Proteomics and the Trypanosoma brucei cytoskeleton: advances and opportunities

Trypanosoma brucei is the etiological agent of devastating parasitic disease in humans and livestock in sub-saharan Africa. The pathogenicity and growth of the parasite are intimately linked to its shape and form. This is in turn derived from a highly ordered microtubule cytoskeleton that forms a tightly arrayed cage directly beneath the pellicular membrane and numerous other cytoskeletal structures such as the flagellum. The parasite undergoes extreme changes in cellular morphology during its life cycle and cell cycles which require a high level of integration and coordination of cytoskeletal processes. In this review we will discuss the role that proteomics techniques have had in advancing our understanding of the molecular composition of the cytoskeleton and its functions. We then consider future opportunities for the application of these techniques in terms of addressing some of the unanswered questions of trypanosome cytoskeletal cell biology with particular focus on the differences in the composition and organisation of the cytoskeleton through the trypanosome life-cycle.     

Tick-host immunology: Significant advances and challenging opportunities

Immunological interactions at the tick-host interface involve innate and acquired host defenses against infestation and immunomodulatory countermeasures by the tick. The cellular and molecular immunological bases of these host-parasite relationships are being defined. Acquired resistance to tick infestation involves humoral and cellular immunoregulatory and effector pathways. Ticks respond by suppressing antibody production, complement, and cytokine elaboration by both antigen-presenting cells and specific T-cell subsets. Tick-borne disease-causing agents probably exploit tick suppression of host defenses during transmission and initiation of infection. Because of the public health importance of ticks and Pick-borne diseases, it is crucial that we understand these interactions and exploit them in novel immunological control strategies. Here, Stephen Wikel and Douglas Bergman discuss recent advances in understanding tick-host immunology and propose future studies.     

Macular degeneration: recent advances and therapeutic opportunities

The central retina mediates high acuity vision, and its progressive dysfunction due to macular degeneration is the leading cause of visual disability among adults in industrialized societies. Here, we summarize recent progress in understanding the pathophysiology of macular degeneration and the implications of this new knowledge for treatment and prevention. The past decade has witnessed remarkable advances in this field, including the development of new, non-invasive retinal imaging technologies, the development of animal models for macular disease, and the isolation of many of the genes responsible for both early- and late-onset macular diseases. These advances have set the stage for the development of effective mechanism-based therapies.     

Recent advances and new opportunities in lung mechanobiology

Lung function is inextricably linked to mechanics. On short timescales every breath generates dynamic cycles of cell and matrix stretch, along with convection of fluids in the airways and vasculature. Perturbations such airway smooth muscle shortening or surfactant dysfunction rapidly alter respiratory mechanics, with profound influence on lung function. On longer timescales, lung development, maturation, and remodeling all strongly depend on cues from the mechanical environment. Thus mechanics has long played a central role in our developing understanding of lung biology and respiratory physiology. This concise review focuses on progress over the past 5 years in elucidating the molecular origins of lung mechanical behavior, and the cellular signaling events triggered by mechanical perturbations that contribute to lung development, homeostasis, and injury. Special emphasis is placed on the tools and approaches opening new avenues for investigation of lung behavior at integrative cellular and molecular scales. We conclude with a brief summary of selected opportunities and challenges that lie ahead for the lung mechanobiology research community.     

Verrucous carcinoma of the cervix uteri: report of a case

A case of verrucous carcinoma of the cervix uteri is reported. The cytologic findings in a Papanicolaou smear of the cervical area that permitted a diagnosis of verrucous carcinoma as opposed to epidermoid carcinoma or hyperkeratotic severe dysplasia are described. The importance of a proper diagnosis of verrucous carcinoma in order to avoid its treatment by radiation is stressed since verrucous carcinoma can turn into a more aggressive malignancy after such treatment.     

Recent advances in understanding apoptosis: new therapeutic opportunities in cancer chemotherapy

Major advances have been made in our understanding of the regulation of the molecular machinery of apoptosis in vitro. Molecules linking proliferation and apoptosis in healthy cells are being identified and here apoptotic cell death provides the 'fail-safe' mechanism to counteract excess proliferation. More recently, pioneering work on the regulation of apoptosis, in animal models of tumour development, has shown that suppression of apoptosis in the presence of a proliferative stimulus is sufficient for tumour development. Progress has also been made towards clarifying the contribution of drug-induced apoptosis to tumour response. With increasing evidence that failure to engage apoptosis after drug treatment contributes to drug resistance in vivo comes renewed confidence that new therapeutic approaches based on drug targets in apoptotic pathways will improve the treatment of cancer patients. As ever, tumour specificity is the major issue to be resolved.     

Conservatively treated glassy cell carcinoma of the cervix

Background

Many cancers are known to be associated with paraneoplastic syndromes. These syndromes are usually treated by chemotherapy with or without immunosupression but they often respond poorly. There are no published reviews on response to endocrine treatment.

Case presentation

We report a case of a patient presenting with papillitis, myositis and sensory peripheral neuropathy 18 months before a diagnosis of metastatic oestrogen receptor positive breast cancer was confirmed. The patient was treated with anastrozole which led not only to a decrease of her tumour burden but also to an improvement in her biochemical markers and amelioration of her clinical symptoms.

Conclusion

This case is an example of breast cancer presenting with paraneoplastic manifestations. It took several months to establish the cause of symptoms in this patient thus illustrating the need for physicians to maintain a high index of suspicion for paraneoplastic syndromes in women presenting with unusual neurological symptoms with no obvious cause. It is a unique case as it illustrates how treatment with an aromatase inhibitor leading to cancer regression can result in an improvement in the paraneoplastic symptoms.     

Pemphigus vulgaris and microinvasive squamous-cell carcinoma of the uterine cervix

Although patients with disseminated pemphigus vulgaris may have involvement of the uterine cervix, such involvement is often detected only after vaginal discharge or bleeding. When a cervical smear is obtained, distinctive cytologic abnormalities may be observed; these may be attributed to the changes of pemphigus or to an associated reparative/inflammatory reaction. This study documents the first two cases of microinvasive squamous-cell carcinoma of the uterine cervix developing in association with uterine cervical pemphigus. The gross pathologic, cytologic and histologic features of these lesions are illustrated. The cytologic criteria that may be helpful in distinguishing between cells derived from microinvasive squamous-cell carcinoma and pemphigus of the uterine cervix are described.     

Cytology of microinvasive squamous-cell carcinoma of the uterine cervix

The cervical cytology in 53 cases with histologically confirmed microinvasive squamous-cell carcinoma of the uterine cervix was studied. The smears were originally correctly diagnosed as showing microinvasion in 42% of the cases and were underinterpreted in 45%. On review, four of the underdiagnosed smears did show features of microinvasion. The depth of invasion did not have much influence on the cellular features. The patients underdiagnosed by cytology showed a tendency to have a smaller surface lesion and to have a history of a prior cervical manipulation within four weeks of the cytologic examination. The mean age of the overdiagnosed cases was distinctly higher than that of other cases. The colposcopic diagnosis correlated well with the cytologic diagnosis; both diagnostic modalities were considered to reflect well the change within the surface epithelium but to be less sensitive in recognizing the subtle changes of early invasion.     

Psammoma bodies in neuroendocrine carcinoma of the uterine cervix

A case of neuroendocrine carcinoma of the uterine cervix with focal papillary clusters and psammoma bodies, features not previously seen in this tumor, is documented. Papanicolaou-stained cervicovaginal smears and pelvic washings are correlated with tissue sections of endocervical curettage, hysterectomy and cul-de-sac biopsy specimens. Although there was some variation in the cytologic features, the tumor cells were generally distinguished by nuclear molding, indistinct nucleoli, finely granular chromatin and scant cytoplasm. Argyrophil-positive intracytoplasmic granules were identified in tissue sections of the tumor. These granules were positive for ACTH and neuron-specific enolase using the immunoperoxidase technique. Ultrastructural studies were consistent with these findings. Neuroendocrine carcinoma of the cervix is therefore a cytologically distinctive tumor in which psammoma bodies may occur.