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In the recent decade, analysis of circulating tumor DNA (ctDNA) has improved cancer care by allowing for rapid detection of actionable molecular targets. A new generation of circulating DNA tests is now becoming available commercially. These tests are characterized by a superior limit of detection of 0.01% vaF or better, allowing for the detection of radiologically occult molecular residual disease (MRD). MRD tests have the potential to revolutionize neoadjuvant and adjuvant treatment. In addition, these tests can be used as tumor markers to assess disease response. We reviewed the current evidence for the use of high-sensitivity MRD assays with particular focus on the genitourinary tumors. Multiple studies have now been reported in urothelial, renal, and recently testicular carcinoma. We find that the sensitivity varies across tumor types in the adjuvant setting and may reach a high of 100% in urothelial cancer. Specificity in tumor-informed MRD appears to be preserved across tumor types (98%-100%). Several trials are now prospectively validating MRD testing in biomarker integral studies, mainly in urothelial carcinoma., (© The Author(s) 2024. Published by Oxford University Press.)

Background: The prognostic significance of programmed cell death-ligand 1 (PD-L1) expression on circulating tumor cells (CTCs) has been explored but is still in controversy. We performed, for the first time, a meta-analysis to systematically evaluate its prognostic value in human cancers., Methods: Literature databases were searched for eligible studies prior to June 30, 2021. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the associations of pre-treatment and post-treatment PD-L1 + CTCs with progression-free survival (PFS) and overall survival (OS). Subgroup analyses with regards to cancer type, treatment, CTC enrichment method, PD-L1 detection method, cut-off, and specifically the comparison model were performed., Results: We included 30 eligible studies (32 cohorts, 1419 cancer patients) in our analysis. Pre-treatment PD-L1 + CTCs detected by immunofluorescence (IF) tended to predict better PFS (HR = 0.55, 95% CI 0.28-1.08, p = 0.084) and OS (HR = 0.61, 95% CI 0.36-1.04, p = 0.067) for immune checkpoint inhibitor (ICI) treatment, but were significantly associated with unfavorable survival for non-ICI therapies (PFS: HR = 1.85, 95% CI 1.21-2.85, p = 0.005; OS: HR = 2.44, 95% CI 1.69-3.51, p < 0.001). Post-treatment PD-L1 + CTCs predicted markedly worse PFS and OS. The prognostic value was obviously modulated by comparison models. Among patients with detectable CTCs, PD-L1 + individuals had comparable survival to PD-L1 - individuals, except ICI treatment for which PD-L1 + may predict better PFS (HR = 0.42, 95% CI 0.17-1.06, p = 0.067). Patients with PD-L1 + CTCs had worse survival prognosis compared to those without PD-L1 + CTCs in overall analysis (PFS: HR = 2.10, 95% CI 1.59-2.77, p < 0.001; OS: HR = 2.55, 95% CI 1.70-3.81, p < 0.001) and in most subgroups., Conclusions: Our analysis demonstrated that PD-L1 positive expression on CTCs predicted better survival prognosis for ICI treatment but worse survival for other therapies, which thus can be potentially used as a prognostic marker of malignant tumor treatment. However, the prognostic value of PD-L1 + CTCs for ICI treatment needs validation by more large-scale studies in the future., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: This communication reports the identification of a new panel of transcriptional changes in inflammation-associated genes observed in response to ionising radiation received by radiotherapy patients., Methods: Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam radiotherapy for breast, lung, gastrointestinal or genitourinary tumours. Nanostring nCounter analysis of transcriptional changes was carried out in samples prior and 24 h post-delivery of the 1st radiotherapy fraction, just prior to the 5th or 6th fraction, and just before the last fraction., Results: Statistical analysis with BRB-ArrayTools, GLM MANOVA and nSolver, revealed a radiation responsive panel of genes which varied by patient group (type of cancer) and with time since exposure (as an analogue for dose received), which may be useful as a biomarker of radiation response., Conclusion: Further validation in a wider group of patients is ongoing, together with work towards a full understanding of patient specific responses in support of personalised approaches to radiation medicine.

There is still no conclusion on the potential effect of the rs2295080 and rs2536 polymorphisms of mTOR (mammalian target of rapamycin) gene on different cancers. Herein, we performed a comprehensive assessment using pooled analysis, FPRP (false-positive report probability), TSA (trial sequential analysis), and eQTL (expression quantitative trait loci) analysis. Eighteen high-quality articles from China were enrolled. The pooled analysis of rs2295080 with 9502 cases and 10,965 controls showed a decreased risk of urinary system tumors and specific prostate cancers [TG vs. TT, TG+GG vs. TT and G vs. T; P<0.05, OR (odds ratio) <1]. FPRP and TSA data further confirmed these results. There was an increased risk of leukemia [G vs. T, GG vs. TT, and GG vs. TT+TG genotypes; P<0.05, OR>1]. The eQTL data showed a potential correlation between the rs2295080 and mTOR expression in whole blood samples. Nevertheless, FPRP and TSA data suggested that more evidence is required to confirm the potential role of rs2295080 in leukemia risk. The pooled analysis of rs2536 (6653 cases and 7025 controls) showed a significant association in the subgroup of "population-based" control source via the allele, heterozygote, dominant, and carrier comparisons (P<0.05, OR>1). In conclusion, the TG genotype of mTOR rs2295080 may be linked to reduced susceptibility to urinary system tumors or specific prostate cancers in Chinese patients. The currently data do not strongly support a role of rs2295080 in leukemia susceptibility. Large sample sizes are needed to confirm the potential role of rs2536 in more types of cancer., (© 2020 The Author(s).)

The RTGene study was focused on the development and validation of new transcriptional biomarkers for prediction of individual radiotherapy patient responses to ionizing radiation. In parallel, for validation purposes, this study incorporated conventional biomarkers of radiation exposure, including the dicentric assay. Peripheral blood samples were taken with ethical approval and informed consent from a total of 20 patients undergoing external beam radiotherapy for breast, lung, gastrointestinal or genitourinary tumors. For the dicentric assay, two samples were taken from each patient: prior to radiotherapy and before the final fraction. Blood samples were set up using standard methods for the dicentric assay. All the baseline samples had dicentric frequencies consistent with the expected background for the normal population. For blood taken before the final fraction, all the samples displayed distributions of aberrations, which are indicative of partial-body exposures. Whole-body and partial-body cytogenetic doses were calculated with reference to a 250-kVp X-ray calibration curve and then compared to the dose to blood derived using two newly developed blood dosimetric models. Initial comparisons indicated that the relationship between these measures of dose appear very promising, with a correlation of 0.88 ( P = 0.001). A new Bayesian zero-inflated Poisson finite mixture method was applied to the dicentric data, and partial-body dose estimates showed no significant difference ( P > 0.999) from those calculated by the contaminated Poisson technique. The next step will be further development and validation in a larger patient group.

Plasma untargeted metabolomics is a common method for evaluation of the mechanisms underlying human pathologies and identification of novel biomarkers. The plasma proteins provide the environment for transport of hydrophobic metabolites. The current sample preparation protocol relies on the immediate precipitation of proteins and thus leads to co-precipitation of a significant fraction of hydrophobic metabolites. Here we present a new simple procedure that overcomes the co-precipitation problem and improves metabolome coverage. Introducing an additional step preceding the protein precipitation, namely limited digestion with proteinase K, allows release of associated metabolites through the relaxation of the native proteins tertiary structure. The modified protocol allows clear detection of hydrophobic metabolites including fatty acids and phospholipids. Considering the potential involvement of the hydrophobic metabolites in human cardiovascular and cancer diseases, the method may constitute a novel approach in plasma untargeted metabolomics.

Purpose: The main objective of this study was to compare the effect of two anaesthetic techniques (general vs combined) on plasma levels of NGAL (Neutrophil Gelatinase Associated Lipocalin) after robotic urogenital oncosurgery. The secondary objective was to correlate NGAL levels with the incidence of acute kidney injury (AKI)., Methods: This was a longitudinal prospective study. Forty patients were included and randomized in 2 groups: group C (N=16 cases; combined general-epidural anesthesia) and group G (N=24 cases; control group with general anesthesia). Demographic data, Charlson Comorbidity Index, Apache II, SOFA and ASA scores were similar in both groups. Serum creatinine was determined preoperatively and every 24 hrs for 4 postoperative days to identify AKI according to RIFLE and AKIN criteria. Serum NGAL was determined at 6 and 12 hrs after induction of anesthesia., Results: Serum creatinine increased at 24 hrs postoperatively in both groups as compared to baseline, but significant changes were registered only in the G group (p(control) = 0.004). Serum NGAL increased significantly in both groups as compared with baseline levels (pcase=0.0034 vs p(control)=0.0001). The incidence of AKI was 12.50% (95% CI 0.4-34) in the C group and 37.50% (95% CI 17-58) in the G group (p=0.0909), respectively., Conclusion: Impaired renal function and AKI occurred in robot-assisted laparoscopic urogenital oncosurgery under both general and combined anaesthesia. The incidence of AKI was lower in patients undergoing combined anesthesia compared to general anaesthesia after robotic urogenital oncosurgery but the difference did not reach statistical significance. However, plasma levels of NGAL were significantly increased at 6 and 12 hrs in the general anaesthesia group as compared with combined anaesthesia. NGAL may be a better marker in detecting postoperative acute kidney injury. Further studies are needed.

During chemotherapy, patients are more susceptible to infectious complications as a result of bone marrow suppression, leading to neutropenia. The purpose of this study is to investigate risk factors for refractory febrile neutropenia (FN) during urological chemotherapy. Our method for suppressing FN is to use granulocyte colony-stimulating factor and prevent upper respiratory infection by masking and gargling. We studied 47 episodes of FN in 39 patients that occurred during urological chemotherapy for urothelial cancer, testicular cancer, and prostate cancer. Among our cases, there were 5 patients with refractory FN; we set risk factors for refractory FN and performed statistical analyses. The average age of the 39 patients was 60.6 years (range, 18-80 years). In 47 FN episodes, the chemotherapy regimen before the occurrence of FN included 15 (31.9 %) MVAC (methotrexate, vinblastine, adriamycin, cisplatin) for urothelial cancer, 5 (10.6 %) DE (docetaxel, estramustin) for prostate cancer, and 3 (6.4 %) TIP (paclitaxel, ifosfamide, cisplatin) for testicular cancer. The antibiotics used to treat FN included 17 (36.3 %) meropenem and 23 (49.0 %) cefepime, and the average duration of antibiotics was 4.4 days (range, 1-12). We investigated risk factors for refractory FN and showed a significant relationship between refractory FN and indwelling urinary catheter or smaller Multinational Association for Supportive Care in Cancer score by multivariate analysis. A future prospective study is needed for further evaluation for risk factors and establishing treatment protocols and guidelines for FN.

Circulating tumor cells (CTCs) are cells circulating in the blood, which in terms of antigenic or genetic profile correspond to a particular type of cancer. It is suspected that CTCs possess properties of cancer stem cells. Detection, quantification and characterization of CTCs in the peripheral blood can be of great importance for modern oncology. In the case of early-stage disease, CTCs may help in cancer detection, estimation of metastasis risk and treatment prognosis. In advanced cancer patients, CTCs may also have prognostic significance and may facilitate monitoring response to treatment. Identification of CTCs in the circulation and their differentiation from hematopoietic cells and normal epithelial cells could be based on physical and biological properties such as size, density and expression of specific proteins. Immunomagnetic techniques are the most commonly used methods of CTCs isolation. CellSearch System (CSS) is the only test for detecting CTCs in the peripheral blood approved by the Food and Drug Administration (FDA) for clinical use. The paper presents the characteristics of circulating tumor cell isolation methods and the results of studies concerning CTCs isolation in patients with prostate, bladder and kidney cancer.

As part of the diagnosis and treatment of cancer objective biological measures are becoming increasingly important and may help to elicit the individual patient's risk of future outcome. Among theses measures are markers as determinants for the biological potential of the malignant disease, the prediction of recurrence after systemic treatment or the response to a specific therapy. In counselling patients with uro-oncologic diseases, the emerging role of evidence-based treatment choices reveals with cumulative certainty that the available information on markers is inconclusive.The aim of this review is to provide a summary of the current evidence of the evaluation of markers, which may be supportive for a treatment decision and/or provide additional valuable information as part of the treatment option. In addition, this may provide access to some of the most promising investigations, which may yield perspectives for future relevant clinical questions.

Regenerating islet-derived family, member 4 (Reg IV) is a candidate marker for cancer and inflammatory bowel disease and is associated with neuroendocrine and intestinal differentiation. We have reported that 14% of prostate cancer (PCa) cases are positive for Reg IV by immunohistochemistry. In the present study, we performed immunohistochemical analysis of Reg IV in other major urological cancers, including 101 renal cell carcinoma (RCC), and 95 urothelial carcinoma (UC) of urinary bladder by immunohistochemistry. We also investigated neuroendocrine differentiation by chromogranin A and synaptophysin staining along with intestinal differentiation by MUC2 staining. Immunohistochemical analysis of Reg IV revealed no expression of Reg IV in RCC, and only one case (1%) of UC expressed Reg IV. Neither neuroendocrine nor intestinal differentiation was found in RCC. Among 95 UC cases, neuroendocrine differentiation was detected in 13 cases (14%), and intestinal differentiation was observed in 33 cases (35%). In one Reg IV-positive UC case, MUC2 staining was observed. Since Reg IV expression was frequently found in PCa, we also measured Reg IV levels in sera from patients with PCa by enzyme-linked immunosorbent assay. The serum Reg IV concentration in PCa patients (n=38, mean +/- SE, 1.69+/-0.16 ng/ml) was significantly higher than that in control individuals (n=40, 1.28+/-0.11 ng/ml, P=0.0199, Mann-Whitney U test). The sensitivity and specificity for detection of PCa were 34% (13/38) and 90% (36/40), respectively. These results suggest that among major urologic cancers, Reg IV is expressed frequently in PCa, and that serum Reg IV represents a novel biomarker for PCa.

The androgen theory of autism proposes that autism spectrum conditions (ASC) are in part due to elevated fetal testosterone (FT) levels, which are positively correlated with a number of autistic traits and inversely correlated with social development and empathy. A medical questionnaire was completed by n=54 women with ASC, n=74 mothers of children with ASC, and n=183 mothers of typically developing children to test whether women with ASC have an increased rate of testosterone-related medical conditions, and to see whether mothers of children with ASC show similar abnormalities, as part of the 'broader autism phenotype'. Compared to controls, significantly more women with ASC reported (a) hirsutism, (b) bisexuality or asexuality, (c) irregular menstrual cycle, (d) dysmenorrhea, (e) polycystic ovary syndrome, (f) severe acne, (g) epilepsy, (h) tomboyism, and (i) family history of ovarian, uterine, and prostate cancers, tumors, or growths. Compared to controls, significantly more mothers of ASC children reported (a) severe acne, (b) breast and uterine cancers, tumors, or growths, and (c) family history of ovarian and uterine cancers, tumors, or growths. These results suggest current hormone abnormalities in women with ASC and their mothers. Direct investigations of serum testosterone levels and genetic susceptibility to high testosterone production or sensitivity in women with ASC would illuminate the origin of these conditions. The relationship between FT and current testosterone levels also needs to be clarified. The present results may be relevant to understanding the increased male risk to developing autism.

Our earlier studies led to the purification of a similar antigen from several types of human tumours which had the following properties: It provoked a delayed reaction in certain cancer patients which could be demonstrated both in vivo and in vitro (1). In contrast, healthy individuals did not react to this antigen. Subsequent studies led to a higher degree of purity of tumour antigen which enabled a partial sequence (2). The eight amino acid sequence obtained led to the synthesis of the corresponding peptide. This synthetic peptide was then used to raise specific antibodies in rabbits. The availability of such antibodies enabled to undertake a range of studies. Those investigations revealed that the antibodies were tumour specific because they reacted only with certain types of tumours but not with normal cells nor with other types of tumour tissues. We decided to name this tumour antigen as TLP for tumour liberated protein.

The possible connection of viruses with tumours was investigated by serologic examinations. Concerning the presence of antibodies against adenoviruses, especially those against the early non-virion antigens of oncogenic adenovirus type 12, approximately 4000 tests were made with sera of 446 urogenital patients with and without tumours and 70 ones with internal diseases. It was found by complement fixation tests that antibodies against nonvirion antigens of adenoviruses were present in 53% of urogenital patients suffering from malignant tumours and prostatic hypertrophy, in 18% of non-tumourous urological patients and in 4% of patients with internal diseases, respectively. The results suggest that adenoviruses may play a role in tumourous diseases of the urogenital organs.

Introduction and Objectives: It is reported that cytokeratin 19 (CK-19) mRNA is not expressed in the peripheral blood cells of the healthy subjects (Am. J. Pathol. 142: 1111. 1993). Detection of DNA fragments of CK-19 in the peripheral blood suggests the existence of epithelial malignant tumor cells. In this study, we detected CK-19 genes in peripheral blood of patients with urogenital malignancy, and thus clarified the possibility of understanding tumor expansion., Methods: Mononuclear cells were separated from the peripheral blood of 39 patients with urogenital tumor and 9 controls. Total cellular RNA was extracted according to the method described elsewhere. The CK-19 gene expression was investigated using nested reverse transcription polymerase chain reaction (nested RT-PCR) and confirmed by Southern Blotting. These results were compared to the clinical stages., Results: CK-19 mRNA was not detected in any of 9 controls. CK-19 mRNA was detected in 3 out of the 10 bladder cancer cases. Two had metastases and 1 had muscle invasion without metastasis. One of 6 urothelial cancer case of the upper urinary tract showed positive amplification, and had liver, bone and lymphnode metastases. After one course of chemotherapy, mRNA became negative. In prostate cancer cases, three among 7 were positive and all 3 cases had distant metastases. In renal, testicular and penile cancer cases, the positive ratio were 3/6, 1/8 and 2/2, respectively. All positive cases of renal and testicular cancer had distant metastases, but one case of penile cancer had no metastasis., Conclusion: The detection of CK-19 mRNA in the circulating blood by nested RT-PCR makes it possible to detect micrometastasis, to evaluate therapeutic effects and to predict the prognosis.

The clinical data of 91 patients with bone metastases were reviewed. The renal cell carcinoma and prostatic carcinoma were diagnosed respectively in 53% and 47% of the patients. 48% of the patients had tumour size stage T3 and 71% had histopathological stage II (G2). 21% of the patients presented a bone pain. In patients with renal cell carcinoma, the level of serum bone alkaline phosphatase and erythrocyte sedimentation rate were correlated with the concentration of serum ferritin (respectively p = 0.008 and p = 0.055). The relationship between the histopathological grade (G) and the stage of tumour size (T), and the concentration of serum ferritin was noted. In patients with prostatic carcinoma, the relationship between general condition and the concentration of prostatic specific antigen (PSA) as well as the relationship between PSA and the intensity of bone pain were observed. Only relationship between the histopathological grade and the concentration of PSA had a statistical significance (p < 0.05).

The reliability of total sialic acid (TSA), lipid sialic acid (LSA) and free sialic acid (FSA) as markers in genitourinary malignancies was evaluated in 20 normal subjects, 21 patients with prostatic cancer, 22 patients with urinary bladder cancer and 14 patients with renal cell carcinoma. We introduce the new concept of 'corrected' lipid sialic acid (CLSA), which expresses the actual concentration of sialic acid bound to glycolipds by subtracting the concentration of FSA determined by a novel ultrafiltration method. TSA did not show significant differences with respect to normal controls, except for renal cell carcinoma, whose mean value (879 +/- 145 micrograms/ml) showed a P value < 0.001. Instead, CLSA showed only significant differences (P = 0.001), with respect to normal controls in stage I and in all grades of renal cell carcinoma. While all data indicated significant increases (P = 0.001) in the FSA values, (means +/- S.D.) of 0.621 +/- 0.272 micrograms/ml were found in patients with prostatic cancer, 0.796 +/- 0.443 micrograms/ml in patients with urinary bladder cancer and 0.667 +/- 0.146 micrograms/ml in patients with renal cell carcinoma. Separate TSA and CLSA measurements appeared to be of limited value in the detection of genitourinary malignancies. However, results show that FSA was the most sensitive of the three markers tested for detecting malignancies.

The most frequently altered gene in diverse tumor types is the tumor suppressor gene p53. Typically, normal function is inactivated by point mutation of one allele and deletion of the other. Therefore, loss of heterozygosity (LOH) of intragenic polymorphic markers is a strong indication for p53 involvement in a cancerous lesion. This study shows that a highly polymorphic short tandem repeat (STR) within intron 1 of p53 is an excellent marker for quantitative evaluation of LOH in tumor samples, whose multicolor, fluorescently tagged PCR products are analyzed and quantitated on an automated DNA sequencer. The range of error was analyzed in detail. Discrete allelic profiles were obtained following amplification of DNA from microdissected cell samples of patients with urogenital tumors. By calculating qLOH, the relative allele ratio of a tumor compared with healthy tissue, a quantitative expression for the LOH is obtained. PCR-based tumor DNA typing using fluorescent STR primers and automated analysis provides an enhanced level of accuracy and sensitivity required for routine analysis in clinical practice, where large numbers of tumor samples have to be processed.

The present investigation was conducted to determine serum levels of basic fibroblast growth factor (FGF) by enzyme immunoassay in patients with various urogenital tumors. Renal cell carcinoma had a higher tendency (28 of 52, 53.8%) toward increased serum levels of basic FGF than any of the other urogenital tumors, and increased serum basic FGF was detected more frequently in patients with advanced renal cell carcinoma. Analysis of histological pattern indicated that renal cell carcinoma with a solid or tubular component is more likely to produce basic FGF. However, no significant difference was seen between the percentage of clear cell type tumor patients with increased serum basic FGF (50.0%) and the percentage of granular cell type tumor patients with increased serum basic FGF (66.7%). Five of 8 patients with renal cell carcinoma who underwent selective renal venous sampling before nephrectomy showed increased serum basic FGF in the renal vein from the affected kidney. After resection of the affected kidney to remove the cancer, serum basic FGF disappeared within 2 weeks. However, residual huge tumor or postoperative disease prolonged the increased levels of basic FGF in 2 patients, indicating that basic FGF is produced from and secreted by tumor tissue itself. These findings suggest that serum basic FGF can be useful in the diagnosis, and in evaluating the prognosis, of patients with renal cell carcinoma.

The presence of a tumor antigen in human colonic carcinomas and their metastases was described about 25 years ago. This antigen, called carcinoembryonic antigen (CEA), is one of the first known tumor markers. Since then, many more have been described, but CEA, determined alone or in combination with others, is still one of the most used. CEA is not organ specific and abnormal values may be found in a wide range of carcinomas, especially those with gastrointestinal involvement. CEA assay should not be used for cancer diagnosis because its sensitivity in patients without cancer metastases is low. In addition, abnormal CEA values may be found in patients with benign diseases. However, the probability of malignancy increases directly with CEA concentration. Its main clinical applications are prognosis, early diagnosis of recurrence and follow-up of patients with carcinomas. In a wide range of malignancies, CEA serum levels are clearly related to tumor stage. Presurgical CEA serum levels are a well-established prognostic factor in colorectal, breast and lung cancer. Patients presenting with increased preoperative CEA serum levels have both a shorter disease-free interval and lower survival than those with normal CEA levels. In the early diagnosis of recurrence, CEA also plays an important role: in about 70-85% of patients with colorectal tumors and in 40-50% with breast cancer, CEA serial increase is the first sign of tumor recurrence. In patients with disseminated tumors, serial determinations are also a useful tool for therapy monitoring: CEA values decrease with effective treatment while stable or increasing values are observed when treatment is not effective.

In order to evaluate the mobilization effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on peripheral blood stem cells (PBSCs), rhG-CSF was given to patients with urogenital malignancy before chemotherapy. Markers for the stem cells, such as colony forming unit-granulocyte/macrophage (CFU-GM) and burst forming unit-erythrocyte (BFU-E), were sequentially monitored in peripheral blood and leukapheresis samples. Five patients, including a 13-year-old boy, were given 5 micrograms/kg rhG-CSF subcutaneously: the pediatric case for four consecutive days and the adult cases for six consecutive days (53-72 years of age). None of the patients had received chemotherapy within the four weeks prior to the start of the rhG-CSF series. PBSC collections were performed on the fifth day in the pediatric case and on the fifth and seventh days in the adult cases. Progenitor cells were monitored by methyl-cellulose cell culture techniques. CFU-GM on day 5 of the rhG-CSF series in peripheral blood increased 14- to 53-fold compared with samples taken immediately before the series. CFU-GM in the leukapheresis products on day 5 was greatest (70 x 10(3)/kg) in the pediatric case and least (14 x 10(3)/kg) in the oldest patient's case. The totals of the CFU-GM collected by two phereses in the adult cases were 21-73 x 10(3)/kg and the totals of CD34 positive cells were 0.6 to 1.4 x 10(6)/kg. The data suggest rhG-CSF to induce sufficient PBSCs for bone marrow rescue into the peripheral blood without any preceding chemotherapy. The patient's age may, however, be a contributory factor in using this method.

Selenium has been shown to be a cancer preventive agent. A few studies have shown that increased selenium level is associated with decreased cancer incidence and decreased cancer mortality. The present study was carried out to find out the relationship of selenium level with site, extent of disease, recurrence of disease, histopathological diagnosis, anaemia and serum protein level of cancer patients. Plasma selenium level were studied in 100 patients and mean selenium level of 75.35 ng/ml in cancer patients was significantly less than control values (116.99 ng/ml) in normal healthy individuals (P < 0.003). The strongest association of plasma selenium level and cancer was found in cancer breast (70.50 ng/ml) and gastrointestinal tract (73.05 ng/ml) cancer. Selenium level decreased with the progress of disease and recurrence of disease. No significant association between histopathological diagnosis and selenium level was observed. Anaemia and hypoproteinemia was also not found to be related with selenium level.

ras oncoproteins and ras-related proteins constitute a large family of the small GTP-binding protein family. The rab branch of the ras superfamily is involved in the intracellular transport along the secretory and endocytic pathway in eukaryotic cells. We here demonstrate that a member of the rab branch, the rab2 protein, is frequently overexpressed in peripheral blood mononuclear cells from patients with solid neoplasms. Moreover, this expression is shown to be greatly modified during the course of therapy. Our results provide strong evidence for the implication of a small GTP-binding protein in immunological events associated with neoplastic diseases. The precise cellular population involved as well as the potential prognostic value of this process remains to be determined.

Patients with renal or bladder cancers exhibit a unique association with adenovirus (Ad) infections. About 60% of them contain antibodies to Ad early antigens. Both in their tumour cells and peripheral blood lymphocytes (PBL) they have detectable early Ad antigens known to be involved in malignant cell transformation. Transfection of tumour cell extracts resulted in complementing temperature-sensitive (ts) Ad mutants at nonpermissive temperatures (39 degrees C) indicating that some cells of the tumour mass possess active functions for Ad. Only 4 to 18% of control subjects were positive in these tests. Here we studied whether lymphocytes might be involved in tumourigenesis by Ad. PBL extracts of patients were transfected into HEp-2 culture cells, which were subsequently superinfected with Ad-5 ts18 and ts19 mutants at 39 degrees C. Titration of virus yields indicated complementation in 76% of patients with renal and bladder cancers in contrast to 20% of control individuals. Complementing ability of lymphocytes which had been prestimulated with phytohaemagglutinin (PHA) approached that of tumour extracts. It means that both specimens contain advanced functions in contrast to resting lymphocytes. Lymphocytes are nonpermissive for latently carried Ad infections. Expression, possible transfer of early Ad gene products via frequent contacts with tissue cells can result in removal of tumour suppressor gene products from complexes regulating cell cycle negatively. Further interaction with hormone-sensitive protooncogenes explains tissue, age and gender specificity of urological malignancies. These phenomena suggest an important cofactorial role for Ad in kidney and bladder tumours.

We investigated the clinical significance of squamous cell carcinoma (SCC) antigen determined by radioimmunoassay on patients with uroepithelial carcinoma. Serum SCC antigen levels and the positive rates were significantly higher in uroepithelial carcinoma having an SCC component than in normal controls, benign urologic diseases, other urogenital carcinomas, or in pure transitional cell carcinoma (TCC) of uroepithelial carcinomas. A substantial number of patients with pure TCC showed a positive serum level of SCC antigen. Immunohistochemical staining of SCC antigen on the uroepithelial carcinomas confirmed that some, not all, pure TCC, mostly grade 3, expressed SCC antigen in their cells. These results suggested a biologic characteristic of grade 3 TCC which is closely related to that of SCC. The serum levels of SCC antigen correlated well with the disease extensions in uroepithelial carcinoma containing SCC component. Changes in serum levels of SCC antigen following treatment reflected the clinical courses of patients, particularly in those with elevated pretreatment levels. The results of our study indicated that the determination of SCC antigen would be clinically useful for monitoring clinical courses of patients with uroepithelial carcinomas containing SCC component and of those with pure TCC whose pretreatment level was elevated.

Ten patients with advanced urologic cancers who were scheduled to receive at least two courses of chemotherapy were enrolled in this trial. Fifty thousand units of recombinant human interleukin-1 (IL-1) beta analogue OCT-43 (Otsuka Pharmaceutical Co., Ltd., Tokyo, Japan) was administered subcutaneously only once or twice when severe neutropenia (less than 500/microliters) continued for 2 consecutive days. In eight patients, OCT-43 was not injected in the first course of chemotherapy as a control, but was injected in the second course. The durations of leukocytopenia (less than 2000/microliters) and neutropenia (less than 1000/microliters) were significantly shortened in the second course compared with those in the first course in those eight patients. Recovery of neutrophil number from the lowest number was also significantly faster in the second course. Thus, OCT-43 was considered to have hematopoietic activities. However, single or double injection of OCT-43 did not affect the numbers of eosinophilic or basophilic granulocytes, monocytes, or platelets. Adverse effects associated with OCT-43 injections were high fever and chills, but they were controlled by indomethacin.

A patient is described in whom a circulating heparin-like anticoagulant developed during the terminal course of metastatic transitional cell carcinoma. The anticoagulant, which was identified as heparan sulfate, was the clinical sign of global abnormalities in the patient's plasma glycosaminoglycans. Subsequent analysis disclosed increased amounts of chondroitin sulfate as well as heparan sulfate. In addition, the charge density and molecular weight of the patient glycosaminoglycans and their organization into proteoglycans differed significantly from glycosaminoglycans isolated from normal plasma samples.

Immunosuppressive acidic protein (IAP) is a non-specific immunoreactive protein arising from inflammatory or malignant conditions in the human body. We determined the IAP levels in 65 cases with urological malignancies and in 31 cases with benign diseases as a control group during a 9-month period. There were significantly higher serum levels of IAP in cases of bladder transitional cell carcinoma (p = 0.025), prostate adenocarcinoma (p less than 0.00001) and upper urinary tract urothelial cancer (kidney and/or ureter, p = 0.013) as compared with those of the control group. Significant differences in IAP between different tumor stages were found in the bladder cancer group with high stage cases having higher IAP levels (p less than 0.0005). However, no significant differences were found between different tumor gradings. Most of the prostate cancer patients had extremely high IAP values (1,029 +/- 490 micrograms/ml) in this study. Renal cell carcinoma and testicular tumors showed no statistical differences from the control group (p = 0.89 and 0.37, respectively). No differences could be found in the different age groups (by decades) or sexes. The serum IAP level can be a good non-specific tumor marker for bladder cancer staging and probably a good follow-up tool for most urological malignancy patients.

The present investigation has analyzed 249 patients suffering from urogenital cancer in respect to aberrant concentration of prolactin, TSH, LH and FSH. A simultaneous pattern of acute phase reactants (alpha 1-glycoprotein, alpha 1-antitrypsin, beta 2-glycoprotein and haptoglobin) was related to the content of these hormones. Abnormal results of prolactin and TSH were present in 30% of all patients, whereas frequent aberrations of alpha 1-acid glycoprotein and alpha 1-antitrypsin were detected in 60--80%. Acute phase reactants changed to more pathological values when correlated to elevated prolactin.

Ulex europaeus agglutinin I binds specifically to vascular endothelium of various human tissues irrespective of the blood group type or secretive status of the tissue. Using this property, we have developed an immunoperoxidase technique to identify vessel structures in urogenital tissues. Most vessels in malignant and nonmalignant tissues of bladder, prostate and testis of different blood types (A, B, AB and O) can be readily identified by this method. This technique has potential application in detecting tumor cell invasion of vessels and in studying distribution of vessels in relation to various normal and pathological events.

The bioassay using the polythemic mice demonstrated persistent erythropoietin (Ep) activity in 24 renal carcinoma patients. Eight patients without clinical evidence of renal carcinoma had Ep levels that were slightly higher than those of controls, suggesting the possibility of occult disease. Increased levels of Ep were noted in 5 patients with other genitourinary carcinomas. This selective study reaffirms the value of Ep as a biologic marker in some renal cell cancers, and occasionally in other genitourinary tumors.

The plasma acute phase reactant proteins are a group consisting mainly of glycosialated proteins, whose levels rise in response to a wide variety of injuries. This review discusses how by considering several APRPs coincidentally the pattern of change can have a discriminant function which can be used alone or to enhance other biochemical tests, especially in the monitoring of disease.

Serum beta-2-microglobulin levels were measured in patients with renal, vesical and prostatic cancer. Measurements were made only on samples with a serum creatinine less than or equal to 105 mumol./l. to eliminate the possibility of elevated beta-2-microglobulin being a result of impaired renal function. This criterion eliminated 28 to 50 per cent of the patients with bladder cancer and 73 per cent of those who had undergone nephrectomy for renal carcinoma, which, obviously, limits the value of beta-2-microglobulin measurement for the surveillance in these cancers. Beta-2-microglobulin values in patients with prostatic cancer were seldom increased to more than 3.0 mg./l. In bladder cancer patients with normal serum creatinine the frequency of an elevated serum beta-2-microglobulin increased with the increase in tumor stage.

The level of serum gamma-seminoprotein (gamma-Sm) was determined by enzyme immunoassay using an EIA gamma-Sm test kit in 32 patients with prostatic cancer (before treatment for 12 and after treatment was started for 20), 24 patients with benign prostate hypertrophy and 22 patients with other urogenital cancer. A gamma-Sm level of over 4.0 ng/ml was considered to be positive. The positive rate was 43.8% in prostatic cancer patients (83.3% before and 20.0% after treatment), 25.0% in benign prostate hypertrophy and 0% in other urogenital cancer. Since the positive rate of prostatic acid phosphatase (PAP) was 34.3% in prostatic cancer patients (75.0% before and 10.0% after treatment) and 16.7% in benign prostate hypertrophy patients, gamma-Sm may be more sensitive but less specific as an indicator of prostatic cancer in PAP. In 9 patients with prostatic cancer before treatment, the levels of serum gamma-Sm and PAP were serially determined for up to 11 months. The level of gamma-Sm decreased in 7 patients, and PAP in all patients after hormone therapy. One patient showed a consistently positive gamma-Sm level and the level of the others became positive only for gamma-Sm during follow-up. There was a statistical correlation between the levels of serum gamma-Sm and PAP in patients with prostatic cancer (r = 0.595, p less than 0.01), in patients with benign prostate hypertrophy (r = 0.882, p less than 0.01) and also in the patients in both groups together (r = 0.590, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

It was previously shown (Am J Clin Pathol 55: 65-67, 1971) that sera from patients with chronic lymphocytic leukemia (CLL) produce a characteristic pattern on disk-acrylamide gels. Other observations indicating the presence of immunosuppressive proteins in the sera of patients with cancer suggested the search for characteristic protein patterns employing the same technic. Utilizing sera from patients with various types of malignancies and appropriate controls, the results appear to indicate that there is a consistent and distinctive pattern to the gels. The nature of the (different) protein(s) remains to be elucidated.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered at a dose of 1-60 micrograms/kg of body weight to 22 patients with transitional cell carcinoma before chemotherapy as part of a Phase I/II study. In all patients, a specific dose-dependent increase in the absolute neutrophil count (ANC) of 1.8-12 fold was seen. In addition, this augmentation in the ANC was accompanied by an increase in leukocyte alkaline phosphatase, a marker of secondary granule formation. In six of eight patients analyzed, an increase in bone marrow myeloid to erythroid cell ratio was seen. Day 14 peripheral blood cell derived colony forming unit granulocyte macrophage were also increased by day 6 of rhG-CSF treatment. Circulating levels of eosinophils and basophils were unchanged; however, a 10-fold increase in monocytes was observed in patients treated at the highest doses. There was also a small increase in CD3+ lymphocytes that was not dose dependent. Hemoglobin, hematocrit, and platelet count remained near baseline throughout the period of rhG-CSF administration. These findings demonstrate that rhG-CSF is a potent stimulus for normal neutrophil proliferation and maturation.