Oncogene-mediated multistep transformation of C3H10T1/2 cells

We have examined the response of the mouse embryonic cell line C3H10T1/2 to transfection with the activated human c-H-ras oncogene and the gag-myc oncogene from avian myelocytomatosis virus 29. C3H10T1/2 cells are not morphologically transformed following transfection with the gag-myc oncogene. A low level of focus formation is observed following transfection of the c-H-ras oncogene. When C3H10T1/2 cells are cotransfected with the ras and myc oncogenes, focus formation is increased by an average of 13 fold. In addition, C3H10T1/2 ras/myc foci have a distinct, transformed morphology which correlates with an increased potential for anchorage-independent growth. Although morphological transformation in this system is largely a function of ras oncogene expression, our studies demonstrate that it is potentiated by the presence of a functional gag-myc protein. Oncogene-mediated multistep transformation, which was first described in primary embryo cultures, is not a general property of established cell lines. The C3H10T1/2 cell line is an exception and provides a model system in which partially transformed phenotypes, in a progression toward malignant transformation, can be isolated and studied.     

Cefepime versus ticarcillin and clavulanate potassium and aztreonam for febrile neutropenia therapy in high-dose chemotherapy patients

An open labeled randomized trial comparing the efficacy and cost of empirically applied cefepime (C) as monotherapy versus combination therapy consisting of ticarcillin and clavulanate potassium and aztreonam (T/A) was performed in febrile neutropenic patients following high-dose chemotherapy (HDC) +/- radiation, with or without peripheral blood stem cell support. Over a 28-month period, 126 patients were screened and included in the study. Using afebrile status following 3 days of therapy as a primary endpoint, both regimens produced comparable clinical response rates (C = 55% vs. T/A = 61%). Also, the use of vancomycin for resistant gram-positive infections and alteration of gram-negative infection coverage was similar in both groups (C = 40% vs. T/A = 47% and C = 29% vs. T/A = 24%). Both treatment groups had similar needs for empirical antifungal therapy (C = 25% vs. T/A = 22%). There was a postrandomization difference between the two groups in that the "C" group had a significantly higher number of allogeneic transplants and non-stem-cell-supported patients, whereas the "T/A" group had a significantly greater number of autologous peripheral blood stem cell patients (p < 0.0001). Despite this difference, the C group had a significantly lower cost ratio than the T/A group (p = 0.016). In conclusion, we have shown that C treatment of febrile neutropenic patients following HDC results in similar efficacy and lower cost when compared to T/A, despite the inclusion of higher risk patients in the C group.     

Novel phenotype of C3H 10T1/2 fibroblasts cotransfected with the c-Ha-ras and adenovirus 5 E1A oncogenes

C3H 10T1/2 fibroblasts are converted to fully transformed phenotype following coexpression of an activated c-Ha-ras gene and either a constitutively expressed viral or cellular myc gene. In this report, we examined whether the early region 1A (E1A) of adenovirus 5, which synergizes with ras to convert primary embryonic cells to a transformed phenotype, can synergize with ras to transform the established mouse embryonic cell line, C3H 10T1/2. We demonstrate that coexpression of ras and E1A generated a transformed phenotype that could be scored by colony assays and by soft agarose assays but not by standard focus assays. The ras-E1A-transformed phenotype relies on sequences present in conserved regions 1 and 2 of the E1A proteins and, in part, on information encoded by the extreme carboxy terminus of E1A. The contrast between the transformed phenotypes generated following the transfection of C3H 10T1/2 cells with either ras and myc or ras and E1A suggests that myc and E1A cooperate with ras to transform C3H 10T1/2 cells by mechanisms that can be distinguished using this established cell line as a model system.     

Impact of VEGF,VEGFR, PDGFR,HIF and ERCC1 gene polymorphisms on thymic malignancies outcome after thymectomy

We aimed to analyze genotypes of VEGF-A, VEGFR2, Flt4, PDGFRα, HIF-1α and ERCC1 and their correlation with thymic tumor risk and patient outcome.DNA of 57 consecutive patients (43 thymomas and 14 thymic carcinomas) who underwent total thymectomy at our Institution was extracted from paraffin-embedded tissue. We selected polymorphisms in the following genes:HIF1-α (rs2057482T > C, rs1951795A > C, rs2301113C > A, rs10873142C > T, rs11158358G > C, rs12434438G > A, rs11549465C > T, rs11549467G > A), VEGF-A (rs2010963G > C, rs699947A > C), VEGFR-2 (rs2305948C > T, rs1870377T > A), VEGFR-3 (rs307826T > C, rs307821C > A), PDGFR-α (rs35597368C > T) and ERCC1 (rs11615A > G). Gene polymorphisms were determined by Real-Time PCR using TaqMan assays.As compared to the general population, the allele frequency of PDGFR-α rs35597368T was significantly higher (95% vs. 87%, p = 0.036), while the frequency of alleles HIF1-α rs2057482C (78% vs. 90%), rs1951795C (69% vs. 87%), rs2301113A (70% vs. 83%), rs10873142T (70% vs. 87%), rs11158358C (75% vs. 88%), rs12434438A (67% vs. 84%) were significantly lower. VEGFR-3 rs307821C frequency was significantly higher in thymomas vs. thymic carcinomas (79% vs. 72%, p = 0.0371). The following factors were significantly correlated with a longer overall survival: VEGFR-3 rs307826C, VEGFR-2 rs1870377A, PDGFR-α rs35597368T/C, HIF1-α rs2301113C, rs2057482C/T, rs1951795C, rs11158358G/C and rs10873142T/C, ERCC1 rs11615A (p < 0.05).Our results suggest, for the first time, that PDGFR-α, HIF-1α and VEGFR-3 SNPs are associated with thymic cancer risk and survival.     

G:C > A:T mutations and potential epigenetic regulation of <Emphasis Type="Italic">p53</Emphasis> in breast cancer

Analysis of germline p53 mutations in breast cancer reveals that the Li-Fraumeni and Li-Fraumeni-like syndromes are mostly related to the loss of initiation codon 133 of regulatory TP53 isoforms (Delta133p53). In eight codons of exons 5-8 (including 133), mutations are frequent in Li-Fraumeni-related, but scarce in sporadic breast cancer, while in six more codons they are frequent both in familial and sporadic breast cancers. At the proximity of these codons, we observed in somatic mutation databases, 16 codons (minihotspots mostly in exons 7, 8) which undergo frequent G:C > A:T transitions (non-CpG) in all sporadic cancers. In addition, in sporadic breast cancer we observed 35 adjacent codons in which the following types of mutation are observed: frequent G:C > A:T transitions at CCs/GGs, frequent silent mutations in exons 5,6 and suppressed nonsense mutations (5 codons, few records). Non-CpG G:C > A:T transitions in the 35 codons are rare in familial cancers (p53, BRCA1, or BRCA2-related), but frequent in sporadic cancers in organs where Li-Fraumeni-related carcinogenesis is common e.g. adrenal cortex, soft tissues. These data are in support of the following tissue-specific processes: in sporadic breast cancer (sarcomas etc.), loss of methylation sites (in 35 codons mostly next to codon 133), might lead to loss of silencing of TP53 isoforms which are suppressed in these tissues. On the contrary, "spreading" of cytosine methylation (asymmetric) in a G:C-rich region next to common hotspots (codons 238-252 in minihotspots) and mutagenesis probably destabilizes all tissues. Frequent C > T activation at non-CpG is also observed in prostate sporadic cancer, which similarly to breast, undergoes age-related crisis. The above data reveal that tissue-specific epigenetic regulatory mechanisms might be involved in p53 instability.     

A Case of Central Pontine Myelinolysis Confirmed by Computed Tomography

The case we present is of a previously well deaf lady who, following the treatment of hyponatraemia due to gastro-enteritis developed quadriparesis, hyper-reflexia and bilateral extensor plantar responses. Although the patient is not known to be alcoholic, her clinical presentation and C.T. scan are characteristic of central pontine myelinolysis. The clinical diagnosis of central pontine myelinolysis is important because affected patients may make remarkable recovery if vigorously supported. Computed tomography has been shown to be an invaluable adjunct to the antemortem diagnosis of this condition. Repeated C.T. examination may demonstrate some resolution of the radiographic findings many months subsequent to clinical improvement (Gerber et al 1983).     

Carboplatin/paclitaxel or carboplatin/vinorelbine followed by accelerated hyperfractionated conformal radiation therapy: report of a prospective phase I dose escalation trial from the Carolina Conformal Therapy Consortium.

PURPOSE: To prospectively determine the maximum-tolerated dose of accelerated hyperfractionated conformal radiotherapy (RT; 1.6 Gy bid) for unresectable locally advanced lung cancer (IIB to IIIA/B) following induction carboplatin/paclitaxel (C/T) or carboplatin/vinorelbine (C/N). METHODS: Induction chemotherapy, C/T or C/N, was followed by escalating doses of conformally-planned RT (73.6 to 86.4 Gy in 6.4-Gy increments). Concurrent boost methods delivered 1.6 and 1.25 Gy bid to the gross and clinical target volumes, respectively. RESULTS: Between November 1997 and February 2002, 44 patients were enrolled (median age, 59 years; 59% male; stage III, 98%; median tumor size, 4 cm). Thirty-nine patients completed induction chemotherapy: 19 had a partial response, seven progressed, 15 had no response, and three were not assessable. Chemotherapy-associated toxicities were similar in the two chemotherapy groups. The incidence of grade > or = 3 RT-induced toxicity was 1/13, 2/14, and 4/12 at 73.6, 80, and 86.4 Gy, respectively, thus defining the maximum tolerated dose at approximately 80 Gy. Toxicities were in both lung and esophagus and were similar in the two chemotherapy arms. With a median followup of 34 months in the survivors, the actuarial 2-year survival was 47%, the median survival was 18 months. Fifteen patients had tumor relapse: 5 local failures in the high-dose volume, 2 regional failures outside of the high-dose volume, and 8 distant metastases. CONCLUSION: High-dose conformal twice-daily radiation therapy to approximately 80 Gy appears tolerable in well-selected patients with unresectable lung cancer following either C/T or C/N. Dose-limiting toxicities are mainly pulmonary and esophageal.     

A model of multiple myeloma: culture of 5T33 murine myeloma cells and evaluation of tumorigenicity in the C57BL/KaLwRij mouse.

The 5T33 multiple myeloma is one of a series of transplantable murine myelomas arising spontaneously in C57BL/KaLwRij mice. This study describes the establishment and characterisation of the 5T33 murine myeloma in vitro as a cultured cell line in terms of its morphology, growth rate, expression of paraprotein (IgG2b) and tumorigenicity in syngeneic animals. The 5T33 cell line has been in continuous culture for over 10 months and has achieved more than passage 34. In culture, 5T33 myeloma grows as single cells or in small clusters of loosely adherent cells on an adherent stromal cell layer. Maximum doubling time is approximately 25 h, and over 90% of the cells express cytoplasmic IgG2b paraprotein. The cultured 5T33 myeloma cells are highly tumorigenic in C57BL/KaLwRij mice with as few as 500 cells inducing paralysis and death as early as day 36 post-tumour inoculation. Kinetics of tumour development and detection of IgG2b paraprotein are dose dependent. Two weeks following intravenous inoculation of 5 x 10(5) cultured 5T33 myeloma cells, tumour cells were readily identified in the bone marrow. By 3 weeks post-tumour inoculation, 5T33 myeloma cells were found in various tissues throughout the animal. Studies are now underway to determine the sensitivity of this cell line to various therapeutic modalities.     

Glutathione depletion suppresses conjugation of benzo[a]pyrene metabolites and ({+/-})-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene metabolites with glutathione but does not affect their binding to DNA in C3H/10T1/2 mouse fibroblasts

The study was aimed at determining the role of glutathione (GSH)conjugation in the binding of reactive benzo[a]pyrene (BaP)species to DNA of C3H/10T1/2 cells. In order to suppress GSHconjugation cells were depleted of GSH by treatment with buthioninesulfoximine for 18 h and 1-chloro-2,4-dinitrobenzene for 1 hprior to incubation with radiolabelled substrates. Under theseconditions GSH levels decreased to <1% of the control value.C3H/10T1/2 cells produced GSH conjugates with 7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydro-benzo[a]pyrene(BaPDE) comprising 6% of the total metabolites formed from BaPor (±)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene(BaP-7,8-diol). In GSH-depteted cells formation of GSH conjugateswith metabolic products of BaP or BaP-7,8-diol was suppressedto 1% of total metabolites during an 8-h incubation period.Metabolic activation of BaP and BaP-7,8-diol by C3H/10T1/2 cellsresulted in the formation of DNA adducts which largely consistedof BaPDE:deoxyguanosine. Depletion of GSH altered neither thedegree of DNA binding nor the pattern of DNA adducts to anysignificant extent. When C3H/10T1/2 cells were co-incubatedwith microsomes from liver of 3-methylcholanthrene-treated ratsfor 1 h in order to activate BaP or BaP-7,8-diol extracellularly,the same pattern of GSH conjugates and DNA adducts was generatedas by intracellular metabolism of the polycyclic hydrocarbons.No GSH conjugates were detected following co-incubation of microsomeswith GSH-depleted C3H/10T1/2 cells. The formation of DNA adductsagain remained unaffected by the suppression of conjugation.C3H/10T1/2 cells are apparently capable of conjugating BaPDEwith GSH but are not capable of trapping by GSH conjugationthose BaPDE moieties which bind to DNA. The results are compatiblewith the notion that BaPDE is partially contained in a cellularcompartment—presumably the lipid environment of membranes—whereit is inaccessible to GSH transferases of C3H/10T1/2 cells.     

不同配比HES 130/0.4电解质注射液在老年肝癌患者肝部分切除术前 急性高容量血液稀释中的应用

目的:评估不同配比HES 130/0.4电解质注射液在老年肝癌患者肝部分切除术前行急性高容量血液稀释（acute hypervolemic hemodilution,AHH）的效果。方法:选取2016年1月至2016年12月就诊于西安交通大学第一附属医院拟行肝部分切除术的老年男性患者45例,将其随机分为A组、B组和C组,每组15例。术前30 min 三组患者分别以HES 130/0.4电解质注射液10 mL/kg、乳酸钠林格注射液5 mL/kg+HES 130/0.4电解质注射液5 mL/kg、乳酸钠林格注射液10 mL/kg行AHH。术中监测患者心率（heart rate,HR）、平均动脉压（mean arterial pressure,MAP）、中心静脉压（central venous pressure,CVP）。于AHH前（T0）、AHH开始后10 min（T1）、AHH开始后20 min（T2）、AHH结束即刻（T3）、AHH后1 h（T4）、AHH后2 h（T5）以及手术结束即刻（T6）采血样监测凝血功能;在T0、T3及T6采血样监测血栓弹力图（thromboela-stogram,TEG）参数及Na+、K+、Ca2+、Cl－水平。同时记录术中出血量、尿量、输血量及输液量,随访记录术后24 h腹腔引流量。结果:AHH后,与T0时比较,A、B两组MAP在T3之后显著升高,三组CVP在T4之后显著升高（P<0.05）。A组术中输血量及输液量显著少于B、C组（P<0.05）。与T0比较,A、B两组PT、APTT在T3后均明显延长,大于同时间点C组;FIB水平在T4后显著降低,低于同时间点C组;血栓弹力图R值在T6时明显升高,高于同时点C组（P<0.05）。与T0时比较,B、C两组K+浓度在T6时显著减低,且明显低于同时间点A组（P<0.05）。结论:术前应用HES 130/0.4电解质注射液行AHH对机体血流动力学、凝血功能、电解质水平等无明显不良影响,可安全应用于老年患者肝切除术中,有效减少异体血输入量。     

Interleukin-1B (IL1B) and interleukin-6 (IL6) gene polymorphisms are associated with risk of chronic lymphocytic leukaemia

Common polymorphisms in genes encoding for cytokines implicated in the inflammatory response and Th1/Th2 balance might play a role in the development and prognosis of chronic lymphocytic leukaemia (CLL). To test the hypothesis, we investigated 13 single nucleotide polymorphisms (SNPs) in nine of such genes in a population-based case-control study, conducted in the Italian region of Sardinia in 1999-2003. Forty incident CLL cases and 113 population controls were available for study. The following SNPs were selected: IL1A-889C > T, IL1RN 9589A > T, IL1B-31C > T, IL1B-511C > T, IL2-384T > G, IL6-174G > C, IL6-597G > A, IL10-1082A > G, IL10-3575T > A, TNF-308G > A, LTA- 91A > C, LTA 252A > G and CARD15 nt1007. After adjusting by age and gender, individuals homozygous for the IL1B-511T allele run a lower risk of CLL (OR = 0.1, 95% CI 0.0, 0.8, p = 0.032), while risk showed a 4.5-fold increase associated with the genotype homozygous for the IL6-174C allele (OR = 4.5; 95% CI 1.1, 19.3, p = 0.041). Individuals homozygous for the IL6-174C allele and carrying the homozygous IL1B-511C allele showed an 11-fold increase in CLL risk (OR = 11.4, 95% CI 1.9, 69.4, p = 0.008). None of the other interleukin SNPs evaluated showed any association with CLL risk. Large multicentre pooled studies are warranted, achieving the statistical power required to confirm whether IL6 and IL1B gene polymorphisms might play a role in CLL development and prognosis, as well as the null associations herein reported.     

Narcotrend监测在腹腔镜下胃肠道恶性肿瘤切除术麻醉中的应用

目的:探讨Narcotrend监测在腹腔镜下胃肠道恶性肿瘤切除手术中的应用价值。方法:选择择期行胃肠道恶性肿瘤切除患者60名,随机分入N组（Narcotrend监测组）和C组（常规组）,每组30例。术中根据NI值及临床体征和临床经验调整丙泊酚和瑞芬太尼用量。分别记录两组诱导前（T0）、诱导后（T1）、气腹后5min（T2）、气腹后30min（T3）、肿瘤切完时（T4）、停止输注丙泊酚时（T5）、清醒拔管后（T6）、听从指令（T7）不同时间点的SBP、DBP、HR、RPP与丙泊酚效应室浓度（Ceo Prop）,记录N组相应时间点的Narcotrend指数（NI）;记录两组患者术毕后苏醒时间、定向力恢复时间、自主呼吸恢复时间和清醒拔管时间,不良反应、随访及术后术中知晓情况并进行视觉模拟评分（VAS评分）。结果:与T0时比较,T2、T3时N组与C组SBP、DBP、HR、RPP均显著增高（P＜0.05）;N组NI值随着丙泊酚效应室浓度的增加而降低,呈负相关（r=-0.784,P＜0.05）。N组患者丙泊酚及瑞芬太尼使用量均少于C组患者（P＜0.05）,术后N组患者苏醒时间、自主呼吸恢复时间、定向力恢复时间及清醒拔管时间较C组均明显缩短,差别具有显著性（P＜0.05）。N组术中发生不良反应的比例远低于C组,差别具有显著性（P＜0.05）。两组患者术后一天VAS评分比较差别无显著性（P＞0.05）,均未出现术中知晓。结论:Narcotrend监测用于胃肠道恶性肿瘤切除术能精确调节手术麻醉深度,有效监测患者的意识状态和麻醉深度,减少麻醉用药,缩短苏醒时间,有利于提高麻醉质量和安全系数,值得临床推广使用。     

The usefulness of the level of the muscularis mucosae in the staging of invasive transitional cell carcinoma of the urinary bladder

The initial biopsy specimens from 50 patients with high-grade invasive transitional cell carcinoma of the urinary bladder were evaluated for depth of invasion. Stages were assigned according to the following system: T1A, invasion of connective tissue superficial to the level of the muscularis mucosae; T1B, invasion to the level of the muscularis mucosae; T1C, invasion through the level of the muscularis mucosae but superficial to the muscularis propria; and B, invasion into the muscularis propria. Follow-up from the Yale Tumor Registry at a median time of 4.6 years showed that tumors invasive to levels T1A and T1B had a 75% 5-year survival, but tumors invasive through the level of the muscularis mucosae but apparently superficial to the muscularis propria (level T1C) had an 11% 5-year survival, which was comparable with the survival of patients with tumors invasive of the muscularis propria. This study suggests the prognostic importance of assessing the depth of invasion in initial biopsy specimens, even when the specimens lack a muscularis propria.     

The oncostatic effect of methyl-CCNU on various experimental lymphoreticular neoplasms

Studies on the chemotherapeutic potential of methyl-CCNU on experimental leukemias were undertaken. A number of murine transplantable in vivo lines (chemical carcinogen-induced T and B leukemias; radiation- and viral-induced T leukemias of C57BL/6, C3H/eb and SJL/J origin; radiation-induced myeloid leukemias and spontaneous reticulum cell neoplasms of SJL/J mine) were used in these studies. The optimal dose of methyl-CCNU and optimal timing of administration were extensively investigated on two sample lines of T cell leukemias of C57BL/6 mice. Leukemic cell eradication could be achieved in almost all of the different leukemias treated, irrespective of whether induction was brought about by chemical or physical means or due to a viral leukemogenic agent. Studies undertaken to elucidate the effect of methyl-CCNU on the establishment of preleukemic cells following induction of leukemia by the radiation leukemia virus (RadLV) or by total body irradiation, indicated the oncostatic effect of methyl-CCNU on early preleukemic cells.     

Thermal radiosensitization in Chinese hamster (V79) and mouse C3H 10T 1/2 cells. The thermotolerance effect.

The sensitivity of V79 cells and normal or morphologically transformed C3H-10T 1/2 cells to X-rays, heat or heat plus X-rays was examined. The normal and transformed C3H-10T 1/2 cell lines were equally sensitive to heat at 42.0 degrees C and radiation. The V79 cells were more heat sensitive. Thermal radiosensitization occurred for all 3 cell lines for the combined heat and radiation treatments and was greatest for simultaneous treatment. Recovery occurred when the treatments were separated by an incubation interval at 37 degrees C. For the V79 cells, recovery was much greater for X-rays preceding heat compared to X-rays following heat. This difference was not as great in the C3H-10T 1/2 cell lines. The transformed C3H-10T 1/2 cells were more sensitive compared to the normal for the simultaneous treatment or for heating followed by irradiation. For prolonged heating at 42.0 degrees C, after which thermotolerance occurred in all 3 cell lines, the radiosensitivity still increased as a function of heating time even though no additional cell killing occurred from the heat treatment alone. For heating V79 cells at 41.0 degrees C no further increase in radiosensitivity occurred, as cells became thermotolerant during prolonged heating. Also for the development of thermotolerance during incubation at 37 degrees C between two heat treatments, thermal radiosensitization decreased demonstrating that thermotolerance can affect radiosensitization by hyperthermia.     

Interleukin-2 and antibody to the T cell receptor regulate proliferation of a radiation leukemia virus-transformed T cell lymphoma

In this report, a Radiation leukemia virus-transformed murine T cell lymphoma is described which is dependent on the interleukin-2 (IL-2) growth factor for proliferation under single cell conditions of growth. It was isolated from a C57BL mouse which had been primed with the Radiation leukemia virus-induced thymoma, C6VL/1, and has been shown to be phenotypically and karyotypically distinct from C6VL/1. IL-2 dependency has been stable over many in vitro passages, and this property also serves to distinguish this cell line from C6VL/1. 5C2 constitutively expresses a T cell receptor (TCR) and can respond by increased proliferation to external stimulation with anti-TCR antibody. This antibody acts to stimulate 5C2 growth in the absence of added IL-2. Maximum stimulation was achieved in the presence of a 50-ng/ml concentration of purified antibody. 5C2 has also been shown to produce detectable levels of IL-2 which can be increased by 8- to 16-fold after exposure of cells to anti-TCR antibody. The C6VL/1 T cell lymphoma has served as a control cell line in three experiments since it cannot be stimulated either to increased proliferation or to lymphokine release by this same antibody. However, a 10-ng/ml concentration of anti-TCR antibody was found to inhibit proliferation of both T cell lymphomas when they were cultured under optimal conditions, i.e., in the presence of an IL-2 source for 5C2. The proliferation of both T cell lymphomas appears to be regulated, although in different ways, by the binding of antibody in the vicinity of the TCR complex. While 5C2 is dependent on IL-2 production (and TCR triggering) to proliferate, C6VL/1 replicates independently of any growth factors. Signal transduction through the TCR/T3 complex, together with the subsequent production of growth factors, may be important for driving the proliferation of T cells such as 5C2 at an early stage in oncogenic progression following infection with an RNA tumor virus.     

Catheter Embolic Therapy in Vascular Tumours

Selective use of catheter embolic therapy both prior to tumour resection and in control of bleeding from recurrent and irresectable tumour is discussed. Experience with pre-operative infarction of renal carcinomas and selective occlusion of the internal maxillary artery in troublesome epistaxis following radiotherapy and excision of an angiofibroma of the nasopharynx is presented. Excision of bulky vascular renal tumours was achieved with minimal blood loss and with shortening of operating time. Catheter occlusion of the internal maxillary artery obviated a further attempt at operative ligation of this vessel. Two cases (multifocal hepatoma and carcinoma in a solitary kidney) were considered for C.E.T. but in each case relative benefits appeared to be outweighed by potential risks. Further clinical experience with C.E.T. for inoperable hepatoma and multiple hypervas-cular liver metastases is required. These results, together with other reports, suggest a useful role for C.E.T. in selected cases.     

Comparison of noninvasive MRT procedures for temperature measuremnt for the application of medical heat therapies

Novel methods for hyperthermia tumor therapy, such as high-intensity focused ultrasound (HIFU) or laser-induced thermotherapy (LITT), require accurate non-invasive temperature monitoring. Non-invasive temperature measurement using magnetic resonance imaging (MRI) is based on the analysis of changes in longitudinal relaxation time (T1), diffusion coefficient (D), or water proton resonance frequency (PRF). The purpose of this study was the development and comparative analysis of the three different approaches of MRI temperature monitoring (T1, D, and PRF). Measurements in phantoms (e.g., ultrasound gel) resulted in the following percent changes: T1-relaxation time: 1.98%/degree C; diffusion coefficient: 2.22%/degree C; and PRF: -0.0101 ppm/degree C. All measurements were in good agreement with the literature. Temperature resolutions could also be measured from the inverse correlation of the data over the whole calibration range: T1: 2.1 +/- 0.6 degrees C; D: 0.93 +/- 0.2 degree C; and PRF: 1.4 +/- 0.3 degrees C. The diffusion and PRF methods were not applicable in fatty tissue. The use of the diffusion method was restricted due to prolonged echo time and anisotropic diffusion in tissue. Initial tests with rabbit muscle tissue in vivo indicated that MR thermometry via T1 and PRF procedures is feasible to monitor the local heating process induced by HIFU. The ultrasound applicators in the MR scanner did not substantially interfere with image quality.     

Assesssment of the effect of pretreatment with neoadjuvant therapy on primary breast cancer.

Patients with invasive cancer of the breast (T1-4, N0-2, M0) were assigned to pretreatment based on oestrogen receptor (ER) status; patients with ER-negative tumours received chemotherapy [mitozantrone, methotrexate and mitomycin C (MMM)] for 3 months, patients with ER-positive tumours underwent endocrine therapy [luteinising hormone releasing hormone (LHRH) agonist goserelin (leuprolide-premenopausal) or 4-hydroxyandrostenedione (formestane-post-menopausal)] for 3 months. Of the first 100 patients assessed at 3 months, 47 with ER-positive tumours had a 40.4% response (premenopausal 53.8%; post-menopausal 35%) and 53 with ER-negative tumours had a 60% response (premenopausal 57%; post-menopausal 63%). Patients with early breast cancer (T1/T2) had a complete clinical resolution in 41% (16/39) of cases after MMM and in 20% (7/35) of cases following endocrine therapy compared with 14% (2/14) advanced tumours (T3/T4) following MMM and (0/12) following endocrine therapy. However, in those patients achieving a complete clinical response, subsequent appropriate surgery showed that 16 of 19 patients (84%) had evidence of residual viable tumour on histological examination.