Alice L. Tang

UM-SCC-104: A New human papillomavirus-16–positive cancer stem cell–containing head and neck squamous cell carcinoma cell line†

Few human papillomavirus (HPV)(+) head and neck squamous cell carcinoma (HNSCC) cell lines exist. We established University of Michigan‐squamous cell carcinoma‐104 (UM‐SCC‐104), a new HPV(+) HNSCC cell line from a recurrent oral cavity tumor, and characterized it for the presence of cancer stem cells (CSCs).

The nasal cavity microbiota of healthy adults

BackgroundThe microbiota of the nares has been widely studied. However, relatively few studies have investigated the microbiota of the nasal cavity posterior to the nares. This distinct environment has the potential to contain a distinct microbiota and play an important role in health.ResultsWe obtained 35,142 high-quality bacterial 16S rRNA-encoding gene sequence reads from the nasal cavity and oral cavity (the dorsum of the tongue and the buccal mucosa) of 12 healthy adult humans and deposited these data in the Sequence Read Archive (SRA) of the National Center for Biotechnology Information (NCBI) (Bioproject: PRJNA248297). In our initial analysis, we compared the bacterial communities of the nasal cavity and the oral cavity from ten of these subjects. The nasal cavity bacterial communities were dominated by Actinobacteria, Firmicutes, and Proteobacteria and were statistically distinct from those on the tongue and buccal mucosa. For example, the same Staphylococcaceae operational taxonomic unit (OTU) was present in all of the nasal cavity samples, comprising up to 55% of the community, but Staphylococcaceae was comparatively uncommon in the oral cavity.ConclusionsThere are clear differences between nasal cavity microbiota and oral cavity microbiota in healthy adults. This study expands our knowledge of the nasal cavity microbiota and the relationship between the microbiota of the nasal and oral cavities.

Sensitization of Head and Neck Cancer to Cisplatin Through the Use of a Novel Curcumin Analog

OBJECTIVE To determine whether a novel small molecule inhibitor derived from curcumin (FLLL32) that targets signal transducer and activator of transcription (STAT) 3 would induce cytotoxic effects in STAT3-dependent head and neck squamous cell cancer (HNSCC) cells and would sensitize tumors to cisplatin. DESIGN Basic science. Two HNSCC cell lines, UM-SCC-29 and UM-SCC-74B, were characterized for cisplatin [cis-diammineplatinum(II) dichloride] sensitivity. Baseline expression of STAT3 and other apoptosis proteins was determined. The FLLL32 50% inhibitory concentration (IC(50)) dose was determined for each cell line, and the effect of FLLL32 treatment on the expression of phosphorylated STAT3 and other key proteins was elucidated. The antitumor efficacy of cisplatin, FLLL32, and combination treatment was measured. The proportion of apoptotic cells after cisplatin, FLLL32, or combination therapy was determined. RESULTS The UM-SCC-29 cell line is cisplatin resistant, and the UM-SCC-74B cell line is cisplatin sensitive. Both cell lines express STAT3, phosphorylated STAT3 (pSTAT3), and key apoptotic proteins. FLLL32 downregulates the active form of STAT3, pSTAT3, in HNSCC cells and induces a potent antitumor effect. FLLL32, alone or with cisplatin, increases the proportion of apoptotic cells. FLLL32 sensitized cisplatin-resistant cancer cells, achieving an equivalent tumor kill with a 4-fold lower dose of cisplatin. CONCLUSIONS FLLL32 monotherapy induces a potent antitumor effect and sensitizes cancer cells to cisplatin, permitting an equivalent or improved antitumor effect at lower doses of cisplatin. Our results suggest that FLLL32 acts by inhibiting STAT3 phosphorylation, reduced survival signaling, increased susceptibility to apoptosis, and sensitization to cisplatin.

Head and Neck Cancer Stem Cells The Effect of HPV—An In Vitro and Mouse Study

Objectives To determine if the behavior of cancer stem cells (CSCs) is affected by human papillomavirus (HPV) status. Study Design An in vitro and in vivo analysis of HPV and CSCs. Setting University laboratory. Subjects and Methods We isolated CSCs from HPV-positive and HPV-negative cell lines. Two HPV-negative cell lines underwent lentiviral transduction of E6/E7. Chemoresistence was determined using colony formation assays. Native HPV-positive and HPV E6/E7-transduced cells were compared for lung colonization after tail vein injection in NOD/SCID mice. Results The proportion of CSC is not significantly different in HPV-positive or HPV-negative head and neck squamous cell carcinoma (HNSCC) cell lines. The HNSCC CSCs are more resistant to cisplatin than the non-CSCs, but there were no significant differences between HPV-positive and HPV-negative cells. The HPV-negative cancer cells yielded low colony formation after cell sorting. After transduction with HPV E6/E7, increased colony formation was observed in both CSCs and non-CSCs. Results from tail vein injections yielded no differences in development of lung colonies between HPV E6/E7-transduced cells and nontransduced cells. Conclusions Human papillomavirus status does not correlate with the proportion of CSCs present in HNSCC. The HPV-positive cells and those transduced with HPV E6/E7 have a greater clonogenicity than HPV-negative cells. The HNSCC CSCs are more resistant to cisplatin than non-CSCs. This suggests that common chemotherapeutic agents may shrink tumor bulk by eliminating non-CSCs, whereas CSCs have mechanisms that facilitate evasion of cell death. Human papillomavirus status does not affect CSC response to cisplatin therapy, suggesting that other factors explain the better outcomes for patients with HPV-positive cancer.

Influence of Tonsillar Size on OSA Improvement in Children Undergoing Adenotonsillectomy

Objective To determine if pediatric obstructive sleep apnea (OSA) improves after adenotonsillectomy (AT) regardless of tonsil size. Study Design Case series with chart review. Setting Pediatric Otolaryngology Department, Johns Hopkins Hospital. Subjects Seventy children 1 to 18 years of age who underwent polysomnography (PSG) before and after AT. Methods Tonsil size was evaluated using the Brodsky grading scale. Results Children were stratified by tonsil size as 2+ (n = 20), 3+ (n = 36), and 4+ (n = 14). There was a significant improvement in obstructive apnea-hypopnea index (oAHI), apnea index (AI), and saturation nadir across all 3 groups after AT. Preoperative oAHI, AI, and hypopnea index (HI) were similar regardless of tonsil size (P > .05). Overall, oAHI improved from a median of 11.8 ± 21.7 to 2.0 ± 6.1 events/h, with 40% (28/70) of children having complete resolution. The oAHI (P < .0001-0.02), AI (P < .0001-0.017), HI (P < .0001-0.058), and saturation nadir (P < .0001-0.017) significantly improved for the 2+, 3+, and 4+ groups. Only the HI (P = .058) in the 2+ group did not. The median oAHI improvement was 3.4 ± 26.4 events/h in the 2+ group, 8.3 ± 16.6 events/h in the 3+ group, and 12.3 ± 19.5 events/h in the 4+ group, with 25% (5/20), 50% (18/36), and 36% (5/14), respectively, having complete resolution. There was no correlation between OSA severity and tonsil or adenoid size (P > .32). Conclusion Tonsil size did not correlate with OSA severity. While a larger proportion of patients classified as 3+ and 4+ had complete resolution after surgery, significant improvement was seen in AI and saturation nadir even in those classified as 2+.

Head and neck squamous cell carcinoma in pregnant women.

The aim of this study was to investigate oral cancer in pregnant women, a rare but therapeutically challenging patient subset.

Epigenetic alterations in metastatic cutaneous carcinoma

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) are the 2 most common cutaneous carcinomas. Molecular profiles predicting metastasis of these cancers have not been identified.

Integration of high-risk human papillomavirus into cellular cancer-related genes in head and neck cancer cell lines: HPV integration into cancer genes in HNSCC cell lines

Human papillomavirus (HPV)‐positive oropharyngeal cancer is generally associated with excellent response to therapy, but some HPV‐positive tumors progress despite aggressive therapy. The purpose of this study was to evaluate viral oncogene expression and viral integration sites in HPV16‐ and HPV18‐positive squamous cell carcinoma lines.

Gaps in evidence: Management of pediatric obstructive sleep apnea without tonsillar hypertrophy

Persistent obstructive sleep apnea (OSA) is demonstrated in 40% of children after adenotonsillectomy. We previously evaluated the basis of management decisions in children with OSA without tonsillar hypertrophy and found that 61% of decisions were non–evidence based. The aim of this study was to identify gaps in evidence for the management of children with OSA without tonsillar hypertrophy.

Decision Making for Children with Obstructive Sleep Apnea without Tonsillar Hypertrophy

Objective Evidence-based medicine is the gold standard practice model for patient management. Our aim was to determine whether decisions made by pediatric subspecialists regarding management of obstructive sleep apnea in children without tonsillar hypertrophy adhered to this model or were based on clinical experiences. Study Design Single-institution prospective study. Setting Multidisciplinary upper airway center in an academic pediatric hospital. Subjects and Methods Twelve pediatric subspecialists representing 8 specialties participating in upper airway clinics and management conferences. Real-time decisions made in treatment conferences and upper airway clinics were collected. Physicians were queried regarding the basis of their decisions, and these decisions were then classified into 10 categories. Results Over 13 days (10 case conferences, 3 half-day clinics), 324 decisions were made for 58 patients (mean age = 8.9 ± 7.4 years, mean body mass index percentile = 75 ± 29); 34% (n = 108) of decisions were evidence based; 59% (n = 193) were nonevidence based; and 7% (n = 23) were based on parental preference. Providers were able to cite specific studies for <20% of these decisions. There was no significant increase in the proportion of evidence-based decisions made over time. Conclusions We deemed 34% of decisions regarding the management of obstructive sleep apnea in children without tonsillar hypertrophy to be evidence based and found that sharing the basis for decisions did not improve the percentage of evidence-based decisions over time. These findings reflect significant evidence gaps and highlight the need for a systematic literature evaluation to identify best practice in managing this population. We recommend that these evidence gaps be further characterized and incorporated into an agenda for future research.