Douglas K Trask's scientific contributionswhile working at University of Iowa Children's Hospital (Iowa City, United States) and other institutions

Publications (23)

Publications citing this author (952)

    • Discussion VC represents 2–12 % of oral cancers, occurring mainly in older men; mean age of presentation is 69 years [7]. However some studies have reported equal sex distribution [16], and some with female predominance [6, 12].
    [Show abstract] [Hide abstract] ABSTRACT: Studies have reported 20 % of conventional squamous cell carcinoma in patients with verrucous carcinoma (VC), later these cancers were termed as hybrid VC. It is important to distinguish both while planning treatment since hybrid VC requires addressing regional lymphatics in addition to respective surgery. Information on odds of missing the foci of invasion on routine incision biopsy might be useful in this regard. Records of all the patients surgically treated for oral cancer from Jan 2010 to Oct 2013 in a Tertiary Cancer Centre was analyzed. Patients diagnosed with primary VC or Verrucous Hyperplasia on incision biopsy were included in the study. Proportion of patients undiagnosed for invasive component on incision biopsy was calculated, multivariate analysis of the sample was performed to find associated cofounders. Fifty-five patients who reported with the diagnosis of VC (n = 53) or Verrucous Hyperplasia (n = 2) on incision biopsy were included in the study. Twenty-seven were diagnosed as VC and 28 as hybrid VC after excision. This corresponded to 51 % (n = 28) of cases missing invasive component on incision biopsy. VC was significantly more commonly seen in lip and in buccal mucosa, hybrid VC was more commonly seen in tongue and gingiva and this association was statistically significant (p = 0.031) in our study. Incision biopsy is extremely unreliable to diagnose and differentiate oral Hybrid VC from VC or Verrucous Hyperplasia. Caution is required while planning treatment of these patients regarding possibility of presence of conventional squamous cell carcinoma within these tumors.
    Full-text · Article · Sep 2015
    • miR-205 expression is down-regulated in several types of cancers including breast [20], prostate [21] and renal cancer [22] and serves as a tumor suppressor by inhibiting tumor proliferation and invasion. Conversely, miR-205 is overexpressed in ovarian [23], lung [24] and head and neck squamous cell carcinoma [25] and acts as an oncogene by facilitating tumor initiation and proliferation. Recently, one study reveals that miR-205 is upregulated in response to IR and promotes radioresistance in nasopharyngeal carcinoma (NPC) [6].
    [Show abstract] [Hide abstract] ABSTRACT: Radiotherapy for esophageal squamous cell carcinoma (ESCC) patients is limited by resistance to ionizing radiation (IR). However, the roles and mechanisms of microRNAs in radioresistance are obscure. Here, we investigated that microRNA-205 (miR-205) was upregulated in radioresistant (RR) ESCC cells compared with the parental cells. Overexpression of miR-205 promoted colony survival post-IR, whereas depletion of miR-205 sensitized ESCC cells to IR in vitro and in vivo. Further, we demonstrated that miR-205 promoted radioresistance by enhancing DNA repair, inhibiting apoptosis and activating epithelial-mesenchymal transition (EMT). Mechanistically, miR-205, upregulated post-IR, was demonstrated to be activated by Sp1 in parallel with its host gene, miR-205HG, both of which showed a perfect correlation. We also identified and validated phosphatase and tensin homolog (PTEN), as a target of miR-205 that promoted radioresistance via PI3K/AKT pathway. Lastly, increased miR-205 expression was closely associated with decreased PTEN expression in ESCC tissues and miR-205 expression predicted poor prognosis in patients with ESCC. Taken together, these findings identify miR-205 as a critical determinant of radioresistance and a biomarker of prognosis. The Sp1-mediated transcriptional activation of miR-205 promotes radioresistance through PTEN via PI3K/AKT pathway in ESCC. Inhibition of miR-205 expression may be a new strategy for radiotherapy in ESCC.
    Full-text · Article · Dec 2016
    • Sulindac sulfide induced similar responses after treatment for 48 h; however, at this time point, there was a pronounced downregulation of Sp1, Sp3 and Sp4 proteins in SW480 (Fig. 2c) and RKO (Fig. 2d) cells. Thus, sulindac sulfide was the most active sulindac derivative as observed in previous studies [33, 34] and the results suggest that the growth inhibitory effects of sulindac sulfide are correlated with downregulation of pro-oncogenic Sp proteins, and previous studies show that knockdown of one or more [35, 36] Sp proteins in colon cancer cells decreases cell cycle progression and induces apoptosis. We also investigated the effects of sulindac sulfide on Sp-dependent pro-apoptotic, growth inhibitory and anti-angiogenic responses in colon cancer cells.
    [Show abstract] [Hide abstract] ABSTRACT: Background: Specificity protein (Sp) transcription factors play pivotal roles in maintaining the phenotypes of many cancers. We hypothesized that the antineoplastic effects of sulindac and its metabolites were due, in part, to targeting downregulation of Sp transcription factors. Methods: The functional effects of sulindac, sulindac sulfone and sulindac sulfide on colon cancer cell proliferation were determined by cell counting. Effects of these compounds on expression of Sp1, Sp3, Sp4 and pro-oncogenic Sp-regulated genes were determined by western blot analysis of whole cell lysates and in transient transfection assays using GC-rich constructs. Results: Sulindac and its metabolites inhibited RKO and SW480 colon cancer cell growth and the order of growth inhibitory potency was sulindac sulfide > > sulindac sulfone > sulindac. Treatment of SW480 and RKO cells with sulindac sulfide downregulated expression of Sp1, Sp3 and Sp4 proteins. Sulindac sulfide also decreased expression of several Sp-regulated genes that are critical for cancer cell survival, proliferation and angiogenesis and these include survivin, bcl-2, epidermal growth factor receptor (EGFR), cyclin D1, p65 subunit of NFκB and vascular endothelial growth factor (VEGF). Sulindac sulfide also induced reactive oxygen species (ROS) and decreased the level of microRNA-27a in colon cancer cells, which resulted in the upregulation of the Sp-repressor ZBTB10 and this resulted in downregulation of Sp proteins. Conclusions: The results suggest that the cancer chemotherapeutic effects of sulindac in colon cancer cells are due, in part, to its metabolite sulindac sulfide which downregulates Sp transcription factors and Sp-regulated pro-oncogenic gene products.
    Full-text · Article · Dec 2015
    • This study also demonstrate that ABT7-37, alone or in combination with radiation therapy, showed a preferential cytotoxicity towards HNSCC CSCs, which is a promising approach to reduce cancer relapse and metastasis. ABT-737 binds Bcl-2 and Bcl-X L with high affinity and has shown single-agent efficacy against multiple cell lines as well as in combination with standard therapy in human leukemia and multiple myeloma models [3, 25], lymphoma [26], melanoma [13], cholangiocarcinoma [14] or HNSCC [8]. Except some reports on Hela cells [27], non-small-cell-lung cancer cells [19] and breast cancer cells [20, 28], no more data are available on a synergistic effect of BH3-mimetics with radiation, especially on HNSCC.
    [Show abstract] [Hide abstract] ABSTRACT: Head and neck squamous cell carcinomas (HNSCC) are common human malignancies with poor clinical outcomes. The 5-year survival rates for patients with advanced stage HNSCC have not changed appreciably in the past few decades, underscoring a dire need for improved therapeutic options. HNSCC is frequently characterized by overexpression of anti-apoptotic Bcl-2 family members. Increased levels of these anti-apoptotic proteins have been associated with radio- and chemoresistance and poor clinical outcome. The aim of this study was to evaluate combined effects of radiation and ABT-737, a BH3-mimetic molecule, in HNSCC. Although ABT-737, as a single agent, was largely ineffective at promoting HNSCC cell death, we found that combining ABT-737 and radiation induced strong synergistic apoptosis in HNSCC cell lines and delayed tumoral growth in vivo. Moreover, we demonstrated for the first time that ABT-737, alone or in combination with radiation, can efficiently eliminate cancer stem cells (CSCs). Altogether, our results indicate that therapy targeting anti-apoptotic Bcl-2 family members could be a highly effective potential adjuvant to radiotherapy capable of targeting CSCs in HNSCC and therefore overcoming cancer recurrence and metastasis.
    Full-text · Article · Feb 2016
    • Terris et al. [12] reported that transoral minimal invasive lingual thyroid resection decreased morbidity and duration of hospitalization compared to other open approaches. Coblation assisted lingual thyroid and lingual tonsil resection techniques were used and successful results were reported131415. Leitzbach et al. [14] reported successful results and low complication rates in 108 patients undergoing coblation assisted resection due to tongue root and lingual tonsil hypertrophy. However, transoral resection techniques have limited point of view and lead to difficulty in resection owing to difficulty in manipulation, which restricts their use [7].
    [Show abstract] [Hide abstract] ABSTRACT: Ectopic thyroid gland may be detected at any place between foramen caecaum and normal thyroid localization due to inadequacy of the embryological migration of the thyroid gland. It has a prevalence varying between 1/10.000 and 1/100000 in the community. Usually follow-up without treatment is preferred except for obstructive symptoms, bleeding, and suspicion of malignity. Main symptoms are dysphagia, dysphonia, bleeding, dyspnea, and obstructive sleep apnea. In symptomatic cases, the first described method in surgical treatment is open approach since it is a region difficult to have access to. However, this approach has an increased risk of morbidity and postoperative complications. Transoral robotic surgery, which is a minimally invasive surgical procedure, has advantages such as larger three-dimensional point of view and ease of manipulation due to robotic instruments. In this report, a case at the age of 49 who presented to our clinic with obstructive symptoms increasing within the last year and was found to have lingual thyroid and underwent excision of ectopic thyroid tissue by da Vinci surgical system is presented.
    Full-text · Article · Jun 2015
    • There is also encouraging evidence that quality of life is improved in the IMRT era compared with those patients previously treated with two-or three-dimensional conformal radiotherapy , reflecting reduced doses to organs at risk [79]. In comparing surgical and chemoradiotherapy approaches, a matched pair study of 54 patients showed similar healthrelated quality of outcomes for both groups [80]. These outcomes persist and may evolve.
    [Show abstract] [Hide abstract] ABSTRACT: Treatments for head and neck cancer are improving, yet they remain toxic and challenging. The incidence of some forms of head and neck cancer (e.g. oropharyngeal) is rising. This creates an enlarging cohort of survivors with complex needs. These needs may be overlooked and undertreated. This overview presents evidence for the unmet survivorship needs of head and neck cancer patients and identifies strategies for the recognition and remedy of these needs in the clinic. There is sufficient evidence to challenge services to redesign follow-up strategies around unmet need using the full multidisciplinary team and to widen focus away from a sole aim of recognition and treatment of recurrent disease. Problems presented include depression, comorbid disease, second malignancy, alcohol and nicotine dependence, eating and drinking difficulties (including dysphagia, dental problems, trismus and sense disturbance) and hypothyroidism.
    Article · Apr 2016
    • Gulmann et al (2003) reported a loss of 15% of cores in their study (23). Fernebro et al (2002) and Griffin et al (2003) reported 17% loss of tissue samples (17, 20) whereas Monteiro et al (2010) reported the highest,19.8% loss of TMA core samples (21).
    [Show abstract] [Hide abstract] ABSTRACT: Background: There is significant amount of research done on Oral Squamous cell carcinoma (OSCC). One research technique is immunohistochemical (IHC) analysis using whole sections. With little availability of OSCC tissues high throughput analysis such as Tissue Microarray (TMA) are capable of efficient analysis of small samples. However, the results become questionable if the tumor exhibits high degree of heterogeneity as TMA cores might not accurately represent the whole section. Aim: The aim of this study is to determine the optimal number of TMA cores required to provide an accurate representation of the whole section with IHC analysis in OSCC. Materials and Methods: Twenty tissue samples stained with anti-p53 antibody were scanned at 40x magnification. Three to six virtual cores of size 0.6 mm, 1.0 mm and 1.5 mm were drawn on the scanned slides. H-scores were obtained for both whole sections and cores using NuclearQuant (3DHistech, Budapest, Hungary) software after eliminating non-tumour cells and artifacts manually. The correspondence between the cores and whole sections were calculated using intra-class correlation and one sample t-test. Results: Good correlation was obtained with just a single core of 0.6mm (0.826). Subsequent increase in core number and size resulted in improved correlation coefficient and smaller confidence interval. Conclusion: Three TMA cores of 0.6 mm would be the most optimal, as not only was there very strong correlation with the whole tissue section, the extra core will also be able to act as confirmation if the results of the first 2 cores are in doubt.
    Full-text · Article · Jan 2014 · International Journal of Molecular Sciences
    • Spongiosis and acanthosis may be noted. The lesion has a tendency to regress after incisional biopsy or after the offending stimulus is removed [32,33].
    [Show abstract] [Hide abstract] ABSTRACT: Oral mucosa under physiological condition contains a certain degree of chromic variation. Differentiating such physiological variations from pigmented lesions appears challenging without a histopathological confirmation. In several oral lesions, pigmentation is a part of the primary pathology or a secondary change to an existing entity. The pigments involved in both physiological and pathological conditions can be broadly categorised as exogenous or endogenous. Among these, melanin accounts for the majority of black to brown pigmentation including malignant melanoma. Clinically, their biological behaviour shows an ambiguity which makes it challenging to arrive at diagnosis for even the experienced practitioner. Although biopsy confirms and reassures the patient, it is impractical to biopsy all pigmented lesions. The standard diagnostic algorithm given below is to aid the clinician to diagnose and treat this diverse group of lesions.
    Full-text · Article · Jan 2015 · International Journal of Molecular Sciences
    • The intra-oral site most commonly affected is the buccal mucosa but involvement of other sites such as the mucosa of the lip, palate, gingiva and alveolar mucosa has also been reported (Table 1). Clinically, the lesion is a flat or slightly raised black or brown macule and may rapidly increase in size, ranging from a few millimeters to several centimeters [1,12,13]. The lesions are usually solitary and well circumscribed though a few authors have reported bilateral or multiple (Table 1) melanoacanthomas.
    [Show abstract] [Hide abstract] ABSTRACT: Oral melanoacanthoma is a rare, benign pigmented lesion characterized clinically by the sudden appearance and rapid growth of a macular brown-black lesion and histologically by acanthosis of the superficial epithelium and proliferation of dendritic melanocytes. We present a case report of oral melanoacanthoma in a 24-year-old Asian Indian man. He presented with an intra-oral brown macular lesion on the left buccal mucosa with a duration of one and a half months. Microscopic examination revealed acanthosis of stratified squamous surface epithelium and dendritic melanocytes diffusely distributed in the epithelium; the Masson-Fontana silver impregnation technique was used to demonstrate the dendritic melanocytes. Based on the history, clinical features and histological presentation, the lesion was diagnosed as melanoacanthoma. This is the first reported instance of oral melanoacanthoma in the Indian sub-continent. This report details the course of the lesion from diagnosis to its resolution. Melanoacanthoma must be differentiated from other intra-oral pigmented lesions and biopsy may be required to rule out melanoma.
    Full-text · Article · Feb 2009
    • The material should be injected lateral to the vocal cord at the level of the vocal process. Transnasal, Endoscopic [19] This approach can be performed in the office setting under topical anesthesia. A flexible telescope with a working channel is introduced transnasally to the level of the laryngopharynx.
    [Show abstract] [Hide abstract] ABSTRACT: Since it was first introduced in 1911, injection laryngoplasty has evolved into a versatile technique for the treatment of dysphonia in patients with a glottic insufficiency. Currently, there are a number of materials available for injection augmentation with duration of efficacy that may last from weeks to years. Furthermore, the various approaches available for injection have provided for injection laryngoplasty to be performed accurately in both the office and operating room.
    Article · Jun 2014
    • Indomethacin and diclofenac have been shown to induce cell cycle arrest and apoptosis in several cancer cell types [12], [20], [21], [22], [23], [24]. In our study, indomethacin and diclofenac reduced ovarian cancer cell growth, at least in part through the induction of cell cycle arrest in the three ovarian cancer cell lines examined.
    [Show abstract] [Hide abstract] ABSTRACT: Epidemiological studies have shown that the regular use of non-steroidal anti-inflammatory (NSAIDs) drugs is associated with a reduced risk of various cancers. In addition, in vitro and experiments in mouse models have demonstrated that NSAIDs decrease tumor initiation and/or progression of several cancers. However, there are limited preclinical studies investigating the effects of NSAIDs in ovarian cancer. Here, we have studied the effects of two NSAIDs, diclofenac and indomethacin, in ovarian cancer cell lines and in a xenograft mouse model. Diclofenac and indomethacin treatment decreased cell growth by inducing cell cycle arrest and apoptosis. In addition, diclofenac and indomethacin reduced tumor volume in a xenograft model of ovarian cancer. To identify possible molecular pathways mediating the effects of NSAID treatment in ovarian cancer, we performed microarray analysis of ovarian cancer cells treated with indomethacin or diclofenac. Interestingly, several of the genes found downregulated following diclofenac or indomethacin treatment are transcriptional target genes of E2F1. E2F1 was downregulated at the mRNA and protein level upon treatment with diclofenac and indomethacin, and overexpression of E2F1 rescued cells from the growth inhibitory effects of diclofenac and indomethacin. In conclusion, NSAIDs diclofenac and indomethacin exert an anti-proliferative effect in ovarian cancer in vitro and in vivo and the effects of NSAIDs may be mediated, in part, by downregulation of E2F1.
    Full-text · Article · Apr 2013
    • The lesions may be white, pink or erythematous. Lymph node involvement and distant metastasis are rare in VC. [3,5,6] VC occurs more frequently in males over the sixth decade. [5,6] Histopathologic and clinical diagnosis of oral VC may be difficult, so close cooperation between pathologist and surgeon is required in order to identify the nature of the lesion.
    [Show abstract] [Hide abstract] ABSTRACT: Verrucous carcinoma (VC) of oral cavity is a rare variant of well-differentiated squamous cell carcinoma and squamous papilloma is a benign proliferation of the stratified squamous epithelium, which results in a papillary or verrucous exophytic mass. There is a certain clinical similarity between squamous cell papilloma and VC. We presented a report of two cases which are VC and squamous cell papilloma that are showed the same clinical appearance but different pathological appearance, with a review of the literature.
    Full-text · Article · Oct 2015
    • A uniform scaling of 0.9533 was adopted for vibrational frequencies obtained from HF/6-311þþG (d, p) and a scaling factor of 0.9615 for B3LYP/6- 311þþG (d, p) method. The computed Raman activities (S i ) were converted to relative Raman intensities (I i ) using the equation [1] which was derived from the basic theory of Raman scattering [12,13].
    [Show abstract] [Hide abstract] ABSTRACT: Extensive quantum mechanical studies are carried out on Celecoxib (CXB), a new generation drug to understand the vibrational and electronic spectral characteristics of the molecule. The vibrational frequencies of CXB are computed by HF and B3LYP methods with 6-311++G (d, p) basis set. The theoretical scaled vibrational frequencies have been assigned and they agreed satisfactorily with experimental FT-IR and Raman frequencies. The theoretical maximum wavelength of absorption of CXB are calculated in water and ethanol by TD-DFT method and these values are compared with experimentally determined λmax values. The spectral and Natural bonds orbital (NBO) analysis in conjunction with spectral data established the presence of intra molecular interactions such as mesomeric, hyperconjugative and steric effects in CXB. The electron density at various positions and reactivity descriptors of CXB indicate that the compound functions as a nucleophile and establish that aromatic ring system present in the molecule is the site of drug action. Electronic distribution and HOMO – LUMO energy values of CXB are discussed in terms of intra-molecular interactions. Coputed values of Mulliken charges and thermodynamic properties of CXB are reported.
    Full-text · Article · May 2016
    • It is known that inherited polymorphisms of key genes may affect function and contribute to increased risk of tumour formation[32]. Identifying genes that are up or down regulated
    [Show abstract] [Hide abstract] ABSTRACT: This paper highlighted the peculiar clinical presentation of ameloblastoma in Black Africans. The recent reports of mutations associated with this tumour were highlighted. The authors proposed the formation of an African Ameloblastoma Research Network (AARN) to further explore mutations that may be peculiar to this population and may have diagnostic or therapeutic applications.
    Full-text · Article · Mar 2017 · International Journal of Molecular Sciences
    • In view of our findings and those of others in literature we suggest that the antioxidants possessing anticancer and apoptosis inducing activities mobilize copper ions, possibly endogenous chromatin-bound copper, and lead to the generation of reactive oxygen species [19,20]. Gossypol, a polyphenolic aldehyde produced in the roots, stem, and seeds of the cotton plant, has been shown to have antiproliferative property against a wide range of cancers (breast [21]; bladder [22]; pancreas [23]; lung [24]; colon [25]; prostate [26]; and head and neck [27,28]). Although gossypol is an effective antitumor compound in vitro, the toxicity of gossypol does not permit it to be used clinically.
    [Show abstract] [Hide abstract] ABSTRACT: There is compelling evidence that serum, tissue and intracellular levels of copper are elevated in all types of cancer. Copper has been suggested as an important co-factor for angiogenesis. It is also a major metal ion present inside the nucleus, bound to DNA bases, particularly guanine. We have earlier proposed that the interaction of phenolic-antioxidants with intracellular copper leads to the generation of reactive oxygen species (ROS) that ultimately serve as DNA cleaving agents. To further validate our hypothesis we show here that the antioxidant gossypol and its semi-synthetic derivative apogossypolone induce copper-mediated apoptosis in breast MDA-MB-231, prostate PC3 and pancreatic BxPC-3 cancer cells, through the generation of ROS. MCF10A breast epithelial cells refractory to the cytotoxic property of these compounds become sensitized to treatment against gossypol, as well as apogossypolone, when pre-incubated with copper. Our present results confirm our earlier findings and strengthen our hypothesis that plant-derived antioxidants mobilize intracellular copper instigating ROS-mediated cellular DNA breakage. As cancer cells exist under significant oxidative stress, this increase in ROS-stress to cytotoxic levels could be a successful anticancer approach.
    Full-text · Article · Jun 2016