An electro-osmotic microfluidic system to characterize cancer cell migration under confinement.

We have developed a novel electro-osmotic microfluidic system to apply precisely controlled osmolarity gradients to cancer cells in micro-channels. We observed that albeit adhesion is not required for cells to migrate in such a confined microenvironment, the migrating velocity of cells is strongly influenced by the interactions between the cells and the channel wall, with a stronger adhesion leading to diminished cell motility. Furthermore, through examining more than 20 different types of cancer cells, we found a linear positive correlation between the protein concentration of the aquaporin-4 (AQP4) and the cell migrating speed. Knockdown of AQP4 in invasive re-populated cancer stem cells reduced their migration capability down to the level that is comparable to their parental cancer cells. Interestingly, these observations can all be quantitatively explained by the osmotic engine model where the cell movement is assumed to be driven by cross-membrane ion/water transport, while adhesion acts as a frictional resistance against the cell motility. By providing versatile and controllable features in regulating and characterizing the migration capability of cells, our system may serve as a useful tool in quantifying how cell motility is influenced by different physical and biochemical factors, as well as elucidating the mechanisms behind, in the future.

Cadherin- and Rigidity-Dependent Growth of Lung Cancer Cells in a Partially Confined Microenvironment.

During tumor development, cancer cells constantly confront different types of extracellular barriers. However, fundamental questions like whether tumor cells will continue to grow against confinement or away from it and what key factors govern this process remain poorly understood. To address these issues, here we examined the growth dynamics of human lung epithelial carcinoma A549 cells partially confined in micrometer-sized cylindrical pores with precisely controlled wall stiffness. It was found that, after reaching confluency, the cell monolayer enclosed by a compliant wall was able to keep growing and pushing the boundary, eventually leading to a markedly enlarged pore. In contrast, a much reduced in-plane growth and elevated strain level among cells were observed when the confining wall becomes stiff. Furthermore, under such circumstance, cells switched their growth from within the monolayer to along the out-of-plane direction, resulting in cell stacking. We showed that these observations can be well explained by a simple model taking into account the deformability of the wall and the threshold stress for inhibiting cell growth. Interestingly, cadherins were found to play an important role in the proliferation and stress buildup within the cell monolayer by aggregating at cell-cell junctions. The stiff confinement led to an elevated expression level of cadherins. Furthermore, inhibition of N-cadherin resulted in a significantly suppressed cell growth under the same confining conditions.

Management of extremity soft tissue sarcoma after unplanned incomplete resection: experience of a regional musculoskeletal tumour centre.

This study reviews the presentation and management of extremity soft tissue sarcoma after unplanned incomplete resection in a musculoskeletal tumour centre in Hong Kong. Medical records of 18 patients who were referred to our centre for further management from January 1995 to May 2001 after inadequate tumour excision were reviewed. Fourteen patients had been referred from private clinics and four from public hospitals. At initial presentation, 10 patients had lesions exceeding 5 cm, nine had a tumour deep in the subfascial plane, and eight had tumours that had recently increased in size. Sixteen had no preoperative radiological assessment or biopsy performed before excision. All except two patients needed additional skin and muscle reconstruction in a subsequent re-resection, and 12 required postoperative radiotherapy. Two patients subsequently developed distant metastases, and one patient died of an unrelated cause. No amputations were required, and no major complications arose from second surgery. Physicians' alertness towards the possible malignancy of soft tissue masses in extremities is important to avoid a potentially mutilating second resection. Well-planned re-resection in a specialised tumour centre can achieve satisfactory local control of disease.

Autologous stem cell transplantation for nasal NK/T-cell lymphoma: a progress report on its value.

Nasal NK/T-cell lymphoma is an Epstein-Barr virus-related, highly aggressive but localized disease in Orientals. The median survival is <1 year. Here, we update our experience on 18 patients treated with autologous stem cell transplantation (ASCT). Two patients died of mucositis and septicemia during ASCT. Relapse occurred in nine cases, including six local relapses. Compared with patients treated in remission, all patients treated in active or disseminated disease died of early relapse. Within this cohort, there was no significant survival difference between patients treated in first (CR1, n = 7) or second (CR2, n = 5) complete remissions. However, among consecutive cases analyzed, the patients receiving ASCT at CR1 showed a trend towards better overall survival compared with historical matched controls (P = 0.064). Disease relapse beyond 6 months was not seen after ASCT. Our retrospective data suggest that ASCT in CR1 is a viable consolidation therapy for local-stage NK/T lymphoma, but a randomized trial is needed to prove any definite survival benefit. For patients with relapsed, refractory or extranasal disease, early consideration for allogeneic transplantation and alternative therapy may be warranted.

Chondroblastoma of the lumbar spine with cauda equina syndrome.

STUDY DESIGN: Case report. OBJECTIVE: To describe the clinical presentations, radiological features and clinical progress of a rare case of chondroblastoma of the lumbar spine. SETTING: Regional Hospital, Hong Kong, China. METHOD: A 54-year-old male patient presented with low back pain and left sciatica. X-ray and MRI revealed tumour infiltration of the fifth lumbar vertebrae and left paraspinal muscles, which was found to be a chondroblastoma by repeated open biopsies. The tumour was removed surgically by combined anterior and posterior approaches, followed by spinal fusion and instrumentation. RESULTS: The anterior tricortical bone graft was complicated with fracture and nonunion. Surgical re-exploration confirmed local recurrence of tumour macroscopically and histologically. The patient developed symptoms and signs of cauda equina syndrome gradually despite repeated surgery and irradiation. The patient eventually died of complications of local recurrence and neurological deficit at 3 years and 8 months after the first operation. CONCLUSION: This is the first case report of chondroblastoma of the lumbar spine. The clinical profile of this patient and the evidence from the literature review suggests that spinal chondroblastoma has a very aggressive behaviour with high recurrence and mortality rate.

Sphenoidal sinus mucocoele and yawning after radiation treatment for nasopharyngeal carcinoma.

The long term complications of radiotherapy in treating patients with nasopharyngeal carcinoma (NPC) are well recognized. Among these, neurological and endocrinological complications are usually considered to be more clinically important. On the other hand, postirradiation sinusitis is often neglected or overlooked because symptoms are usually non-specific or not clinically disturbing. This leads to the under-reporting of this complication. We report the case history of a patient with NPC who developed recurrent and debilitating bouts of yawning attacks 13 years after radiotherapy. The attacks were thought to be due to the compression of the hypothalamus by a large mucocoele in the sphenoidal sinus, which was successfully managed by surgical drainage.

Primary mucoid adenocarcinoma of the larynx.

Mucous glands carcinomas of the larynx are rare, with most being represented by 'non-specific' adenocarcinoma and adenoid cystic carcinoma. Here we report a unique case of mucoid adenocarcinoma of the larynx occurring in a 46-year-old woman. Despite the presence of regional lymph node metastasis, she remained well four years after surgery.

Angiocentric T-cell lymphoma of the skin. An aggressive lymphoma distinct from mycosis fungoides.

Among 37 consecutive cases of malignant lymphoma in which the skin was either the only site of disease or one of the prominent sites of initial involvement, 19 cases had a distinctive histological appearance. These cases corresponded to what has been termed "angiocentric lymphoma," and all were found to exhibit a T-cell phenotype either by frozen-section immunohistochemistry or by using monoclonal antibodies reactive in paraffin sections. There were nine men and 10 women; the mean age was 48.2 years. The lesions were nodular and were either ulcerated or had intact skin. One case presented with involvement of one anatomical region of skin, five had involvement of multiple regions of skin, and 13 had concurrent extracutaneous disease. The disease pursued an aggressive course and was not uncommonly resistant to treatment. Histologically, the lymphomatous infiltrate occurred predominantly in the mid to deep dermis with involvement of the subcutaneous layer. The pattern was mainly perivascular and peri-adnexal with or without confluence; the overlying epidermis and papillary dermis were often spared. A prominent feature was invasion of small or large blood vessels by lymphoma cells. Eight cases showed extensive coagulative necrosis of the neoplastic and normal tissues, and 12 cases showed intraneural invasion. The neoplastic lymphoid cells consisted of either a monomorphous population or a variable mixture of small, medium-sized, and large cells with stippled chromatin and distinct nucleoli. Although the nuclei were often irregularly folded, few exhibited a cerebriform configuration. The cytoplasm was pale to clear. These cases exhibit a remarkable histological similarity to the T-cell lymphomas of the nasal/nasopharyngeal region; in addition, there are features that overlap with so-called lymphomatoid granulomatosis of the skin.