Mathematical modelling of the spatio-temporal response of cytotoxic T-lymphocytes to a solid tumour.

In this paper a mathematical model describing the growth of a solid tumour in the presence of an immune system response is presented. In particular, attention is focused upon the attack of tumour cells by so-called tumour-infiltrating cytotoxic lymphocytes (TICLs), in a small, multicellular tumour, without necrosis and at some stage prior to (tumour-induced) angiogenesis. At this stage the immune cells and the tumour cells are considered to be in a state of dynamic equilibrium--cancer dormancy--a phenomenon which has been observed in primary tumours, micrometastases and residual disease after ablation of the primary tumour. Nonetheless, the precise biochemical and cellular mechanisms by which TICLs control cancer dormancy are still poorly understood from a biological and immunological point of view. Therefore we focus on the analysis of the spatio-temporal dynamics of tumour cells, immune cells and chemokines in an immunogenic tumour. The lymphocytes are assumed to migrate into the growing solid tumour and interact with the tumour cells in such a way that lymphocyte-tumour cell complexes are formed. These complexes result in either the death of the tumour cells (the normal situation) or the inactivation (sometimes even the death) of the lymphocytes. The migration of the TICLs is determined by a combination of random motility and chemotaxis in response to the presence of chemokines. The resulting system of four nonlinear partial differential equations (TICLs, tumour cells, complexes and chemokines) is analysed and numerical simulations are presented. We consider two different tumour geometries--multi-layered cell growth and multi-cellular spheroid growth. The numerical simulations demonstrate the existence of cell distributions that are quasi-stationary in time and heterogeneous in space. A linear stability analysis of the underlying (spatially homogeneous) ordinary differential equation (ODE) kinetics coupled with a numerical investigation of the ODE system reveals the existence of a stable limit cycle. This is verified further when a subsequent bifurcation analysis is undertaken using a numerical continuation package. These results then explain the complex heterogeneous spatio-temporal dynamics observed in the partial differential equation (PDE) system. Our approach may lead to a deeper understanding of the phenomenon of cancer dormancy and may be helpful in the future development of more effective anti-cancer vaccines.     

The value of MCA, CA 15-3, CEA and CA-125 for discrimination between metastatic breast cancer and adenocarcinoma of other primary sites

MCA, CA 15-3, CEA and CA 125 were determined in the serum of 49 patients with metastatic breast cancer and 38 patients with metastatic adenocarcinoma of other primary sites. By using the 99th percentile of the normal value distribution as the cut-off point, the positive predictive value (PV+) was found to be 85% (95% CI 76-94) for MCA, and 71% (95% CI 61-81) for CA 15-3. When receiver-operating-characteristic (ROC) curves were constructed, the PV+ for CA 15-3 was increased to 82% (95% CI 72-92), using 60 U ml-1 as the cut-off point. With the exception of two patients who had a slightly elevated MCA, MCA and CA 15-3 identified the same patients with breast cancer. By combining a positive MCA or CA 15-3 with a negative CEA and CA 125, further improvement of the PV+ could be achieved; 100% (95% CI 91-100). We conclude that MCA and CA 15-3 may play a useful role in discrimination between patients with metastatic breast cancer and those with adenocarcinoma of other primary sites.     

Characteristics of rhabdomyosarcoma cell lines derived from uterine carcinosarcomas

 Rhabdomyosarcoma (RMS) is occasionally found in the female genital tract, and mostly appears as one of the heterologous mesenchymal components in uterine carcinosarcoma designated as malignant mixed müllerian tumour (MMMT). We examined the biological properties of a pure rhabdomyosarcoma (RMS) cell line designated FU-MMT-3, which was newly established from a surgical specimen taken from a patient with uterine MMMT. We also evaluated c-myc and MYCN gene amplification in three RMS cell lines (including FU-MMT-3) derived from three MMMTs by Southern blot analysis. FU-MMT-3 cells were propagated continuously for 57 serial passages over a 2-year period in vitro. FU-MMT-3 was able to produce tumours demonstrating pure RMS in athymic nude mice. Cytogenetically, FU-MMT-3 showed a triploidy pattern, with complex karyotypic abnormalities including trisomy of chromosome 8. All three RMS cell lines, including FU-MMT-3, showed amplification of the c-myc gene (approximately fourfold to eightfold), while no cell lines demonstrated MYCN gene amplification. FU-MMT-3 is considered to provide a useful system for the study of the biological behaviour of RMS in MMMTs. Extra copies of chromosome 8 and c-myc gene amplification may be associated with the rhabdomyoblastic differentiation in MMMT. Received: 7 January 1997 / Accepted: 2 May 1997     

原发性胸腰椎管内肿瘤延误诊治原因探讨（附44例报告）

本文报告一组44例原发性椎管内肿瘤初期延误诊治,其中10例为腰椎间盘突出而手术,2例为腰椎管狭窄症手术治疗。原发性椎管内肿瘤与脊柱退变性疾病分属两种不同的疾病范畴。为提高诊断和治疗效果,本文就误诊原因作以下讨论。     

Benign osteoblastoma of the parietal bone

A 5-year-old girl presented with a 1-year history of a subcutaneous swelling in the right parietal region. There were no cerebral symptoms or signs. Plain X-ray of the skull showed a lytic bony lesion with sclerotic margin. Computed tomography showed a hypodense, osteolytic lesion with thinned and bulged inner and outer skull tables with intact continuity. There was no intracranial lesion. At operation, the mass was found to be pink and granular, and was totally enucleated. Histology revealed it to be a benign osteoblastoma.     

Stereotactic craniotomy and intraoperative lesion localisation using the Brown-Robert-Wells frame

Summary A simple technique of stereotactic craniotomy and intraoperative lesion localisation that uses the Brown-Robert-Wells (BRW) stereotactic frame is presented. The method optimises craniotomy placement and facilitates localisation of small intracerebral lesions. Using the system, 16 patients have had resection of intracranial neoplasms from deep and/or eloquent areas of the brain with no neurological morbidity.     

Granular cell tumours of the lower respiratory tract

Granular cell tumours rarely involve the lower respiratory tract. We report eight cases surgically resected at our institution. There were four females and four males, aged between 18 to 56 years (mean 40). One tumour associated with a peripheral lung adenocarcinoma was asymptomatic. The other lesions presented with obstructive pneumonitis (3 cases), haemoptysis (2), dyspnea (1) or cough (1). These tumours were tracheal (1) or bronchial (6) and one case was located in the lung parenchyma. Four cases were multicentric with associated lesions located in a bronchus (2), the oesophagus (1) or a mediastinal lymph node (1). All tumours, with the largest diameter ranging from 0.5–4.5 cm, were histologically invasive. The tumours were positive for S-100 protein, neuron specific enolase, KP1 (CD68) and vimentin. No tumour expressed desmin, keratin or p53 oncoprotein. Our study demonstrates that, in spite of marked anatomical and clinical polymorphism, the rare granular cell tumours of the lower respiratory tract have a constant histological appearance. Our observations confirm that large tumours (> 8–10 mm) usually extend beyond the tracheo-bronchial cartilages and, therefore, only surgical treatment may avoid recurrence.     

Imaging of thoracic and lumbar spinal extradural arachnoid cysts: report of two cases

Extradural arachnoid cysts are uncommon expanding lesions in the spinal canal which may communicate with the subarachnoid space. Usually in the lower thoracic spine, they may cause symptoms by compressing the spinal cord or nerve roots. We report cases of thoracic and lumbar arachnoid cysts studied by cystography, myelography, CT and MRI. These techniques showed extradural cystic lesions containing cerebrospinal fluid, with variable communication with the subarachnoid space, causing anterior displacement and flattening of the spinal cord. Received: 3 November 1995 Accepted: 16 April 1996     

Desmoplastic malignant melanoma presenting with orbital involvement

Desmoplastic malignant melanoma (DMM) is a rare variant of spindle cell melanoma. We report a case of DMM of the forehead secondarily involving the orbit. The diagnosis was based on light microscopic features, including prominent peripheral cell nest formation and spindle cell fascicles in densely collagenous stroma. Immunohistochemical studies showed strong uniform staining for S100 antigen throughout the tumour. It was negative for HMB 45, smooth muscle actin, desmin, cytokeratins and Type IV collagen. Electron microscopy showed neither melanosomes nor myelin figures. The clinical and histological characteristics of desmoplastic malignant melanoma, and its differential diagnosis of malignant schwannoma, are discussed. DMM has a poor prognosis, since it tends to invade deeply, recur locally and metastasise readily.