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1.
Schweiz Arch Tierheilkd ; 163(3): 219-225, 2021 Mar.
Article in German | MEDLINE | ID: mdl-33650522

ABSTRACT

INTRODUCTION: Based on a donation of more than 1000 Swiss dog license tags to the museum of veterinary medical history in Zurich, historic dog license taxes and tags are compared between Switzerland and other European countries. In 2006 the microchip was launched as mandatory identification for dogs in Switzerland and dog license tags became redundant.


INTRODUCTION: Dans le cadre du don d'une collection de plus de 1000 médailles d'identité suisses pour chiens au Musée d'histoire de la médecine vétérinaire de Zurich, le sujet des taxes et médailles pour chiens est étudié en Suisse et comparé à d'autres pays européens. Avec l'introduction de l'identification des chiens au moyen d'une puce électronique en 2006, il n'était plus nécessaire de remettre ces médailles.


Subject(s)
Animal Identification Systems/veterinary , Dogs , Prostheses and Implants/veterinary , Taxes , Animal Identification Systems/instrumentation , Animals , Switzerland
2.
Chirurg ; 88(4): 317-327, 2017 Apr.
Article in German | MEDLINE | ID: mdl-27678402

ABSTRACT

BACKGROUND: Gastric stump carcinoma develops in the gastric remnant after partial gastrectomy. While the frequency of gastric cancer is declining, the incidence of gastric stump carcinoma has remained stable due to the long latency period. As the surgical treatment of gastric ulcers by partial gastrectomy has become much less important, more and more gastric stump carcinomas develop after oncological resection. AIM: This study compared the surgical therapy of gastric stump carcinoma with the therapy of primary gastric cancer. MATERIAL AND METHODS: From 2001 to 2014 a total of 24 patients were surgically treated for gastric stump carcinoma in the University Hospital of Heidelberg. In the same time 428 patients underwent resection due to primary gastric cancer. Both groups were analyzed and compared with a focus on preoperative therapy, intraoperative differences, complications and overall survival. RESULTS: Patients with gastric stump carcinoma were older at disease onset (68 years vs. 62 years, p = 0.003). Compared with primary gastric cancer, patients with gastric stump carcinoma were more often suspected of having lymph node (cN+) involvement (51.4 % vs. 41.7 %, p < 0.001) but neoadjuvant therapy was applied less often (48.7 % vs. 14.3 %, p < 0.01). For resection of gastric stump carcinoma, extended resections were more often necessary (54.5 % vs. 28.2 %, p < 0.001). There were no significant differences in mean overall survival between the two patient groups (64.4 months vs. 45.8 months, p = 0.34) CONCLUSION: Despite the differences described, the treatment of gastric stump carcinoma does not essentially differ from that of primary gastric cancer. Carcinomas of the gastric stump are more often locally advanced and in our opinion a neoadjuvant therapy should be applied analogue to gastric cancer even if evidence-based data on this point are limited.


Subject(s)
Gastrectomy , Gastric Stump/surgery , Neoplasm Recurrence, Local/surgery , Postoperative Complications/etiology , Stomach Neoplasms/surgery , Aged , Cross-Sectional Studies , Female , Gastric Stump/pathology , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Postoperative Complications/mortality , Prognosis , Prospective Studies , Stomach Neoplasms/mortality , Stomach Neoplasms/pathology , Survival Rate
3.
Chem Commun (Camb) ; 52(91): 13361-13364, 2016 Nov 08.
Article in English | MEDLINE | ID: mdl-27782248

ABSTRACT

Despite intense research in FLP chemistry, nothing is known about monomolecular anionic FLPs and/or complexes thereof. Herein, synthesis and reaction of the first anionic FLP complex is described using [(OC)5W{(Me3Si)2HCP(H)OLi(12-crown-4)}], Cy2BCl and subsequent deprotonation by KHMDS. The obtained anionic FLP complex reacts readily with CO2 in a concerted manner.

4.
Chirurg ; 86(10): 955-62, 2015 Oct.
Article in German | MEDLINE | ID: mdl-25715974

ABSTRACT

BACKGROUND: Salvage surgery as an additional therapy option is currently discussed for an increasing number of patients with esophageal cancer after definitive radio(chemo)therapy after tumor progression, recurrence or on explicit request of the patient. OBJECTIVES: The objective of this study was an analysis of the surgical option of salvage esophagectomy after definitive radiation in patients with esophageal cancer. Additionally the current literature on this topic was evaluated. MATERIAL AND METHODS: A total of 92 patients with esophageal cancer from a prospective database were included in this study who underwent esophagectomy either after neoadjuvant radio(chemo)therapy (< 50 Gy) or definitive radio(chemo)therapy (> 50 Gy) between 2002 and 2012. The analysis was performed retrospectively. RESULTS: The median survival of the two groups of patients was not significantly different after initial diagnosis with 24.2 months (95 % CI 0.0-51.93) for patients undergoing definitive radio(chemo)therapy and 30.7 months (95 % CI 9.3-52.2) for patients after neoadjuvant therapy (p = 0.96). Both patient groups showed no differences in pretherapeutic characteristics and response to radio(chemo)therapy. Postoperative complications and perioperative mortality were not different. DISCUSSION: Salvage esophagectomy is now an additional treatment option after definitive radio(chemo)therapy in patients with esophageal cancer. In preselected patients with tumor recurrence, progression or with a strong wish for surgical therapy, salvage surgery should be discussed in interdisciplinary tumor boards after exclusion of distant metastases.


Subject(s)
Adenocarcinoma/surgery , Carcinoma, Squamous Cell/surgery , Chemoradiotherapy , Disease Progression , Esophageal Neoplasms/surgery , Esophagectomy/methods , Neoplasm Recurrence, Local/surgery , Salvage Therapy/methods , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adult , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Chemoradiotherapy, Adjuvant , Combined Modality Therapy , Cooperative Behavior , Esophageal Neoplasms/mortality , Esophageal Neoplasms/pathology , Feasibility Studies , Female , Germany , Hospital Mortality , Humans , Interdisciplinary Communication , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Postoperative Complications/mortality , Prospective Studies , Retrospective Studies , Survival Rate
5.
Schweiz Arch Tierheilkd ; 156(1): 13-6, 2014 Jan.
Article in German | MEDLINE | ID: mdl-24394173

ABSTRACT

The goldsmith Eligius lived probably from 589 to 660 A. D. and was mint master of the Merovingian royal court in Paris. Some rare gold coins from his workshop have survived. Later Eligius became a priest and died as the Bishop of Noyon. His life was marked by charity, the reason he was canonized and became patron of many artisanal and artistic professions, including the veterinarians and farriers. As a patron of the mint masters his image appears on little medals to control the weight of coins. On modern coins his name can only be found once on a shilling dated 1623 from the Maccagno mint near the Lake Maggiore; however his picture is on numerous medals and pilgrims' plaques as well as on the merit medal from the veterinarians of Quebec.


Subject(s)
Numismatics/history , Saints/history , Veterinary Medicine/history , History, 16th Century , History, 19th Century , History, 20th Century , History, Medieval , Humans , Paris , Switzerland
6.
Ann Hematol ; 85(8): 502-13, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16715299

ABSTRACT

We retrospectively studied 89 consecutive patients diagnosed with primary myelodysplastic syndrome (MDS) over a period of 10 years to (1) identify prognostic factors for overall survival (OS) and leukemia-free survival (LFS); (2) to assess and compare the Bournemouth-, Spanish-, Düsseldorf-, Lille-, and the International prognostic scoring systems (IPSS); and to (3) compare the French-American-British (FAB) and World Health Organization (WHO) classifications. The median age of patients was 63 years (range, 26-85). Karyotype analyses were done in 85 patients (96%). Median OS was 3 years; 67 patients (75%) have died, and 28 (31%) had progression to acute myeloid leukemia (AML). Major independent prognostic variables for both OS and LFS (multivariate analysis) were percentage of bone marrow (BM) blasts (P < 0.0001), and in patients with cytogenetic data available, cytogenetic risk groups by Lille-score (OS, P = 0.031/LFS, P = 0.002) and IPSS (OS, P = 0.024). All five prognostic scoring systems successfully discriminated risk groups as regards OS and LFS, but in patients with cytogenetic data available, the major independent prognostic score for OS (P < 0.0001) and LFS (P = 0.006) was the IPSS. The FAB and WHO classifications also successfully discriminated between risk groups. The new WHO subgroups [refractory cytopenia with multilineage dysplasia (RCMD), with (RCMD-RS) or without ringed sideroblasts] showed a significantly (P = 0.0454) different prognosis for OS, but not for LFS (P = 0.0839), in comparison to the subgroups having erythroid dysplasia only (RA/RARS). Risk stratification into refractory anemia with excess blast-I (RAEB-I) and RAEB-II tended to yield different prognoses for OS and LFS. The 5q-minus syndrome strongly predicted for a good prognosis. In patients treated with the demethylating agent decitabine (n = 24), IPSS "poor risk" cytogenetics were unable to predict for the expected worse prognosis when compared to "intermediate-risk" cytogenetics. In conclusion, we confirm in a single-center patient cohort that the use of the WHO classification improves the predictive value of the FAB classification and that, in patients with cytogenetic data available, the IPSS can be used for clinical decision-making.


Subject(s)
Anemia, Refractory, with Excess of Blasts , Anemia, Sideroblastic , Adult , Aged , Aged, 80 and over , Anemia, Refractory, with Excess of Blasts/diagnosis , Anemia, Refractory, with Excess of Blasts/mortality , Anemia, Sideroblastic/diagnosis , Anemia, Sideroblastic/mortality , Disease-Free Survival , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk Factors , Survival Rate , World Health Organization
7.
Leuk Res ; 30(8): 1043-7, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16464494

ABSTRACT

Distinct morphologic and clinical features associated with specific chromosomal abnormalities have been described in subgroups of myelodysplastic syndromes (MDS), which often are losses or gains and only rarely translocations. Among 103 consecutive MDS patients diagnosed and karyotyped at the Albert-Ludwigs University of Freiburg (ALU) between 1993 and 1999, two chronic myelomonocytic leukemias (CMMoL) displayed trisomy 19 (+19) as the sole chromosomal abnormality. Three further CMMoL cases with +19 as the single abnormality, two of which previously reported, were collected from other centers. Four of the five patients presented with leukocytosis and splenomegaly, and an increased number of ringed sideroblasts was observed in two cases. Treatment was low-dose Decitabine (cases 1 and 2), oral steroids (case 3), hydroxyurea (case 4), and daunorubicin/Ara-C (case 5). Transformation to acute myeloid leukemias (AML) occurred in three/five patients (cases 1, 2, and 4) 26, 12, and 22 months after diagnosis of CMMoL, respectively. We conclude that +19 as the sole anomaly is a rare but recurrent change in CMMoL, in particular of the proliferative type. It is at present unclear which gene(s) located on chromosome 19 might have a functional role for the development of this phenotype.


Subject(s)
Chromosome Aberrations , Chromosomes, Human, Pair 19/genetics , Leukemia, Myelomonocytic, Chronic/genetics , Myelodysplastic Syndromes/genetics , Aged , Azacitidine/analogs & derivatives , Azacitidine/therapeutic use , Cytarabine/therapeutic use , Cytogenetic Analysis/methods , Daunorubicin/therapeutic use , Decitabine , Dose-Response Relationship, Drug , Fatal Outcome , Female , Humans , Hydroxyurea/therapeutic use , Leukemia, Myelomonocytic, Chronic/diagnosis , Leukemia, Myelomonocytic, Chronic/drug therapy , Male , Middle Aged , Myelodysplastic Syndromes/diagnosis , Myelodysplastic Syndromes/drug therapy , Phenotype , Steroids/therapeutic use , Treatment Outcome
8.
Ann Hematol ; 82(7): 381-9, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12756497

ABSTRACT

Since few studies focus on prognostic factors in unselected elderly acute myeloid leukemia (AML) patients, a retrospective analysis of 138 consecutive patients aged >55 years (median age: 67, range: 56-89) with AML diagnosed at a single center over an 8-year period was performed: 69% had de novo AML and 31% secondary (s) AML; 67% of the patients were karyotyped. Of the patients, 73 (53%) were treated with standard induction therapy protocols and 65 (47%) received palliative treatment only. Univariate and multivariate analyses of the effects of the following factors on overall survival (OS) were performed: sex, age > or = vs <65 years, de novo vs sAML, serum (s) lactate dehydrogenase (LDH) > or = vs <400 U/l, leukocytes > or = vs <50,000/ microl, induction therapy, and karyotype. Additionally, in patients receiving induction therapy, complete remission (CR) rates and survival from CR were analyzed. CR rate was 47% [95% confidence interval (35%, 59%)], 53% (39%, 66%) in de novo AML, and 21% (5%, 51%) in sAML. After a median follow-up of 4 years, 130 deaths were observed (94%). In a univariate analysis, significant factors for longer OS were induction therapy, age <65 years, sLDH <400 U/l, and de novo AML. In a multivariate analysis, significant factors for longer OS were sLDH <400 U/l and induction therapy. However, the difference between treatment outcome may also be due to selection criteria not captured, such as performance status, comorbid conditions, wish of the patient, etc. The effects of intensive and nonintensive treatment in this patient group need to be investigated in prospective, randomized trials in which these clinical parameters of high relevance for treatment decisions in older patients are also considered.


Subject(s)
Leukemia, Myeloid/diagnosis , Leukemia, Myeloid/mortality , Acute Disease , Aged , Aged, 80 and over , Analysis of Variance , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cytogenetic Analysis , Female , Humans , Leukemia, Myeloid/therapy , Male , Middle Aged , Neoplasms, Second Primary , Prognosis , Remission Induction , Retrospective Studies , Risk Factors , Survival Analysis , Treatment Outcome
9.
Br J Haematol ; 114(2): 349-57, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11529854

ABSTRACT

Decitabine (5-aza-2'-deoxycytidine) acts as a powerful demethylating agent in vitro. Clinically, low-dose decitabine ameliorates cytopenias including induction of trilineage responses in approximately 50% of patients with high-risk myelodysplastic syndrome (MDS). We examined the incidence and kinetics of cytogenetic responses to decitabine in these patients. Of 115 successfully karyotyped patients, 61 (53%) had clonal chromosomal abnormalities prior to treatment. Major cytogenetic responses were observed in 19 patients (31% of those with abnormal cytogenetics, 17% of all patients by intention-to-treat) after a median of three courses (range, 2-6) until best cytogenetic response. Progressive decrease of the abnormal clone over time was also determined using fluorescence in situ hybridization (FISH) analysis in two patients. Median duration of cytogenetic responses was 7.5 months (range, 3-15). Analysis of response by the International Prognostic Scoring System (IPSS) cytogenetic risk groups revealed three out of five cytogenetic responses (60%) in the IPSS 'low-risk' group, 6 out of 30 with 'intermediate risk' (20%) and 10 out of 26 in the 'high-risk' group (38%). Median survival in these cytogenetic subgroups was 30, 8 and 13 months respectively. The relative risk of death in patients achieving a major cytogenetic response was 0.38 (95% confidence interval 0.17-0.88) compared with patients in whom the cytogenetically abnormal clone persisted (P = 0.0213). In conclusion, repeated courses of low-dose decitabine induce cytogenetic remissions in a substantial number of elderly MDS patients with pre-existing chromosomal abnormalties; these are associated with improved survival compared with patients in whom the cytogenetically abnormal clone persists. Patients with 'high-risk' chromosomal abnormalities may particularly benefit from this treatment.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/therapeutic use , Myelodysplastic Syndromes/drug therapy , Adult , Aged , Aged, 80 and over , Anemia, Refractory/drug therapy , Anemia, Refractory/genetics , Anemia, Refractory/mortality , Anemia, Refractory, with Excess of Blasts/drug therapy , Anemia, Refractory, with Excess of Blasts/genetics , Anemia, Refractory, with Excess of Blasts/mortality , Anemia, Sideroblastic/drug therapy , Anemia, Sideroblastic/genetics , Anemia, Sideroblastic/mortality , Azacitidine/analogs & derivatives , Chromosome Aberrations , Chromosome Disorders , Decitabine , Drug Administration Schedule , Female , Humans , In Situ Hybridization, Fluorescence , Karyotyping , Leukemia, Myelomonocytic, Chronic/drug therapy , Leukemia, Myelomonocytic, Chronic/genetics , Leukemia, Myelomonocytic, Chronic/mortality , Male , Middle Aged , Myelodysplastic Syndromes/genetics , Myelodysplastic Syndromes/mortality , Risk , Survival Rate
10.
Br J Haematol ; 111(1): 303-13, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11091217

ABSTRACT

Despite improvements in HLA typing, graft-versus-host disease (GVHD) continues to impair the results after volunteer unrelated donor bone marrow transplantation (VUD-BMT) in adult patients compared with matched sibling BMT. Here, the outcome after VUD-BMT using a specific regimen with high-dose anti-T-lymphocyte globulin (ATG) was analysed. Fifty-five adult patients, median age 34 years (range 17-55 years), with acute or chronic leukaemia or myelodysplastic syndrome (MDS) were transplanted in first complete remission (CR1)/first chronic phase (CP1) (early disease) (n = 21) or in advanced (CR2/CP2, no remission) disease (n = 34) from an unrelated marrow donor. GVHD prophylaxis consisted of ATG-S (Fresenius) 60-90 mg/kg b.w. prior to transplantation, in addition to cyclosporin A and short-course methotrexate. Graft failure did not occur and white blood cell count (WBC) > 1.0 x 10(9)/l was reached at median day +16. The cumulative incidence of acute (a)GVHD grade II-IV was 15% [95% CI (8%, 28%)] and of chronic GVHD was 51% [95% CI (38%, 68%)]. The cumulative incidence of relapse within 1 year was 0% [95% CI (0%, 19%)] and 21% [95% CI (11%, 40%)] for patients with early and advanced disease respectively. With a median follow-up of 28 months (range 16-45 months), 2-year disease-free and overall survival for patients transplanted in CR1/CP1 was 81% and 81% [95% CI (64%, 98%)], respectively, and for patients with advanced disease was 33% [95% CI (17%, 50%)] and 40% [95% CI (23%, 57%)] respectively. Complete and persistent donor chimaerism was seen in 77.5% of 40 patients evaluated. All 14 chronic myeloid leukaemia (CML)-CP1 patients became bcr-abl negative within 250 d. High-dose ATG pretransplant results in a low incidence of severe aGVHD without compromising donor chimaerism or elimination of minimal residual disease. Our results are similar to data obtained after matched sibling donor transplantation.


Subject(s)
Antilymphocyte Serum/therapeutic use , Bone Marrow Transplantation/methods , Graft vs Host Disease/prevention & control , Myelodysplastic Syndromes/therapy , T-Lymphocytes/immunology , Acute Disease , Adolescent , Adult , Anemia, Sideroblastic/therapy , Disease-Free Survival , Follow-Up Studies , Graft vs Host Disease/immunology , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Leukemia, Myeloid/therapy , Leukocyte Count , Middle Aged , Myelodysplastic Syndromes/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Transplantation, Homologous
11.
Bone Marrow Transplant ; 26(3): 243-50, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10967561

ABSTRACT

Between August 1998 and July 1999, 21 patients received a novel protocol of reduced conditioning with fludarabine, carmustine and melphalan (FBM) followed by matched-related allogeneic peripheral blood stem cell transplantation (PBSCT) in a prospective multi-center phase I/II study. Cyclosporin A and 'mini-methotrexate' were used for GVHD prophylaxis. Patients were included because of age, advanced disease, previous transplantation or co-morbidity. Hematopoietic engraftment after allogeneic transplantation was rapid with a median white blood count (WBC) >1 x 10(9)/l on day +11 (range 10-17) and a median platelet count >20 x 10(9)/l on day +13 (range 9-36). Donor chimerism was complete in 16/21 (76%) patients at all time points during follow-up and mixed at least on one occasion in 5/21 (24%) patients. The conditioning regimen was well tolerated with low toxicity even in previously transplanted patients. Thirteen patients (62%) developed acute GVHD grades II-IV. Nineteen out of 21 patients achieved complete (CR, n = 15) or partial remission (PR, n = 4) with a median patient follow-up of 354+ days (range 258-577) for patients alive. The reduced intensity protocol FBM is feasible with rapid engraftment, early achievement of complete donor chimerism, low toxicity, especially in heavily pretreated patients, and good response rates in advanced disease patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Hematopoietic Stem Cell Transplantation , Neoplasms/therapy , Transplantation Chimera , Transplantation Conditioning/methods , Adult , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carmustine/administration & dosage , Carmustine/adverse effects , Cyclosporine/therapeutic use , Female , Follow-Up Studies , Graft vs Host Disease/etiology , Graft vs Host Disease/immunology , Graft vs Host Disease/prevention & control , Humans , Immunosuppressive Agents/therapeutic use , Leukapheresis , Male , Melphalan/administration & dosage , Melphalan/adverse effects , Methotrexate/therapeutic use , Middle Aged , Neoplasms/drug therapy , Neoplasms/immunology , Prospective Studies , Survival Analysis , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Transplantation Tolerance/drug effects , Transplantation Tolerance/immunology , Vidarabine/administration & dosage , Vidarabine/adverse effects , Vidarabine/analogs & derivatives
12.
Br J Haematol ; 109(4): 743-50, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10929024

ABSTRACT

In the light of reduced intensity conditioning regimens for allogeneic transplantation, monitoring of donor cell engraftment acquires new relevance. We analysed the clinical significance of haematopoietic chimaerism as a parameter of patient outcome and detection of relapse for early intervention by donor lymphocyte infusion (DLI) after allogeneic transplantation. Between July 1994 and March 1999, 101 adult patients with malignant disease were evaluated. Median follow-up was 15 months (range 0.7-56.5) after transplantation. Patients received busulphan-containing (n = 82) or total body irradiation (TBI)-containing (n = 19) regimens. Fifteen out of 98 (15%) patients with predictive chimaerism analyses relapsed, 5 out of 20 (25%) with mixed chimaerism (MC) and 10 out of 78 (13%) with complete donor chimaerism (CC) before apparent relapse. Seven patients received donor lymphocyte infusions (DLI) as relapse therapy with conversion from MC to CC in all three patients with successful DLI. Our data stress the importance of chimaerism monitoring after allogeneic transplantation and demonstrate the more frequent occurrence of disease relapse in patients showing MC, rather than CC, after transplantation. Moreover, the assessment of chimaerism has been shown to be a valuable tool in monitoring the efficiency of donor lymphocyte infusions for relapse.


Subject(s)
Hematopoietic Stem Cell Transplantation , Myelodysplastic Syndromes/surgery , Transplantation Chimera , Transplantation Conditioning/methods , Adult , Bone Marrow Transplantation , Female , Follow-Up Studies , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/surgery , Leukemia, Myeloid, Acute/surgery , Lymphoma/surgery , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/surgery , Recurrence , Transplantation, Homologous , Treatment Outcome
13.
Eur Urol ; 35(1): 70-80, 1999 Jan.
Article in English | MEDLINE | ID: mdl-9933797

ABSTRACT

OBJECTIVES: The objectives of this study were to assess cytokine secretion in human renal cell carcinoma (RCC) and to identify cytokines contributing to the immunomodulatory effect of tumor cells. METHODS: Cytokine secretion in the supernatant of primary tumor cell cultures (PTCC) and corresponding cell lines (CL) was assayed using ELISA. Tumor cells were characterized by morphology, immunocytochemistry, and flow-cytometric analysis. Tumor-cell-induced T cell activation was determined by coculture of gamma delta and alpha beta T cell clones with tumor CL. RESULTS: We assessed the cytokine secretion of tumor cells from 27 PTCC and their corresponding CL (3/27) of RCC. We found that RCC predominantly produced both pro-inflammatory and T-cell-inhibitory cytokines, such as IL-8, IL-6, GM-CSF, TNF-alpha, IL-10 and TGF-beta 1. CL were adapted to serum-free medium which may prove as a useful tool in future studies of cytokine secretion in RCC. In addition, we used gamma delta and alpha beta T cell clones to assess the immunomodulatory effect of tumor cells from RCC and found that predominantly gamma delta T cells were activated by RCC. CONCLUSIONS: Our data suggest that RCC produce large amounts of both pro-inflammatory and T-cell-inhibitory cytokines that potentially could influence the immune response of the host, especially tumor-specific cytotoxic T cells.


Subject(s)
Carcinoma, Renal Cell/metabolism , Cytokines/metabolism , Kidney Neoplasms/metabolism , T-Lymphocytes/metabolism , Biomarkers, Tumor , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/pathology , Cytokines/biosynthesis , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Humans , Kidney Neoplasms/immunology , Kidney Neoplasms/pathology , Lymphocyte Activation , Tumor Cells, Cultured
14.
Anticancer Res ; 18(2A): 1153-8, 1998.
Article in English | MEDLINE | ID: mdl-9615781

ABSTRACT

MFE-280 endometrial cancer cells express PP14 (placental protein 14) in vitro. PP14 is normally found in the secretory endometrium and in placental tissue. MFE-280 cells, which are tumorigenic in nude mice, were derived from a recurrent, poorly differentiated endometrial carcinoma. The cells were initially grown in suspension culture and later transferred to monolayer cultures. Karyotyping revealed near-diploidy with a complex heterogeneous aberration pattern. MFE-280 cells were positive for the cytokeratins 7, 8, 18 and 19 as well as for vimentin. The expression of PP14 in MFE-280 cells was demonstrated by immunochemistry and reverse transcriptase--polymerase chain reaction. PP14-mRNA was also detected in one out of five endometrial cancer specimen. In tumor tissue the expression of PP14 was not dependent on progestins.


Subject(s)
Endometrial Neoplasms/chemistry , Glycoproteins/analysis , Pregnancy Proteins/analysis , Animals , Cell Division , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Female , Glycodelin , Glycoproteins/genetics , Glycoproteins/physiology , Humans , Karyotyping , Mice , Mice, Nude , Pregnancy Proteins/genetics , Pregnancy Proteins/physiology , RNA, Messenger/analysis , Receptors, Progesterone/analysis , Tumor Cells, Cultured
15.
Oncology ; 54(5): 429-37, 1997.
Article in English | MEDLINE | ID: mdl-9260606

ABSTRACT

We compared the cytogenetic pattern of 20 different primary tumor cell cultures (PTCC) of renal cell carcinoma (RCC) to their cytokine secretion and oncogene expression. High secretion of IL-6 (gene locus on chromosome 7p21-p14) was correlated with the gain of an additional chromosome 7. Structural changes involving chromosome 5q22, the site of the GM-CSF gene, were matched with the high secretion of GM-CSF in PTCC. No such association was found for beta 2-microglobulin, TGF-beta 1, TNF-alpha, IL-8, and oncogenes, such as c-fos, c-myc, and pan-ras. Our approach may be useful in simultaneously analyzing several factors contributing to tumor progression and may contribute to understanding the multistep development of RCC.


Subject(s)
Carcinoma, Renal Cell/metabolism , Cytokines/biosynthesis , Gene Expression Regulation, Neoplastic , Proto-Oncogenes , Adult , Aged , Carcinoma, Renal Cell/genetics , Cytokines/genetics , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Epidermal Growth Factor/biosynthesis , Female , Granulocyte-Macrophage Colony-Stimulating Factor/biosynthesis , HSP70 Heat-Shock Proteins/biosynthesis , Humans , Intercellular Adhesion Molecule-1/biosynthesis , Interleukins/biosynthesis , Male , Middle Aged , Proto-Oncogenes/genetics , Transforming Growth Factor alpha/biosynthesis , Tumor Cells, Cultured , Tumor Necrosis Factor-alpha/biosynthesis , Tumor Suppressor Protein p53/biosynthesis
16.
Leukemia ; 11(2): 281-3, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9009093

ABSTRACT

Adoptive immunotherapy with donor-derived buffy coat cells for relapsed hematological malignancies after allogeneic BMT is an established and highly effective treatment. We report a patient who relapsed on day +330 after allogeneic sibling BMT for multiple myeloma with multiple solid subcutaneous tumors consisting of plasma cells. Histology and immunocytology of the bone marrow did not show plasma cell infiltration. After cessation of the immunosuppression consisting of cyclosporine and methylprednisolone, a total of 6.2 x 10(7)/kg recipient body weight CD3+ T cells derived from the donor by leukapheresis were transfused on 4 consecutive days. To enhance the T cell effect six doses of 5 million units alpha interferon were given subcutaneously. Five days later the tumors started to shrink and have completely vanished since day x400 after BMT. The patient developed acute GVHD grade III of the liver and gut which was treated by reinduction of various immunosuppressive drugs. Up to now there is no evidence for relapse of the multiple myeloma, but the patient suffers from extensive chronic GVHD (gut and liver). This is the first report to demonstrate a graft-versus-myeloma effect for relapse with solid tumor manifestation after sibling BMT with donor-derived buffy coat cells as adoptive immunotherapy.


Subject(s)
Bone Marrow Transplantation , Immunotherapy, Adoptive , Multiple Myeloma/therapy , T-Lymphocyte Subsets/transplantation , Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow Transplantation/immunology , Combined Modality Therapy , Cytotoxicity, Immunologic , Dexamethasone/administration & dosage , Doxorubicin/administration & dosage , Graft vs Host Disease/etiology , Humans , Immunotherapy, Adoptive/adverse effects , Interferon-alpha/therapeutic use , Male , Middle Aged , Multiple Myeloma/drug therapy , Multiple Myeloma/immunology , Multiple Myeloma/pathology , Neoplasm Recurrence, Local/therapy , Plasma Cells/pathology , Salvage Therapy , T-Lymphocyte Subsets/immunology , Vincristine/administration & dosage
17.
Bone Marrow Transplant ; 18(6): 1081-6, 1996 Dec.
Article in English | MEDLINE | ID: mdl-8971376

ABSTRACT

Hematopoietic progenitor and stem cells are contained within the CD34+ cellular compartment of the bone marrow. Positively selected cytokine primed peripheral blood derived CD34+ cells have been shown to support autologous hematopoiesis after myeloablative therapy. We investigated hematologic reconstitution and incidence of graft-versus-host disease (GVHD) after transplantation of allogeneic peripheral blood CD34+ cells. CD34+ cells were selected from the peripheral blood of 10 matched related donors after treatment with rG-CSF followed by one to four apheresis procedures and biotin-avidin immune affinity purification. Ten patients with advanced hematologic malignancies were subsequently transplanted with cryopreserved allogeneic CD34+ cells after myeloablative chemotherapy. Immune affinity purification of CD34+ cells resulted in a 370-fold T cell reduction. Patients were grafted with a median number of 4.1 x 10(6) kg (1.6-6.4) CD34+ cells and 0.42 x 10(6)/kg (0.29-2.2) CD3+ cells. All patients received rG-CSF 5 micrograms/kg post-transplant and completely engrafted with neutrophils > 500/microliter after a median time of 10 days (9-15) and platelets > 20,000/microliter after 16 days (10-74). Complete donor chimerism was demonstrated by cytogenetic and molecular methods up to day +385 post-transplant. Cyclosporin A only was used for GVHD prophylaxis. Four of 10 patients developed acute GVHD with grade I (one) and II (three) which completely resolved with treatment. Two patients died from infectious complications. Three patients died from relapse or progressive disease. Five patients are alive in remission without GVHD with a median follow-up time of 254 (93-457) days and three of five are without immunosuppression. Allogeneic transplantation of positively selected peripheral blood-derived CD34+ cells is feasible and safe and leads to long-term engraftment without severe GVHD suggesting that peripheral blood-derived CD34+ cells contain pluripotent hematopoietic stem cells. The reduced number of T cells transplanted appears to be sufficient for engraftment.


Subject(s)
Antigens, CD34/analysis , Bone Marrow/drug effects , Granulocyte Colony-Stimulating Factor/pharmacology , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cells/drug effects , Leukapheresis/methods , Tissue Donors , Adult , Anemia, Refractory, with Excess of Blasts/therapy , Bone Marrow Cells , Chromatography, Affinity , Feasibility Studies , Female , Filgrastim , Graft Survival , Graft vs Host Disease/epidemiology , Graft vs Host Disease/prevention & control , Hematologic Neoplasms/mortality , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Immunosorbent Techniques , Male , Middle Aged , Recombinant Proteins , Salvage Therapy , Transplantation Conditioning , Transplantation, Homologous , Treatment Outcome
18.
Immunogenetics ; 45(1): 27-34, 1996.
Article in English | MEDLINE | ID: mdl-8881034

ABSTRACT

Daudi Burkitt's lymphoma cells, unlike other tumor cell lines, stimulate human T cells coexpressing the variable (V) region genes TCRG-V9 and V TCRD-V2 to proliferate and secrete lymphokines. Hybrids, derived by the fusion of Daudi cells with the human melanoma cell line MZ2-MEL 2.2, retain the morphology of melanoma cells. Unlike the parental melanoma cell line, these Daudi x MZ2-MEL 2.2 hybrids stimulate secretion of tumor necrosis factor (TNF) and granulocyte/macrophage colony stimulating factor (GM-CSF) by CD4-positive Vgamma9/Vdelta2 T-cell clones. Whereas the stimulator phenotype of Daudi cells behaves as a dominant trait in Daudi x melanoma hybrids, the expression of B-cell differentiation markers is suppressed. Thus, the gamma/delta T-cell ligand expressed by Daudi cells behaves as a dominant tumor antigen in Daudi x melanoma hybrids and is unrelated to the differentiated B-cell phenotype. Dominant expression of the Daudi ligand for human Vgamma9/Vdelta2 T cells in these hybrids may provide a basis for defining the stimulatory principle at the molecular level.


Subject(s)
Burkitt Lymphoma/immunology , Melanoma/immunology , T-Lymphocyte Subsets/immunology , CD4-Positive T-Lymphocytes/immunology , Clone Cells , DNA Fingerprinting , Genotype , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Hybrid Cells , Karyotyping , Lymphocyte Activation , Phenotype , Receptors, Antigen, T-Cell, gamma-delta/immunology , Tumor Cells, Cultured , Tumor Necrosis Factor-alpha/metabolism
19.
Leukemia ; 9(6): 988-92, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7596190

ABSTRACT

A 32-year-old white woman was admitted with a diagnosis of T lymphoblastic lymphoma and a bone marrow and peripheral blood cytology that was suggestive of a myeloproliferative syndrome (MPS). In addition, islets of myeloid precursors were found in the lymph node where the lymphoma had been diagnosed. Cytogenetic examination was negative for the Philadelphia chromosome (Ph) as well as the RT-PCR for bcr/abl rearrangement, but surprisingly a t(8;13)(q10;p10) was detected. To our knowledge, this translocation has not been reported in such a clinical setting. The patient was treated for the lymphoblastic lymphoma and underwent autologous bone marrow transplantation. She has been in complete remission since induction chemotherapy with a Karnofsky score of 100%. The difficulty of classifying this case is discussed.


Subject(s)
Chromosomes, Human, Pair 13 , Chromosomes, Human, Pair 8 , Lymph Nodes/pathology , Lymphoma, T-Cell/genetics , Myeloproliferative Disorders/genetics , Translocation, Genetic , Adult , Bone Marrow Transplantation , Chromosome Mapping , Female , Follow-Up Studies , Humans , Karyotyping , Lymphoma, T-Cell/pathology , Lymphoma, T-Cell/therapy , Myeloproliferative Disorders/pathology , Myeloproliferative Disorders/therapy , Polymerase Chain Reaction , Syndrome , Transplantation, Autologous
20.
Leukemia ; 8(8): 1406-8, 1994 Aug.
Article in English | MEDLINE | ID: mdl-8057681

ABSTRACT

Pre-T-ALL is an important subgroup of ALL with clinical features different from adult T-ALL. Expression of intracytoplasmic CD3 represents the earliest marker for the prethymic phenotype. We studied four consecutive adult patients with this phenotype. Three of the four patients did not respond to the induction chemotherapy with vincristine, daunorubicin, prednisone and asparaginase. They reached a delayed remission only after chemotherapy with cyclophosphamide and cytosine arabinoside. All four patients relapsed 3, 9, 10 and 13 months after diagnosis. One patient died 2 months after relapse, another one 2 months after allogeneic BMT performed in second relapse. We conclude that patients with early T-cell precursor leukemia do not respond adequately to conventional chemotherapy and should be considered as a high-risk subgroup within the T-lineage ALL.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia-Lymphoma, Adult T-Cell/drug therapy , Preleukemia/drug therapy , Adult , Antigens, CD/analysis , Asparaginase/administration & dosage , B-Lymphocytes/immunology , Cyclophosphamide/administration & dosage , Cytarabine/administration & dosage , Daunorubicin/administration & dosage , Follow-Up Studies , Humans , Immunophenotyping , Leukemia-Lymphoma, Adult T-Cell/immunology , Middle Aged , Prednisone/administration & dosage , Preleukemia/immunology , Prognosis , Remission Induction , T-Lymphocytes/immunology , Time Factors , Vincristine/administration & dosage
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