bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant interferon‐ALPHA2b and high dose methyl prednisolone in relapsed and resistant multiple myeloma
Authors: Ganjoo R. K. , Johnson P. W. M. , Evans M. L. , Williams A , Rohatiner A. Z. S. , Lister T. A. , Malpas J. S.
Published: February 2007

Twenty‐one patients with referactory myeloma (10 primary resistant and 11 relapsed resistant) were treated with a combination of high dose methyl prednisolone and recombinant interferon alpha2b (IFN‐α2b). This treatment included three megaunits/m2 of IFN‐α2b three times a week for 12 weeks, plus 5‐day pulsed high dose methyl prednisolone every 3 weeks for two courses. A partial response (more than 50 per cent reduction in paraprotein) was observed in six patients; two of these had a greater than 75 per cent reduction in paraprotein, and evaluation of bone marrow showed <5 per cent plasma cells. A minimal response (more than 25 per cent reduction in paraprotein) was seen in four patients, giving an overall objective response rate of 10/21 (48 per cent). Subjective response, in terms of subsidence of pain and improvement of performance status, was seen in all patients who had adequate therapy.

The protocol was generally well tolerated with minimal side‐effects. There were 4/21 (19 per cent) treatment‐related deaths which, though considerable, was anticipated in such a study population. The excellent subjective response seen supplements the objective response observed, and suggests a potential role for the combination of methyl prednisolone and IFN‐α2b in refractory myeloma.
Oligonucleotides in the treatment of leukemia
Authors: Bayever Eliel , Iversen Patrick
Published: February 2007

The use of synthetic oligonucleotides directed towards specific genes in the therapy of leukemias has evolved rapidly over the past 5 years to early clinical trials. Undoubtedly, use of these compounds for systemic therapy and bone marrow‘purging’ will escalate. Such trials will be models for the treatment of many other malignant diseases and, indeed, non‐malignant diseases which may be expected to respond to eradication of a specific gene function. We are currently at the threshold of a new era of therapy which holds the promise of totally transforming clinical medicine in the next decade.
Prognosis in low grade non‐Hodgkin's lymphoma: relevance of the number of sites involved, absolute lymphocyte count and serum immunoglobulin level
Authors: Parker D. , Alison D. L. , Barnard D. L. , Child J. A. , Dovey G. , Farish J. , Norfolk D. R. , O'brien C. J. , Parapia L. A. , Sharp J. , Simmons A. V.
Published: February 2007

Eighty‐eight patients with low grade non‐Hodgkin's lymphoma were followed for a median period of 63 months. Sixty‐eight per cent of the group were centrocytic/centroblastic B cell lymphomas by the updated Kiel classification. Fifty‐one (58 per cent) of the patients were stage IV by the Ann Arbor classification. In 18 of these patients the bone marrow was the only site of extranodal involvement. Univariate survival analysis showed that the sum of involved sites was more discriminatory than Ann Arbor stage. Analysis by site of involvement showed that the liver and other intraabdominal sites were associated with worse survival than involvement of peripheral lymph nodes. Bone marrow and spleen involvement were not significantly associated with short survival. Increasing age at presentation was strongly associated with shorter survival and was also inversely correlated with serum albumin. Both low absolute lymphocyte count (<1.0 × 10 9/1), low serum IgG level (<10 g/1) and low total immunoglobulins on presentation were significantly associated with short survival. Multivariate analysis showed that age, serum albumin and number of involved sites gave the best survival prediction. The sum of involved sites, immunoglobulin level and absolute lymphocyte count may be useful objective markers of prognosis in low‐grade non‐Hodgkin's lymphoma.
Reactive hemophagocytic syndrome in childhood—frequent occurrence of atypical mononuclear cells
Authors: Wong K. F. , Chan J. K. C. , Ha S. Y. , Wong H. W.
Published: February 2007

Reactive hemophagocytic syndrome, which is characterized by systemic proliferation of benign hemophagocytic histiocytes, usually presents as an acute febrile illness with pancytopenia and hepatosplenomegaly. The commoner diseases associated with the syndrome are infection and malignant lymphoma. In this report, eight cases of reactive hemophagocytic syndrome occurring in infants and young children are described. Unlike the disease occurring in adults, there is frequent occurrence of atypical mononuclear cells both in the peripheral blood and bone marrow. The morphological spectrum of these atypical cells is however still within that seen in infectious mononucleosis, and their reactive nature is substantiated by their spontaneous disappearance and subsequent recovery of the patients. It is important to distinguish this reactive proliferation from the neoplastic cells of‘malignant histiocytosis’ or malignant lymphoma, since cytotoxic drugs are not warranted for treatment of this non‐neoplastic condition.
Non‐cryopreserved, limited number (1 or 2) peripheral blood progenitor cell (PBPC) collections following GCSF administration provide adequate hematologic support for high dose chemotherapy
Authors: Bezwoda W. R. , Dansey R. , Seymour L. , Glencross D.
Published: February 2007

Sixty‐two patients with a variety of malignant diseases including 44 with breast cancer, seven with sarcomas, five with germ cell tumours, four with Hodgkin's disease and two with multiple myeloma received short duration, high dose chemotherapy, with non‐cryopreserved peripheral blood progenitor cell rescue as treatment for malignancy. Limited, (one or two) peripheral blood precursor cell collections were performed following either cyclophosphamide, cyclophosphamide + GCSF or GCSF priming. Total nucleated cell and CD34+ cell yields were significantly higher with either of the two GCSF priming regimens as compared to cyclophosphamide only priming. Cell viability at the time or reinfusion was also enhanced by GCSF priming. Chemotherapy regimens included either high dose cyclophosphamide, mitoxantrone and VP16 (HD‐CNV); high dose melphelan plus VP16; high dose BCNU, cyclophosphamide and VP16 (BCV); or high carboplatin, cyclophosphamide and VP16 (PCV) all given over 8–12 h. Non‐cryopreserved blood progenitor cells, stored at 4 °C, were reinfused 24 h after completion of chemotherapy. Sixty‐one of 62 patients showed hematologic recovery. Median time to hematologic recovery was significantly shorter for patients receiving GCSF primed cell collections. There was also significantly less hospitalization and antibiotic usage for patients receiving GCSF primed precursor cell collections. The addition of post chemotherapy GCSF did not, however, appear to enhance the rate of hematologic recovery. This study shows that simplified schedules for high dose chemotherapy administration together with simple precursor cell collection procedures provide safe and effective methods for administering myeloablative chemotherapy treatment.
Recent progress in multiple myeloma
Authors: Moscinski Lynn C. , Ballester Oscar F.
Published: February 2007

Multiple myeloma is recognized as a neoplasm of phenotypically mature plasma cells which produces a variety of clinical symptoms related both to tumour infiltration of the bone marrow and cytokine production. The latter results in bone disease and a complex interactive network between plasma cells, marrow stromal cells and other hematopoietic cells. This serves to sustain the myeloma proliferative pool and promote maturation and secretion of monoclonal immunoglobulin. Whereas the recognizable tumour cells in myeloma are the most mature B cells, early lymphoid cells are involved in the disease and probably represent the proliferative pre‐plasma cell compartment. The definition of the myeloma‘stem cell’ remains controversial, but our understanding of early pre‐plasma cell differentiation in multiple myeloma has been aided by studies on normal non‐neoplastic equivalents. Techniques like high resolution flow cytometry, flow cytometric DNA analysis and improvements in our ability to obtain karyotypic data in multiple myeloma will improve our understanding of myeloma cell biology, hopefully yielding new prognostic information. Finally, improvements in assessing prognosis will help identify patients whose survival with standard therapy is limited and how may require innovative or aggressive treatment protocols. These individuals must be separated from patients who either require no initial therapy or who are likely to have good outcomes with standard approaches.
Primary mediastinal large cell lymphoma
Authors: Rodriguez Jose , Pugh William C. , Romaguera Jorge E. , Cabanillas Fernando
Published: February 2007

Purpose: Primary mediastinal large cell lymphoma PMLCL is a recently described entity which has provoked considerable interest lately. The unique immunophenotype of the malignant cell, as well as conflicting reports regarding its response to therapy, prompted us to review the current literature focusing on the pathological and clinical aspects of this disease.

Design: We reviewed the current literature that contained details on the clinical presentation, pathological profile and clinical outcome.

Results: Most reports agree that PMLCL typically affects a young female population and presents with symptoms related to compression of mediastinal structures. Pathologically, the malignant cells may arise from a distinctive thymic medullary B cell subpopulation which is characterized by the following phenotype: CD19+, CD21 –, CD20+, CD22+. Alterations of c‐myc and lack of expression of HLA class 1 antigens on the tumour cell surface have been described. Response to treatment and clinical outcome have varied from one series to another and is possibly explained by the small number of patients in most series and by the heterogeneity of therapy. In general, the outcome does not appear to be worse than that of other large cell lymphomas although, given the young age of these patients, it might be expected to be more favourable.

Conclusions: Primary mediastinal large cell lymphoma is a distinct clinico‐pathological entity characterized by: (1) a predominance of young adults; (2) female predominance (female/male ratio of 2:1) in contrast to the other large cell lymphomas; (3) CD19+/CD21 – immunophenotype; (4) absence of HLA‐class 1 antigen expression; (5) possible involvement of c‐myc; (6) frequent dissemination at relapse to unusual anatomic sites in a pattern reminiscent of Burkitt's lymphoma.

The role of radiotherapy and the optimal treatment for this disorder are issues that remain unresolved.
Alternating chemotherapy regimen (P‐VABEC) for intermediate and high‐grade non‐Hodgkin's lymphoma of the middle aged and elderly
Authors: Caracciolo F. , Petrini M. , Capochiani E. , Papineschi F. , Carulli G. , Grassi B.
Published: February 2007

An intensive third generation regimen (P‐VABEC) including adriamycin, etoposide, cyclophosphamide, vincristine, bleomycin and prednisolone was administered to 43 unselected elderly patients with intermediate or high‐grade non‐Hodgkin's lymphomas (NHL). The median age was 67, 40 per cent were Ann Arbor stage IV, 73 per cent had‘B’ symptoms, 55 per cent had bulky disease, 48 per cent had serum lactate dehydrogenase greater than 450 U/1, 85 per cent had serum thymidine‐kinase greater than 4 U/1. Thirty patients were previously untreated. The complete remission (CR) rate was 74 per cent, and the partial remission (PR) rate 23 per cent, with an overall response rate of 97 per cent. The regimen was carried out on an outpatient basis in all patients. No death occurred during therapy. The Kaplan‐Meier actuarial survival of all patients at 3‐years is 47 per cent, and 50 per cent (16/32) of all patients who attained CR remain alive and in remission at a median of 21+ months (range 6+ to 42+). These results confirm that high remission and failure‐free survival rates can be achieved also in elderly unselected patients with aggressive NHL treated with curative intent.
Novel leukemic lymphoma with probable derivation from immature stage of natural killer (NK) lineage in an aged patient
Authors: Kawano Seiji , Tatsumi Eiji , Yoneda Noriko , Yamaguchi Nobuo , Goji Junko , Ito Hiroshi , Nagai Tomoko , Nishikori Masaru , Okamura Akiharu , Koiwai Osamu
Published: February 2007

A 66‐year‐old male patient was admitted with dyspnea; physical examination revealed petechiae and systemic lymphadenopathy. Laboratory findings showed leukemia. The blasts in the peripheral blood were negative for cytochemical myeloperoxidase, and had condensed nuclear chromatin with a nucleolus. The histological diagnosis of the biopsied neck lymph node was lymphoblastic lymphoma. The leukemia cells expressed CD2, CD6, CD7, CD13low, CD56, β chain of IL‐2 receptorlow (IL‐2Rβ), and HLA‐DR antigens, but not other pan‐T (CD5, CD3, CD4, and CD8); pan‐B (CD10, CD19, CD20, and CD24); natural killer (NK) (CD16, CD57); or myeloid (CD33) antigens. Electronmicroscopy revealed convoluted nuclei with conspicuous nucleoli and peripherally condensed heterochromatin. Membrane‐bound granules containing an electron dense matrix were observed in the cytoplasm, indicating the NK cell nature of the neoplastic cells. While terminal deoxynucleotidyl transferase (TdT) and cytoplasmic CD3 were not detected by immunofluorescence on fixed smears, Northern blot analysis revealed the gene expression of CD3σ, CD3ζ, and TdT. Gene rearrangement analysis revealed that the β, γ, and δ chains of T‐cell receptor (TCR) and immunoglobulin heavy chain (IgH) were of germline genotype.

While the overall interpretation of the phenotype and genotype was difficult, the derivation of an immature stage of NK lineage was strongly suggested, based predominantly on the electronmicroscopic features. Despite initially successful chemotherapy, the patient died 14 months after initial presentation.
Persistent growth of BALB/C mouse plasmacytoma and human myeloma cell lines in the presence of phorbol myristate acetate is associated with continued expression of Lap18 (stathmin)
Authors: Jones N. A. , Rowlands D. C. , Johnson W. E. B. , Maclennan I. C. M. , Brown G.
Published: February 2007

Lap 18 is a highly conserved cytosolic protein that is expressed in dividing cells. Data from a number of studies show that a range of cell lines and mitogen‐stimulated normal cells cultured in PMA phosphorylate and subsequently down‐regulate Lap 18. This has been found to be associated with growth arrest, although it is not clear that these events are causally related. In the present study we confirm that the HL60 promyelocytic leukemia and K562 erythroleukemia cell lines, when cultured with PMA, behave in this manner. This was not the case for any of five mouse plasmacytoma cell lines and six lines derived from patients with multiple myeloma or plasma cell leukemia. All of these lines contain Lap18, although the level of this protein in the mouse but not the human plasmacytoma cell‐line cells is relatively low. All the neoplastic plasma cell‐line cells phosphorylate Lap18 on culture with PMA, but this does not induce growth arrest nor result in down‐regulation of Lap18 expression. Further experiments are required to test whether there is a mechanistic relationship between the continued growth of plasmacytoma cell lines and their failure to down‐regulate Lap18 on culture in PMA.
Polyradiculopathy complicating acute lymphoblastic leukemia
Authors: Banerjee P. , Maccallum P. K. , Walker R. W. H. , Lister T. A.
Published: February 2007

A patient who presented with a symmetrical polyradiculopathy 6 months before the onset of acute lymphoblastic leukemia (ALL) is described. This case shows that bone marrow aspiration should be considered in such presentations when no other cause has been identified, even if the CSF is not initially diagnostic and the full blood count appears normal.
Simultaneous presentation of hairy cell leukemia and follicular small cleaved cell lymphoma in a patient with previous diagnosis of renal cell carcinoma
Authors: Diaz‐Pavon Jose Rodriguez , Pugh William , Cabanillas Fernando
Published: February 2007

Hairy cell leukemia is a lymphoproliferative disorder of the B lymphoid system that is associated with an increased incidence of second malignancies. Most of these second neoplasma have been solid tumours and few reports of lymphoid malignancies exist. We report here a case of simultaneous presentation of hairy cell leukemia diagnosed in the spleen of a patient under therapy for follicular lymphoma who had an antecendent history of renal cell carcinoma. The hairy cell leukemia and the follicular lymphoma were studied by means of molecular techniques and they were found to contain two different clonal B cell proliferations. This suggests an independent origin of these two B cell neoplasms. As far as we know, this is the first report of the coexistence of hairy cell leukemia and follicular lymphoma.
Multiple myeloma: An immunoclinical study of disease and response to treatment
Authors: Thavasu P. W. , Ganjoo R. K. , Maidment S. A. , Love S. B. , Williams A. H. , Malplas J. S. , Balkwill F. R.
Published: February 2007

Plasma cytokines and immune markers were assessed during the clinical management of 42 patients with multiple myeloma, MM. Of the patients 22/42 (all with progressive disease) were studied from the time of diagnosis, through various treatment regimes, to remission, progression or death. 5/42 patients had monoclonal gammopathy of undertermined significance (MGUS), 8/42 others had either indolent MM or stable MM, and a further 7/42 with progressive disease were also studied. IL‐6, TNF‐α, IL‐1α, IL‐1β, β2 microglobulin (β2M), and neopterin were estimated in bloods taken under optimal conditions for cytokine detection. The levels were compared with a panel of samples from healthy volunteers. Both immunoreactive and bilogically active plasma IL‐6 levels were measured. Pretreatment IL‐6 levels (both immunoreactive and biologically active) were found to correlate with severity of disease. In 13/22 patients with progressive disease who had been followed from the time of diagnosis over a 12‐month period or until death, pretreatment IL‐6 levels were predictive of response to therapy. Elevated plasma levels of TNF‐α, β2M and neopterin were found in patients with progressive multiple myeloma, and this correlated with renal impairment. The analytes measured during the course of chemotherapy did not show correlation with disease progression or response to therapy.
High grade non‐Hodgkins lymphoma in the elderly—12 year experience in the grampian region of scotland
Authors: Neilly Ian J. , Ogston Marie , Bennett Bruce , Dawson Audrey A.
Published: February 2007

A retrospective examination of patients with high grade non‐Hodgkin's lymphoma (HG NHL) presenting in the Grampian Region of Scotland from 1980–1992 was undertaken to determine the disase characteristics and outcome in patients over the age of 60 years at diagnosis. This group of patients was found to account for 68 per cent of HG NHL presenting in this region. No difference in clinical stage or histology was noted compared to their younger counterparts. The elderly had a signficantly poorer survival with an increase in lymphoma‐related and unrelated deaths. On Cox regression analysis the main survival advantage was conferred by completion of‘radical’ treatment; elderly patients who were given‘radical’ therapy had a median survival of 50 months compared to median survival of 10 months in the‘non‐radical’ group. Patients who had a good performance status at diagnosis had also a significant survival advantage. Histology, clinical stage at diagnosis and age over 60 had no independent significant effect on survival. Not all the factors that resulted in‘non‐radical’ therapy being given are explicable but we conclude that‘radical’ therapy is achievable in 50 per cent of patients over the age of 60 years with an effective outcome and should be pursued in the elderly when the condition of the patient allows.
Diagnosis of avascular necrosis of the femoral head in patients treated for lymphoma
Authors: Ratcliffe Marcia A. , Gilbert Fiona J. , Dawson Audrey A. , Bennett Bruce
Published: February 2007

Avascular necrosis of bone (AVNB) is a well‐known but rare complication of chemotherapy for lymphoma with a reported incidence ranging from 1 to 10 per cent. Early diagnosis is essential for optimal therapeutic management. Using MRI, the most sensitive means of detecting the earlier stages of AVNB, 100 patients treated with standard chemotherapy for lymphoma were assessed. Fifteen were found to have changes of AVNB, 10 with early changes but five with advanced segmental collapse of the femoral head. None with AVNB had more than the standard course of corticosteroids.

Almost a quarter of the study group complained of joint pain during and/or after their treatment, a third of whom were found to have AVNB; a strong indicator to screen all those with pain. However, 40 per cent of those with AVNB were asymptomatic. The clinical significance of the‘silent hip’ is yet to be elucidated.
Comparison of the performance of anti‐CD7 and anti‐CD38 bispecific antibodies and immunotoxins for the delivery of saporin to a human T‐cell acute lymphoblastic leukemia cell line
Authors: Flavell David J. , Cooper Sue , Okayama Keiko , Emery Loretta , Flavell Sopsamorn U.
Published: February 2007

We have investigated the cytotoxic performance of two different anti‐CD7/anti‐saporin BsAb's (HB2 × DB7‐18 and Q1.1), three anti‐CD38/anti‐saporin BsAb's (OKT10 × RabSap, OKT10 × DB7‐18 and Q4.1) and an anti‐CD7 (HB2‐Sap) and anti‐CD38‐saporin (OKT10‐Sap) immunotoxin for delivering the ribosome inactivating protein (rip) to the human T‐cell acute lymphoblastic leukemia cell line HSB‐2. In the case of CD7 as target molecule the immunotoxin outperformed both anti‐CD7 BsAb's being six times more effective than HB2 × DB7‐18 and 98 times more so than Q1.1 at effectively inhibiting protein synthesis in a dose dependent manner. The chemically constructed HB2 × DB7‐18 BsAb was more effective at inhibiting protein synthesis and cell growth in target HSB‐2 cells in a dose dependent manner than the quadroma produced BsAb Q1.1. Both BsAb demonstrated a prozone effect used at concentrations above 0.1 nM though this was more pronounced for Q1.1 than for HB2 × DB7‐18. The prozone effect was partially though not completely reversed by increasing the concentration of saporin in the system. In the case of CD38 as target molecule the anti‐CD38 IT OKT10‐Sap performed poorly, never actually achieving its IC50. Two BsAb's constructed with monoclonal anti‐saporin Fab arms each recognizing a different epitope on the saporin molecule also performed poorly. IN contrast the BsAb OKT10 × RabSap constructed with Fab derived from a rabbit polyclonal anti‐saporin antiserum performed in a dose dependent manner achieving its IC50 at a concentration of 1.3 nM. This BsAb also exhibited a prozone effect. These results exemplify the importance of cross linking adjacent target molecules on the cell surface in order to achieve effective delivery of saporin to the cell interior.
Molecular evidence for central nervous system involvement in children with newly diagnosed acute lymphoblastic leukemia
Authors: Januszkiewicz D. A. , Nowak J. S.
Published: February 2007

Central nervous system (CNS) involvement in children with newly diagnosed acute lymphoblastic leukemia (ALL) would have profound implication for the prognosis and accurate stratification of CNS prophylactic therapy. Using PCR technique with specific primers for V, D and J segments of TCRD gene, the pattern of TCRD gene rearrangements in bone marrow lymphoblasts and in cells from cerebrospinal fluid (CSF) have been investigated. The study involved 21 children at the time of diagnosis with B‐lineage ALL. In nine of 21 patients incomplete TCRDVD gene rearrangement has been found in CSF cells, which was identical to that observed in bone marrow of the same children. It can be concluded that at least in 43 per cent of all analysed cases, there were signs of CNS involvement in newly diagnosed ALL patients.
Transplantation of t‐lymphocyte depleted marrow with an addback of T cells
Authors: Clark Richard E. , Pender Norman
Published: February 2007

Depletion of T‐lymphocytes from allogeneic marrow prior to transplantation decreases the risk of serious graft versus host disease (GvHD), but also increases the risk of relapse. We have used a partial T‐cell depletion technique, in the hope of controlling GvHD without compromising relapse risk. Allogeneic marrow was fully T‐cell depleted ex vivo with Campath 1M, and infused together with an‘addback’ of 2 × 105 donor peripheral blood T‐cells/kg in 16 consecutive patients undergoing BMT from HLA‐identical family members. Post‐transplant immunosuppression was with cyclosporin A in conventional dosage.

Eight cases developed grade I or II GvHD, limited to the skin in all cases. Only the two grade II cases required steroid therapy; the remainder were easily controlled with simple emollients. No cases of more advanced GvHD were seen. All patients engrafted promptly. With a median follow‐up for the survivors of 976 days, seven cases have relapsed, with an overall projected actuarial disease‐free survival of 37.5 per cent at 36 months. The overall outcome (good control of GvHD but high relapse rate) is therefore similar to that expected in patients receiving fully T‐depleted marrow without post‐transplant immunosuppression.
Tumour incidence in mammary glands transplanted from the strains C3H and O20 into their mammectomized F1‐hybrids
Authors: Dux Anna , Mühlbock O.
Published: February 2007

It has been demonstrated that genetic factors play an important role in the genesis of mammary cancer in mice but it was not known if the genetic action is localized in the mammary gland tissues or if the genetic influence is effective through some systemic mechanism. In this investigation the mammary glands from the inbred strains C3Hf and O20, differing in the incidence of mammary tumours, were transplanted into a common host, the F1 hybrid, so that systemic influences would be equal. A difference in susceptibility to tumour development was found between the transplanted C3Hf and O20 mammary glands. In the group of animals free of the agent there is a difference in tumour frequency. In the animals carrying the mammary tumour agent this difference is expressed in the average tumour age at which the tumours develop. The genetic susceptibility in these two strains is, therefore, retained in the transplanted mammary glands.

Transplantation per se has no influence on tumour development.

Transplanted mammary glands react in the same manner as mammary glands in situ. All transplantations have been done into completely mammectomized hosts to avoid interference with tumours developing in the glands of the host. Investigations with partly mammectomized animals have shown that the mammary tumour frequency and the average tumour age are related to the amount of mammary gland tissue present. A reduction of the mammary gland tissue also reduces the tumour frequency or delays the appearance of mammary tumours.
HeLa cells resistant to bromodeoxyuridine and deficient in thymidine kinase activity
Authors: Kit Saul , Dubbs D. R. , Frearson Peter M.
Published: February 2007

Mutant sublines of HeLa S3 cells resistant to growth inhibition by bromodeoxyuridine (BUdR) have been isolated. The resistant cell lines (HeLa BU‐10, HeLa BU‐15, HeLa BU‐25, HeLa BU‐50, and HeLa BU‐100) proliferated in the presence of 10, 15, 25, 50, and 100 μg/ml BUdR, respectively. Extracts from HeLa BU‐25, HeLa BU‐50, and HeLa BU‐100 cells exhibited 2–5 per cent of the thymidine‐3H, deoxyuridine‐3H, and bromodeoxyuridine‐3H phosphorylating activities of parental HeLa S3 cells. HeLa BU‐10 and HeLa BU‐15 cell extracts were also deficient in thymidine kinase activity, yielding approximately 43 per cent and 8 per cent, respectively, the thymidine kinase activity of parental HeLa S3 cells.

The deficiency in thymidine kinase activity of HeLa BU‐100 cells was not due to negative feedback inhibition by high levels of BUdR or to interference with the thymidine kinase assay by inhibitors or competing enzymes in the HeLa BU‐100 cell extracts. Following 5 weekly passages in media lacking BUdR, the HeLa BU‐100 cells did not exhibit increased thymidine kinase activity. Moreover, mixtures of extracts from HeLa S3 and HeLa BU‐100 cells displayed a thymidine kinase activity equivalent to the sum of the activities of extracts prepared, respectively, from the HeLa S3 and HeLa BU‐100 cells.

Radioautographic studies have shown that after HeLa S3 cells were incubated for 6 hours with thymidine‐3H, 35–45 per cent of the nuclei were heavily labeled with radioactivity. However, fewer HeLa BU‐100 cells displayed labeled nuclei and the nuclei were only lightly labeled.

HeLa BU‐100 cell extracts contained normal amounts of thymidylate synthetase, thymidylate kinase, and uridine kinase activities. Following infection by vaccinia virus, high levels of thymidine kinase activity were induced in HeLa BU‐100 cells.
The reaction of rabbits to rous sarcoma virus
Authors: Ahlström C. G. , Mark Joachim
Published: February 2007

Rous chicken sarcoma virus (strain SR) was injected intramuscularly into new‐born or young rabbits. After an interval of about 2 weeks it induced a fibromatous nodular swelling at the site of injection which always regressed spontaneously after a few weeks. Fibromatous nodules appeared in the liver and lungs after intravenous and sometimes also after intraperitoneal inoculation of the virus. Large amounts of acid mucopoly‐saccharides were found in the fibromatous lesions. In cortisone‐treated rabbits the lesions were usually larger than in untreated controls. Intravenously injected Rous virus was localized to the site of intramuscularly injected carcinogenic and non‐carcinogenic hydrocarbons, producing fibromatous nodules which, however, regressed after a few weeks. Many of the hydrocarbon‐treated rabbits showed numerous fibromatous nodules in the lungs and liver, sometimes also in the spleen and kidneys. Vessels connected to the nodules showed endovasculitis obliterans owing to an attack of the virus on the vessel wall. All attempts to transplant the rabbit tumour to new rabbits failed. Virus could be recovered from early rabbit lesions. It is assumed that the spontaneous regression of the lesions is due to antibodies against virus or against tumour‐specific antigens.
Modification persistante des mitochondries dans des cellules tumorales de hamster transformées par l'adenovirus 12
Authors: Bernhard W. , Tournier P.
Published: February 2007

Le microscope électronique a révélé dans des tumeurs induites chez le hamster par l'adénovirus 12 une anomalie mitochondriale qui intéresse une portion variable du chondriome cellulaire. Cette anomalie est caractérisée par une taille exceptionnelle de ces organites, ou par des atypies, diverses de leur structure interne. Les sept tumeurs primitives examinées ont montré ces lésions plus ou moins prononcées qui persistent dans plusieurs lignées cellulaires, entretenues in vitro à travers de nombreux passages, pendant une durée allant jusqu'à deux ans et demi. Réimplantées chez l'animal, ces cellules forment des tumeurs solides dans lesquelles ces lésions restent visibles. Les anomalies persistent également lorsque ces tumeurs greffées sont remises en culture. Ce type d'anomalies mitochondriales n'a été vu ni dans sept tumeurs primitives induites par le virus SV40, ni dans sept tumeurs induites par le virus du polyome ou dans des lignées cellulaires dérivées de ces tumeurs. Le chondriome est toujours resté normal dans 35 cultures de fibroblastes embryonnaires de hamsters normaux, entretenues dans les mémes conditions de culture. Cependant l'apparition de mitochondries géantes et atypiques a été observée dans 8 sur 10 sarcomes primitifs ou greffés, induits par le méthylcholanthrène. Cette modification semble plus sporadique et sa transmission régulière par culture n'est pas encore prouvée. L'ensemble de ces faits est discuté. Tenant compte des découvertes récentes concernant la présence de DNA et de RNA dans les mitochondries, les auteurs se demandent si l'apparition d'un nouveau phènotype mitochondrial et sa transmission de cellule à cellule peuvent étre dues à une action directe de l'agent cancérigène sur ces organites, ou si ce phénomène dépend d'un changement survenu au niveau du noyau.
Leukemogenic activity of centrifugates from irradiated mouse thymus and bone marrow
Authors: Haran‐Ghera Nechama
Published: February 2007

The leukemogenic activity of centrifugates from radiation‐induced lymphomas and irradiated tissues of C57BL mice was tested by injecting these directly into 5 to 7‐day‐old thymus implants beneath the kidney capsule in thymectomized irradiated hosts of the same strain. A series of 12 centrifugates from radiation‐induced lymphomas were tested for leukemogenic activity. Of these, six were found to be active, inducing about 14 per cent lymphomas at an average latent period of 166 days. Centrifugates from thymus plus bone marrow taken from irradiated donor mice 5 or 10 days after completion of irradiation demonstrated leukemic activity—an incidence rate of up to 30 per cent. Centrifugates of irradiated tissues taken 20, 30, 45 and 60 days after irradiation showed only borderline activity. Thymic tissue, taken from the same irradiated donor mice, transplanted beneath the kidney capsule of normal hosts, revealed neoplastic transformation only when taken from donors 30 days after completion of the irradiation.

Urethane was found to increase the leukemogenic activity of the centrifugate. Centrifugates prepared from tissues taken from mice treated concurrently with X‐rays and urethane 10 days after completion of treatment yielded 75 per cent lymphoma incidence, with a marked decrease in the average latent period. The first passage of this active centrifugate similarly revealed an 80 per cent lymphoma incidence, with a short latent period.

Centrifugates of tissues taken 20, 30 and 45 days after irradiation and urethane treatment showed no activity.

It is concluded that irradiation causes the “release” of a transmissible leukemogenic agent in C57BL mice, and that urethane potentiates the activity of this agent.
Morphologic, cytogenetic and virologic studies in vitro of a malignant lymphoma from an African child
Authors: Rabson Alan S. , O'Conor Gregory T. , Baron Samuel , Whang Jacqueline J. , Legallais Frances Y.
Published: February 2007

A cell line of human lymphoblasts (AL1), derived from a malignant lymphoma involving the jaw of an African child, has been established in a medium containing 20 per cent fetal bovine serum. The cells grow in aggregates in suspension and are morphologically similar to previously described human lymphoma cell lines grown in media containing human serum. The chromosome number distribution was wide, ranging from 40 to 77. The modal number was 46 with a pseudodiploid karyotype. Electron microscopically, herpes‐like virus particles were found in less than 1 per cent of the cells during the first 4 months of culture, but subsequently no cells containing virus particles have been seen. Although the medium was free of human serum which might contain antibodies to many human viruses, numerous and varied attempts to isolate viruses from the cells were unsuccessful.

Following the report of interferon production by other cells lines derived from lymphomas of African children, we were able to demonstrate interferon in the supernatant fluids of AL1 cultures. The interferon was demonstrable even when virus particles could no longer be found in the cells electron microscopically. Attempts to serially pass the antiviral activity in the absence of lymphoma cells were unsuccessful. The significance of the interferon production by the lymphoma cells is not known.

Cultures of AL1 cells infected with SV40 became SV40 carrier cultures but there were no morphological changes in the lymphoma cells and there was no increase in herpes‐like particles electron microscopically. AL1 cells infected with herpes simplex virus developed degenerative changes, and typical immature and mature herpes particles were seen by electron microscopy in most of the cells. AL1 cultures infected with adenoviruses 7 and 12, vaccinia, reovirus 3 and cytomegalovirus showed no evidence of growth of these viruses in the lymphoma cells and no increase in numbers of herpes‐like virus particles by electron microscopy.
Azo‐dye carcinogenesis. The reactions of 4‐hydroxymethylaminoazobenzene with cytosine derivatives
Authors: Roberts J. J. , Warwick G. P.
Published: February 2007

A mixture of formaldehyde and aminoazobenzene condensed readily under physiological conditions to form covalently bound products with purines or pyrimidines and their corresponding nucleosides and nucleotides bearing amino groups. In the case of cytosine derivatives it was established that Mannich type condensations occurred with the pyrimidine amino group and the N‐1 position to form substituted triazines, derived from two molecules of formaldehyde, one of aminoazobenzene and one of the corresponding pyrimidine. The triazine ring structure derived from cytosine was stable at pH values greater than 7, while those derived from cytosine nucleosides and nucleotides opened at the N‐1 position at pH 9. At higher pH values decomposition of these substituted cytosine rings occurred, accompanied by hydrolysis of both methylene bonds. All compounds were hydrolysed by dilute mineral acid into the original constituents. The properties of these in vitro condensation products were compared to those formed by reaction of metabolites of 4‐dimethylaminoazo [G‐3H]‐benzene with RNA in vivo with respect to their stability at different pH values.
Incorporation de thymidine dans L'ADN de cellules de souris et de hamsters infectés par le virus polyome
Authors: Cramer Robert , Feinendegen Ludwig E.
Published: February 2007

L'incorporation de thymidine‐14C dans l'ADN a été examinée pour une période de 24 heures après infection avec le virus polyome dans le cycle lytique (cellules de souris) et le cycle de transformation (cellules BHK 21 de hamsters).

Dans le cas du cycle lytique, l'incorporation de thymidine‐14C a été inhibée entre la 4e et la 7e heure et stimulée à partir de la 12e heure. Les mitoses étaient presque complétement absentes à partir de la 4e heure.

Dans le cycle de transformation il n'y avait pas de diminution significative de l'incorporation de thymidine dans l'ADN. Pendant la période initiale on a observé une stimulation qui n'était que temporaire entre la 8e et la 14e heure suivant l'infection.

La diminution de l'incorporation de thymidine 5 heures après infection dans les cellules de souris (cycle lytique) a été examinée de plus près. D'après ces recherches, elle serait surtout due à une dilution du pool acidosoluble par des catabolites d'ADN correspondant à moins de 10% de l'ADN cellulaire.
Concentration and purification in density gradients of virus from gross lymphoma homogenates
Authors: Wahren Britta
Published: February 2007

Homogenates of Gross lymphomas and lymphomas of no known viral origin were concentrated, using the density gradient centrifugation method. The fractions revealed virus‐like particles in Gross lymphoma gradients at a density of 1.16–1.18. The same fractions were shown to contain material rich in ribonucleic acid, which was not found in similarly prepared homogenate fractions of normal tissues or of lymphomas of no known viral origin.
The metabolism of tritiated thioacetamide in the rat
Authors: Rees K. R. , Rowland G. F. , Varcoe J. S.
Published: February 2007

A method is described for preparing tritiated thioacetamide.

Thioacetamide‐3H was fed daily to rats at a level which is known to produce liver tumours after six months' feeding. It was shown that less than 1% was excreted unchanged in the urine. Radioactivity was found in all the organs examined and in the chemical constituents of all cell fractions of the liver suggesting metabolism of thioacetamide to acetate.

Measurements of the acetate pool size and of the quantity of thioacetamide entering the pool showed that over 95% of the carcinogenic dose of thioacetamide was converted to acetate in 24 hr.

Following incubation of thioacetamide with liver slices it was shown that the pathway of metabolism is through acetamide.

Liver slices were seen to be three times more active than kidney slices in converting thioacetamide to acetamide and it is suggested that this metabolic step is a necessary prerequisite to the toxic and carcinogenic effects of thioacetamide in the liver.
Increased glycolytic capacity and associated enzyme changes in BHK21 cells transformed with polyoma virus
Authors: Paul J. , Broadfoot M. M. , Walker P.
Published: February 2007

Some features of the metabolism of untransformed and polyoma‐transformed clones of the BHK21 cell strain were studied. 1) No difference in the oxygen uptake of the two groups was detected but in all cases the transformed clones had greater glycolytic capacity than the untransformed clones at pH 7.4, in both aerobic and anaerobic conditions. 2) The transformed clones had more hexokinase and isocitric dehydrogenase, and probably more malic dehydrogenase, than the untransformed clones. 3) The untransformed clones had more glucose‐6‐phosphate dehydrogenase than the transformed clones. 4) No differences could be detected in 6‐phosphogluconate dehydrogenase or lactic dehydrogenase activity. 5) It is suggested that these differences may be related either to differences in the permeability of the cell membranes to glucose or to an altered rate of synthesis of mucopolysaccharides.
Papovavirus SV40: Similarity of tumor antigens in transformed virus‐free hamster cells and in virus‐infected monkey cells
Authors: Kitahara Tsunehiro , Melnick Joseph L. , Rapp Fred
Published: February 2007

Sera from hamsters bearing tumors induced by papovavirus SV40 reacted with tumor antigen prepared either from cells transformed by, or from cells infected with, the homologous virus. Serum titurs against both antogens were comparable. A high degree if correlation was obtained with the use of either complement‐fixation or immunofluorescence to detect the antigen. The immunoflurescent intranuclear antigen present in cells transformed by SV40, an the early virus‐induced intranuclear antigen found during the cytolytic cycle following infection of monkey cells by SV40, therefore appear to be similar, and they are either identival with or similar to the antigens detected by complement‐fixation techniques. Synthesis of antibody against this antigen was detected only in hamsters bearing tumors induced by SV40 or by cells transformed by the virus. Hamsters immunized with SV40 usually reject cells transformed by the homologous virus; the few vaccinated animals which fail to reject such cells also fail to produce antibodies against tumor antigen although the tumor cells in such animals continue to synthesize the antigen.
The carcinogenic action and metabolism of N‐hydroxyurethane in newborn mice
Authors: Boiato L. , Mirvish S. S. , Berenblum I.
Published: February 2007

Ten weekly intraperitoneal injections, starting at birth, of N‐hydroxyurethane into C57BL/6 mice, produced thymic lymphosarcomas in 44 per cent and lung adenomas in 78 per cent of survivors. Similar injections of urethane produced lymphosarcomas in 39 per cent and lung adenomas in 75 per cent of survivors.

Metabolic studies in newborn C57BL/6 mice, with N‐hydroxyurethane‐14C, demonstrated about 70 per cent conversion into urethane and also the formation of metabolite X (probably a glucuronide). These conversions were similar in extent to those reported for adult mice, but proceeded at slower rates. The reverse conversion of urethane into N‐hydroxyurethane was not detected.

These results are consistent with the view that the carcinogenic action of N‐hydroxyurethane proceeds mainly by prior conversion into urethane.
Comparative effects of DL‐glyceraldehyde, 6‐mercaptopurine, methotrexate and 5‐fluorouracil on the ehrlich ascites carcinoma in vivo
Authors: Bennett Leslie R. , Connon Frank E.
Published: February 2007

Female white Swiss mice bearing the Ehrlich ascites carcinoma were treated with 6‐mercaptopurine, methotrexate, 5‐fluorouracil and DL‐glyceraldehyde, alone and in combination. DL‐glyceraldehyde was more effective against Ehrlich ascites tumor, as judged by 30‐day post‐inoculation survival time, than any of the three compounds with which it was compared. Combination of glyceraldehyde and 5‐fluorouracil resulted in a slight potentiation of carcinostatic effect. DL‐glyceraldehyde at carcinostatic dose levels was shown to have little toxic effect when administered for several days to white Swiss control mice.
The incidence of leukemia in the lebanese population
Authors: Abou‐Daoud Kamal T.
Published: February 2007

An account is given of the yearly incidence and distribution according to age, sex, religion and type of leukemia in Lebanon during two years, 1963–1965.
Comparison of nitrogen‐mustard‐sensitive and ‐resistant yoshida sarcomas
Authors: Ball C. R. , Connors T. A. , Double J. A. , Ujhazy V. , Whisson M. E.
Published: February 2007

The Yoshida sarcoma and a line derived from it showing acquired resistance to alkylating agents have been compared from a number of aspects: chromosome number, growth rate, nucleic acid, protein and free thiol content. Although the degree of resistance to the alkylating agent Melphalan has been demonstrated to be at least 100 times greater than in the sensitive strain, the two tumours have been very similar in all aspects so far studied. A small, and not highly significant, increase in glutathione content of the solid resistant tumour has been the only difference so far demonstrated.
The influence of the route of administration of nitrogen mustard and melphalan upon their anti‐tumour activity in the rat
Authors: Cobb L. M.
Published: February 2007

The influence of routes of administration upon the therapeutic activity and lethal effect of nitrogen mustard (HN2) and Melphalan is described. The intra‐arterial, intravenous, intraperitoneal and intraportal routes were used and logarithmic dose‐response curves constructed for cure‐rate of the established Walker rat carcinosarcoma 256 and for the LD50. From these results therapeutic indices were calculated. These indices (LD50/ED5) for HN2 were 50, 30, 7.5 and 7.5 respectively. Intraperitoneal and intraportal injection of HN2 greatly reduced the anti‐tumour activity by comparison with intravenous and intra‐arterial injection. It appears that the loss of activity of intraportally injected HN2 is effected, to a large extent, on the initial passage through the liver. The reduction in activity that occurs with intraperitoneal injections is also thought to be partly due to this effect by the liver. Evidence is presented that lethal intraperitoneal doses of HN2 produce their effect upon the intestinal tract largely without passing into the general blood circulation. It is suggested that the drug passes directly through the intestinal wall to bring about the destruction of the lining epithelium. The LD50 for HN2 was similar for the four routes of administration. The possible reasons for this are discussed. The route of administration did not influence the therapeutic index for Melphalan.