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Biomedical subjects

M Raderer

Publications and source records attributed to M Raderer.

144 records · Page 8Linked to original sources

Treatment of advanced colorectal cancer with 5-fluorouracil and interferon-alpha: an overview of clinical trials.

5-Fluorouracil (5-FU) is the most active single agent for treatment of advanced colorectal cancer, although objective responses occur in only 20% of patients, and there seems to be no impact on overall survival. Experimental findings suggesting that interferon-alpha (IFN-alpha) enhances 5-FU cytotoxicity have stimulated an increasing number of clinical trials to evaluate the therapeutic potential of this combination. This article summarises the possible mechanisms of interaction of 5-FU and IFN-alpha, and provides an overview of the current status of this approach in advanced colorectal cancer. A computerised (Medline) and manual search were performed to identify all trials using 5-FU and IFN-alpha for the treatment of advanced colorectal cancer published in the English literature between 1960 and 1994. Information abstracted included treatment regimen, number of patients, pretreatment status, complete and partial remissions, remission duration, overall survival, and toxicity. A total of 417 patients were enrolled in 16 trials using different regimens of 5-FU and IFN-alpha, and double modulation of 5-FU with leucovorin (LV) and IFN-alpha was investigated in nine trials involving 332 patients. The mean overall response rate in these phase II trials was only 31% (range 3-76) and 35% (range 0-54), respectively. Early results of six prospectively randomised studies of 5-FU or 5-FU/LV +/- IFN-alpha also did not suggest a significant enhancement of the antitumour effectiveness with the addition of IFN-alpha. There is increasing evidence, however, that administration of IFN-alpha along with 5-FU enhances toxicity. Because of their modest therapeutic index, currently employed regimens of 5-FU +/- LV plus IFN-alpha cannot be recommended for routine use at the present time. The combination of 5-FU plus LV represents an equally effective and less expensive alternative. Nevertheless, there is still hope that further attempts to elucidate the complex mechanisms of this potentially synergistic drug combination will allow the rational design of regimens with a superior therapeutic index.

Clinical Trials, Phase II as Topic↗

Tissue polypeptide-specific antigen (TPS) in monitoring palliative treatment response of patients with gastrointestinal tumours.

The new proliferation marker, tissue polypeptide-specific antigen (TPS), representing the specific epitope M3 of tissue polypeptide antigen, and three conventional biochemical markers, CEA, CA 19-9 and CA-195, were analysed in 69 patients with advanced gastrointestinal tumours. The aim of our study was to assess the clinical relevance of these markers and to determine whether their use in monitoring the course of the disease can reduce the need for serial imaging procedures. At baseline, pathologically elevated TPS levels occurred in 90% of patients. CEA was elevated in 73%, CA 19-9 in 59% and CA-195 in 68%. With a detection rate of > 90% in both advanced colorectal (n = 37) and pancreatic cancer (n = 20), and of 75% in gastric cancer (n = 12), TPS was the most sensitive marker in all three tumour types included in this analysis. Serial evaluations of TPS and other biochemical markers were available in 39 patients undergoing palliative systemic chemotherapy. Treatment with a fluorouracil-based regimen resulted in a partial response in 5/27 patients with colorectal cancer, whereas 2/12 patients with pancreatic cancer responded to therapy with a high-dose epirubicin combination regimen. All other patients had disease stabilisation or suffered from progressive disease. When compared with the results of serial CT scanning, the TPS correlated best with the course of the disease, the positive predictive value being 75% for a partial response, 96% for stable disease and partial response combined and 100% for progressive disease. The corresponding values for CEA were 50%, 81% and 62% and were similar to those for CA 19-9 and CA-195. In summary, TPS seems to represent a sensitive, clinically relevant and specific marker of proliferative activity in gastrointestinal cancer. According to our preliminary results in colorectal and pancreatic cancer, TPS may be considered as the primary means of monitoring treatment, and imaging reduced to confirm the response.

Adult↗

Vasoactive intestinal peptide receptor scintigraphy.

UNLABELLED: This study presents the biodistribution, safety and absorbed dose of 123I-VIP administered to 18 patients with intestinal adenocarcinomas or endocrine tumors. METHODS: To achieve high-specific activity, 123I-VIP was purified by HPLC. Following intravenous administration of 123I-VIP (172 +/- 17 MBq (4.65 +/- 0.5 mCi); < 300 pmole ( < 1 microgram)/patient), sequential images were recorded during the initial 30 min. Thereafter, whole-body images were acquired in anterior and posterior views at various time points. Dosimetry calculations were performed on the basis of gamma camera data, urine, feces and blood activities. RESULTS: After injection of labeled peptide, the lung was the primary site of 123I-VIP uptake. Peak lung activity represented 40% +/- 7% of the injected dose at 0.7 hr and declined to 21% +/- 7% at 3.5, to 14% +/- 3% at 7 and to 8% +/- 4% 22 hr postinjection. Radioactivity was excreted into the urine and amounted to 37% +/- 16% of the injected dose within 4, 68% +/- 12% within 8, 82% +/- 16% within 16 and 93% +/- 8% within 24 hr postinjection. The mean effective half-life of 123I-VIP in the lungs was 2.2 and 6 hr in the urinary bladder. The highest radiation absorbed doses were calculated for the lungs [67 muGy/MBq (248 mrad/mCi)], urinary bladder [77 muGy/MBq (284 mrad/mCi)] and thyroid gland [104 muGy/MBq (386 mrad/mCi)]. The effective dose was 28 muSv/MBq (104 mrem/mCi). CONCLUSION: HPLC-purified 123I-VIP shows favorable dosimetry and is a safe and promising peptide tracer for localization of tumors expressing receptors for VIP.

Adenocarcinoma↗

Technetium-99m-galactosyl-neoglycoalbumin combined with iodine-123-Tyr-(A14)-insulin visualizes human hepatocellular carcinomas.

UNLABELLED: Human hepatocellular carcinoma (HCC) is the most frequent primary hepatic malignancy and its diagnosis by conventional methods is still difficult. We hypothesized that the expression of specific receptors could possibly be used to improve in vivo localization of HCC with specific receptor-based radioligands. METHODS: In initial in vitro studies, receptor binding of 99mTc-galactosyl-neoglycoalbumin (99mTc-NGA) and 123I-Tyr-(A14)-insulin to HCC was investigated. Scintigraphy was performed in 45 patients with histologically confirmed HCC using either 99mTc-NGA (75-150 MBq; 25-50 nmole, n = 27) and/or 123I-Tyr-(A14)-insulin (100-150 MBq; 7.5-10 micrograms, n = 30). RESULTS: HCC (1256 +/- 290 pmole bound/mg protein, Kd = 3.4 +/- 2.9 nM) expressed a 1000-fold higher number of specific receptors for 123I-Tyr-(A14)-insulin compared to normal liver tissue (2.4 +/- 0.8 pmole bound/mg protein, Kd = 4.2 +/- 2.4 nM), whereas HCC did not express receptors specific for 99mTc-NGA. All HCC lesions were identified as cold spots after injection of 99mTc-NGA, whereas 123I-Tyr-(A14)-insulin accumulated in these lesions, indicating HCC-to-normal liver ratios of 1.6 +/- 0.4 in the mean. Subtraction images obtained from planar studies visualized 123I-Tyr-(A14)-insulin in HCC lesions detected by 99mTc-NGA as cold spots. CONCLUSION: This hepatocyte receptor-specific, double-tracer method using 99mTc-NGA and 123I-Tyr-(A14)-insulin could become clinically useful in the diagnosis of HCC.

Aged↗

Vasoactive intestinal peptide-receptor imaging for the localization of intestinal adenocarcinomas and endocrine tumors.

BACKGROUND: Intestinal adenocarcinomas and various endocrine tumors express large numbers of high-affinity receptors for vasoactive intestinal peptide (VIP). We have evaluated the usefulness of scanning with VIP labeled with iodine-123 for tumor localization in patients with gastrointestinal tumors. METHODS: Radioiodinated VIP was purified by high-pressure liquid chromatography and administered as a single intravenous bolus injection (300 pmol [1 microgram]). Scanning with radiolabeled VIP was compared with computed tomography and scanning with somatostatin analogues in 79 patients with colorectal cancer, pancreatic carcinoma, gastric cancer, carcinoid tumor, or insulinoma. RESULTS: Visualization of gastrointestinal tumors and metastases was obtained with radiolabeled VIP. Binding of the labeled peptide by primary tumors and metastases was visible shortly after the injection and was still demonstrable at 24 hours. In patients with colorectal adenocarcinomas, primary or recurrent tumors were visualized in 10 of 10, liver metastases in 15 of 18, lung metastases in 2 of 3, and lymph-node metastases in 4 of 4. Primary pancreatic adenocarcinomas were visualized by imaging in 10 of 12 patients, and liver metastases were seen in 7 of 7. Primary or recurrent gastric adenocarcinomas were visualized in 5 of 5 patients, and liver metastases were seen in 2 of 2 patients. VIP scans were positive in 9 of 10 patients with carcinoid tumors and in 4 of 4 patients with insulinomas. Some tumors with positive VIP scans were also visualized with somatostatin analogues (4 of 17 colorectal adenocarcinomas, 8 of 9 carcinoids, and 2 of 2 insulinomas). In vitro binding studies confirmed the presence of VIP receptors on gastrointestinal tumors. CONCLUSIONS: Scanning with radiolabeled VIP can visualize intestinal tumors and metastases that express receptors for VIP.

Adenocarcinoma↗

Amonafide as first-line chemotherapy for metastatic breast cancer.

In a phase II study, 32 patients with advanced breast cancer previously unexposed to palliative cytotoxic chemotherapy were treated with amonafide, 800-900 mg intravenously over 3 h repeated every 4 weeks. Objective response was seen in 8 patients including 1 complete response, 10 patients had stable disease and 14 patients progressed so the overall response was 25% (95% confidence interval, 11-43%). The most frequently encountered side-effects were haematological (granulocytopenia > or = WHO grade 3 was encountered in 7/24 patients at 800 mg/m2 and in 3/8 patients at 900 mg/m2 amonafide) and nausea/vomiting (62%), despite prophylactic use of ondansetron. Non-haematological severe adverse reactions included neurotoxicity WHO grade 3 in 1 patient and orthostatic hypotension WHO grade 4 in another. In summary, the results of this trial suggest a limited therapeutic index of amonafide if used at this dose with this administration schedule.

Adenine↗

Postchemotherapy rheumatism following adjuvant therapy for ovarian cancer.

The occurrence of a recently discovered musculosceletal pain syndrome, termed postchemotherapy rheumatism, is described in a 52-year-old female who had received adjuvant therapy for ovarian cancer. Although the etiology as well as the pathophysiologic mechanisms of this syndrome remain uncertain, our data support the hypothesis that the alkylating agent cyclophosphamide rather than other chemotherapeutic drugs, corticosteroid withdrawal, or chemically-induced menopause may represent a causal factor.

Antineoplastic Combined Chemotherapy Protocols↗

[Helicobacter pylori, a risk factor for stomach cancer and primary stomach lymphoma?].

Helicobacter pylori has been implicated as a possible etiologic factor in gastric cancer. Recent epidemiologic studies, in fact, have demonstrated that there is a significantly higher prevalence of H. pylori in patients with gastric cancer than in matched controls. In addition to these and other epidemiologic findings, there is evidence that several of the pathogenic consequences of H. pylori infection may be relevant to carcinogenesis. In accordance with the theory that the etiology of gastric cancer is likely to be multifactorial, it is believed that the overall risk is determined by dietary, genetic and other cofactors. A causal relationship between H. pylori and gastric cancer, however, remains to be proven by randomized intervention trials of the long-term effects of H. pylori eradication. Until conclusive results become available from these studies, bacterial eradication cannot be recommended as prophylactic measure to reducing the risk of gastric cancer. In patients with low-grade B-cell gastric lymphomas of the mucosa-associated lymphoid tissue type (MALT) a causal pathogenic association with H. pylori-associated gastritis was demonstrable not only in cell culture but also in preliminary clinical trials. Several investigators have reported that eradication of H. pylori results in complete regression of early stage gastric MALT lymphomas. Answers to the questions whether healing is permanent, whether lymphomas at a more advanced stage will respond as well, and how regression comes about will have to be established in future studies.

Cell Transformation, Neoplastic↗

Clinical trials of agents that reverse multidrug resistance. A literature review.

BACKGROUND: The discovery of the P-170 glycoprotein as a mediator of multidrug resistance (MDR) represents one of the most important research accomplishments in antineoplastic pharmacology during the last decade. Demonstration of P-170 in epithelial tissues, untreated and chemotherapeutically pretreated human malignancies, and identification of various agents capable of reversing resistance in vitro generated enthusiasm for clinical studies throughout the world. The authors provide an overview of the current status of clinical investigations of MDR1 reversing agents in hematologic and solid malignancies. METHODS: The authors performed an extensive literature search and selected more than 70 articles concerning the potential clinical relevance of P-glycoprotein/MDR1 modulating agents. Information abstracted included type of reverting agent and chemotherapeutic regimen, number of patients, tumor type, histologic proof of P-glycoprotein expression, and objective response rates. RESULTS: Proof of the involvement of MDR1 in clinical drug resistance has been slow to accumulate, primarily because of difficulties in adapting assays of MDR1 expression and in planning appropriate trials. Pilot studies have shown that verapamil, cyclosporine, and other chemosensitizers may reverse resistance in a subset of patients, but significant (cardiovascular) side effects are common. For leukemias, lymphomas, and multiple myeloma, response rates of 60-80% may be achieved with the potential for cure, whereas in solid tumors, only a few patients appear to benefit. CONCLUSIONS: Because of predominantly negative results and unanswered fundamental questions regarding the biology of P-glycoprotein, additional clinical trials with less toxic modulators or their combination are appropriate to delineate optimal strategies for MDR1 reversal and to define the spectrum of responsive tumors. Additional attention also must be given to the coexistence of other resistance mechanisms that may offer separate opportunities for modulation.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Successful symptomatic management of a patient with Ménétrier's disease with long-term antibiotic treatment.

We present the case of a 79-year-old female patient with criteria typical for Ménétrier's disease, i.e. enlargement of the gastric folds due to foveolar hyperplasia associated with severe protein-loss along with epigastric pain, nausea, vomiting and weight loss. Gastrin levels were within the normal range, but elevated Helicobacter pylori antibody titers (83 microg/ml) were indicative of a recent infection. Histologic examination of a gastric polyp, which was removed in toto, revealed the presence of early gastric cancer of the mucosal type. After initiation of antibiotic treatment with clarithromycin (3 x 250 mg/day) and metronidazole (2 x 500 mg/day) in combination with lansoprazole (30 mg/day), the patient's condition improved rapidly along with abrogation of protein loss. Under maintenance treatment as indicated above, the patient has been free of symptoms now for a period of more than 2 years. On repetitive endoscopic follow-up, there was no change in gastric mucosa morphology either endoscopically or histologically, and also no evidence of recurrence of a malignant lesion. We conclude that this therapeutic regimen represented an effective alternative to surgical intervention in this patient and should be considered in similar cases.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Coincidence of Crohn's disease and a high-risk gastrointestinal stromal tumor of the terminal ileum.

A 51-year-old male patient presented with characteristic radiologic features of Crohn's disease in the terminal ileum plus a large tumorous lesion in the right lower abdomen. Because of rapid crescent symptoms of bowel obstruction, the patient underwent surgery revealing a high-risk gastrointestinal stromal tumor (GIST) of the terminal ileum within an area of Crohn's ileitis. Whereas the association of chronic inflammatory bowel disease (IBD) and gastrointestinal adenocarcinoma is well known, other primary intestinal tumors are rare in these patients, particularly at the time of onset of clinical symptoms. This is the 3rd patient reported in the literature with a sarcoma complicating IBD, and in fact, the first description of the coincidence of Crohn's disease and GIST. Though the present case is likely to be a mere coincidence of two pathologically distinct entities (without any potential causal relationship), it should remind one of the possibility of small bowel 'Crohn's carcinoma' in patients with a sudden change in symptomatology as well as in those in whom intestinal obstruction fails to resolve with adequate therapy.

Crohn Disease↗

Association between Helicobacter pylori infection and pancreatic cancer.

PURPOSE: In order to determine whether infection with Helicobacter pylori might be associated with pancreatic adenocarcinoma, we performed a study to compare the H. pylori seroprevalence rate between patients with pancreatic carcinoma and matched control subjects. PATIENTS AND METHODS: Blood samples from 92 patients with histologically confirmed diagnosis of pancreatic adenocarcinoma admitted to our hospital between January 1994 and July 1995 were analyzed for the presence of IgG antibodies against H. pylori by a commercially available enzyme-linked immunosorbent assay. Thirty patients with gastric cancer, 35 patients with colorectal cancer, and 27 healthy volunteers served as controls. In addition to these serological analyses, tumor specimens from 20 patients with pancreatic adenocarcinoma were microscopically investigated for the presence of H. pylori. RESULTS: 65% of pancreatic cancer patients and 69% of those with gastric cancer were found to be seropositive, while only 45% of the other controls tested positive. Statistical analysis revealed no difference in seropositivity between the cohort of patients suffering from pancreatic and gastric cancer. The rate of seropositivity was more prominent, however, in pancreatic cancer patients when compared with those suffering from colorectal cancer combined with normal controls (p = 0.035), with an odds ratio of 2.1 (1.1-4.1). Microscopic evaluation of human pancreatic cancer specimens showed no evidence for the presence of H. pylori. CONCLUSION: Our data suggest an association between H. pylori infection and pancreatic cancer. Despite demonstration of a positive relationship and its physiological plausibility, larger prospective studies are needed to confirm our preliminary findings and to assess H. pylori as a potential carcinogenic risk factor.

Adenocarcinoma↗

Mitomycin C, vinorelbine, carboplatin plus granulocyte-macrophage colony-stimulating factor for treatment of advanced non-small cell lung carcinoma.

BACKGROUND: The therapeutic potential of chemotherapy in the treatment of recurrent or metastatic non-small cell lung carcinoma (NSCLC) seems modest. Thus, the search for novel agents and combination regimens with a superior therapeutic index has a high priority. The present combination regimen consisting of mitomycin C, vinorelbine, carboplatin and granulocyte-macrophage colony-stimulating factor (GM-CSF) was chosen because of the known activity of these agents in NSCLC and their potential drug synergism without (nonhematologic) cross-toxicity. To prevent/counteract neutropenia that was assumed to represent the dose-limiting toxicity, the hematopoietic growth factor GM-CSF was routinely adminstered. The objective of our trial was to determine the antitumor efficacy and tolerance of this combination regimen in patients with advanced NSCLC. PATIENTS AND METHODS: Forty consecutive patients with nonresectable, measurable NSCLC (stage IIIB, 7; stage IV, 33) were treated with an intravenous combination chemotherapy regimen consisting of mitomycin C 8 mg/m2 on day 1, vinorelbine 40 mg/m2 on days 1 and 21, and carboplatin 250 mg/m2 on days 1 and 21; GM-CSF 5 microg/kg was administered subcutaneously on days 2-8 and 22-28. Treatment cycles were repeated every 6 weeks. All patients are evaluable in terms of toxicity and response assessment. A total of 123 courses was administered. RESULTS: Objective tumor response was notes in 16 patients (40%; 95% confidence interval 24.9-56.7%), including 3 (7.5%) complete and 13 partial responses. There was no change in 12 (31.5%) patients, and 12 had progressive disease. Median duration of response was 6 (range 3-15) months, the median time to progression for all patients was 6.2 (range 1-17.5) months, and the projected median survival time was 8.7 (range 1-23.3) months; the 1-year survival rate was 27.5%. Myelosuppression was the most frequently encountered adverse reaction; WHO grade 3 or 4 granulocytopenia and/or thrombocytopenia occurred in 42.5 and 12.5%, respectively. Other toxicities were generally mild to moderate, and always fully reversible. CONCLUSION: With a 40% major response rate and disease stabilization in one additional third of our patients, this drug combination seems to have significant activity against advanced metastatic NSCLC. Due to its subjective tolerance and ease of administration, further investigation of this regimen in the palliative-intent care setting seems warranted.

Adult↗

Serum levels of vasoactive intestinal peptide (VIP) in patients with adenocarcinomas of the gastrointestinal tract.

BACKGROUND: VIP acts as a neuroendocrine mediator under physiological conditions, with an important role in water and electrolyte secretion in the gut. Recent findings suggest that VIP also promotes growth and proliferation of normal as well as malignant cells. We have investigated the VIP-serum levels in patients with pancreatic cancer and colonic adenocarcinoma as compared to healthy controls. This was accompanied by immunohistochemical investigations and in vitro experiments to further define the role of the peptide in pancreatic and colorectal cancer. MATERIALS AND METHODS: Serum levels of VIP were evaluated under standardized conditions in a total of 135 patients; 45 patients had metastatic colorectal cancer, 45 suffered from metastatic pancreatic cancer, and 45 healthy volunteers served as controls. Human pancreatic and colorectal carcinoma cell lines were incubated over 5 days with VIP in increasing concentrations. RESULTS: In healthy controls, a median VIP-serum level of 42.44 +/- 2.540 pg/ml (range, 12.9-98.5 pg/ml) was found, while patients with pancreatic cancer had a median level of 40.58 +/- 3.013 pg/ml (range, 6.9-102.4 pg/ml). In patients with cancer originating in the colon, however, a median serum level of 116 +/- 10.14 pg/ml (range, 51.6-487 pg/ml) was found. While no difference between healthy controls and patients with pancreatic cancer could be detected (p = 0.6381), a significant difference between patients with colorectal cancer and healthy controls (p < 0.0001) and patients with pancreatic cancer (p < 0.0001) was demonstrated. The median VIP-concentrations found in the patients sera for pancreatic and colonic tumor patient groups, 40 pg/ml and 115 pg/ml respectively, had no significant effect on the proliferation of PANC-1 and HT29, inhibited ASPC-1, BxPC3, COLO201 and HCT-15 cells, and stimulated the growth of one pancreatic (CAPAN-1) and one colonic (COLO320DM) cell line under these conditions. CONCLUSIONS: As opposed to pancreatic cancer and healthy controls, patients in our series had elevated serum VIP-levels. Further studies are warranted to evaluate whether VIP can be used as a tumor marker in this disease.

Adenocarcinoma↗

Beta-2-microglobulin levels in patients with extranodal B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT)-type: a retrospective analysis.

BACKGROUND: Serum levels of beta-2 microglobulin (B2M) have been reported as a predictor of clinical outcome, prognosis and tumor burden in patients with various types of lymphomas. In case of lymphoma of the mucosa-associated lymphoid tissue (MALT)-type, no clear data exist to define the role of B2M in terms of staging or prognosis. In a retrospective analysis we investigated the serum B2M-levels in patients suffering from histologically verified MALT-type lymphoma in correlation to stage and response to treatment. PATIENTS AND METHODS: All patients admitted to our institution since 1996 with a diagnosis of MALT-type lymphoma were retrospectively evaluated for staging procedures and measurements of serum B2M levels. Patients with a staging work-up including otorhinolaryngologic evaluation, gastroscopy with multiple biopsies, endosonography of the upper GI-tract, enteroclysis, colonoscopy, CT of thorax and abdomen and bone marrow biopsy were analysed, while staging was performed according to the Ann Arbor system as modified by Musshoff. In addition, only patients with histologic samples amenable to re-assessment by a reference pathologist were included. RESULTS: A total of 68 patients with a diagnosis of MALT-type lymphoma were identified from our records. However, only in 32 patients exact staging according to our inclusion criteria had been performed and serum B2M-levels prior to the initiation of therapy were available in all these patients. Twenty-five patients; suffered from gastric lymphoma, while the remaining 7 patients had extragastric manifestations. In total, 13 out of 32 patients presented with stage I disease, 17 patients were rated as stage II and 2 patients suffered from stage III disease. Nineteen patients had elevated B2M-levels prior to therapy: 6 patients were rated as stage 1, II had stage II and two had stage III disease. Five patients still had elevated B2M-levels following treatment despite radiologically and histologically verified complete remission. CONCLUSION: In this series, no correlation between serum B2M levels, tumor burden and clinical outcome was apparent in patients with MALT-type lymphomas. While the number of patients with disseminated disease was small we could not demonstrate a difference for B2M-levels between stage I and stage II. While we cannot rule out that B2M might be different in patients with stage I/II disease as compared to more advanced disease, further investigations are necessary to determine the role of this marker in patients with MALT-type lymphoma.

Adult↗

Modulation of CD99/MIC2 expression of human AHTO-7 osteoblasts by carcinoma cell line-conditioned media.

BACKGROUND: Prostate cancer metastases induce a predominantly osteoblastic response in bone tissue, resulting in new bone formation and associated morbidity; however, the mechanisms of these tumor-host responses are not fully understood. MATERIALS AND METHODS: Supernatants of prostate (PC3, DU145, LNCaP), breast (BT20, ZR-75-1), colon (SW620, Colo 320DM), pancreatic (ASPC1, Capan-1), renal cell (ACHN) and hepatoma (HepG2) cell lines were tested for their capacity to modulate proliferation, activity of alkaline phosphatase (ALP) and CD99/MIC2 expression in AHTO-7 (large T antigen transfected human trabecular osteoblasts) cells in vitro. RESULTS: Osteoblastic stimulation is not restricted to prostate cancer derived conditioned media CM and high activity is found in CM from Capan-1, HepG2 and ACHN lines. Furthermore these CM down-regulate the expression of the CD99/MIC2 antigen in comparison to medium by AHTO-7 cells as detected by HBA-71 immunofluorescence, with the exception of prostate cancer-derived CM. Induction of the differentiation marker ALP was detected in response to CM derived from Capan-1, BT-20 and Colo320DM. Stimulation of the proliferation of AHTO-7 cells (105-138% of control), induction of ALP (1.17-5.29-fold) and down-regulation of CD99 (13.6-57.5%) exhibited no correlation. CM derived from PC3 and LNCaP metastatic prostate cancer cell lines specifically resulted in the retention/stimulation of the expression of CD99/MIC2 in AHTO-7 cells in contrast to all other cell lines tested. CONCLUSION: The CD99/MIC2 antigen, which is expressed on human osteoblasts and osteosarcoma cells, seems to constitute a new and independent response marker of osteoblasts in the triggering of osteoblastic reaction by prostate cancer cells.

12E7 Antigen↗