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Biomedical subjects

A Benner

Publications and source records attributed to A Benner.

At least 37 records · Page 2Linked to original sources
PubMed2003

Helium pneumoperitoneum reduces tumor recurrence after curative laparoscopic liver resection in rats in a tumor-bearing small animal model.

BACKGROUND: After exposure of neoplastic tissue to helium, a significant reduction of tumor growth has been detected in experimental studies, both in vitro and in vivo. This tumor-suppressive effect of helium is controversly discussed in the literature. It was therefore the aim of this study to investigate the influence of pneumoperitoneum with CO2, room air, or helium in a tumor-bearing small animal model comparing laparoscopic partial hepatic resection for hepatocellular carcinoma with conventional open partial hepatectomy. METHODS: One-hundred forty-eight male American Cancer Institute rats underwent partial hepatectomy for curative resection of previously induced hepatocellular carcinoma (Morris hepatoma 3924A). Resection was performed either in open laparotomy (n = 30) or laparoscopically under the employment of CO2 (n = 30), room air (n = 30), or helium (n = 30) for the pneumoperitoneum. Twenty-eight animals served as controls receiving anesthesia but no tumor resection. All animals were sacrificed on postoperative days 21, 35, or 56 for autopsy and evaluation of possible tumor recurrence and metastasis. RESULTS: Significant reduction of postoperative tumor recurrence and metastasis was observed in the group of animals receiving laparoscopic tumor resection under helium insufflation compared to open surgery or laparoscopic resection with air pneumoperitoneum. CONCLUSIONS: The results of this study suggest a suppressive effect of helium pneumoperitoneum on postoperative tumor growth and metastatic spread. Furthermore, tumor exposure to room air appears to have a stimulative influence on tumor recurrence and metastasis compared to a pneumoperitoneum established with CO2.

Animals↗
PubMed2003

Laparoscopically assisted colectomy and ileoanal pouch procedure with and without protective ileostomy.

BACKGROUND: Apart from an obviously better cosmetic situation, there is controversy on the actual benefit of laparoscopic and laparoscopically assisted techniques in restorative proctocolectomy. The need for a protective ileostomy remains unclear. METHODS: Fifty-nine consecutive patients with ulcerative colitis and familial polyposis were included in this prospective cohort study. The colon was mobilized laparoscopically with a four-trocar technique, facilitating vascular dissection, rectal resection, and ileoanal pouch construction to be done through a Pfannenstiel incision. A protective ileostomy was constructed only in patients where the operation was difficult or where the anastomosis was under tension. Intra- and postoperative data were recorded; statistical analyses were performed by exact logistic regression. RESULTS: Laparoscopic mobilisation was successful in 54 patients (91.2%). Two patients had to be primarily converted because of exceeding the set time limit; 3 other patients had to have an additional median laparotomy. These 5 patients all had an increased body mass index (BMI), which was a statistically significant risk factor for failure of the laparoscopic technique. 18.6% of patients developed major complications (n = 11). Nine patients required secondary ileostomies; all of them either were under high dose immunosuppressants (n = 5) or had an increased BMI (average 28.42 kg/m2). Failure of the laparoscopic technique was associated with major complications. CONCLUSION: Laparoscopically assisted restorative proctocolectomy is technically feasible; an increased BMI is a relevant risk factor for failure. The minimally invasive approach probably does not reduce the need for a protective ileostomy in selected patients. The selection criteria for the addition or omission of a protective ileostomy in minimally invasive restorative proctocolectomy remain to be clearly defined.

Adenomatous Polyposis Coli↗
PubMed2003

Risk-adapted postremission therapy in acute myeloid leukemia: results of the German multicenter AML HD93 treatment trial.

The objective of the AML HD93 treatment trial was to evaluate the outcome in young adults with acute myeloid leukemia (AML) after postremission therapy was stratified according to cytogenetically defined risk. The rationales for the study design were based (i) on previous favorable results with high-dose cytarabine in AML with t(8;21), inv/t(16q22) and in AML with normal karyotype, and ii) on encouraging results obtained in several phase II trials using autologous stem cell transplantation (SCT). Between July 1993 and January 1998, 223 eligible patients, 16-60 years of age with newly diagnosed AML other than French-American-British type M3/M3v, were entered into the trial. Risk groups were defined as follows: low risk: t(8;21) or inv/t(16q22); intermediate risk: normal karyotype; high risk: all other chromosomal abnormalities. Following intensive double induction therapy with idarubicin, cytarabine and etoposide, all patients in complete remission (CR) received a first consolidation therapy with high-dose cytarabine and mitoxantrone (HAM). A second consolidation therapy was stratified according to the risk group: low risk: HAM; intermediate risk: related allogeneic SCT or sequential HAM; high risk: related allogeneic or autologous SCT. Double induction therapy resulted in a high CR rate of 74.5%, and 90% of the responding patients were eligible for consolidation therapy. Survival for all 223 trial entrants was 40%, and for the 166 patients who entered CR, disease-free (DFS) and overall survival were 40 and 51% after 5 years, respectively. Within the low-, intermediate- and high-risk groups, DFS and survival after 5 years were 62.5 and 87, 40 and 49 and 17 and 26% respectively, without advantage for allogeneic transplantation in the intermediate- and high-risk groups. Postremission therapy-related mortality was 0, 7 and 14%, respectively. This study demonstrates the feasibility of cytogenetically defined risk-adapted consolidation therapy. The overall trial results are at least equivalent to those of published trials supporting the risk-adapted treatment strategy.

Acute Disease↗
PubMed2003

Centrosome aberrations as a possible mechanism for chromosomal instability in non-Hodgkin's lymphoma.

Recently, centrosome aberrations have been described as a possible cause of aneuploidy in many solid tumors. To investigate whether centrosome aberrations occur in non-Hodgkin's lymphoma (NHL) and correlate with histologic subtype, karyotype, and other biological disease features, we examined 24 follicular lymphomas (FL), 18 diffuse large-B-cell lymphomas (DLCL), 33 mantle cell lymphomas (MCL), and 17 extranodal marginal zone B-cell lymphomas (MZBCL), using antibodies to centrosomal proteins. All 92 NHL displayed numerical and structural centrosome aberrations as compared to nonmalignant lymphoid tissue. Centrosome abnormalities were detectable in 32.3% of the cells in NHL, but in only 5.5% of lymphoid cells from 30 control individuals (P<0.0001). Indolent FL and MZBCL contained only 25.8 and 28.8% cells with abnormal centrosomes. In contrast, aggressive DLCL and MCL harbored centrosome aberrations in 41.8 and 35.0% of the cells, respectively (P<0.0001). Centrosomal aberrations correlated to lymphoma grade, mitotic, and proliferation indices, but not to the p53 labeling index. Importantly, diploid MCL contained 31.2% cells with abnormal centrosomes, while tetraploid samples harbored centrosome aberrations in 55.6% of the cells (P<0.0001). These results indicate that centrosome defects are common in NHL and suggest that they may contribute to the acquisition of chromosomal instability typically seen in NHL.

Cell Division↗
PubMed2003

Analysis of reelin as a candidate gene for autism.

Genetic studies indicate that chromosome 7q is likely to contain an autism susceptibility locus (AUTS1). We have followed a positional candidate gene approach to identify relevant gene(s) and report here the analysis of reelin (RELN), a gene located under our peak of linkage. Screening RELN for DNA changes identified novel missense variants absent in a large control group; however, the low frequency of these mutations does not explain the relatively strong linkage results on 7q. Furthermore, analysis of a previously reported triplet repeat polymorphism and intragenic single nucleotide polymorphisms, using the transmission disequilibrium test, provided no evidence for association with autism in IMGSAC and German singleton families. The analysis of RELN suggests that it probably does not play a major role in autism aetiology, although further analysis of several missense mutations is warranted in additional affected individuals.

Autistic Disorder↗
PubMed2002

PTEN/MMAC1 expression in melanoma resection specimens.

PTEN/MMAC1, a tumour suppressor gene located on chromosome 10q23.3, has been found to be deleted in several types of human malignancies. As the chromosomal region 10q22-qter commonly is affected by losses in melanomas, we addressed this gene as tumour suppressor candidate in melanomas. Investigating PTEN/MMAC1 expression at mRNA level by semi-quantitative reverse transcription-polymerase chain reaction, we did not find a statistically significant down-regulation in melanoma resection specimens in comparison to acquired melanocytic nevi from which melanomas quite often are known to arise. Upon immunohistochemistry, PTEN/MMAC1 protein expression in melanomas was not lost. Sequencing the PTEN/MMAC1 cDNAs in 26 melanoma resection specimens (21 primary melanomas, five metastases), we detected three point mutations and two nucleotide deletions which did not represent genetic polymorphisms. With respect to the predicted protein sequences, all three point mutations were silent whereas the two frame shifts at the extreme C-terminus resulted in a loss of the putative PDZ-targeting consensus sequence. As loss of this motif possibly impairs localization and function of PTEN/MMAC1 in the two corresponding primary tumours, alterations of this tumour suppressor protein may participate in some melanomas.

Adult↗
PubMed2002

Comparison of laparoscopic versus conventional technique in colonic and liver resection in a tumor-bearing small animal model.

BACKGROUND: Laparoscopic procedures in oncological surgery are either done in curative or palliative intent. We present two experiments comparing laparoscopic to conventional surgery in the curative and palliative setting regarding short-term (stress and immune alteration) and long-term aspects (survival time and recurrence rate). METHODS: We established two syngenic tumor-bearing small animal models for curative liver resection (Morris hepatoma 3924A, ACI rats) and palliative colon resection (BSp73 ASML, BOX rats). Male rats were operated on, performing laparoscopic and conventional liver resection as well as laparoscopic and conventional colon resection; control groups (anesthesia) were included. The following parameters of the stress and immune system were measured: corticosterone, neopterine, Il-1-b, Il-6, and body weight as a parameter of postoperative recovery. Analyzed long-term parameters were survival time, tumor weight, and recurrence rate (histology). RESULTS: After colon resection, analysis of variance showed significant differences in all short-term parameters, including body weight after laparoscopic versus conventional colon resection (p <0.05). In the case of laparoscopic versus conventional liver resection, only Il-6 showed globally statistically significant differences for the short-term parameters (p = 0.05). Long-term parameters were not significantly different between the laparoscopic and conventional groups, regardless of the type of resection (colon or liver) or the operative setting (curative or palliative). However, there were differences after curative liver resection compared to the control group (anesthesia alone). CONCLUSION: These results suggest that the type of intraabdominal operation (colon or liver) may influence the degree of trauma of an operation more than the type of technique (laparoscopic or open). The perioperative alteration of stress and immune function has no implications on the long-term results, such as survival time or recurrence, neither in the curative nor in the palliative setting. The thesis that laparoscopic surgery results in less pain, which in turn means less stress and less alteration of the immune system and therefore results in a lower rate of postoperative metastasis is only valid for laparoscopic colonic resection in our model. The part of the thesis that states that fewer metastases should occur after laparoscopic oncological surgery cannot be confirmed in our study.

Adenocarcinoma↗
PubMed2001

Salvage therapy for multiple myeloma with thalidomide and CED chemotherapy.

The feasibility and efficacy of a combination of thalidomide, cyclophosphamide, etoposide, and dexamethasone were studied in 56 patients with poor-prognosis multiple myeloma. Of 50 patients evaluable for response, 4% achieved complete response (CR), 64% partial response (PR), 18% minimal response (MR), 6% stable disease (SD), and 8% progressive disease (PD), resulting in an objective response rate (> or = MR) of 86.0% (76.7% overall objective response rate in intent-to-treat analysis; n = 56). Subsequent to successful remission induction, 18 patients received autologous or allogeneic stem cell transplantation. The median progression-free survival in all patients was 16 months. The median overall survival time could not be calculated, since the last observed death occurred after 16 months of follow-up (median follow-up of 14 months) with a corresponding estimated survival probability of 55%. Severe adverse effects (World Health Organization III/IV) included infectious complications (35.7%) and cardiovascular events (7.1%). The data suggest that Thal improves antitumor activity of salvage chemotherapy regimens in poor-prognosis multiple myeloma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Comparative analysis of tumor cell dissemination in mesenteric, central, and peripheral venous blood in patients with colorectal cancer.

BACKGROUND: Metastatic disease in colorectal cancer results from hematogenic dissemination of tumor cells. This dissemination can be explained by 2 concepts: (1) regional spread of tumor cells via portal venous drainage into the liver as the first site of metastasis and (2) early spread of tumor cells into central and peripheral venous blood as evidence of systemic hematogenic tumor cell dissemination. HYPOTHESIS: Tumor cell detection in different blood compartments could help to understand the predominant pattern of hematogenic tumor cell dissemination in colorectal cancer. DESIGN: Prospective consecutive series. SETTING: University hospital. PATIENTS AND METHODS: Mesenteric, central, and peripheral venous blood samples from 40 patients with colorectal cancer were examined by cytokeratin 20 reverse transcriptase polymerase chain reaction. MAIN OUTCOME MEASURES: Sensitivity and specificity of cytokeratin 20 reverse transcriptase polymerase chain reaction, and frequency of tumor cell detection in different blood compartments. RESULTS: Tumor cells were found in mesenteric venous blood of 20 of 40 patients, central venous blood of 6 of 40 patients, and peripheral venous blood of 2 of 19 patients. The detection rate in mesenteric venous blood was significantly higher than that in central and peripheral venous blood (P<.001). CONCLUSIONS: The significantly higher detection rate in mesenteric venous blood emphasizes the importance of the filter function of the liver for circulating tumor cells in portal venous blood. Tumor cell detection in central and peripheral venous blood, however, shows that this filtering process is limited and indicates early systemic hematogenic tumor cell dissemination in colorectal cancer.

Biomarkers, Tumor↗
PubMed2001

Association of decreased perfusion of the ileoanal pouch mucosa with early postoperative pouchitis and local septic complications.

BACKGROUND: After ileoanal pouch operation, 5% to 40% of patients with ulcerative colitis and 2% to 8% of patients with familial adenomatous polyposis develop pouchitis. Seven percent to 32% of all patients have local septic complications. Pouch ischemia is discussed as a pathophysiologic factor. Tonometry is a minimally invasive method for estimating intramucosal pH (pHi), with a decreased pHi showing intramucosal acidosis characteristic of hypoperfusion. HYPOTHESIS: Decreased perfusion of the iloanal pouch measured by pHi is associated with local septic complications and the development of pouchitis. DESIGN: Prospective cohort study. SETTING: Surgical department of a university hospital. PATIENTS AND METHODS: The pHi in the ileoanal pouch of 98 patients was measured directly after the pouch procedure and correlated to the clinical course. Endoscopic examination of the pouch with biopsy and blinded histologic assessment, including calculation of a histologic pouchitis score, were routinely performed 3 months postoperatively. MAIN OUTCOME MEASURES: Development of pouchitis and local septic complications in correlation to pHi. RESULTS: A decreased pHi was statistically significantly associated with the development of pouchitis and the rate of local septic complications. All 3 patients with anastomotic stenosis had a pHi less than 7.00. The diagnosis of ulcerative colitis just failed in statistical significance as a risk factor for pouchitis. An increased body mass index just failed as a statistically significant risk factor for complications but was a risk factor for the development of acute pouchitis. CONCLUSION: Pouch hypoperfusion is a risk factor for the development of pouchitis and local septic complications.

Adenomatous Polyposis Coli↗
PubMed2001

Bone marrow microcirculation analysis in multiple myeloma by contrast-enhanced dynamic magnetic resonance imaging.

The aim of our study was to investigate the quantitative microcirculation parameters amplitude A (hypothetical intravascular volume) and exchange rate constant k(21) (hypothetical vascular permeability) by contrast-enhanced dynamic magnetic resonance imaging (dMRI) as markers of angiogenesis in multiple myeloma (MM). Therefore lumbar spine and spina iliaca superior posterior of 16 normal controls and 41 patients with active MM were assessed using a dMRI protocol with a pump controlled bolus infusion of Gadolinium-DTPA. Pharmacokinetic parameters, amplitude A and exchange rate constant k(21) were calculated according to a 2-compartment model. Color-coded parameter images were generated from pharmacokinetic data analysis and superimposed onto the conventional MR images. Amplitude A and k(21) parameters were significantly increased in patients with MM compared with controls (p = 0.001; median A(ctr), 0.2 [range, 0.09-0.4]; median A(MM), 0.93 [range, 0.2-2.2]; median k(21ctr), 0.09 min(-1) [range, 0.03-0.9]; median k(21MM), 4.58 [range, 0.22-23.8]). Within the group of MM patients the pattern of color-coded parameter images were found to be either of "diffuse" (n = 13, 31%) or "focal" (n = 28, 69%) type of distribution of microcirculation. Comparison of amplitude A in patients with "focal" vs. "diffuse" pattern of the pharmacokinetic maps revealed a significant increase in the median of amplitude A in the "focal" group. Amplitude A values allowed a classification of patients according to severe osteolytic bone involvement (p = 0.023) with the best cutoff value of 0.7 for amplitude A. Downmodulation of amplitude A was observed in a MM patient treated with standard VAD chemotherapy. Our data demonstrate that dMRI is a novel imaging technique for the detection and monitoring of MM bone lesions. It provides independent evidence for angiogenesis in MM.

Adult↗
PubMed2001

Evaluation of Bethesda guidelines in relation to microsatellite instability.

PURPOSE: The Bethesda guidelines were developed for selection of patients whose tumors should be tested for high microsatellite instability. This study examined the validity of the different Bethesda criteria in relation to microsatellite instability status to simplify their use in clinical practice. METHODS: A total of 164 patients with colorectal or hereditary nonpolyposis colorectal cancer-associated cancers were registered on the basis of the Amsterdam criteria without age limitations (11 cases), multiple tumors (2 cases), the accumulation of colorectal cancer in the family (no first-degree relatives affected or the index patient's age up to 50 years; 45 cases), an early age at onset up to 50 years (13 cases), morphologic and histopathologic manifestations (right-sided colorectal cancer, mucinous undifferentiated histology; 1 case), and the Bethesda criteria (92 cases). The microsatellite instability status of tumors was determined using the International Collaborative Group on Hereditary Non-Polyposis Colorectal Cancer marker reference panel. RESULTS: When applying all Bethesda criteria, high microsatellite instability tumors were identified in our hereditary nonpolyposis colorectal cancer registry with a sensitivity of 87 percent. Twenty-nine percent (27/92) of the Bethesda-positive patients displayed high microsatellite instability compared with 6 percent of patients (4/72) not meeting these criteria (P < 0.001). Only Bethesda Criteria 1, 3, and 4 showed a significantly different distribution of the microsatellite instability status when compared with those of the remaining patients registered (P < or = 0.001). These three criteria detected high microsatellite instability tumors in 48 percent (10/21), 50 percent (18/36), and 31 percent (21/67) of patients, respectively. When applying these criteria only, a cumulative detection rate of 77 percent of all (24/31) high microsatellite instability cases was found, thereby identifying 89 percent of high microsatellite instability tumors among the Bethesda-positive patients. Patients matching Criteria 1, 3, and 4 frequently showed hMSH2 or hMLH1 germline mutations and tumor-specific loss of protein expression. CONCLUSION: In our hereditary nonpolyposis colorectal cancer registry the complete Bethesda criteria showed the highest sensitivity to identify patients with high microsatellite instability tumors. However, for general medical practice outside academic centers, three criteria are reasonably accurate for adequate high microsatellite instability tumor selection.

Adult↗
PubMed2001

Flux of amino acids and energy substrates across the leg in weight-stable HIV-infected patients with acute opportunistic infections: indication of a slow protein wasting process.

Increased whole-body proteolysis with muscle protein net degradation has been suggested as one of the causes of weight loss in patients infected with human immunodeficiency virus (HIV). We studied the exchange rates of amino acids and energy substrates across the lower extremity in 16 HIV patients and 16 age-matched controls with similar body cell mass. The patients had either opportunistic infections or chronic diarrhea but no signs of clinical malnutrition. The following findings were obtained in the HIV patients: an augmented peripheral net release of arginine and lysine; an increase in both the negative arterial-venous difference and the efflux of the nitrogen contained in nonmetabolized amino acids; diminished export of 3-methylhistidine; lowered plasma and erythrocyte amino acid concentrations; reduced output of glycerol and furthermore; and neither a net release nor a net uptake of free fatty acids. The findings concerning nitrogen metabolism support the hypothesis that, in the presence of a reduction in protein breakdown, peripheral protein synthesis is severely depressed, making a slow protein wasting process likely to occur. The balances of glycerol and free fatty acids are due not only to the leg tissues but perhaps also in part to increased net retention of these substrates by skeletal muscle.

AIDS-Related Opportunistic Infections↗
PubMed2001

[Clinical effectiveness of m-THPC-PEG in a new xenogenic animal tumor model for human squamous epithelial carcinomas].

BACKGROUND: Animal tumor models are still essential for the development of new medication and therapy concepts. For the field of oropharyngeal cancer only few reliable xenogeneic tumor models are available. In a two-part experiment a new xenogeneic tumor model was established. PART 1 OF THE STUDY: The growth rates of two different tumor cell lines were compared in the RAG-2 mouse, the SCID mouse and the Swiss nude mouse. Cells from a lymph-node metastasis of an oral squamous cell carcinoma (XF-354) showed a better growth rate and clearer histology than cells from a primary squamous cell carcinoma of the floor of the mouth (UM-SCC-14C). The tumor growth rate was highest on the RAG-2 mouse, followed by the SCID mouse. The Swiss nude mouse showed no tumor growth at all. The combination of the XF-354 tumor cell line and the RAG-2 mouse was the most successful, with a tumor growth rate of 95%. The animal model is very reliable and robust and enables manipulations under anaesthesia outside the sterile barrier for up to 30 min. The single steps for cell cultivation and tumor implantation are described and discussed in detail. PART 2 OF THE STUDY: The second part of this study investigated the clinical efficacy of the macromolecular linked photosensitizer--mTHPC-PEG compared with the free photosensitizer mTHPC. Macromolecular linked photosensitizers have theoretical advantages owing to their pharmacokinetics and tumor selectivity. For the animal experiment, the photosensitizer mTHPC showed significantly better results than the macromolecular linked photosensitizer mTHPC-PEG. The reasons for these in vivo results are discussed in detail.

Animals↗
PubMed2001

Response to thalidomide in progressive multiple myeloma is not mediated by inhibition of angiogenic cytokine secretion.

Thalidomide (Thal) is a drug with anti-angiogenic properties. To explore whether the effect of Thal on angiogenesis is associated with a reduction of angiogenic cytokine levels in progressive multiple myeloma (MM), plasma levels of basic fibroblast growth factor, vascular endothelial growth factor, interleukin 6, tumour necrosis factor-alpha and hepatocyte growth factor (HGF) were measured in 51 patients at 0, 3 and 6 months of Thal therapy. After 6 months of treatment, 26 patients were considered to be responsive to Thal therapy, including 17 minimal responses, eight partial responses and one complete response. Only HGF (decreasing, P = 0.02) in the group of responsive patients showed a statistically significant change over a period of 6 months. Because HGF levels are known to correlate to MM tumour burden, we conclude that the mechanism of action of Thal in MM is not caused by a specific inhibition of angiogenic cytokine secretion.

Adult↗
PubMed2001

Predominant mutation of codon 41 of the beta-catenin proto-oncogene in rat colon tumors induced by 1,2-dimethylhydrazine using a complete carcinogenic protocol.

Constitutive activation of the wnt-signaling pathway plays an important role during both human and rat colon carcinogenesis and can be brought through mutations in either the adenomatous polyposis coli or the beta-catenin gene. Mutations found in the beta-catenin gene typically affect one out of four regulatory phosphorylation sites near the N-terminus of the beta-catenin protein. Whereas in human colon cancers, however, the majority of beta-catenin mutations directly alter threonine 41 or serine 45; the beta-catenin mutations found in chemically induced rat colon tumors seemed to cluster around codon 33 instead. Unlike previous studies, that have used relatively short-term (2-5 weeks) treatment with one of the alkylating agents 1,2,-dimethylhydrazine (DMH) or azoxymethane, we have investigated the mutational spectrum of the beta-catenin gene in a panel of rat colon tumors induced by long-term (20 weeks) DMH-treatment. We detected beta-catenin mutations in 12 of 33 (36%) tumors. Interestingly, only one of the beta-catenin mutations found affected the previously implicated codon 33 cluster region (Asp32Asn), whereas 11 of 12 (>90%) mutations represented identical C-->T transitions within codon 41 resulting in the common replacement of threonine by isoleucine. We propose a model in which codon 41 mutations bear higher oncogenic potential but are induced by DMH less frequently than mutations in the codon 33 cluster region. Consequently, only after sustained carcinogenic treatment, as is achieved in the long-term DMH-protocol, codon 41 mutations will be induced frequently enough to be present in all developing malignant lesions and, then, because of their higher oncogenic potential, these are selected for.

Animals↗
PubMed2001

Are responses to therapy of metastasized malignant melanoma reflected by decreasing serum values of S100beta or melanoma inhibitory activity (MIA)?

In metastatic melanoma S100beta as well as melanoma inhibitory activity (MIA) are elevated in the serum in the majority of patients. Elevation has been found to correlate with shorter survival, and changes in these parameters in the serum during therapy were recently reported to predict therapeutic outcome in advanced disease. However, the value of these markers with respect to other possible markers by multivariate analysis has not yet been proven for individual patients. In this prospective study, S100beta and MIA were measured in the serum of 67 consecutive patients before and following treatment. Analysing both the sensitivity and the specificity of the serum parameters by the areas under the receiver operating characteristics (ROC) curves, decreases in S100beta and MIA during therapy were associated with response to therapy, while increases indicated progressive disease. Unexpectedly, the individual diagnostic value of changes in tumour markers during therapy was not superior to one-point measurements at restaging. Moreover, S100beta and MIA were not superior to the conventional parameters lactate dehydrogenase and C-reactive protein (CRP) on multiple logistic regression analysis. Applying classification and regression trees (CARTs), one-point measurements of CRP was shown to be the most relevant overall parameter.

Adult↗