High molecular weight transforming growth factor beta is excreted in the urine in active nodular sclerosing Hodgkin's disease.

To measure the in vivo secretion of high molecular weight (HMW) transforming growth factor (TGF)beta by Reed-Sternberg cells from patients with nodular sclerosing Hodgkin's disease, we studied the urine samples from untreated patients. The urinary proteins did not promote the proliferation of NIH-3T3 cells in monolayer culture and contained similar amounts of total TGF activity when compared with normal controls. Urinary proteins from 24 different control and test urines were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Either of two primary antibodies were used for immunoblot detection: (a) affinity column purified polyclonal anti-TGF beta 1 prepared against platelet TGF beta 1 or (b) monoclonal anti-HMW-TGF beta prepared against HMW-TGF beta secreted by cloned L-428 Reed-Sternberg cells. All patients with active nodular sclerosing Hodgkin's disease had a detectable HMW-TGF beta (approximately 300,000) which cross-reacted with both anti-TGF beta 1 and anti-HMW-TGF beta. Purification demonstrated HMW-TGF beta which was active at physiological pH. Twelve control urine samples from healthy adults and 5 follow-up samples from the Hodgkin's patients after successful treatment contained no detectable urinary HMW-TGF beta. The in vivo production of HMW-TGF beta in untreated nodular sclerosing Hodgkin's disease supports the conclusion that this growth factor is secreted in large amounts by Reed-Sternberg cells or cells stimulated by Reed-Sternberg cells.

Prognostic markers of disease activity in Hodgkin's disease.

The erythrocyte sedimentation rate (ESR), liver alkaline phosphatase (ALP), serum copper (Cu) and urinary nucleoside excretion (UNs) have been proposed as independent prognostic markers in Hodgkin's Disease (HD). However, their prognostic value has not satisfactorily been directly compared to recognised clinical prognostic factors. One hundred and sixty-eight patients with HD had the above markers performed prior to initial treatment. At a median follow-up of 10.9 yrs, the predicted 10 year relapse free survival (RFS) and overall survival (OS) for the entire cohort is 64% and 66%, respectively. In general, patients with elevated markers were significantly less likely to achieve CR, remain in CR and survive. However, multivariate analysis revealed this was due to the association of elevated markers with stage and constitutional symptoms. Following therapy, elevated markers were also correlated with evidence of clinically detectable disease. We conclude that although UNs, Cu, ALP and ESR reflect disease activity, they do not provide independent information beyond that of clinical assessment.

Modified nucleosides in body fluids of tumor-bearing patients.

The catabolism of nucleic acids, particularly tRNA, produces a variety of modified nucleosides which are not reutilized by mammalian cells. Investigation of these compounds in body fluids, mainly urine, has recently provided evidence of altered metabolic situations in tumor-bearing patients. The factors involved in the alterations of modified nucleosides formation are connected with altered tRNA-modifying enzymes and/or altered turnover of subpopulations of tRNA. A common pattern in tumor cells or tissues is the presence of isoaccepting tRNA species containing aberrant nucleoside modifications. Several modified nucleosides have been detected and quantitated by HPLC analysis of the urine of normal subjects and cancer patients. Results obtained, in the authors' laboratory, among others, indicate a possible correlation between urinary excretion of these compounds and the course of the disease, with implications for the follow-up of therapeutic treatment. Particular reference should be made to psi, which appears to be a suitable marker for monitoring these subjects. The data from the authors' laboratory also show that the analysis of modified nucleosides in blood may be considered a useful tool in the search for proper markers associated with the cancer status. In this respect psi is suggested as a biochemical indicator for cancer patients.

Urinary neopterin in malignant lymphoma.

Urinary neopterin levels were studied in 96 patients with malignant lymphomas. Twenty-eight had Hodgkin's disease and 68 non-Hodgkin's lymphoma. Neopterin excretion was significantly related to the clinical stage of the disease. Mean neopterin excretion in patients with active disease (634 +/- 527 mumol neopterin/mol creatinine) was significantly higher (p = 0.000) than in patients in complete remission (198 +/- 105 mumol neopterin/mol creatinine). Mean neopterin levels of patients in stage III-IV were higher than for patients in stage I-II. These findings were the same in patients with Hodgkin's disease and those with non-Hodgkin's lymphoma (659 +/- 593-425 +/- 316 mumol neopterin/mol creatinine), regardless of the histological subtype. A significant correlation was found between neopterin excretion, ESR (r = 0.31; p = 0.003) and hemoglobin (r = -0.40; p = 0.000). Longitudinal analysis showed a trend towards a correlation between response to therapy and neopterin excretion. These findings suggest that neopterin may be a useful prognostic marker in non-Hodgkin's lymphoma.

Deoxypyrimidineuria in the course of chemotherapy in M. Hodgkin.

In patients with Hodgkin's disease the excretion of pyrimidine deoxyribonucleosides in urine was followed up within the course of 92 chemotherapeutical series with cytostatics of COOP group. In 14-day chemotherapy series, the excretion of deoxycytidine, deoxyuridine, thymidine, and their sum was significantly increased. In this paper the results are analyzed and a possibility of utilization of this finding for the judgment in the clinical course of the disease is considered.

Urinary neopterin levels in hematologic malignancies.

We studied urinary excretion levels of neopterin in 30 cancer patients affected by non-Hodgkin's lymphomas, Hodgkin's disease and multiple myeloma compared to 30 healthy subjects. Mean value of neopterin excretion in cancer patients (576.01 +/- 620.37) appeared significantly increased (p less than 0.001) compared to normal controls (134.40 +/- 41.65). A neopterin excretion above the upper normal limit was observed in 23/28 (82%) patients with active disease. A trend to an increased urinary level of neopterin with more advanced stage was observed, namely in patients with bone marrow involvement and constitutional symptoms. We suggest that the evaluation of urinary neopterin levels may be of value in the diagnosis and follow-up of hematologic malignancies.

[Paraneoplastic hypouricemia in Hodgkin's lymphoma secondary to a renal tubular reabsorption defect of uric acid (author's transl)]. / Hipouricemia paraneoplástica en el linfoma de Hodgkin por defecto en la reabsorción tubular postsecretora de ácido úrico.

A patient is reported with stage IV-B Hodgkin's lymphoma, lymphocyte depletion type, and associated hypouricemia (1,7 mg/dl). In the few cases described of this association hypouricemia was secondary to a high renal clearance of urate, but in no case was the involved tubular level precisely delimited. In the present case the pyrazinamide and the probenecid tests were performed, disclosing the existence of a possible defect in the postsecretory reabsorptive phase which was improved by therapy. The different pathogenetic mechanisms described to explain this transitory tubular defect are reviewed.

[The significance of analysis and detection of Bence Jones protein in the urine in clinical laboratory diagnosis]. / A vizelet Bence Jones fehérje kimutatásának és vizsgálatának jelentösége a klinikai laboratóriumi diagnosztikában.

Bence Jones proteins (monoclonal free light-chains of immunoglobulins) are the earliest known biologic markers of malignant plasma cell dyscrasia, but Bence Jones proteinuria is also found in many types of B-cell related neoplasms. In some cases it may occur in Hodgkin disease. In some cases benign monoclonal gammopathy related to non-tumor conditions was found. The type of the monoclonal light-chain, the polymerisation and the isoelectric point of the molecules are considerable factors in the development of the disease. Urine specimens from 637 patients with (or suspected) lymphoproliferative diseases were investigated in a two year period using different immunochemical methods. Bence Jones proteinuria was found in 71 cases with the new method (isoelectric focusing combined with immunofixation) and 63 cases by the conventional ones. Bence Jones proteins can be detected by this new method at level below the sensitivity of conventional procedures. Bence Jones proteins in the urine may call the attention to the malignant tumor or the malignant transformation of the disease. The early detection of the monoclonal light-chain excretion may be important in the respect of clinical diagnosis, therapy and the follow-up the clinical status of the patient.