Pro-gastrin-releasing peptide as a marker for the Ewing sarcoma family of tumors.

BACKGROUND: Pro-gastrin-releasing peptide (ProGRP) is an established tumor marker of small cell lung cancer. The purpose of this study was to determine if ProGRP could serve as a tumor marker for the Ewing sarcoma family of tumors (ESFTs). METHODS: Sixteen patients with ESFTs (mean age 32 years) were included in this study. As a control group, 42 patients with other tumor types that clinically or pathologically mimic ESFTs were also analyzed. Pre-treatment serum ProGRP and neuron-specific enolase (NSE) levels, the relationships between these levels, and tumor volume were investigated. In addition, serial changes in the serum or plasma ProGRP (6 patients) and NSE levels (5 patients) were measured over the course of treatment. RESULTS: Pre-treatment serum ProGRP levels were higher than the normal range in 8 of 16 patients; for these eight patients, ProGRP levels positively correlated with tumor volume (R = 0.99). In the control group, ProGRP levels were within the normal range, except for the two patients. Changes in ProGRP levels during treatment were consistent with tumor volume. Serum NSE levels were elevated in 14 of 16 patients with ESFTs and 8 of 42 patients with other tumor types. The range of NSE elevation was much smaller compared to that of ProGRP. Our data indicate that ProGRP is superior to NSE in terms of specificity. CONCLUSIONS: Serum ProGRP levels were elevated in half of the patients with ESFTs and reflected therapeutic response. ProGRP is a reliable tumor marker for the diagnosis of ESFTs and evaluation of treatment response.

[Typical Carcinoid of the Lung with Abnormal Elevation of Serum Pro-gastrin-releasing Peptide (ProGRP)].

A 40-year-old male was referred to our hospital because of a nodular shadow detected in the left lower lobe with the tendency to increase gently. Because fluoro-2-deoxy-D-glucose (FDG) uptake was extremely low on a FDG positron emission tomography (PET-CT), the tumor was highly suspected of the benign tumor. Five years later, a follow-up computed tomography (CT) showed the shadow to be enlarged. FDG uptake was changed to be high, and serum level of pro-gastrin-releasing peptide (Pro-GRP) was extremely elevated. Surgical treatment was chosen under suspicious diagnosis of neuroendocrine tumor, such as small cell carcinoma, large cell neuroendocrine carcinoma, and carcinoid. By the intraoperative aspiration cytology, a small cell carcinoma or a carcinoid was suspected and left lower lobectomy with systemic lymph node dissection was performed. The final histological diagnosis was a typical carcinoid. The elevated serum ProGRP immediately decreased to normal postoperatively.

Influence of abiraterone acetate on circulating neuromediators in chemotherapy-naïve castration-resistant prostate cancer.

BACKGROUND: Abiraterone Acetate (AA) represents a highly effective androgen-receptor (AR) axis targeted agent. Treatment with AA in castration-resistant prostate cancer (CRPC) may partly mediate neuroendocrine differentiation (NED) as an escape mechanism, which may have implications for the choice of sequential therapy in CRPC. We evaluated how treatment with AA influences circulating neuromediators chromogranin A (CGA), neuron-specific enolase (NSE), and pro-gastrin-releasing peptide (Pro-GRP) in chemotherapy-naïve CRPC patients. METHODS: We conducted an analysis in chemotherapy-naïve CRPC patients with clinical or radiographic progression of disease. A total of 35 patients were included at five institutions between February 2013 and December 2014. Sixteen of them had received AA. Serum samples were obtained before a docetaxel-based chemotherapy and analyzed in a reference laboratory. Univariable and multivariable analyses were performed to test the influence of AA treatment, its duration of treatment, and other clinicopathological variables on circulating neuromediators. RESULTS: CGA and NSE levels were above the upper limit of normal (ULN) in n = 20 (57.1%) and n = 13 (37.1%), respectively. Treatment with AA and duration of treatment were not associated with levels above the ULN (CGA and NSE) or higher levels (Pro-GRP) of neuromediators. CGA levels were associated with age (P = 0.092), lymph node metastasis (P = 0.014), duration of androgen deprivation therapy (ADT; P = 0.083), and intake of proton pump inhibitors (P = 0.069). Pro-GRP levels were significantly associated with PSA levels (P = 0.002). On multivariate analysis, CGA levels above the ULN were significantly correlated with ADT (P = 0.01) and intake of proton pump inhibitors (P = 0.03). CONCLUSIONS: Circulating neuromediators in chemotherapy-naïve CRPC patients were elevated in a high percentage of patients. ADT was found to be a relevant NED driver in this cohort. Our results may imply that patients with CRPC after first-line treatment with AA in CRPC are not at a higher risk for developing NED. The major limitation of the study represents the one-time analysis of neuromediators. Larger studies with serial blood measurements or biopsy analysis before and after treatment are needed to confirm our results.

Synthesis and characterization of Bombesin-superparamagnetic iron oxide nanoparticles as a targeted contrast agent for imaging of breast cancer using MRI.

The targeted delivery of superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent may facilitate their accumulation in cancer cells and enhance the sensitivity of MR imaging. In this study, SPIONs coated with dextran (DSPIONs) were conjugated with bombesin (BBN) to produce a targeting contrast agent for detection of breast cancer using MRI. X-ray diffraction, transmission electron microscopy, and vibrating sample magnetometer analyses indicated the formation of dextran-coated superparamagnetic iron oxide nanoparticles with an average size of 6.0 ± 0.5 nm. Fourier transform infrared spectroscopy confirmed the conjugation of the BBN with the DSPIONs. A stability study proved the high optical stability of DSPION-BBN in human blood serum. DSPION-BBN biocompatibility was confirmed by cytotoxicity evaluation. A binding study showed the targeting ability of DSPION-BBN to bind to T47D breast cancer cells overexpressing gastrin-releasing peptide (GRP) receptors. T2-weighted and T2*-weighted color map MR images were acquired. The MRI study indicated that the DSPION-BBN possessed good diagnostic ability as a GRP-specific contrast agent, with appropriate signal reduction in T2*-weighted color map MR images in mice with breast tumors.

Exploring the application value of pro-gastrin-releasing peptide in the clinical diagnosis and surgical treatment of medullary thyroid carcinoma.

OBJECTIVE: To investigate the relationship between pro-gastrin-releasing peptide (ProGRP) and the clinical characteristics of patients with medullary thyroid carcinoma (MTC) and the value of ProGRP in surgical treatment monitoring. PATIENTS AND METHODS: A total of 347 patients with MTC and non-MTC malignant and benign thyroid diseases were enrolled. The concentrations of neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), calcitonin (CT), and ProGRP were determined by Elecsys® assays. The NSE, CEA, CT, and ProGRP levels in different thyroid disease groups were compared, and ProGRP levels in different clinicopathological feature groups pre and postoperatively were further compared. RESULTS: The CT, CEA, NSE, and ProGRP levels were upregulated in the MTC group compared to those in the non-MTC malignant and benign thyroid disease groups. The area under the receiver operating characteristic curve (AUC) of ProGRP for the diagnosis of MTC was 0.832(0.787-0.871), similar to that of CT and CEA. The sensitivity and specificity were 71.4% and 92.7%, respectively, and the optimal cut-off value was 61.8 pg/mL. The AUC of ProGRP combined with CT or CEA for the diagnosis of MTC was 0.933 (0.900-0.958) and 0.922 (0.886-0.949), respectively, which were higher than those of a single index. ProGRP levels were higher in patients with lymph nodes and distant metastases than in patients without metastases. The postoperative level of ProGRP was lower than that before treatment. CONCLUSION: ProGRP is comparable to CEA and CT as an MTC biomarker with broad prospects. It has potential application value in the progression of MTC assessment and the evaluation of surgical intervention effects.

Gastrin-releasing peptide receptor antagonism induces protection from lethal sepsis: involvement of toll-like receptor 4 signaling.

In sepsis, toll-like receptor (TLR)-4 modulates the migration of neutrophils to infectious foci, favoring bacteremia and mortality. In experimental sepsis, organ dysfunction and cytokines released by activated macrophages can be reduced by gastrin-releasing peptide (GRP) receptor (GRPR) antagonist RC-3095. Here we report a link between GRPR and TLR-4 in experimental models and in sepsis patients. RAW 264.7 culture cells were exposed to lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-α and RC-3095 (10 ng/mL). Male Wistar rats were subjected to cecal ligation and puncture (CLP), and RC-3095 was administered (3 mg/kg, subcutaneously); after 6 h, we removed the blood, bronchoalveolar lavage, peritoneal lavage and lung. Human patients with a clinical diagnosis of sepsis received a continuous infusion with RC-3095 (3 mg/kg, intravenous) over a period of 12 h, and plasma was collected before and after RC-3095 administration and, in a different set of patients with systemic inflammatory response syndrome (SIRS) or sepsis, GRP plasma levels were determined. RC-3095 inhibited TLR-4, extracellular-signal-related kinase (ERK)-1/2, Jun NH(2)-terminal kinase (JNK) and Akt and decreased activation of activator protein 1 (AP-1), nuclear factor (NF)-κB and interleukin (IL)-6 in macrophages stimulated by LPS. It also decreased IL-6 release from macrophages stimulated by TNF-α. RC-3095 treatment in CLP rats decreased lung TLR-4, reduced the migration of cells to the lung and reduced systemic cytokines and bacterial dissemination. Patients with sepsis and systemic inflammatory response syndrome have elevated plasma levels of GRP, which associates with clinical outcome in the sepsis patients. These findings highlight the role of GRPR signaling in sepsis outcome and the beneficial action of GRPR antagonists in controlling the inflammatory response in sepsis through a mechanism involving at least inhibition of TLR-4 signaling.

Gastrin-releasing peptide: predictor of castration-resistant prostate cancer?

BACKGROUND: Neuroendocrine (NE) cells of the prostate are known to be androgen-independent and NE peptides like gastrin-releasing peptide (GRP) or neuron-specific enolase (NSE) can stimulate growth in a paracrine manner, and this is thought to be one of the escape mechanisms in castration-resistant prostate cancer (CRPCa). In a longitudinal study, we investigated the development of the NE serum factors GRP, NSE, and chromogranin A and their correlation with prostate-specific androgen (PSA) during hormonal treatment. MATERIALS AND METHODS: Thirty two patients, with histology-proven, localized or metastatic prostatic carcinoma (PCa), who were undergoing therapy with LHRH analogue or a combination of LHRH analog and peripheral androgen blockade, took part in the study. In addition, eight healthy volunteers were each tested twice for serum GRP to elicit a "physiological" standard value. Blood samples were taken periodically from each patient within an 18-month time frame. RESULTS: We defined the standard value for GRP in the healthy participants as 0.852 ng/ml (mean + 2 SD) and observed that the GRP values for patients with PCa were significantly higher (P = 0.034). There was a positive correlation between PSA and GRP in patients with biochemical failure. CgA correlated with PSA development in the CRPCa patients. NSE values rose steadily over the study period, but with no correlation to PSA. CONCLUSION: Our data confirm that NE factors are elevated during hormonal treatment of prostate cancer. GRP is higher in PCa patients undergoing androgen deprivation therapy and is possibly involved in the initiation of hormonal escape in PCa.

An elevated progastrin-releasing peptide level in patients with well-differentiated neuroendocrine tumours indicates a primary tumour in the lung and predicts a shorter survival.

BACKGROUND: Progastrin-releasing peptide (proGRP) is a recently identified biomarker of small-cell lung cancer. In well-differentiated neuroendocrine tumours (WDNETs), this study investigates the association between proGRP and tumour characteristics and the prognostic value of proGRP levels compared with chromogranin A (CgA) levels. PATIENTS AND METHODS: Serum samples were obtained in 282 patients with WDNET. The receiver operating characteristic (ROC) curve technique was used to assess specificity and sensitivity in the identification of a primary tumour location. Cox proportional hazards models and Kaplan-Meier curves were constructed to determine the association of patients' characteristics and tumour markers with survival. RESULTS: For proGRP, the ROC curve indicated a cut-off level of 90 ng/l (approximately twice the upper reference value), with a specificity of 99% and a sensitivity of 43% in distinguishing primary pulmonary tumours from other sites. In the multivariate Cox model, both proGRP and CgA were strongly associated with survival (P < 0.0001 for both variables). CONCLUSIONS: A high-risk proGRP level (more than twice the upper reference value) in patients with WDNETs is a strong indication for a primary tumour in the lung. Besides CgA, proGRP is a complementary tumour marker for prognosis and treatment monitoring in patients with neuroendocrine tumour.

Reduction in serum levels of substance P in patients with rheumatoid arthritis by etanercept, a tumor necrosis factor inhibitor.

We determined the effects of etanercept on the serum concentrations of neuropeptides in RA patients. In a total of 11 patients who had been injected with etanercept, the serum levels of substance P, calcitonin gene-related peptide (CGRP), and gastrin-releasing peptide (GRP) were analyzed. Average levels of serum substance P were significantly reduced from 1.53 to 0.62 ng/ml after the injection of etanercept. In the CGRP and GRP analyses, these average levels dropped from 1.57 and 0.51 ng/ml to 0.44 and 0.04 ng/ml, respectively. Etanercept appears to decrease substance P levels with an improvement in disease activities.

The influence of different blood samples treatment methods on pro-gastrin-releasing peptide.

Pro-gastrin-releasing peptide (ProGRP) is the promising molecular tumor marker of small cell lung cancer (SCLC). Here we study the influence of different blood samples treatment methods on ProGRP.Serum with and without separation gel and heparin plasma from 10 SCLC patients and 5 healthy individuals were assayed for ProGRP immediately and 2, 4, 6, 8, 24, and 48 hours after collection.ProGRP of serum with and without separation gel and heparin plasma detected immediately was basically consistent, whereas there was a significant difference in the level of them assayed after 2 hours. No significant variation with time was observed in heparin plasma, but in serum with and without separation gel, ProGRP concentrations gradually declined with time, with statistical significance. When assayed within 2 hours, each time point of ProGRP in heparin plasma had no significant difference and the difference of PrpGRP in serum separating gel existed at 1.5 hours.Heparin plasma is the best option for clinical test of ProGRP. If serum with separation gel is used, optimization methods of turn-around-time which guarantee samples detected within 1 hour after collection can make results more instructive for clinical treatment.

New and old biomarkers in the differential diagnosis of lung cancer: Pro-gastrin-releasing peptide in comparison with neuron-specific enolase, carcinoembryonic antigen, and CYFRA 21-1.

BACKGROUND: Testing for circulating biomarkers in lung cancer is hampered by the insufficient specificity. We aimed to assess the relative diagnostic accuracy of pro-gastrin-releasing peptide (ProGRP) for the differential diagnosis of small cell lung cancer and compare it with more conventional biomarkers. METHODS: We enrolled a cohort of 390 patients with a clinical suspicion of lung cancer and for whom a histologic assessment was available. Serum or plasma samples were assessed for ProGRP, carcinoembryonic antigen, CYFRA 21-2, and neuron-specific enolase. The performance of each biomarker in discriminating the small cell lung cancer and squamous cell carcinoma/adenocarcinoma from non-malignant lung disease, and small cell lung cancer from squamous cell carcinoma/adenocarcinoma, was assayed by receiver operating characteristic curve analysis. RESULTS: At the cut-off levels suggested by the manufacturers, ProGRP and neuron-specific enolase showed an almost identical sensitivity of 55.2% and 55.6%, respectively, in discriminating small cell lung cancer with respect to non-malignant lung disease. In order to quantify the added value of ProGRP to other conventional markers, we ran a multivariable logistic regression analysis, but the results showed that no markers improve the performance of ProGRP. CONCLUSIONS: ProGRP and neuron-specific enolase individually appear more accurate than other conventional biomarkers for small cell lung cancer, but the union of two markers does not increase the accuracy. The very small target group of patients with small cell lung cancer is a limitation of this study, which can explain why ProGRP alone does not show a sensitivity higher than neuron-specific enolase, as reported by other authors.

Pro-gastrin-releasing peptide and outcome in patients with heart failure and anaemia: results from the RED-HF study.

AIMS: Neuroendocrine activation is associated with poor outcome in heart failure (HF). The neuropeptide gastrin-releasing peptide (GRP), derived from the precursor proGRP1-125 (proGRP), has recently been implicated in inflammation and wound repair. We investigated the predictive value of proGRP on clinical outcomes in HF patients with reduced ejection fraction. METHODS AND RESULTS: The association between plasma proGRP (time-resolved immunofluorometric assay) and the primary endpoint of death from any cause or first hospitalization for worsening of HF was evaluated using multivariable Cox proportional hazard models in 1541 patients with systolic HF and mild to moderate anaemia, enrolled in the Reduction of Events by Darbepoetin alfa in Heart Failure (RED-HF) trial. Median proGRP levels in the RED-HF cohort were markedly increased [95 ng/L (25th, 75th percentile, 69-129 ng/L)] with 64% patients above the 80 ng/L reference limit. Baseline proGRP correlated with estimated glomerular filtration rate (r = 0.52), N terminal pro brain natriuretic peptide (r = 0.33), troponin T (r = 0.34), and haemoglobin (r = 0.16) (all P < 0.001). The incidence outcome increased with increasing tertiles of baseline proGRP (primary endpoint third tertile vs. the lowest tertile; hazard ratio 1.91; 95% confidence interval 1.60-2.28, P < 0.001). However, these associations were markedly attenuated and non-significant in adjusted models. No interaction between baseline proGRP and the effect of darbepoetin alfa treatment was detected. Moreover, no significant association between changes in proGRP during 6 month follow-up and outcome was observed. CONCLUSIONS: Pro-gastrin-releasing peptide is increased in patients with HF with reduced ejection fraction and anaemia, in particular in patients with poor renal function. However, proGRP adds little as a prognostic marker on top of conventional HF risk factors.

Serum pro-gastrin-releasing peptide in diagnosis of small cell lung cancer: A meta-analysis.

OBJECTIVE: The purpose of this study was to assess the diagnostic sensitivity and specificity for serum pro-gastrin-releasing peptide (Pro-GRP) in diagnosis of small cell lung cancer (SCLC) through pooling all the open published data. MATERIALS AND METHODS: Databases of PubMed, Cochrane, ISI Web of Knowledge, and CNKI were electronic, searched by two reviewers to find the diagnostic study serum Pro-GRP in diagnosis of SCLC. The diagnostic sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic (ROC) were calculated by Med DiSc1.4 software. RESULTS: Finally, 21 studies were included in this meta-analysis. Because of statistical heterogeneity, the specificity, specificity, positive/negative likelihood ratio, and DOR were pooled by random effect model. The pooled sensitivity, specificity, PLR, NLR, DOR, and area under the ROC were 64% (95% confidence interval [CI]: 62%-66%), 94% (95% CI: 94%-95%), 11.87% (95% CI: 8.62-11.35), 0.32% (95% CI: 0.26%-0.39%), 40.98% (95% CI: 27.77%-60.64%), and 0.94 (95% CI: 0.91%-0.96%). CONCLUSION: Serum Pro-GRP was promising biomarker for SCLC diagnosis.

Relationships among plasma granzyme B level, pruritus and dermatitis in patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a multifactorial inflammatory skin disease characterized by skin barrier dysfunction, allergic inflammation and intractable pruritus resistant to conventional antipruritic treatments, including H1-antihistamines. Granzymes (Gzms) are a family of serine proteases expressed by cytotoxic T lymphocytes and natural killer cells that have been shown to modulate inflammation. However, the relationship between Gzms and pathology in AD remains unclear. OBJECTIVE: This study assessed the correlation between plasma GzmB levels and severity of pruritus and dermatitis, in AD patients. METHODS: Plasma was collected from 46 patients with AD, 24 patients with psoriasis, and 30 healthy controls. AD severity was assessed with the scoring atopic dermatitis (SCORAD) index, psoriasis severity with the psoriasis area and severity index (PASI), and degree of pruritus by visual analogue scale (VAS) score. GzmA, GzmB and gastrin releasing peptide (GRP) levels were measured by enzyme-linked immunosorbent assays. RESULTS: Plasma GzmB concentrations were significantly higher in patients with AD and psoriasis than in healthy controls. Correlation analyses showed that plasma GzmB concentrations positively correlated with SCORAD and serum levels of severity markers such as thymus and activation-regulated chemokine, and lactate dehydrogenase in AD patients. Moreover, plasma levels of GRP, an itch-related peptide, were higher in patients with AD, positively correlating with VAS score and plasma GzmB level. In addition, plasma GzmB concentration was significantly lower in the treatment group than the untreated group with AD. Meanwhile, there were no correlations among GzmB levels, VAS score and PASI score in patients with psoriasis. In contrast to the results of plasma GzmB, plasma GzmA levels were unchanged among AD, psoriasis and healthy groups, and showed no correlations with VAS score and SCORAD index in patients with AD. CONCLUSION: Plasma GzmB levels may reflect the degree of pruritus and dermatitis in patients with AD.

Serum levels of pro-gastrin-releasing peptide for follow-up of patients with small cell lung cancer.

To assess the clinical usefulness of serum pro-gastrin-releasing peptide (Pro-GRP) as a tumor marker for small cell lung carcinoma (SCLC), we measured serum levels of Pro-GRP with a newly developed ELISA and measured serum levels of neuron-specific enolase (NSE) in 44 patients with untreated SCLC and 77 patients with untreated non-SCLC. We prospectively measured serum levels of Pro-GRP and NSE in SCLC patients after initial treatment until relapse. The sensitivity (70%) and specificity (91%) of Pro-GRP were similar to those of NSE (70 and 86%). Thirty-nine % of patients who had a partial response still had elevated serum levels of Pro-GRP at the time of restaging after initial treatment. In follow-up study, 94% of patients had elevated serum levels of Pro-GRP again at the time of relapse, whereas 37% of patients showed elevated levels of NSE. Levels of Pro-GRP increased a median of 35 (-95 to 151) days before clinical evidence of relapse was detected with successive physical examinations and imaging studies, whereas levels of NSE increased 20 (-85 to 124) days after relapse was detected (P < 0.05). Pro-GRP was helpful as a diagnostic aid and a marker for therapeutic effect and relapse in patients with SCLC, supplemented to serum NSE.

[The value of serum tumor marker in the diagnosis of lung cancer].

OBJECTIVE: To evaluate five serum tumor markers used alone or in combination for the diagnosis of lung cancer. METHODS: The level of five serum tumor markers: NSE, pro-GRP, CYFRA21-1, p53 antibody and CEA was detected by ELISA in 50 healthy adults, 170 lung cancer patients and 60 patients with respiratory infection. RESULTS: The level of the five serum tumor markers in lung cancer patients was significantly higher than that of healthy adults and patients with respiratory infection (P < 0.01). The level of NSE and pro-GRP in patients with small-cell lung cancer was significantly higher than those of the other subtypes of lung cancer (P < 0.01); The level of CYFRA21-1 in patients with squamous-cell carcinoma was significantly higher than that of other subtypes (P < 0.01). The specificity of p53 antibody was 100% in diagnosing lung cancer and the sensitivity of NSE, pro-GRP was much higher for small-cell lung cancer than for other subtypes (P < 0.01); The same was observed in CYFRA21-1 for the diagnosis of squamous-cell carcinoma (P < 0.01). The sensitivity of the tumor markers in diagnosing lung cancer was significantly enhanced if used in combination (P < 0.01). CONCLUSION: These five tumor markers are valuable auxiliary parameters in diagnosing lung cancer. The combination of NSE and pro-GRP is more appropriate than other combinations in diagnosing small-cell lung cancer; the combination of CYFRA21-1, CEA and p53 antibody is the most valuable combination for diagnosing non-small-cell lung cancer. p53 antibody has the highest specificity for diagnosing lung cancer; CYFRA21-1 is the most valuable parameter for diagnosing squamous carcinoma.

Tobacco smoke exposure and bombesin-like peptides in guinea pigs.

Bombesin-like peptides (BLPs) are associated with tobacco smoke (TS)-induced diseases. We sought to determine if acute TS exposure releases BLPs into the pulmonary circulation. Sensitized and non-sensitized guinea pigs were chronically exposed to TS or compressed air. Thereafter, the lungs were acutely challenged with TS while perfused. Perfusates were analyzed for BLPs. TS increased BLPs in non-sensitized guinea pigs. A separate study determined daily bombesin exposure increased lung cell counts but not airway hyperresponsivensess. TS exposure releases BLPs into the pulmonary circulation but can be modified by host factors and bombesin itself does not induce airway hyperresponsiveness.

Serum levels of five tumor markers for lung cancer in patients with chronic renal failure.

The soluble cytokeratin 19 fragment (CYFRA) and pro-gastrin-releasing peptide (ProGRP) are recently described promising tumor markers for lung cancers. To assess their alterations in renal dysfunction, serum levels of CYFRA and ProGRP were determined together with conventional markers including carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), neuron specific enolase (NSE) in patients with renal failure of varying degrees. The mean concentration of all these markers but NSE significantly increased with the severity of renal failure. After hemodialysis (HD), the mean concentration of ProGRP, the molecular weight of which is comparable to that of 2-microglobulin, was significantly decreased. High false positive rates for tumor markers of lung cancer in patients with renal failure should be considered to avoid unnecessary diagnostic procedures.

Serum peptide profiles in patients with carcinoid tumors.

BACKGROUND: Patterns of elevated serum peptides may reveal additional markers and permit better classification of tumors based on (secondary) peptide secretion. METHODS: Fasting peptide profiles were obtained from 31 carcinoid patients. vasoactive intestinal peptide (VIP), pancreatic polypeptide (PP), neurotensin, substance P, gastrin-releasing polypeptide (GRP), calcitonin, gastrin, and pancreastatin were measured. Peptide elevation patterns were correlated with disease sites, syndrome, and survival. RESULTS: Elevations in patients were as follows: VIP 0%, PP 13%, neurotensin 10%, substance P 20%, GRP 3%, calcitonin 10%, and gastrin 3%. There were no consistent patterns of elevated peptides with regard to site or syndrome. Pancreastatin was elevated in 81% of profiles and was the only abnormal peptide in 57% of patients. CONCLUSION: Peptide profile results do not permit improved classification, predict syndrome development, or correlate with survival. In contrast, pancreastatin is elevated in most cases and may be utilized to monitor disease progression and evaluate response to therapy.