Facial Tumor Research Articles

Marsupial chromosomics: bridging the gap between genomes and chromosomes.

Marsupials have unique features that make them particularly interesting to study, and sequencing of marsupial genomes is helping to understand their evolution. A decade ago, it was a huge feat to sequence the first marsupial genome. Now, the advances in sequencing technology have made the sequencing of many more marsupial genomes possible. However, the DNA sequence is only one component of the structures it is packaged into: chromosomes. Knowing the arrangement of the DNA sequence on each chromosome is essential for a genome assembly to be used to its full potential. The importance of combining sequence information with cytogenetics has previously been demonstrated for rapidly evolving regions of the genome, such as the sex chromosomes, as well as for reconstructing the ancestral marsupial karyotype and understanding the chromosome rearrangements involved in the Tasmanian devil facial tumour disease. Despite the recent advances in sequencing technology assisting in genome assembly, physical anchoring of the sequence to chromosomes is required to achieve a chromosome-level assembly. Once chromosome-level assemblies are achieved for more marsupials, we will be able to investigate changes in the packaging and interactions between chromosomes to gain an understanding of the role genome architecture has played during marsupial evolution.

The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease

SummaryThe marsupial Tasmanian devil (Sarcophilus harrisii) faces extinction due to transmissible devil facial tumor disease (DFTD). To unveil the molecular underpinnings of this transmissible cancer, we combined pharmacological screens with an integrated systems-biology characterization. Sensitivity to inhibitors of ERBB tyrosine kinases correlated with their overexpression. Proteomic and DNA methylation analyses revealed tumor-specific signatures linked to the evolutionary conserved oncogenic STAT3. ERBB inhibition blocked phosphorylation of STAT3 and arrested cancer cells. Pharmacological blockade of ERBB or STAT3 prevented tumor growth in xenograft models and restored MHC class I expression. This link between the hyperactive ERBB-STAT3 axis and major histocompatibility complex class I-mediated tumor immunosurveillance provides mechanistic insights into horizontal transmissibility and puts forward a dual chemo-immunotherapeutic strategy to save Tasmanian devils from DFTD.Video

Thylacine and Tasmanian devil: between hope and reality – a lesson to be learnt from Google Trends search data

The two iconic Tasmanian species, the Tasmanian devil (Sarcophilus harrisii) and the thylacine (Thylacinus cynocephalus), are of great interest to the general public and the media. The most likely extinct Tasmanian wolf or tiger, the thylacine, symbolises human responsibility for nature and species conservation and inspired the ‘National Threatened Species Day’, which commemorates the death of the last thylacine at Beaumaris Zoo in Hobart on 7 September 1936 to raise awareness of endangered plants and animals. Since the spread of the Devil Facial Tumour Disease critically endangered the survival of the largest remaining native carnivore (S. harrisii) today, this has generated both scientific interest and the interest of the general public. Google Trends has already been used as a tool for documenting and investigating the information needs and concerns of the population, as has been shown using the example of diseases. In this study, Google Trends data were used to examine the seasonality of the search term ‘thylacine sightings’ and the development of the frequency of different search terms in the period between 2004 and 2020. As a result, relative search intensities for ‘thylacine cloning’ and ‘cloning extinct species’ have shown a decrease over time. While Google Trends cannot clearly determine search motivation, search terms can be selected for the examinations that document more hope or a rational need for information or concern.

Saving the Tasmanian Devil: How Science Is Helping the World’s Largest Marsupial Carnivore Survive by Dorothy Hinshaw Patent

Reviewed by: Saving the Tasmanian Devil: How Science Is Helping the World’s Largest Marsupial Carnivore Survive by Dorothy Hinshaw Patent Deborah Stevenson, Editor Patent, Dorothy Hinshaw Saving the Tasmanian Devil: How Science Is Helping the World’s Largest Marsupial Carnivore Survive. Houghton Mifflin Harcourt, 2019 [80p] illus. with photographs (Scientists in the Field) Trade ed. ISBN 978-0-544-99148-4 $18.99 E-book ed. ISBN 978-0-358-05605-8 $9.99 Reviewed from galleys R Gr. 5-8 Trailblazing nature writer for youth Patent returns to the Scientists in the Field series, and she’s focusing on Australia’s Tasmanian devil, a species threatened by Devil Facial Tumour Disease, a form of contagious cancer with frighteningly high fatality rates. Patent visits devil sanctuaries and refuges and consults with scientists involved with studying the disease and searching for ways to protect the species. The book leaves some holes (what do the tumors actually do to the animals?) and misses opportunities to synthesize or acknowledge contradictory opinions (about [End Page 32] what behavior actually transfers the disease, for instance), but there’s also solid information about the genetics of the tumors, the possibilities of a vaccine, and the efforts to preserve uninfected reservoirs of the animals in remote and isolated locations. Though the devils are largely nocturnal, there is still a satisfying amount of daytime photographs of the critters, who hover in that Australian biological limbo of odd yet cute, and there are many helpful maps and diagrams. Overall, it’s a sympathetic introduction to an animal most readers will only know from cartoon and legend. A brief glossary and list of resources is appended, along with source notes and an index. Copyright © 2019 The Board of Trustees of the University of Illinois

Complex problems need detailed solutions: Harnessing multiple data types to inform genetic management in the wild.

For bottlenecked populations of threatened species, supplementation often leads to improved population metrics (genetic rescue), provided that guidelines can be followed to avoid negative outcomes. In cases where no “ideal” source populations exist, or there are other complicating factors such as prevailing disease, the benefit of supplementation becomes uncertain. Bringing multiple data and analysis types together to plan genetic management activities can help. Here, we consider three populations of Tasmanian devil, Sarcophilus harrisii, as candidates for genetic rescue. Since 1996, devil populations have been severely impacted by devil facial tumour disease (DFTD), causing significant population decline and fragmentation. Like many threatened species, the key threatening process for devils cannot currently be fully mitigated, so species management requires a multifaceted approach. We examined diversity of 31 putatively neutral and 11 MHC‐linked microsatellite loci of three remnant wild devil populations (one sampled at two time‐points), alongside computational diversity projections, parameterized by field data from DFTD‐present and DFTD‐absent sites. Results showed that populations had low diversity, connectivity was poor, and diversity has likely decreased over the last decade. Stochastic simulations projected further diversity losses. For a given population size, the effects of DFTD on population demography (including earlier age at death and increased female productivity) did not impact diversity retention, which was largely driven by final population size. Population sizes ≥500 (depending on the number of founders) were necessary for maintaining diversity in otherwise unmanaged populations, even if DFTD is present. Models indicated that smaller populations could maintain diversity with ongoing immigration. Taken together, our results illustrate how multiple analysis types can be combined to address complex population genetic challenges.

Sex bias in ability to cope with cancer: Tasmanian devils and facial tumour disease.

Knowledge of the ecological dynamics between hosts and pathogens during the initial stages of disease emergence is crucial to understanding the potential for evolution of new interspecific interactions. Tasmanian devil (Sarcophilus harrisii) populations have declined precipitously owing to infection by a transmissible cancer (devil facial tumour disease, DFTD) that emerged approximately 20 years ago. Since the emergence of DFTD, and as the disease spreads across Tasmania, the number of devils has dropped up to 90% across 80% of the species's distributional range. As a result, the disease is expected to act as a strong selective force on hosts to develop mechanisms of tolerance and/or resistance to the infection. We assessed the ability of infected devils to cope with infection, which translates into host tolerance to the cancer, by using the reaction norm of the individual body condition by tumour burden. We found that body condition of infected hosts is negatively affected by cancer progression. Males and females presented significant differences in their tolerance levels to infection, with males suffering declines of up to 25% of their body condition, in contrast to less than 5% in females. Sex-related differences in tolerance to cancer progression may select for changes in life-history strategies of the host and could also alter the selective environment for the tumours.

A Tasmanian devil breeding program to support wild recovery.

Tasmanian devils are threatened in the wild by devil facial tumour disease: a transmissible cancer with a high fatality rate. In response, the Save the Tasmanian Devil Program (STDP) established an 'insurance population' to enable the preservation of genetic diversity and natural behaviours of devils. This breeding program includes a range of institutions and facilities, from zoo-based intensive enclosures to larger, more natural environments, and a strategic approach has been required to capture and maintain genetic diversity, natural behaviours and to ensure reproductive success. Laboratory-based research, particularly genetics, in tandem with adaptive management has helped the STDP reach its goals, and has directly contributed to the conservation of the species in the wild. Here we review this work and show that the Tasmanian devil breeding program is a powerful example of how genetic research can be used to understand and improve reproductive success in a threatened species.

Two Decades of the Impact of Tasmanian Devil Facial Tumor Disease.

The Tasmanian devil, a marsupial carnivore, has been restricted to the island state of Tasmania since its extinction on the Australian mainland about 3000years ago. In the past two decades, this species has experienced severe population decline due to the emergence of devil facial tumor disease (DFTD), a transmissible cancer. During these 20years, scientists have puzzled over the immunological and evolutionary responses by the Tasmanian devil to this transmissible cancer. Targeted strategies in population management and disease control have been developed as well as comparative processes to identify variation in tumor and host genetics. A multi-disciplinary approach with multi-institutional teams has produced considerable advances over the last decade. This has led to a greater understanding of the molecular pathogenesis and genomic classification of this cancer. New and promising developments in the Tasmanian devil's story include evidence that most immunized, and some wild devils, can produce an immune response to DFTD. Furthermore, epidemiology combined with genomic studies suggest a rapid evolution to the disease and that DFTD will become an endemic disease. Since 1998 there have been more than 350 publications, distributed over 37 Web of Science categories. A unique endemic island species has become an international curiosity that is in the spotlight of integrative and comparative biology research.

Surgical Management of Intrinsic Tumors of the Facial Nerve

Intrinsic tumors of the facial nerve are a rare entity. Dealing with this subset of tumors is challenging both in terms of decision making and surgical intervention. To review the outcomes of surgical management of facial nerve tumors and cable nerve graft interpositioning. A retrospective analysis was performed at a referral center for skull base pathology. One hundred fifteen patients who were surgically treated for facial nerve tumors were included. In case of nerve interruption during surgery, the cable nerve interpositioning technique was employed wherein the facial nerve palsy lasted for less than 1-yr duration. In cases of facial nerve palsy lasting for greater than 1 yr, the nerve was restituted by a hypoglossal facial coaptation. Various degrees of progressive paralysis were seen in 84 (73%) cases. Sixty nine (60%) of the tumors involved multiple segments of the facial nerve. Sixty-two (53.9%) tumors involved the geniculate ganglion. Seventy four (64.3%) of the cases were schwannomas. Hearing preservation surgeries were performed in 60 (52.1%). Ninety one (79.1%) of the nerves that were sectioned in association with tumor removal were restituted primarily by interposition cable grafting. The mean preoperative House-Brackmann grading of the facial nerve was 3.6. The mean immediate postoperative grading was 5.4, which recovered to a mean of 3.4 at the end of 1 yr. In patients with good facial nerve function (House-Brackmann grade I-II), a wait-and-scan approach is recommended. In cases where the facial nerve has been interrupted during surgery, the cable nerve interpositioning technique is a convenient and well-accepted procedure for immediate restitution of the nerve.

Tasman-PCR: a genetic diagnostic assay for Tasmanian devil facial tumour diseases

Tasmanian devils have spawned two transmissible cancer clones, known as devil facial tumour 1 (DFT1) and devil facial tumour 2 (DFT2). DFT1 and DFT2 are transmitted between animals by the transfer of allogeneic contagious cancer cells by biting, and both cause facial tumours. DFT1 and DFT2 tumours are grossly indistinguishable, but can be differentiated using histopathology, cytogenetics or genotyping of polymorphic markers. However, standard diagnostic methods require specialist skills and equipment and entail long processing times. Here, we describe Tasman-PCR: a simple polymerase chain reaction (PCR)-based diagnostic assay that identifies and distinguishes DFT1 and DFT2 by amplification of DNA spanning tumour-specific interchromosomal translocations. We demonstrate the high sensitivity and specificity of this assay by testing DNA from 546 tumours and 804 normal devils. A temporal–spatial screen confirmed the reported geographic ranges of DFT1 and DFT2 and did not provide evidence of additional DFT clones. DFT2 affects disproportionately more males than females, and devils can be co-infected with DFT1 and DFT2. Overall, we present a PCR-based assay that delivers rapid, accurate and high-throughput diagnosis of DFT1 and DFT2. This tool provides an additional resource for devil disease management and may assist with ongoing conservation efforts.

Lessons learnt from the Tasmanian devil facial tumour regarding immune function in cancer.

Genetic and genomic technologies have facilitated a greater understanding of the Tasmanian devil immune system and the origins, evolution and spread of devil facial tumour disease (DFTD). DFTD is a contagious cancer that has caused significant declines in devil populations across Tasmania. Immune responses to DFTD are rarely detected, allowing the cancer to pass between individuals and proliferate unimpeded. Early immunosenscence in devils appears to decrease anti-tumour immunity in older animals compared to younger animals, which may increase susceptibility to DFTD and explain high DFTD prevalence in this age group. Devils also have extremely low major histocompatibility complex (MHC) diversity, and multiple alleles are shared with the tumour, lowering histocompatibility barriers which may have contributed to DFTD evolution. DFTD actively evades immune attack by down-regulating cell-surface MHC I molecules, making it effectively invisible to the immune system. Altered MHC I profiles should activate natural killer (NK) cell anti-tumour responses, but these are absent in DFTD infection. Recent immunisation and immunotherapy using modified DFTD cells has induced an anti-DFTD immune response and regression of DFTD in some devils. Knowledge gained from immune responses to a transmissible cancer in devils will ultimately reveal useful insights into immunity to cancer in humans and other species.

Subunit Reconstruction of Mid-Facial Defects With Free Style Facial Perforator Flaps.

Reconstruction of facial defects is not only important for cosmesis but also for the function. Local flaps are considered the best reconstruction method for facial defects. The authors want to show the feasibility of free style facial perforator flap for the reconstruction of moderate sized mid-facial defects. Free style facial artery and lateral nasal artery perforator flaps were performed in 22 patients (11 males and 11 females) who had removal of facial tumor between March 2015 and December 2016 RESULTS:: The median age of patients was 62 years (range: 35-84). The mean follow-up period was 12.6 months (range: 5-24). Pathology results were basal cell carcinoma in 13 patients, squamous cell carcinoma in 6 patients, and other skin tumors in 3 patients. The defect size ranged from 2 × 2 to 5 × 5 cm. No major or minor complication happened but 1 flap had venous congestion that healed without any intervention CONCLUSION:: Free style facial perforator flaps are highly reliable flaps with wide range of motion. In addition, they provide single-stage closure with esthetic subunit reconstruction. With the current knowledge of reconstruction and skills of microsurgery, they can be easily the first choice for the closure of mid-facial defects.

Retrograde approach for parotid benign tumours: A review

IntroductionParotidectomy for benign tumours is usually performed after facial nerve trunk discovery through an anterograde approach (AA) of the nerve. More recently, a retrograde approach (RA) toward the facial nerve, which begins on the facial nerve branches and ends on the nerve trunk, has been described. A literature review of the RA was conducted to evaluate the RA and to compare it with AA. MethodsA literature review was conducted for the years 1980 through 2016. Nine studies out of 216 were included, including 558 parotidectomies and 370 RA. We studied the operative time (OT), the postoperative complications including facial paralysis (FP), tumour recurrences, and possibilities for reoperation. ResultsOperative time was shorter in RA than in AA. Transitory FP significantly less frequent in RA than in AA in only one studies and not significantly in four studies. Incidence of Frey syndrome was similar in RA and AA. Tumour relapses were reported in 1.8% of cases with RA, comparable to AA. ConclusionRetrograde parotidectomy is recommendable. OT was significantly shorter for the RA. The FP rate was lower for RA than for AA, but the difference was not significant. The recurrence rate appeared to be similar between RA and AA. Possibilities of reoperation were better after RA.

A 'devil' of a problem.

The discovery of a second facial tumor disease in the Tasmanian devil has provided insights into the emergence of contagious cancers.

The newly-arisen Devil facial tumour disease 2 (DFT2) reveals a mechanism for the emergence of a contagious cancer.

Devil Facial Tumour 2 (DFT2) is a recently discovered contagious cancer circulating in the Tasmanian devil (Sarcophilus harrisii), a species which already harbours a more widespread contagious cancer, Devil Facial Tumour 1 (DFT1). Here we show that in contrast to DFT1, DFT2 cells express major histocompatibility complex (MHC) class I molecules, demonstrating that loss of MHC is not necessary for the emergence of a contagious cancer. However, the most highly expressed MHC class I alleles in DFT2 cells are common among host devils or non-polymorphic, reducing immunogenicity in a population sharing these alleles. In parallel, MHC class I loss is emerging in vivo, thus DFT2 may be mimicking the evolutionary trajectory of DFT1. Based on these results we propose that contagious cancers may exploit partial histocompatibility between the tumour and host, but that loss of allogeneic antigens could facilitate widespread transmission of DFT2.

Cancer- and behavior-related genes are targeted by selection in the Tasmanian devil (Sarcophilus harrisii).

Devil Facial Tumor Disease (DFTD) is an aggressive cancer notorious for its rare etiology and its impact on Tasmanian devil populations. Two regions underlying an evolutionary response to this cancer were recently identified using genomic time-series pre- and post-DTFD arrival. Here, we support that DFTD shaped the genome of the Tasmanian devil in an even more extensive way than previously reported. We detected 97 signatures of selection, including 148 protein coding genes having a human orthologue, linked to DFTD. Most candidate genes are associated with cancer progression, and an important subset of candidate genes has additional influence on social behavior. This confirms the influence of cancer on the ecology and evolution of the Tasmanian devil. Our work also demonstrates the possibility to detect highly polygenic footprints of short-term selection in very small populations.

The devil is in the details: Genomics of transmissible cancers in Tasmanian devils.

Cancer poses one of the greatest human health threats of our time. Fortunately, aside from a few rare cases of cancer transmission in immune-suppressed organ transplant recipients or a small number of transmission events from mother to fetus, cancers are not spread from human to human. However, transmissible cancers have been detected in vertebrate and invertebrate animals, sometimes with devastating effects. Four examples of transmissible cancers are now known: 1) canine transmissible venereal tumor (CTVT) in dogs, 2) a tumor in a laboratory population of Syrian hamsters that is no longer cultured, 3) infectious neoplasias in at least four species of bivalve mollusks, and 4) two independently derived transmissible cancers (devil facial tumor disease [DFTD]) in Tasmanian devils (Fig 1A and 1B). The etiologic agents of CTVT, the bivalve cancers, and DFTDare the transplants (allografts) of the neoplastic cells themselves, but the etiologic agent is unknown for the hamster tumor. The effects of these transmissible cancers on their respective host populations vary. CTVT is spread in dogs through sexual contact and is at least 11,000 years old, placing the timing of its origin close to that of the domestication of dogs. Although genomic analyses of the tumor suggest evasion of multiple components of the dog immune system, dogs most commonly survive and often show evidence of spontaneous tumor regression within a year of initial diagnosis. For the infectious bivalve neoplasias, which have existed for at least 40 years, population effects vary from enzootic infections with no noticeable effects on population sizes to evidence of a catastrophic population decline. In Tasmanian devils (Fig 1A), the first infectious tumor discovered (DFT1; Fig 1B) has spread across approximately 95% of the geographic range of Tasmanian devils since 1996 (Fig 1C). DFTD is almost always fatal (Fig 1B), with >90% declines in infected localities and an overall species-wide decline exceeding 80%. Transmission dynamics appear consistent with frequency dependence, with DFTD spread by biting during social interactions, resulting in predictions of extinction from standard epidemiological models. Despite these predictions, long-infected devil populations persist at reduced densities, suggesting that individual-level variability in fecundity and tumor growth rate in infected individuals are key for understanding epidemiological dynamics. Additionally, the origin of the second, independent lineage of DFTD (i.e., DFT2) within 20 years of the discovery of DFT1 suggests that transmissible cancers may be a recurring part of the Tasmanian devils' evolutionary history, without causing extinction.

The application of modified cosmetic incision and skin adhesive in parotid benign tumor functional surgery

Objective:To investigate the clinical application value and related technology of modified cosmetic incision and cyanoacrylate octyl ester skin adhesive (Dermabond) in functional surgery of parotid benign tumor. Method:Forty-two cases of clinical cases were collected and randomly divided into groups of A and B. Group A used the approach of modified cosmetic incision,intradermal suture with 6-0 absorbable Vicryl stitches and gluing the skin with Dermabond. Group B used the approach of traditional S shaped incision and continuous suture of skin with 4-0 Prolene stitches.The operative time, postoperative drainage volume, facial nerve function, salivary leakage, Frey syndrome, postoperative numbness, scar and aesthetic satisfaction were compared between the two groups. Result:The operation time, facial nerve function,Frey syndrome, salivary fistula, facial deformity and tumor recurrence in the two groups had no significant difference (P>0.05); but for postoperative drainage, postoperative numbness, facial appearance satisfaction, scar assessment, Group A was lower than Group B and there was statistical significance difference (P<0.05). Conclusion:The application of modified cosmetic incision and Dermond is safe and feasible. Its complication is lower than the traditional operation. The scar is smaller and more hidden, and the patient's satisfaction is higher. It doesn't affect the daily social interaction of patients, and achieves the effect of minimally invasive treatment.

Researching new diseases: assumptions and trajectories

New diseases in humans and animals have been the subject of considerable research as well as policy development and popular attention. Researchers commonly proceed on the basis of plausible assumptions about mechanisms, pathways, and dangers but seldom question the assumptions themselves. Studies in the history and sociology of science show that research trajectories are conditioned by social, political, and economic arrangements. The assumptions underlying research into three new diseases—devil facial tumor disease in Tasmanian devils, AIDS in humans, and leukemia in soft-shell clams—are examined, and dominant and alternative research programs compared. In each case, most research has assumed the disease is spread through “natural processes”, while research about possible human influences has been left undone.

The inflammatory pseudotumor presenting periodic acid-Schiff-positive inclusions with acute unilateral facial nerve palsy

Although most acute peripheral facial palsies can be attributed to Bell’s palsy, other factors, such as infection, trauma, and neoplasm, can cause facial palsy as well. Among these, facial nerve tumors are rare but should be considered in the differential diagnosis of facial palsy. Palsies due to facial nerve tumors usually present with slow onset but occasionally present as acute episodes. In such cases, facial nerve decompression is the treatment of choice to allow the tumor room to grow without compressing the nerve or its blood supply. We describe a case of severe, acute facial palsy presenting with a spindle-shaped bone erosion on the mastoid portion of the facial canal. Although facial neuroma was suspected preoperatively, emergency decompression surgery revealed that an unusual inflammatory pseudotumor was responsible for the finding. Postoperative histological analysis revealed extensive destruction of the nerve fibers, with extensive infiltration of foamy macrophages containing characteristic, diastase-resistant, periodic acid-Schiff (PAS)-positive inclusions, which are hallmark of the uncommon bacterial infections. This was a case of facial palsy with an unusual etiology. The case shows the benefit of decompression surgery not only as treatment for the palsy but also as exploratory surgery in cases of facial nerve tumor.