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Biomedical subjects

C Rochlitz

Publications and source records attributed to C Rochlitz.

35 records · Page 2Linked to original sources
PubMed1999

Axl expression is associated with adverse prognosis and with expression of Bcl-2 and CD34 in de novo acute myeloid leukemia (AML): results from a multicenter trial of the Swiss Group for Clinical Cancer Research (SAKK).

Receptor tyrosine kinases (RTK) play a significant role in the signal transduction of normal, and malignant hematopoietic cells. We have previously shown that Axl, a novel RTK, is mainly expressed in leukemias of myeloid origin, and that its expression may be associated with cells of monocytic origin. Since expression of certain RTKs in cancer may be associated with different biology and survival, we investigated whether the expression of Axl is associated with clinical characteristics and survival in acute myeloid leukemia (AML). RNA from 54 patients with AML treated in a cooperative group trial was analyzed in a retrospective and blinded manner using a semi-quantitative reverse transcriptase polymerase chain reaction-based assay with primers specific for the Axl gene. Axl expression was found in 19 out of the 54 cases (35%). Axl expression was not detected more frequently in patients of older age, specific FAB categories, or cases with extramedullary disease. However, there existed a correlation between Axl and bcl-2 expression levels. AML cells with high bcl-2 expression showed higher Axl expression (r = 0.32; P = 0.02), and furthermore, Axl transcript numbers were also higher in AML with high CD34 expression (n = 38, r = 0.42; P = 0.008). No significant difference between leukemias expressing and not expressing Axl was found with regard to complete remission rate. However, quantitative Axl expression was associated with worse progression-free and overall survival. Higher Axl levels had worse prognosis for progression-free (beta: 0.68, s.e.: 0.28, P = 0.015) and overall survival (beta: 0.61, s.e.: 0.31, P = 0.05) using multivariate Cox models adjusted for age, Auer rods and leukocyte counts. In conclusion, in this retrospective analysis, no difference with regard to clinical characteristics at diagnosis was found between AML patients whose leukemia cells show Axl expression vs patients whose cells are Axl negative. The association between Axl and bcl-2 and Axl and CD34 expression in de novo AML needs further investigation. Similarly, the negative impact of Axl levels on outcome should be confirmed in a larger cohort.

Acute Disease↗
PubMed1998

A phase I study of adenovirus-mediated wild-type p53 gene transfer in patients with advanced non-small cell lung cancer.

Mutations of the tumor suppressor gene p53 are the most common genetic alterations observed in human cancer. Loss of wild-type p53 function impairs cell cycle arrest as well as repair mechanisms involved in response to DNA damage. Further, apoptotic pathways as induced by radio- or chemotherapy are also abrogated. Gene transfer of wild-type p53 was shown to reverse these deficiencies and to induce apoptosis in vitro and in preclinical in vivo tumor models. A phase I dose escalation study of a single intratumoral injection of a replication-defective adenoviral expression vector encoding wild-type p53 was carried out in patients with incurable non-small cell lung cancer. All patients enrolled had p53 protein overexpression as a marker of mutant p53 status in pretreatment tumor biopsies. Treatment was performed either by bronchoscopic intratumoral injection or by CT-guided percutaneous intratumoral injection of the vector solution. Fifteen patients were enrolled in two centers, and were treated at four different dose levels ranging from 10(7) to 10(10) PFU (7.5 x 10(9) to 7.5 x 10(12) particles). No clinically significant toxicity was observed. Successful transfer of wild-type p53 was achieved only with higher vector doses. Vector-specific wild-type p53 RNA sequences could be demonstrated in posttreatment biopsies of six patients. Transient local disease control by a single intratumoral injection of the vector solution was observed in four of those six successfully transduced patients. There was no evidence of clinical responses at untreated tumor sites. Wild-type p53 gene therapy by intratumoral injection of a replication-defective adenoviral expression vector is safe, feasible, and biologically effective in patients with advanced non-small cell lung cancer.

Adenoviridae↗
PubMed1997

[Hip pain].

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Adult↗
PubMed1996

BRCA1 mutations in a selected series of breast/ovarian cancer patients.

Germline mutations in the BRCA1 gene have been associated with familial breast/ ovarian cancer in large families showing high penetrance of the disease. Little is known, however, about the contribution of BRCA1 mutations to breast/ovarian cancer in small families with few affected members or in isolated early onset cases. Therefore we examined the BRCA1 gene in 63 breast/ovarian cancer patients who either came from small families with as few as one affected first degree relative, or in patients who had no family history but had developed breast cancer under 40 years of age. Using the protein truncation test, we were able to identify three unique BRCA1 germline mutations (4.8%). Two of the probands had only one affected first degree and several second degree relatives and the third had three affected first degree relatives including two sisters who, when tested, were also found to carry the mutation. There was no family history of ovarian cancer in any of the three families.

Adult↗
PubMed1995

Treatment of malignant obstruction of the superior vena cava with the self-expanding Wallstent.

BACKGROUND: Obstruction of the superior vena cava (SVC) in malignant disease can cause considerable distress to patients. Symptomatic relief can be achieved by the percutaneous implantation of a self-expanding stent (Wallstent) into the stenosis. METHODS: Fourteen patients with obstruction of the SVC were treated with one to three Wallstent endoprostheses. They suffered from advanced bronchogenic carcinoma (n = 12), thyroid carcinoma (n = 1), and breast carcinoma (n = 1). The indication for stent placement was symptomatic obstruction of the SVC and incurable disease. Stenting was performed for symptom relief, and before, during, and after courses of radiotherapy or chemotherapy as needed. RESULTS: Twelve patients experienced complete symptomatic relief within two days of stent placement. Two patients did not benefit. Three patients not given anticoagulation developed stent thrombosis between one week and eight months after initial placement, and within one day of endobronchial stent implantation with bronchial laser therapy or balloon dilatation in all three. Patency of the SVC was achieved again by a repeat procedure. CONCLUSIONS: Stent placement for obstruction of the SVC gives rapid symptomatic relief. Subsequent endobronchial stent implantation with bronchial laser therapy or balloon dilatation could be a risk for caval stent occlusion. Stent thrombosis remains a problem in patients who are not anticoagulated.

Aged↗
PubMed1994

Expression and mutational analysis of Nm23-H1 in liver metastases of colorectal cancer.

It has been proposed that nm23-H1, a candidate suppressor gene for metastasis, plays an important role in metastasis formation of human tumours. In order to investigate its role in the progression of colorectal cancer, we analysed 22 liver metastases of this malignancy with respect to mutational changes, loss of heterozygosity and expression levels of nm23-H1. Although genetic alterations in nm23-H1 have recently been described in those colorectal adenocarcinomas which give rise to distant metastases, we were unable to detect any mutation in the coding sequence of nm23-H1 in the metastatic tissue itself. We further analysed the metastases with respect to allelic deletions at the chromosomal locus of nm23. However, no loss of heterozygosity could be detected in ten informative cases. Moreover, the mRNA expression levels of nm23-H1 in the metastatic tissues were not significantly different from those in normal colon mucosa. Thus, although nm23-H1 might be involved in metastasis suppression of certain tumour types, in colorectal tumour progression its role remains to be determined.

Base Sequence↗
PubMed1993

Altered expression of the retinoblastoma susceptibility gene in chronic lymphocytic leukaemia.

The pathogenesis of chronic lymphocytic leukaemia (CLL) is unknown. One of the most frequent cytogenetic abnormalities in CLL is a deletion within the long arm of chromosome 13, the region to which the retinoblastoma (Rb) gene has been mapped. Lack of Rb expression has been linked to the carcinogenic process in many human tumours. We therefore sought to investigate the role of Rb gene inactivation in CLL using differential polymerase chain reaction on reverse transcribed RNA. The result of the PCR was quantitated using HPLC. 5/39 patients revealed a lack or significantly impaired expression of the Rb gene upon differential PCR analysis. In addition, immunocytochemical studies were performed using the Rb-specific monoclonal antibody PMG245. 10/56 patients showed a weak or absent expression upon immunocytochemical analysis compared to monocytes or granulocytes. The samples lacking Rb were from both early and late stage CLL. Our results indicate that inactivation of the Rb protein occurs in a fraction of CLL cases and can be found in early and late stages of the disease.

Aged↗
PubMed1992

Treatment of neutropenia in Felty's syndrome with granulocyte-macrophage colony-stimulating factor--hematological response accompanied by pulmonary complications with lethal outcome.

We report on a 67-year-old man with Felty's syndrome (FS) complicated by recurrent pneumonia and an infected wound, which was not healing in spite of maximal antibiotic and local therapy. Encouraged by previous experience, we treated him with granulocyte-macrophage colony-stimulating factor (GM-CSF). His total leukocyte count rose, but the patient's pneumonia deteriorated. In addition, a previously known chronic obstructive lung disease (COLD) was exacerbated acutely. These complications finally led to his death. Postmortem examination revealed widespread pneumonia with invasive aspergillosis and a peripheral adenocarcinoma in his left lung.

Adenocarcinoma↗
PubMed1989

Immunocytochemical detection of p21ras expression in fresh human leukaemic cells and cell lines.

The expression of p21ras proteins was investigated by immunocytochemistry in permanent cell lines and in fresh human leukaemic cells. While high and low levels of p21ras could be detected in most of the cell lines, no significant p21ras immunoreactivity was noted in cells of ten human acute and chronic leukaemias. Thus, notwithstanding its possible role in the initial transformation process in human leukaemias, p21ras expression appears not to be an irrevocable requirement for the maintenance of the transformed state.

Antibodies, Monoclonal↗
PubMed1988

Molecular lesions involved in the progression of a human breast cancer.

Specific genetic alterations are observed in human breast cancer, but little is known about when these occur in the evolution of the disease. Three breast cancer effusions that occurred sequentially in a single patient were examined. Common cytogenic abnormalities were found in all effusion samples suggesting a single progenitor metastatic cell. Only the last effusion, however, exhibited a mutation of the c-K-ras gene and a loss of heterozygosity at the c-H-ras locus. These specific genetic abnormalities detected in the last effusion was correlated with improved in vitro growth of the primary cells, and with the ability to establish breast cancer cell lines. Thus a mutant ras gene and the loss of heterozygosity at the c-H-ras locus were associated with a more aggressive tumor phenotype occurring late in the course of this patient's disease and not with the initiation of the primary breast cancer, or in the establishment of metastases.

Adult↗
PubMed1987

Serum concentration of laminin, and course of the disease in patients with various malignancies.

Serum concentration of laminin was measured radioimmunologically in 96 patients suffering from various malignancies. Laminin levels were significantly elevated in patients with carcinomas and leukemias, but not in patients with sarcomas or lymphomas when compared with healthy controls. A good correlation could be found between serum laminin concentration and response to therapy in patients with carcinoma and leukemia. Elevated laminin levels were associated with a progressive course of the tumor condition. Furthermore, a close correlation has been detected between serum concentrations of laminin and carcinoembryonic antigen (CEA) in patients with carcinoma of the colon. The serum laminin level seems to be a valuable parameter for observation of the course of certain malignancies.

Adult↗
PubMedDate not supplied

Predictions and associations of cholecystectomy in patients with cholecystolithiasis treated with extracorporeal shock wave lithotripsy.

Extracorporeal shock wave lithotripsy (ESWL) is effective in the treatment of symptomatic cholecystolithiasis in well-selected patients. We analyzed the predictors of cholecystectomy in a large series of gallstone patients after ESWL. This was a retrospective follow-up cohort-study of consecutive patients undergoing ESWL for symptomatic cholecystolithiasis over a 9-year period. It was possible to analyze a total of 297 patients; there were 211 women and 86 men, with a mean age of 52 years (range, 8-81 years). Patients that had been cholecystectomized after ESWL were compared to patients with their gallbladder still in situ and determinants of cholecystemctomy in terms of clinical, stone, and gallbladder parameters and symptoms analyzed. The mean duration of follow-up was 99 months (range, 27-134 months). During follow-up, 106 (36%) patients underwent a cholecystectomy at a mean of 34 months (range, 0-127 months) after ESWL. Histological data showed a normal gallbladder wall in only 4 cases; 101 examinations revealed some kind of (chronic) inflammation, which was not different from histological gallbladder results in patients without prior lithotripsy. Three gallbladder polyps were found, but no carcinoma. Cholecystectomy after ESWL of gallbladder stones was strongly associated with persitent and/or renewed biliary symtoms. Nevertheless, only three of four patients became asymptomatic after CE. Thus, ESWL proved to be a valuable organ-preserving alternative to cholecystectomy in selected patients.

Adolescent↗
PubMedDate not supplied

Gene therapy study of cytokine-transfected xenogeneic cells (Vero-interleukin-2) in patients with metastatic solid tumors.

On the basis of compelling preclinical data in cats and dogs, we initiated a clinical gene therapy study in nine patients with advanced solid tumors using xenogeneic fibroblasts secreting human interleukin (IL)-2 (Vero-IL-2 cells). Cohorts of three successive patients with tumors accessible to computed tomography- or ultrasound-guided injection were treated repeatedly with 5 x 10(5), 5 x 10(6), or 5 x 10(7) Vero-IL-2 cells. The endpoints of the study were feasibility, toxicity, and the clinical and biological effects of this novel approach to immunotherapy of cancer. Histopathological, immunological, and molecular analyses were performed on biopsy specimens of tumors and blood samples before, during, and after treatment. Treatment was well tolerated, and toxicity consisted of transient fever in one patient and short-lived, mild itching and erythema in two others. One patient with soft-tissue sarcoma showed a reduction of >90% and >50% of the volume of two distant, noninjected metastases, lasting for 29+ and 26 months, respectively. Four other patients showed stabilization of their disease for 3-9 months; of these patients, one with melanoma developed marked vitiligo. We conclude that repeated injections of < or =5 x 10(7) Vero-IL-2 cells are feasible and safe in heavily pretreated patients with advanced solid tumors. An additional evaluation of an intratumoral application of Vero-IL-2 seems warranted.

Adult↗
PubMedDate not supplied

Sequence dependent synergistic cytotoxicity between etoposide and fluoropyrimidines.

The cytotoxic interactions between etoposide and two fluoropyrimidines (FP), 5-fluorouracil (FUra) and 5-fluoro-2'-deoxyuridine (FdUrd), were determined in L1210 cells by soft agar clonogenic assay and in five human adenocarcinoma cell lines by colony growth assay. The administration of etoposide prior to FP resulted in synergistic cytotoxicity in L1210, HCT-8, Mia PaCa, MCF-7, and T47-D cells while the reverse sequence resulted in additive or antagonistic cytotoxicity in L1210, HCT-8, and Mia PaCa cells. Etoposide prior to FdUrd produced more DNA single strand breaks than expected in L1210 cells, while the reverse sequence produced fewer than expected. The sequence--dependent synergistic cytotoxicity of etoposide--FP correlates with relative DNA single strand break production in L1210 cells.

Animals↗