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At least 271 records · Page 15Linked to original sources
PubMed1990

Phase I trial of tallysomycin S10b, a bleomycin analogue.

Bleomycin is an agent with significant antitumor efficacy whose major dose limiting toxicity is pulmonary fibrosis. Attempts have thus been made to identify congeners with reduced toxicity and with comparable or greater antitumor activity. Tallysomycin S10b is a bleomycin analogue possessing significantly greater potency, equal or reduced lung toxicity, and slightly greater antineoplastic activity when compared to the parent compound in preclinical studies. This report describes our experience with tallysomycin S10b in 30 patients with a variety of non-hematologic neoplasms. Pulmonary toxicity, occurring in 4 patients, was the major toxicity. The recommended cumulative dose of tallysomycin S10b was difficult to establish from the results of this study, as pulmonary toxicity appeared to be more idiosyncratic than dose- or schedule-dependent. The employment of more sensitive methods for detecting pulmonary toxicity in this study suggest that tallysomycin S10b may have reduced pulmonary toxicity compared to the parent compound. Both bleomycin and tallysomycin S10b have similar t1/2 beta half-lives of 2-4 h. Six patients had prolonged terminal elimination half-lives of tallysomycin S10b, but no clear relationship between this phenomenon and efficacy or toxicity was evident. No complete or partial responses occurred. Disease stabilization occurred in 4 of 15 patients with diagnoses of renal cell carcinoma, rectal cancer and lung cancer. Five of eight patients with non-measurable disease had stable disease, including one with mesothelioma, one with carcinoma of the head and neck, two with renal cell cancer and one with colon carcinoma.

Adult↗
PubMed1980

Studies on the human tumor nucleolar antigens.

With rabbit antibodies to nuclear 0.01 M Tris-HCl, pH 8, extract or "nucleolar preparations" of human HeLa S3 cells and fluorescein-labeled goat antirabbit antibodies, bright nucleolar immunofluorescence was observed in human adenocarcinomas, squamous cell carcinomas, sarcomas, hematological neoplasms, and other malignant tumors. With these antibodies, nucleolar immunofluorescence was not found in most normal tissue specimens, benign adenomas, hyperplastic tissues, and specimens of inflammatory diseases. A study was made on the presence in benign and malignant breast tumors of a common nucleolar antigen previously found in a broad range of human malignant tumors. Bright nucleolar immunofluorescence was observed in 19/20 (95%) of known breast cancer specimens. In the group of 80 unknown samples in the "blind" study, 75 (94%) were correctly identified as malignant or benign on the basis of the presence and distribution of the nucleolar fluorescence. In a group of 67 samples in which the nucleolar fluorescence was either readily observed or virtually absent, 47/48 (98%) of the malignant tumors were correctly identified. Of the bening lesions or normal breast specimens, 18/19 (95%) were correctly identified as negative for nucleolar fluorescence. These studies extend the results previously reported for a common nucleolar antigen in a broad range of human cancers to a larger series of malignancies of a particular organ. The tumor nucleolar antigen(s) were partially characterized by isoelectric focusing on 4% polyacrylamide gels. One major band had a pI of 6.3 and a minor band had a pI of 6.1. These antigens were not found in the normal human liver nucleoli.

Antigens, Neoplasm↗
PubMed1990

Enhancement of anthracycline and alkylator cytotoxicity by ethacrynic acid in primary cultures of human tissues.

Ethacrynic acid [2,3-dichloro-4-(2-methylene-1-oxobutyl)phenoxyl] acetic acid, is a water-soluble diuretic agent that has been shown to potentiate the in vitro cytotoxicity of chemotherapeutic agents in established cell lines. We used the differential staining cytotoxicity (DiSC) assay to determine whether ethacrynic acid at 1 and 3.3 microM would potentiate the cytotoxicity of nitrogen mustard and/or doxorubicin in primary cultures of hematologic neoplasms from heavily pretreated patients and in normal peripheral blood lymphocytes. At 3.3 microM, ethacrynic acid was toxic to 8 of 24 (33%) tumor specimens studied. In subsequent studies, ethacrynic acid at 1 microM was toxic to only 2 of 54 (4%) tumor specimens. Significant enhancement for doxorubicin or nitrogen mustard was confined to lymphatic malignancies and to normal peripheral blood lymphocytes. Interspecimen variability was observed, with no enhancement in most individual specimens, 2-fold enhancement in some specimens, and 4-fold enhancement in occasional specimens. Clinical trials will be required to determine whether the observed in vitro activity for ethacrynic acid is associated with clinical benefit in unselected or assay-selected patients.

Cell Survival↗
PubMed2006

[Targeted therapy in the treatment of solid tumors and in hematology-oncology. Advances and disappointments].

The development and clinical introduction of targeted therapies has resulted in significant progress for the treatment of malignant diseases. These forms of therapy supplement traditional methods of chemotherapy, radiation, and surgery. As new therapies increase the complexity of therapeutic options in oncology, the treatment costs steadily climb as well. Parameters need to be identified which will predict a response to new substances, and this effort is the subject of ongoing studies.

Antineoplastic Agents↗
PubMed1996

The expression of costimulatory molecules CD80 and CD86 in human carcinoma cell lines: its regulation by interferon gamma and interleukin-10.

The costimulatory signal through CD80 or CD86 to its counterreceptor CD28 or CTLA-4 on T cells has been shown to play an important role in the induction of T-cell-mediated immunity against tumors. In the present study, we examined the expression of CD80 and CD86 in the cell lines derived from human gastric, esophageal and colorectal carcinomas at the mRNA level, by means of a reverse transcriptase/polymerase chain reaction analysis and, for their surface expression, using a flow-cytometric analysis with monoclonal antibodies (mAb). The expression of mRNA for CD80 or CD86 was detected in all 18 cell lines tested, except for CD86 on one cell line. The cells from 13 (72%) or 12 (67%) of these cell lines expressed the surface CD80 or CD86 molecule, detected with the respective mAb. The surface expression of CD80 or CD86 was increased in four to five of the six cell lines tested after a culture with interferon gamma (IFN gamma). In addition, the up-regulation of CD80 or CD86 expression by IFN gamma was inhibited by interleukin-10 (IL-10). These results indicated that, in the cell lines derived from human gastrointestinal carcinoma, both the costimulatory molecules CD80 and CD86 were detectable in the majority of the cell lines examined at the mRNA and protein levels, and could be regulated with the cytokine IFN gamma or IL-10.

Antigens, CD↗
PubMedDate not supplied

A case of bone marrow mastocytosis associated with multiple myeloma.

Mastocytosis is a term used for a spectrum of disorders characterized by abnormal growth and accumulation of mast cells. The cutaneous variants of the disease have to be distinguished from systemic mastocytosis (SM), in which at least one extracutaneous organ is involved. In contrast to cutaneous mastocytosis, SM is often associated with another hematologic neoplasm. In most cases clonal myeloid malignancies such as a myeloproliferative or myelodysplastic syndrome occur. In a few cases of SM, however, clonal lymphoid disorders have been described. We here report on a case of SM associated with multiple myeloma. At first presentation, the 48-year old female patient showed monoclonal IgGlambda gammopathy and bone marrow (BM) mastocytosis, but no BM plasma cell infiltrates. Eight years later, the patient presented with BM mastocytosis and overt multiple myeloma. The co-existence of myeloma and mastocytosis was demonstrable by staining serial BM sections with antibodies against mast cell tryptase, CD68R, and the plasma cell marker VS38c. Interphase FISH analysis of BM sections revealed a numeric gain of chromosome 5 and chromosome 7 in the plasma cells but not in the mast cell infiltrates, thereby confirming the presence of two different neoplastic cell populations. To our knowledge, this is the first report describing the co-existence of multiple myeloma and mastocytosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Digital clubbing in a patient with progressive mantle cell lymphoma.

Digital clubbing with or without hypertrophic osteoarthropathy may occur in a variety of neoplastic diseases. We present the first description of digital clubbing in a patient with progressive mantle cell lymphoma, in the absence of any other apparent etiology. We suggest that clubbing might be a paraneoplastic manifestation in mantle cell lymphoma. The literature on digital clubbing in hematological neoplasms is reviewed.

Diagnosis, Differential↗
PubMed2001

Outcome of laparoscopic splenectomy based on hematologic indication.

BACKGROUND: Laparoscopic splenectomy is the procedure of choice for elective splenectomy at the Cleveland Clinic Foundation. Although the literature clearly documents the technical feasibility and safety of laparoscopic splenectomy, little data exists concerning the results of this procedure based on the hematologic indication for splenectomy. We sought to examine the clinical experience with laparoscopic splenectomy in a single institution, with particular attention to morbidity and clinical outcomes based on hematologic disease process. METHODS: This study retrospectively reviewed a consecutive series of laparoscopic splenectomies performed for nontraumatic, splenic pathology at the Cleveland Clinic Foundation from August 1995 to January 2001. Patient demographics, operative indications, morbidity, mortality, and clinical outcome were evaluated. Hematologic diagnostic groups were compared using Fisher's exact tests and Wilcoxon rank-sum tests. RESULTS: A total of 147 laparoscopic splenectomies were performed. Seven patients (5%) required conversion to open splenectomy. Indications for splenectomy included idiopathic thrombocytopenic purpura (ITP) in 65 patients, hematologic malignancy in 43 patients, autoimmune hemolytic anemia (AIHA) in 9 patients, thrombotic thrombocytopenic purpura (TTP) in 9 patients, splenomegaly in 5 patients, splenic cyst in 4 patients, splenic abscess in 3 patients, hereditary spherocytosis in 2 patients, splenic artery aneurysm in 2 patients, Felty's syndrome in 1 patient, myelofibrosis in 1 patient, and other in 3 patients. Accessory spleens were identified in 20 patients (14%). Postoperative complications occurred in 23 (16%) patients. Patients with ITP had significantly shorter operation times (134 vs 163 min; p = 0.001), decreased estimated blood loss (126 vs 307 ml; p = 0.001), decreased length of hospital stay (2.8 vs 4.6 days; p < 0.001), and less chance of conversion (0 vs 7; p = 0.02) than patients with any other diagnosis. A mean follow-up period of 20 +/- 14 months showed an 85% rate of remission for ITP, 89% for TTP, and 89% for AIHA. Patients with malignant disease had significantly larger spleens (822 vs 313 g; p < 0.001), more estimated blood loss (380 vs 168 ml; p = 0.04), and longer operative times (170 vs 142 min; p = 0.009), as compared patients treated for benign disease. However, the length of hospital stay (4.3 vs 3.6 days; p = 0.06) and complication rates (19% vs 14%; p = 0.08) were not significantly different between the two groups. CONCLUSIONS: When performed for ITP, laparoscopic splenectomy resulted in shorter operations, minimal blood loss, earlier discharge, no conversions, and excellent remission rates, as compared with other hematologic indications. Despite larger spleens, more blood loss, and longer operations in patients with hematologic malignancies, morbidity and length of hospital stay still were similar to those associated with benign indications for laparoscopic splenectomy. In conclusion, laparoscopic splenectomy is safe and efficacious for a multitude of benign and malignant hematologic indications, and our data compares favorably to those for open series.

Adolescent↗
PubMed2006

Amifostine in the management of radiation-induced and chemo-induced mucositis.

INTRODUCTION: Mucositis is a significant complication of cancer therapy, with important clinical and economic implications. In June 2005, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) conducted an evidence-based update review of the literature on mucositis. The goal of this literature review is to update previously published guidelines for the management of mucositis. RESULTS: This article reports the findings of the subgroup charged with reviewing the literature related to amifostine.

Amifostine↗
PubMed2001

Oral status during radiotherapy and chemotherapy: a descriptive study of patient experiences and the occurrence of oral complications.

The aim of the present study was to describe patients' experiences of their oral status and their relation to oral complications during radiotherapy and chemotherapy. The sample consisted of 41 consecutive patients admitted for radiotherapy with >40 Gy including the oral cavity for tumours within the head and neck area, or for chemotherapy of haematological malignancies. At the start of radiotherapy or the second/third cycle of chemotherapy, patients rated their experiences of oral symptoms on a 100-mm visual analogue scale with endpoints "no oral discomfort" and "worst imaginable oral discomfort". Mucositis was assessed and unstimulated whole saliva was collected. Patients were examined regularly at every 10 Gy increase of radiotherapy or once a week during chemotherapy, and after completion of the radiotherapy or the chemotherapy cycle. In addition, patients given radiotherapy rated their experiences of oral symptoms 1 month after treatment. Patients receiving radiotherapy experienced a significant increase in oral symptoms over time. One month after treatment several oral symptoms were still present. The severity of mucositis increased over time. The unstimulated salivary secretion rate showed a rapid decrease after the start of radiotherapy, followed by a slow recovery. Patients who received chemotherapy reported fewer oral symptoms, with a peak 1-2 weeks after the start of treatment, and their mucositis score showed a parallel pattern of development. Their unstimulated salivary secretion rate did not change over time. There was good agreement between patient experiences and observations recorded by dental staff.

Adolescent↗
PubMed2006

The specificity of interphase FISH translocation probes in formalin fixed paraffin embedded tissue sections is readily assessed using automated staining and scoring of tissue microarrays constructed from murine xenografts.

Implementation of interphase fluorescence in situ hybridization (FISH) assays in the clinical laboratory requires validation against established methods. Validation tools in common use include exchange of consecutive sections with another institution that has already established the FISH assay, comparison with conventional banded metaphase cytogenetics, confirmation of specificity using probed normal metaphases, consecutive paraffin sections of a validation set tested by a reference laboratory, and specificity assessment against well characterized cell lines. We have investigated the feasibility of using tissue microarrays (TMA) constructed from murine xenografts as a preliminary specificity-screening tool for validation of interphase FISH assays. Cell lines currently in use for FISH controls are used to generate xenografts in SCID mice which are fixed in formalin and paraffin embedded. A TMA is constructed using duplicate donor cores from the xenograft blocks. Xenografts used represent a wide range of translocations used routinely for formalin fixed paraffin embedded sections evaluated by FISH. Probe cocktails (Abbott-Vysis), for several non-random translocations associated with hematologic neoplasms and soft tissue sarcomas have been used in this manner. On-line deparaffinization, cell conditioning, and prehybridization steps are automated using a staining workstation (Ventana Discovery XT); hybridization and stringency washes are performed manually offline. FISH-probed TMAs are tracked using a Metasystems image scanner and analyzed using classifiers specifically developed for each molecular abnormality. FISH results for each xenograft in the TMA correspond exactly to the genotype previously established for the parent cell line from which the xenograft was prepared. Moderate complexity tissue microarrays constructed from murine xenografts are excellent validation tools for initial assessment of interphase FISH probe specificity.

Animals↗
PubMed1981

Invasive aspergillosis. Progress in early diagnosis and treatment.

Ninety-one patients with documented invasive infections due to an Aspergillus species were identified at Memorial Sloan-Kettering Cancer Center from July 1, 1971, through December 31, 1976. Of the 29 patients in whom the diagnosis was made during life, 10 had successful treatment and survived the Aspergillus infection by two to 17 months. An immunodiffusion test was useful in the early diagnosis of invasive aspergillosis, and in 11 patients in whom the diagnosis was supported by seroconversion and who underwent treatment, the survival rate was 64 percent. Cultures of respiratory secretions were not reliable because they often reflected only colonization. In one year, only 9 percent of he patients with Aspergillus species isolated from the sputum had an invasive infection. The lung was the commonest site of involvement, 91 percent of the patients having pulmonary lesions. The most frequently affected extrapulmonary organ was the brain (18.3 percent). Eight patients had nonpulmonary aspergillosis as the only manifestation of this infection. Most of the 91 patients had hematologic neoplasms as the underlying disease, and neutropenia and antibacterial therapy preceded the diagnosis of aspergillosis in the majority of cases.

Adolescent↗
PubMed1987

Visceral leishmaniasis in immunocompromised hosts.

Visceral leishmaniasis is infrequently reported in immunocompromised hosts; hence, the clinical manifestations and outcome of the disease in these patients are unknown. In a series of 10 patients with visceral leishmaniasis complicating renal transplantation (three), hematologic neoplasms (two), systemic lupus erythematosus (two), or infection with human immunodeficiency virus (three), typical hallmarks of kalaazar such as enlargement of spleen or hyperglobulinemia were absent in three and six patients, respectively. Extensive visceral involvement was noted by biopsies or autopsies in four patients. Diagnosis was made during evaluation for fever of unknown origin. Myriads of amastigotes were seen in bone marrow smears. Measurement of antibodies against Leishmania donovani was positive in each patient tested. Ultimately, three patients died, and chronic infections refractory to treatment developed in two other patients. Visceral leishmaniasis is a potentially fatal infection in immunocompromised hosts. Current antiparasitic therapy frequently fails to eradicate L. donovani from infected tissues.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Nitrous oxide reduces growth of experimental rat leukemia.

The ability of nitrous oxide to inhibit the in vivo growth of hematological neoplasms was investigated in a rat model for acute myeloid leukemia (BNML). Nitrous oxide, administered in a concentration of 67% with 33% oxygen, resulted in a reduction of spleen and liver weights of approx. 30%, as compared with leukemic rats kept in ambient air. Peripheral white cell counts were also considerably lower in the treated rats. Plasma levels of vitamin B12 were found to be elevated in untreated leukemia, but fell to about normal levels after nitrous oxide exposure. On the contrary, folic acid levels were low in untreated leukemic rats, and significantly higher in animals exposed to nitrous oxide. The observed effects of nitrous oxide appeared to be dose-dependent. The deoxyuridine suppression test performed with leukemic cells became abnormal after nitrous oxide inhalation, in accordance with the effect on normal bone marrow. These results indicate that the interference of nitrous oxide with vitamin B12-related metabolism, which leads to impairment of de novo thymidine synthesis, has the potency to reduce leukemic proliferation in vivo.

Animals↗
PubMed1989

Poorly expressed CD2 antigen on the leukemic cells of adult T-cell leukemia and chronic lymphocytic leukemia of T-cell lineage.

Adult T-cell leukemia (ATL) and T-cell chronic lymphocytic leukemia (T-CLL) are hematologic neoplasms in differentiated stages of peripheral mature T cells. This is suggested by the presence of CD2 (E rosette receptor) and mature and/or pan-T cell membrane surface antigens on their leukemic cells. We recently encountered one patient with ATL and another with T-CLL; their leukemic cells poorly expressed CD2 antigens, but clinical presentation, morphology of the leukemic cells and other marker studies were characteristic of either ATL or CLL. The clinical significance of the poor expression of CD2 remains to be further studied. The two patients reported here died of severe complications 4 and 9 weeks after diagnosis. The poor expression of CD2 in the peripheral T cells in these neoplasms is likely to indicate an aggressive nature of the disease.

Aged↗
PubMed1996

Analysis of the novel cyclin-dependent kinase 4 and 6 inhibitor gene p18 in lymphoma and leukemia cell lines.

The genes for the CDK4/6-inhibitors p16INK4A/MTS1 and p15INK4B/MTS2 are frequently deleted in hematological malignancies. A new member of this family of CDK4/6 inhibitors is p18. In order to assess p18 growth-suppressor gene alterations in hematological neoplasms, we investigated 31 lymphoma and leukemia cell lines by PCR for both exons of this gene. No homozygous deletions were observed. Investigation of a new intragenic restriction fragment length polymorphism revealed no differences in allele distribution between the tumor cell lines and healthy volunteers. Our results suggest that homozygous deletion of the p18 gene does not play a major role in leukemogenesis or lymphomagenesis.

Base Sequence↗
PubMed1987

Trisomy 14 in refractory anemia with excess of blasts in transformation.

Trisomy 14 was demonstrated on four occasions over a 2-year period in the bone marrow cells of a 63-year-old patient with refractory anemia with excess of blasts in transformation (RAEB-t). Trisomy 14 as the sole karyotype abnormality has been documented in only six malignancies, namely, in two cases of acute leukemias, one Philadelphia-negative chronic myeloid leukemia, one pancytopenia, and in two colonic polyps. In hematologic neoplasms, this rare primary change preferentially occurs in elderly adults and seems exclusively associated with the myeloid cell lineage.

Anemia, Refractory, with Excess of Blasts↗