty‐six percent of the patients had hypercalcemia without skeletal involvement; tumor‐produced para‐thormone‐like substances may be responsible for these calcium abnomalities. Calcinosis was a significant complication of neoplastic disease in these patients and contributed to morbidity and mortality.
Therapeutic leukopheresis of acute myelo‐monocytic leukemia in pregnancy
Authors: Meyer Richard J. , Cuttner Janet , Truog Peter , Ambinder Edward P. , Holland James F.
Published: February 2007

Cytopheresis techniques have proven useful in the provision of platelets and granulocytes for transfusion to the pancytopenic patient. Mechanical cell removal has been applied to the treatment of chronic myelocytic and lymphocytic leukemias and the Sezary syndrome. We have treated a 16‐year‐old pregnant acute myelomonocytic leukemia (AMML) patient for 12 weeks solely with the use of intensive leukopheresis utilizing batch processing centrifugation and packed red cell transfusions. The patient presented with a white blood cell count of 54,000/mm3 with 64% myelomonoblasts, a platelet count of 45,000/mm3, marked gingival hyperplasia, and splenomegaly. Patient had a normal spontaneous delivery of a 2.5‐kg male infant without complications. At the time of delivery, 12 weeks later, the white blood count had fallen to 4,900/mm3 with 8% blasts and the platelet count had risen to over 100,000/mm3. Gingival hyperplasia decreased and the patient felt well. We have treated an additional small group of patients with acute myelogenous leukemia (AML) with high white counts with short term intensive leukopheresis followed by chemotherapy with promising results.
Hepatocellular carcinoma in a young woman with prolonged exposure to oral contraceptives
Authors: Gattanell Perry N. , Perloff Marjorie , Holland James F.
Published: February 2007

A case of hepatocellular carcinoma in a young female is presented in which the apparent etiology was the use of oral contraceptives for 51/2 years. Sequential therapeutic trials with intraarterial 5‐fluorouracil, intraarterial adriamycin, and intravenous 1,3 bis[2‐chloroethyl]‐1‐nitrosourea (BCNU) were unsuccessful. The adverse effects of oral contraceptives on the structure and function of hepatic tissue are reviewed.
Cis‐diamminedichloroplatinum (NSC‐119875) in childhood malignancies: A southwest oncology group study
Authors: Nitschke Ruprecht , Starling Kenneth A. , Vats Tribhawan , Bryan Hugh
Published: February 2007

Children with malignancies resistant to conventional therapy were treated with cis‐diamminedichloroplatinum (PDD), 1 5 to 20 mg/m2, given daily by rapid intravenous infusion for 5 days at 3‐wk intervals. Eleven of 24 children with acute lymphocytic leukemia (ALL) received two or more courses; among these no remissions occurred. Fifty‐four children with solid tumors were treated: 25 neuroblastoma, 9 rhabdomyosarcoma, 4 Ewing sarcoma, 2 testicular embryonal carcinoma, 2 retinoblastoma, and 12 miscellaneous tumors. One complete remission, 3 partial remissions, and 2 improvements were observed in children with neuroblastoma. One girl with metastatic osteogenic sarcoma achieved a partial remission. One child with metastatic testicular embryonal carcinoma showed improvement. The side effects were vomiting controlled by antiemetics in 26 children and transient elevations of serum creatinine and BUN in 14 children. Nineteen of 39 children with solid tumors, who received more than one course of PDD, had moderately severe myelosuppression caused by PDD. In summary, PDD is a promising agent in neuroblastoma, osteogenic sarcoma, and testicular embryonal carcinoma, and an ineffective agent in ALL. The effect of PDD on other types of solid tumors should be evaluated in the future.
κ light chain — myeloma associated with adult Fanconi syndrome: Response of the nephropathy to treatment of myeloma
Authors: Gailani Salman , Seon Byeong‐Kuk , Henderson Edward S.
Published: February 2007

The association of Bence Jones proteinuria with adult Fanconi syndrome has been reported in a small number of patients. The nephropathy and the Bence Jones proteinuria often precede by several years the diagnosis of frank myeloma.

A 39‐year‐old woman developed renal glucosuria 2.5 years prior to the diagnosis of a plasma cell disease characterized by k Bence Jones proteinuria, osteolytic lesions, and histologically proven plasmacytomas. Serum phosphorus of 1.1–2.1 mg/dl and uric acid of 1.3–1.6 mg/dl were compatible with Fanconi syndrome. Glucosuria was constantly present, while the glucose tolerance test was normal. Urinary β2 microglobulin (β2M) excretion was up to 135 mg/24 hours (normal less than 0.14 mg), indicating failure of tubular absorption of this protein. Amino‐aciduria was noted. The patient's myeloma responded to irradiation followed by melphalan plus prednisone and vincristine; the result was a marked reduction of the Bence Jones proteinuria. Some of the manifestations of the Fanconi syndrome disappeared, while the others were markedly reduced; this included disappearance of the glucosuria, elevation of the serum phosphorus and uric acid to normal, decrease of the urinary amino acid excretion to the normal range in 11 of the 14 amino acids tested, and decrease in the β2 M excretion to 5.4 mg/24 hours. The response of the Fanconi syndrome to the treatment of myeloma supports the view that the nephropathy is due to the myeloma process, probably through renal tubular injury induced by Bence Jones proteinuria.
Relapse of Hodgkin disease after extended‐field radiotherapy
Authors: Horner Richard J. , Chaffey John T. , Rosenthal David S. , Moloney William C.
Published: February 2007

Thirteen relapses occurred among 51 consecutive surgically staged patients with I, IIA, and IIIA Hodgkin disease who achieved complete remission following extended‐field radiotherapy.

The median disease‐free interval was 14 months, but three disseminated relapses occurred at 36, 36, and 39 months. In 6 of the 13 cases, relapses occurred within treated fields. Relapse frequency was greater with advancing stage, but was not related to histology. In 9 of 12 evaluable cases the patients achieved complete remission with MOPP

MOPP: mustargen, oncovin, procarbazine, prednisone (12).

combination chemotherapy. All responders continue in complete remission a median time of 23 months after completing MOPP.

This report emphasizes the need for sustained, close follow‐up after radical radiotherapy and the excellent response rate of relapsed patients to MOPP combination chemotherapy.
L‐asparaginase‐induced coagulopathy during therapy of acute lymphocytic leukemia
Authors: Sills Richard H. , Nelson Douglas A. , Stockman James A.
Published: February 2007

L‐Asparaginase‐induced coagulation abnormalities were observed in all patients receiving this drug. All patients studied demonstrated low factor IX and fibrinogen levels and most (75%) had low levels of factor XI. Disturbances in other factors were much less frequent. Despite the presence of markedly abnormal coagulation studies, clinical bleeding was not observed.