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Biomedical subjects

R Willers

Publications and source records attributed to R Willers.

At least 73 records · Page 4Linked to original sources
PubMed1995

Incidence and prognostic significance of vascular and neural invasion in squamous cell carcinomas of the esophagus.

The prognostic influence of blood-vessel invasion (BVI), lymphatic-vessel invasion (LVI) and neural invasion (NI) was evaluated retrospectively in a series of 161 patients with squamous cell carcinoma (SCC) of the esophagus who underwent esophageal resection. Evidence of BVI, LVI and NI was found in 32.9%, 48.5% and 26.1%, respectively. Incidence of BVI, LVI and NI was significantly higher in high pT categories (pT3 and pT4) than in low pT categories (pT1 and pT2) and in patients with distant metastases than in patients without distant metastases. Incidence of LVI and NI in lymph-node-positive patients was significantly higher than in lymph-node-negative patients. The 5-year survival rate was significantly lower in patients with BVI or LVI than in patients without BVI or LVI. Patients with evidence of NI showed no significant differences in 5-year survival from patients without evidence of NI. By stepwise multivariate Cox regression analysis, BVI and LVI were shown to be independent prognostic factors. A search for vascular invasion may therefore provide additional prognostic precision in SCC of the esophagus.

Carcinoma, Squamous Cell↗
PubMed1995

[Doppler sonographic evaluation of the effectiveness of an antirejection treatment after kidney transplantation].

Data on 64 rejection reactions in 108 consecutive patients after renal transplantation (61 males, 47 females; mean age 42.8 +/- 12.9 years) were analysed to test what Doppler sonographic measurements can be used to predict whether a given drug regimen is able to suppress rejection. Results were compared with renal function and histological evidence of rejection. The >> pulsatility index << (PI), which is dependent on flow resistance, was determined by Doppler echocardiography: it increases on rejection (measurements made 2.0 +/- 1.1 days apart). The rejection reaction was successfully controlled by drugs (methylprednisolone, azathioprine and cyclosporin) in 44 patients (group 1), but not in 20 patients (group 2). PI before rejection (group 1: 1.8 +/- 0.5; group 2: 1.7 +/- 0.6), PI during histologically confirmed rejection (2.6 +/- 1.2 and 3.1 +/- 1.4, respectively), the size of difference between these values, and parameters of renal function provided no pointers to any drug efficacy in suppressing rejection. But individual changes in PI during suppression treatment proved to be of outstanding value (P < 0.00005). Signs of florid rejection at the end of treatment period correlated with a rising PI in 13 of 17 rejection episodes, while PI fell in only 7 of 47 episodes. Vascular signs of rejection tended to be poor predictors of rejection (P .028). - These findings indicate that serial Doppler sonography can be helpful in monitoring antirejection treatment.

Adult↗
PubMed1995

Successful liver treatment of a juvenile granulosa cell tumor in a 4-year-old child by regional deep hyperthermia, systemic chemotherapy, and irradiation.

Juvenile granulosa cell tumors (JGCT) of the ovary are rare in children and adolescents. About 90% are diagnosed in early-stage FIGO I with favorable prognosis. More advanced stages (FIGO II-IV) have a poor clinical outcome and chemotherapy alone cannot avoid tumor progression. Regional deep hyperthermia (RHT) induced by microwave technique has been established as an additional modality for treatment of different tumors. However, in cases with liver involvement there are technical problems which have not yet been solved. We report on a 4-year-old child who suffered from diffuse liver metastases 10 months after JGCT of the left ovary. After chemotherapy including ifosfamide, etoposide, and carboplatin in combination with RHT and consolidation radiotherapy, the patient has been in complete remission for 1 year of follow-up. This Case Report indicates the feasibility of combining surgery, chemotherapy, hyperthermia, and radiation therapy (which can also be an effective treatment modality for advanced granulosa cell tumor) for the treatment of liver metastases of JGCT, but does not allow comparisons of these treatments.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[An interventional study against cigarette smoking among Dusseldorf high school students 1992-94].

Between 1992 and 1994, an interventional program was held in the secondary schools ("Hauptschulen") in Düsseldorf contra cigarette smoking. The program was conducted in the following way. Half of the schools (intervention schools) were involved in this program which consisted of 15 sessions. The other schools served as control groups. During the first year of this program school-teachers and a physician taught students about the function and the abilities of the healthy heart and lung. The students developed adversions to smoking. In addition, the students learned by role-plays how to say no to a cigarette without embarrassment. These role-plays were videotaped. During the second year of this program the role-plays were repeated and teaching about the heart and the lungs was augmented. Also, every student got the opportunity to meet and talk with a famous athlete. Furthermore, smoking-cessation programs were hold in four intervention schools. The program started in the sixth grade with a questionnaire administered to 878 schoolchildren. During this time the average age of the children was 13 years. Because of a large fluctuation, the questioning could be repeated with only 630 of these children (71.8%) after 2 years. At the end of the study the number of smokers had increased two times greater in the control schools than in the intervention schools (boys: 20.5% points vs 9.4% points; girls: 44.3% points vs 21.0% points). Obviously, the continuation of the program during the second year was important in making the program successful. Among the participants of the intervention program there was a trend to stop smoking. But the program was not able to prevent non-smokers from starting the habit. On the other hand, of the children who started smoking during the program, more girls in the intervention schools quit smoking than in the control schools. At the end of the program more girls than boys (mean age 15 years) smoked. Almost one-fourth of the boys, and from the control schools one-third of the girls were already daily smokers. The smokers obtained cigarettes from kiosks, from friends, vending machines, vendors or shops, but seldom from their homes.

Adolescent↗
PubMed1994

p53 protein expression and prognosis in squamous cell carcinoma of the esophagus.

BACKGROUND: The p53 gene product is known to regulate cell growth and proliferation. Whereas the wild-type p53 protein suppresses cell growth, the mutated p53 protein acts as an oncogene. Mutations in the p53 gene usually result in p53 protein stabilization and accumulation; so that the gene product can be detected by immunohistochemistry. Recently, the immunohistochemical detection of the p53 protein was associated with prognosis in breast, colorectal, and other types of cancer. However, its prognostic role in esophageal cancer remains to be elucidated. METHODS: p53 expression in formalin fixed, paraffin embedded samples of 204 patients with primary squamous cell carcinoma of the esophagus, who underwent esophageal resection, were analyzed immunohistochemically with DO-1, a monoclonal antibody that detects wild-type and mutant forms of p53. The relationship between p53 immunoreactivity and prognostic factors was determined by the Chi-square test, and the prognostic impact of p53 protein expression was analyzed using univariate and multivariate survival analyses. RESULTS: In 137 of 204 tumors (67.2%), nuclear immunoreactivity for the p53 protein was detected. There was no correlation with sex, age, pathologic tumor (pT) category, pathologic lymph node (pN) category, metastasis (M) category, residual cancer (R) category, histologic grade, or preoperative radiation therapy. In contrast to clinicopathologic parameters, p53 expression was not correlated with prognosis in univariate and multivariate survival analyses. CONCLUSIONS: The p53 protein can be detected by immunohistochemistry in a high percentage of squamous cell carcinomas of the esophagus. However, the overexpression of the p53 gene product has no impact on the prognosis.

Adult↗
PubMed1994

The use of intravenous immunoglobulins in symptomatic HIV infection. Results of a randomized study.

To study the efficacy of intravenous immunoglobulin in symptomatic infection with human immunodeficiency virus (HIV) we enrolled 35 patients with CD4 lymphocyte counts below 300/microliter in a randomized three-arm study. In addition to standard HIV treatment (e.g., zidovudine, aerosolized pentamidine), 13 patients were treated with 7.5 g and 11 with 40 g of a 7 S intravenous IgG preparation every 4 weeks over a period of 1 year. A control group of 11 patients remained on standard treatment. Clinical and laboratory parameters, including lymphocyte proliferation and in vitro immunoglobulin synthesis were evaluated prior to intravenous IgG administration. HIV-specific immunological abnormalities such as increased B-cell activation and B-cell immaturity were observed in all three study groups at the beginning of the study. Mitogen-induced lymphocyte proliferation was diminished. These disturbances were not influenced by intravenous IgG treatment. Further laboratory data and the course of the HIV infection (fever, antibiotic treatment, hospitalization, Candida and herpes simplex or cytomegalovirus infection) remained unchanged. Thus, our data with an observation period of 12 months do not support the use of intravenous IgG treatment in adult symptomatic HIV-infected patients with CD4 counts lower than 300/microliter.

AIDS-Related Opportunistic Infections↗
PubMed1993

Activity of C1 esterase inhibitor in patients with vascular leak syndrome after bone marrow transplantation.

Vascular-leak syndrome (VLS) is a common complication in the first 3 weeks after bone marrow transplantation (BMT). The patients present with weight gain, generalized edema, ascites, pericardial or pleural effusions, tachycardia, arterial hypotonia, and/or pre-renal failure. The aim of our study was to investigate the role of the complement system in VLS. The protein concentrations of C3 and C4 were studied by immunodiffusion, and total hemolytic complement activity was studied by assessment of CH50. C1 esterase inhibitor (C1 Inh), the major inhibitor of the classical pathway of complement, was assessed by a functional test. Activation of complement was assessed by C4d (a C4 activation product). Twelve patients were followed prospectively from start of conditioning therapy to day +21 after bone marrow transplantation. Eight of 12 patients did not develop VLS. These patients had an increase of C3 between day +9 and day +13 (range: 1.3- to 1.5-fold, median: 1.4-fold), C4 (range: 1.3- to 1.9-fold, median: 1.4-fold), CH50 (range: 1.3- to 1.6-fold, median: 1.4-fold), and C1 Inh (range: 1.2- to 1.5-fold, median: 1.3-fold). Four of 12 patients developed VLS. C1 Inh activity was decreased to 0.60- to 0.80-fold. This decrease began 2-6 days prior to clinical diagnosis of VLS (n = 3), or at onset of VLS (n = 1). Patients with VLS showed elevated C4d concentrations (up to 2.4 mg/dl, upper normal threshold value: 0.9 mg/dl). Patients with VLS reveal an activated state of the complement system which is accompanied by a reduced activity of C1 Inh. Insufficient control of complement activation may contribute to VLS in patients after BMT.

Adolescent↗
PubMed1992

[Risk factors for fibrinoid reaction after posterior chamber lens implantation--a retrospective study].

Previous ocular diseases (e.g. herpetic keratouveitis), glaucoma, previous ocular surgery and surgery longer than normal turned out to be the main risk factors for a fibrinoid reaction after an extracapsular cataract extraction with posterior chamber lens implantation in patients of the Universitäts-Augenklinik Düsseldorf between June 1989 and March 1990. This result was obtained from a retrospective study of the medical records. No special risks could be concluded neither from the presence of general diseases (e.g. diabetes mellitus, consumptive basic diseases), immuno-suppressive treatment, constitutional factors, nor from age, sex, operative method nor from the surgeon. Preoperative antiexsudative prophylactic treatment is suggested for patients with one or more risk factor.

Adult↗
PubMed1989

Deficiency of the eighth component of complement. Evidence for linkage of C8 alpha-gamma pattern with C8 beta deficiency in sera of twelve patients.

The C8 alpha-gamma subunit of the eighth component of complement was analysed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and immunoblotting in sera from 68 normal individuals, 12 C8 beta-deficient patients (from seven unrelated families), and 10 of the parents of the latter. Three different forms of the C8 alpha-gamma subunit were observed: 34/68 normal individuals were found to have a C8 alpha-gamma triple band (termed C8 alpha-gamma 1, C8 alpha-gamma 2, C8 alpha-gamma 3 variants), 23/68 the C8 alpha-gamma 2 and C8 alpha-gamma 3 variants, and 11/68 the C8 alpha-gamma 1 and C8 alpha-gamma 3 variants. In contrast, all C8 beta-deficient patients had detectable C8 alpha-gamma 2 and C8 alpha-gamma 3 variants but lacked the C8 alpha-gamma 1 variant in addition to the C8 beta subunit. Three out of ten parents of the C8 beta-deficient patients were found to have the C8 alpha-gamma triple band, whereas 7/10, like their children, had the C8 alpha-gamma 2 and C8 alpha-gamma 3 variants only. We conclude that there is a linkage between the C8 alpha-gamma pattern and C8 beta deficiency. These data may support earlier findings that in humans the genes encoding for C8 alpha-gamma and C8 beta are closely linked on chromosome 1.

Adult↗
PubMed1988

[Preventive long-term intravenous immunoglobulin infusion in children with acute lymphatic leukemia. II. Zymosan opsonization is decreased and is not increased by IgG infusions].

Zymosan opsonisation was determined in sera of 38 normal individuals and 20 children with acute lymphocytic leukemia (ALL). All patients underwent chemotherapy according to the CoALL 82 protocol. Intravenous gammaglobulin (ivGG) was given prophylactically to replace deficient specific antibodies. Zymosan opsonisation in normal sera ranged from 65% to 133% of a serum pool, whereas sera of children with ALL exhibited markedly decreased opsonisation ranging from 7% to 141% (of the pooled serum standard) at different times during an observation period of 20 months. No significant changes could be observed over time, neither induced by the ivGG infusion itself (short term effect) nor during the 20 months observation period (long term effect). Before ivGG therapy was initiated, a positive correlation was found between zymosan opsonisation and complement parameters (CH 50: p less than 0.01; AP 50; p less than 0.001; C3: p less than 0.05). No correlation could be noted between zymosan opsonisation and IgG concentration. Experiments with complement deficient sera clearly demonstrated the dependence of zymosan opsonisation from complement function. In contrast, sera with little or no IgG but intact complement, showed normal zymosan opsonisation. Deficient zymosan opsonisation might contribute to the immune deficiency of ALL patients. The present study suggests, that the zymosan opsonisation cannot be corrected by ivGG infusions.

Agammaglobulinemia↗
PubMed1988

[Preventive long-term intravenous immunoglobulin infusion in children with acute lymphatic leukemia. I. Anticomplementary activity of gamma globulin preparations is a function of the preparation and IgG concentration prior to infusions].

The influence of intravenous gammaglobulin infusions (ivGG) on hemolytic complement function and the concentration of serum C3 and its split product C3dg was studied in 20 children with acute lymphocytic leukemia (ALL) undergoing ivGG prophylaxis. IvGG was infused once monthly over a period of 20 months using two different preparations commercially available. Serum and EDTA-plasma were collected before initiation of ivGG therapy (time 1), after 10 and 20 months (time 2 and 3), before and immediately after the infusions. IvGG was infused in connection with chemotherapy (according to the CoAll 82 protocol). 16 of 60 sera collected prior to infusions contained less than 700 mg/dl IgG. Mean IgG concentrations could be raised to 198 mg/dl (time 1), 219 mg/dl (time 2), and 213 mg/dl (time 3), respectively. -CH 50 prior to infusions was below normal in 15 of 59 sera, afterwards in 25 of 59 sera. AP 50 before (after) infusions was decreased in 29 of 59 (36 of 60) sera, C3 in 18 of 60 (24 of 60) sera. C3dg was slightly elevated in one EDTA-plasma prior to ivGG infusions and in 5 of the plasmas following infusions. IvGG infusions resulted in a significant loss of hemolytic activity of serum complement (p less than 0.01, F-test). The effect was more profound if IgG concentrations before infusions were less than 700 mg/dl, but this was true for only one of the two used ivGG preparations. The long term follow up over two years showed no significant changes of complement functions (F-test), indicating complete recovery of complement function from short term anticomplementary effects.

Child↗
PubMed1985

Longterm effect of neonatal whole-body X-ray exposure on ploidy development in mouse liver cells.

Mice of the strains C3H, DBA, NZB, and NMRI were X-irradiated with 0.475 Gy and 2.85 Gy (or 3.80 Gy) at newborn stage or at the age of six months. Their livers were prepared at the age of one to maximum 18 months and the hepatocytes isolated. The DNA content of both whole cells and separated nuclei was measured by flow cytometry and the liver ploidy pattern was determined applying a correcting calculation. Irradiation with 0.475 Gy of newborns of strain C3H results in a relative decrease of octoploid cells and an increase of tetraploid nuclei during lifetime (significance level of 0.001). After irradiation with 3.80 Gy a reversed reaction was observed. However, if the animals were irradiated as adults with a dose of 3.80 Gy the 8c cells decreased significantly three months later. Similarly, newborns of the outbred strain NMRI irradiated with 2.85 Gy, showed an increase of octoploid cells from the third month on, but an oscillating pattern of the 4c nuclear DNA content. In strains DBA and NZB, significantly altered ploidy values could not be found, perhaps due to a too great variance of experimental values.

Age Factors↗
PubMed1984

Flow cytometric analysis of mouse hepatocyte ploidy. I. Preparative and mathematical protocol.

Preparative and mathematical procedures are presented for the investigation of the ploidy pattern of liver cells. The DNA content of enzymatically-isolated liver cells and of nuclei was measured by flow cytometry. The true DNA content could not be measured directly due to super-position of statistical coincidences (demanding "first mode correction") and incomplete separation of the nuclei in binucleate hepatocytes (demanding "second mode correction"). The statistical coincidences (caused by simultaneous measurement of two or more particles or subsequent reaggregation of particles) were corrected by splitting the "unnatural" i.e., aneuploid DNA content, and classifying it with the normal ploidy classes. In addition, the higher normal ploidy classes were reduced by the proportion of the measured coincidences in favour of the lower ones. The second mode correction applied to nuclear distributions only. It is a probability calculation based on counting nuclear pairs on microscope slides, and resulted in a 10% increase of diploid nuclei and a larger standard deviation between the age groups. 8c and 16c values were reduced. The tetraploid values were unchanged.

Animals↗
PubMed1984

Flow cytometric analysis of mouse hepatocyte ploidy. II. The development of polyploidy pattern in four mice strains with different life spans.

The development of liver ploidy in mice aged up to 24 months was investigated by flow cytometry in four mouse strains. A mathematical procedure was applied for correction of flow cytometry histograms. In two of the mouse strains, C3H and DBA, both cellular and nuclear ploidy proceed in the same way. The octoploid cell with two tetraploid nuclei is the most numerous cell type in adulthood. On the other hand, strain NZB and the out-bred strain NMRI show at the corresponding age a higher proportion of diploid cells with strikingly low proportions of 4c cells. In addition, high values of 16c cells and nuclei are present in NMRI. In all strains the proportion of binucleate hepatocytes is in the same range (60%). However, the strains differ in ploidy classes of binucleate cells. Development of liver polyploidization does not depend on life span of the specific strain.

Aging↗
PubMedDate not supplied

Response to treatment of chronic hepatitis C with interferon alpha in patients infected with HIV-1 is associated with higher CD4+ cell count.

The aim of this study was to assess the efficacy and tolerance of interferon alpha (IFN alpha) treatment of chronic hepatitis C in HIV-seropositive patients. Seventeen patients with actively replicating hepatitis C were consecutively enrolled and treated with IFN alpha 5 MIU three times a week and followed up for at least 6 months after cessation of treatment. Eight patients responded to IFN alpha therapy with a complete remission of signs of active hepatitis and viral replication (ALT, HCV-RNA) at the end of treatment with IFN alpha. A sustained complete remission (ALT, HCV-RNA) for at least 6 months after the end of treatment was achieved in five of these eight patients. Complete responders had higher CD4+ cell counts (median 525/microliter) compared to non-responders (median 245/microliter) (p < 0.001). All patients but one completed at least 4 months of treatment. No severe toxicity (> WHO grade 2) due to IFN alpha treatment occurred. The results indicate that IFN alpha treatment of chronic hepatitis C in HIV-seropositive patients is successful in a considerable number of cases. Success of treatment with IFN alpha is related to higher CD4+ cell counts.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

[MRI follow-up study of aseptic osteonecrosis (AON) in children treated with chemotherapy for malignant diseases].

PURPOSE: The aim of the study was to evaluate by MRI the course of aseptic osteonecrosis (AON) after chemotherapy in children with different malignancies. MATERIAL AND METHODS: Retrospective analysis of 72 MRI studies in 20 children (age: 3.2-18.4 years) presenting with AON after chemotherapy. 8 children were treated exclusively with relief of weightbearing structures, whereas 12 children were additionally treated with hyperbaric oxygen therapy (HBO). Within a range of 3-76 months each patient received 1-6 follow-up exams. The acquired series included multi planar spin-echo as well as fatt-suppressed inversion recovery sequences. The MRI examinations were evaluated by a point-score system (1-6) by two radiologists. RESULTS: AON was most commonly seen in the pedal bones (26.4%), in the hip (23.6%), and in the knee joints (19.4%). Initial findings revealed an average score of 3.1 points. Based upon these initial findings, subsequent analyses show a statistically significant (p < 0.05) score increase of 0.6 score-points. For the observed intervals a: < 6 months, b: 6-12 months, and c: > 12 months the mean scores were: a: 3.3, b: 3.7, and c: 4.5 points. During the observed time period 5 patients were surgically treated in the affected bone areas. CONCLUSION: The majority of chemotherapy associated AON which initially present with advanced findings showed in MRI a progression with frequent destruction of the joint surface over their further course. More discrete forms of AON, especially osteoedema, can be positively influenced by conservative therapy.

Adolescent↗
PubMedDate not supplied

In vitro test-system for chemo- and thermosensitivity: an analysis of survival fractions and cell-cycle distributions in human Ewing's sarcomas as a modelfor tumors in pediatric oncology.

BACKGROUND: Tumor cell resistance to anticancer drugs is the primary reason for treatment failure in childhood cancer. Resistance can exist at the onset of treatment or can become clinically apparent under selective pressure of drug exposure. In vitro predictive tests are important for the experimental study of drug resistance. Although in vitro studies appear to be fairly good for predicting drug resistance, they are rarely used in the routine management of individual cases. An exception that proves the rule is the MTT- (3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazoliumbromide) assay in children with acute lymphoblastic leukemias (ALL), which can be correlated with the clinical outcome in this group of patients. In the present study we used a predictive test-system to evaluate the synergistic cytotoxic effects of chemotherapy +/- hyperthermia with respect to cell cycle disturbance. METHODS: As a tumor model two well defined human Ewing's sarcoma cell lines VH64 and SK-ES-1 were treated for 1 h with cis-diamminedichloroplatinum II (cDDP) (0.1, 0.5, 1, 3, 5 micro g/ml) or 4'-demethyl-epipodophyllotoxin-5-(4,6-0-)-ethylidene-beta-D-glycopyranoside (VP-16) (1, 5, 10, 20, 50 micro g/ml) +/- hyperthermia (42 degrees C, 43 degrees C); control: 37 degrees C, without chemotherapy. Cell survival was tested using the XTT- (2,3-bis[2-Methoxy-4-nitro-5-sulfophenyl]-2H-tetrazolium-5-carboxanilide) assay. Assay conditions were optimized for each tumor cell line, extinction was measured 72 h post treatment at 450 nm in an ELISA-reader. Cell cycle fractions (G0/G1-, S-, G2/M-phase) were determined immediately, 12 h and 24 h after treatment by labeling proliferating tumor cells with bromodeoxyuridine (BrdU) and measuring DNA-content with propidium-iodide (PI) and analyzed by flow cytometry. RESULTS: Survival fractions: Hyperthermia alone at 43 degrees C reduced tumor cell survival to 51 % in SK-ES-1 and 74 % in VH64. cDDP (5 micro g/ml): reduction of survival fraction to 23 % in SK-ES-1 and 33 % in VH64. cDDP (5 micro g/ml) + hyperthermia (43 degrees C): enhanced reduction of tumor cell survival compared to 37 degrees C to 11 % in SK-ES-1 and 8 % in VH64. VP-16 (50 micro g/ml): survival fraction of 18 % in SK-ES-1 and of 31 % in VH64. In contrast to cDDP, chemosensitivity of the tumor cells to VP-16 could not synergistically be enhanced by using hyperthermia. Cell cycle analysis: Hyperthermia alone at 43 degrees C induced an accumulation in G2/M and a slight reduction in G0/G1-phase 24 h after treatment, whereas the S-phase was not markedly affected. cDDP (5 micro g/ml) alone led to a prominent S-phase arrest and a G0/G1 decrease 24 h after treatment. Simultaneous application of cDDP (5 micro g/ml) + hyperthermia (43 degrees C) however significantly reduced S-phase cells. VP-16 (50 micro g/ml) alone induced a temporary S-phase arrest 12 h after treatment and a delayed G2/M-arrest after 24 h. Additional hyperthermia at 43 degrees C did not show further effects on VP-16 induced cell cycle disturbances. CONCLUSIONS: Test-system discloses treatment-specific alterations in tumor cell survival and cell cycle distribution, e. g. synergistic enhancement of cDDP cytotoxicity by heat application, which might predict chemo- and thermosensitivity.

Bone Neoplasms↗