Dose-incidence curves for tumour control and normal tissue injury, in relation to the response of clonogenic cells

A probit analysis has been made of data from the literature on local control of tumours and injury to normal tissue as a function of dose of radiation. Fifteen series were analysed for local tumour control in man and ten series for complications. The analysis yielded values for the D50 dose (50% incidence of effect) and the probit width (K), a measure of the steepness of the dose-incidence curve. The same analyses were made of data for rodents. Broadly, K was proportional to D50 in the ratio 1:7, with no major differences between tumours and reported complications. D50 was plotted as a function of dose per fraction for four normal tissues and two tumours in rodents. D50 decreased more rapidly with increasing dose per fraction for the normal tissues than for tumours. The probit width, K, varied inversely with increasing dose per fraction for normal tissues and this contrasted with the tumour response. Thus with increasing dose per fraction, the threshold for effect decreased and the steepness of the ensuing dose-incidence curve increased, relatively more rapidly for normal tissue than for tumour. These curves of gross response have been analysed also by the double negative log method of Gilbert [23], in an attempt to estimate the number and survival characteristics of "tissue-rescuing cells". These were calculated to be less than 1 in 10(4) of the numbers of clonogenic cells measured by excision assays. The D0 values of the derived survival curves for these tissue-rescuing cells were higher than those measured by excision assays.     

Two-step tumour targetting in ovarian cancer patients using biotinylated monoclonal antibodies and radioactive streptavidin

A new method for intraperitoneal tumour targetting in ovarian cancer using biotinylated monoclonal antibodies (MoAb) and radioactive streptavidin is described. Fifteen patients with histologically documented ovarian carcinoma were injected intraperitoneally with 2 mg of biotinylated MoAb MOv18, followed 3–5 days later by 100–150 g of indium-111 streptavidin, at the specific activity of 280–370 MBq/mg in 500 ml of normal saline. No toxicity was observed. Tumours were imaged from 2 to 48 h after radioactivity injection by recording both planar and single photon emission tomography (SPET) data. All patients underwent surgery 1–8 days later (mean 3 days) after scanning. The resected tumour and normal tissue radioactivity were measured. On the day of surgery, the tumour to normal tissue ratio was 9:1 (range 3:1–30:1) and 45:1 (range 12:1–120:1) for intra- and extraperitoneal samples, respectively. The mean tumor to blood ratio was 14:1 (range 4:1–30:1). The injected dose (i.d.) per gram of tumour was 0.112 (range 0.01–0.3) for recurrences and 0.05 for primary tumour (range 0.005–0.2). Over 24–48 h 14% i.d. (range 8–18% i.d.) was found in the urine, 14% i.d. (range 629% i.d.) in the blood and 63% i.d. (range 56–70% i.d.) was still in the peritoneal cavity. These preliminary clinical data suggest that this two-step strategy may be superior to the conventional approach (radiolabelled antibodies) for intraperitoneal radioimmunolocalization and radioimmunotherapy of ovarian cancer. Offprint requests to: G. Paganelli     

Toxicodynamics of tumour promoters of mouse skin

Summary In binding competition assays using a protein kinase C preparation from mouse brain (particulate fraction)³H-labelled 12-O-tetradecanoylphorbol-13-acetate (TPA), for a series of new diterpene esters (DTE) the relative binding affinity [rba=K _i ^a (TPA)/K _i ^a (DTE)] in relation to TPA was determined. A wide range of values was noticed, some of the DTE binding more strongly than TPA (rba >1), others binding less strongly than TPA (rba <1) In comparative terms, competition for specific binding sites appears to correlate better with irritant than with promoting acitvity of the DTE. Using mouse peritoneal neutrophils, binding of [³H]-TPA was determined by a modification of the cold-acetone filter assay; saturation of high-affinity sites (K _d ^a =0.2 nM) was obtained at concentrations 1 nM, but there was also evidence for specific binding at low-affinity sites (K _d ^a =26 nM). Induction of chemoluminescence in the presence of luminol in mouse peritoneal neutrophils with a set of DTE usually elecited two peaks; at concentrations 10 nM DTE a short-lived, spike-like response lasting only from 0 to about 5 min (phase A) ist followed by a plateau response from about 5–120 min (phase B). This latter phase of chemoluminescence stimulation with luminol correlated well with theirritant potential of the DTE used. The sequence of the two phases can be inverted partially by using first TPA at 2,5 nM followed by a quick concentration increase to 100 nM; this indicates two different concentration-dependent events. As regards the intensity of the chemoluminescent response, quantitative but not qualitative differences between DTE were observed, which show some correlation with strong and weak tumour-promoting activity. Inhibition studies suggest the involvement of the myeloperoxidase/H₂O₂/Cl^– system in the luminogenic response; it is suggested that the release of hypochlorite or a closely related oxidant may be instrumental in tumour promotion.Abbreviations DMSO dimethylsulphoxide - DTE diterpene ester - K10 Gnidia factor K10 (Kraussianin) - K _i ^a ,K _d ^a apparent inhibition and dissociation constants - muPMN mouse peritoneal neutrophils - P2 Pimelea factor P2 - PDD phorbol-12,13-didecanoate - RPA 12-O-retinoylphorbol-13-acetate - rba relative binding affinity - TPA 12-O-tetradecanoylphorbol-13-acetate - 3-TI 3-O-tetradecanoylingenol See loc. cit. Kloz et al. 1989 for I. Comm. of this series     

Prediction of survival and recurrence in bladder carcinoma

Summary We have followed a large population of patients receiving radiation treatment for bladder carcinoma with respect to survival and recurrence-free survival. Bivariate and multivariate life table analyses have been performed using a set of independent variables. The most important were T class, grade (G), urinary carcinoembryonic antigen (U-CEA) taken before treatment and cytological analysis 4 months after treatment. We compared the usual way of classifying a patient (T+G) with the combination of U-CEA and cytology since the latter two variables seemed to have great prognostic importance. The analyses show that T+G gives the best significance for survival (P=0.0003) while U-CEA and cytology is better for recurrence-free survival (=0.0002). 0.0002).     

192例恶性肿瘤患者应用重组人肿瘤坏死因子-α免疫功能与疗效的相关性分析

目的：观察重组人肿瘤坏死因子—α(rh—TNFα)静脉输注对恶性肿瘤患者细胞免疫功能的增强作用及影响因素，并分析其与rh—TNFα抗肿瘤作用的相关性。方法：选择具有明确病理诊断的复治或拒绝放、化疗的乳腺癌、恶性淋巴瘤、肾癌和恶性黑色素瘤患者，静脉输注rh—TNFα，100万U／m^2，每日1次，每周连续5日，连用4周为1个疗程。采用免疫荧光直标染色法染色，以流式细胞仪检测治疗前后患者外周血T细胞亚群、NK细胞变化，同时评价抗肿瘤治疗的疗效。治疗前后细胞免疫功能比较采用配对t检验，免疫功能变化与抗肿瘤客观疗效的相关性采用多因素Logistic回归分析。结果：rh—TNFα给药后可提高患者外周血NK细胞和T细胞亚群数量，但CD4／CD8比值变化不明显，NK细胞和T细胞亚群的变化与rh—TNFα的抗肿瘤客观疗效的相关性不显著。结论：rh—TNFα具有一定的改善肿瘤患者细胞免疫功能的作用，但这种免疫增强作用可能不是其抗肿瘤疗效的最主要机制。     

Radioenhancement by cisplatin with accelerated fractionated radiotherapy in a human tumour xenograft

The aim of the present study was to investigate whether cisplatin would enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation therapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tumours were exposed to twice-daily 2-Gy fractions, applied 6 h apart over 2 weeks, 5 days a week, alone or combined with cisplatin given at maximally tolerated doses in three different schedules: (1) i.p. as a single bolus (SB) or (2) i.p. as a daily bolus at 30 min before the first daily radiation fraction or (3) s.c. as a continuous infusion through a mini-osmotic pump over 13 days, commencing 24 h prior to the first daily radiation fraction. The end point for the study was tumour growth delay (TGD), calculated as the difference between the delay in regrowth to 200% of the initial tumour size in treated versus control mice. SB cisplatin plus radiation showed only an additive effect on TGD, whereas daily-bolus and continuous-infusion cisplatin demonstrated a greater than additive effect when combined with accelerated fractionated radiation in this human tumour model. Cisplatin appears to be especially beneficial as a radiation enhancer when given throughout the course of radiation. Received: 15 December 1996 / Accepted: 25 March 1997     

小儿咽侧间隙肿瘤4例报告

为探讨小儿咽侧间隙肿瘤的临床特征，报告４例小儿咽侧间隙肿瘤患者儿的诊治体会。结合临床提出诊断本病宜通过ＣＴ扫描，先确定肿瘤的大小和范围，再选择颈侧径路摘除肿瘤．结果治疗的４例患儿均获得了肯定的结果。并且提示手术中应保护重要的血管和神经。     

脾脏原发性恶性肿瘤

报告原发性脾脏恶性肿瘤7例。临床以左上腹不适，左上腹肿块及体重下降、发热、贫血、白细胞减少及血小板减少为主要特点。病理以淋巴系统及血管源性恶性肿瘤多见。治疗以手术和化疗等手段为主。早期发现、早期手术对提高疗效是非常重要的。     

血清CA125、CA153、CA242三种肿瘤标志物联合检测对肺癌诊断的价值

目的探讨CA125、CA153、CA242联合检测在肺癌筛查与临床诊断中的应用价值.方法采用CanAg诊断试剂盒,对56例肺癌患者及108例健康人血清进行CA125、CA153、CA242测定.结果肺癌患者组CA125、CA153、CA242值分别为54.97±95.70,36.02±40.38,14.38±21.99;阳性率分别为41.07%、44.64%、23.21%.健康人组CA125、CA153、CA242值分别为11.23±1.58,12.73±11.92,15.11±13.60,阳性率均为0%,肺癌患者组CA125、CA153值明显高于健康人组(P＜0.01),肺癌患者组中CA125、CA153阳性率明显高于CA242(P＜0.05),CA125、CA153联合检测阳性率明显大于单独检测(P＜0.05)、Ⅰ-Ⅱ期肺癌患者与Ⅲ、Ⅳ期肺癌患者CA125、CA153值相比有显著性差异(P＜0.05).结论 CA125、CA153联合检测对肺癌筛查与临床诊断有良好辅助价值,CA242测定对肺癌筛查与临床诊断价值不大.     

Targeting the tumour microenvironment in ovarian cancer

The study of cancer initiation, growth, and metastasis has traditionally been focused on cancer cells, and the view that they proliferate due to uncontrolled growth signalling owing to genetic derangements. However, uncontrolled growth in tumours cannot be explained solely by aberrations in cancer cells themselves. To fully understand the biological behaviour of tumours, it is essential to understand the microenvironment in which cancer cells exist, and how they manipulate the surrounding stroma to promote the malignant phenotype.Ovarian cancer is the leading cause of death from gynaecologic cancer worldwide. The majority of patients will have objective responses to standard tumour debulking surgery and platinum-taxane doublet chemotherapy, but most will experience disease recurrence and chemotherapy resistance. As such, a great deal of effort has been put forth to develop therapies that target the tumour microenvironment in ovarian cancer. Herein, we review the key components of the tumour microenvironment as they pertain to this disease, outline targeting opportunities and supporting evidence thus far, and discuss resistance to therapy.