HPV(-) OCSCC resists radiation treatment. The
gene, encoding p16INK4A, is commonly disrupted in OCSCC. p16 inhibits CDK4/CDK6, leading to cell cycle arrest, but the biological sequelae of CDK4/6 ...inhibition in OCSCC remains understudied. This study examines whether inhibition of CDK4/6 enhances radiation response in OCSCC.
MTT assays were performed in OCSCC cell lines HN5 and CAL27 following treatment with palbociclib. Clonogenic survival and synergy were analyzed after radiation (RT-2 or 4Gy), palbociclib (P) (0.5 µM or 1 µM), or concurrent combination treatment (P+RT). DNA damage/repair and senescence were examined. CDK4/6 were targeted via siRNA to corroborate P+RT effects. Three-dimensional immortalized spheroids and organoids derived from patient tumors (conditionally reprogrammed OCSCC CR-06 and CR-18) were established to further examine and validate responses to P+RT.
P+RT demonstrated reduced viability and synergy, increased β-gal expression (~95%), and ~two-fold higher γH2AX. Rad51 and Ku80 were reduced after P+RT, indicating impairment of
HR and NHEJ. siCDK4/6 increased senescence with radiation. Spheroids showed reduced proliferation and size with P+RT. CR-06 and CR-18 further demonstrated three-fold reduced proliferation and organoids size with P+RT.
Targeting CDK4/6 can lead to improved efficacy when combined with radiation in OCSCC by inducing senescence and inhibiting DNA damage repair.
Objective: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) related to human papillomavirus (HPV) is increasing at a dramatic rate, with men affected more commonly than women. ...Individuals who develop this disease suffer significant morbidity and potential mortality from their cancer and its associated treatment. We aim to evaluate the possible impact that the currently available HPV vaccines will have on this group of cancers. Data sources: Available peer-reviewed literature, practice guidelines, and statistics published by the Center for Disease Control and Prevention. Review methods: Contemporary peer-reviewed medical literature was selected based on its scientific validity and relevance to the impact HPV vaccination may have on the morbidity, mortality and cost resulting from HPV-related OPSCC in the United States. Conclusions: The incidence of HPV-related OPSCC is increasing at a near epidemic rate in the United States. The cost of treatment of HPV-related OPSCC is high, and the disease and its therapy result in significant morbidity and potential mortality to individuals. Using a cut-off of $50,000/Quality-Adjusted Life Year, expansion of current HPV vaccine indications to include prevention of OPSCC in both men and women should be recommended.
Crohn's disease (CD) is an inflammatory disease that can affect any portion of the gastrointestinal tract (GIT). Although it can present with a number of complications, perianal fistulae are among ...the most common consequences in patients with CD. In very rare cases, these patients can develop fistula-associated anal adenocarcinoma (FAAA). In this case report, we discuss a 72-year-old man with a long-term history of CD complicated by perianal fistulae, which failed medical and surgical management, ultimately presenting with acute anal pain in the outpatient setting. The physical examination revealed a seton traversing through a fistula surrounded by circumferential granulation tissue suspicious for malignancy. A biopsy of the tissue confirmed grade 3 mucinous-type infiltrating adenocarcinoma of the perianal skin. The patient was diagnosed with an anal verge malignancy associated with a fistula in the context of long-standing CD, and MRI staging demonstrated a T3N1 lesion with potential left inguinal node involvement. He completed neoadjuvant chemo-radiotherapy using capecitabine for five weeks with minimal tumor response, and subsequently, an abdominoperineal resection (APR) was performed with patient discharge on the fifth post-procedure day. Post-operative chemotherapy with oxaliplatin/leucovorin/fluorouracil was administered with minimal complications. Although rare, this report demonstrates the importance of consistent follow-up and mitigation of risk factors in patients with CD, along with the significance of prompt multimodal treatment in the event of developing FAAA.
The role of restorativeness in attracting and retaining people on commercial streets has been under-researched. To examine this topic, this convergent parallel mixed methods study was conducted on ...four commercial streets in Brazil. It included a quantitative evaluation of correlations between a set of microscale aspects of commercial streets and liveliness, and a qualitative thematic analysis of users' experiences informed by the Attention Restoration Theory. The results showed restorativeness as one pathway linking microscale aspects of commercial streets to liveliness. The perceived restorative potential of microscale aspects of commercial streets should be considered when adopting fine-grained approaches to enhance their liveliness.
Words, type and letters - as signs and artifacts - have an immense promise to convey meaning in the urban environment. Letterforms are the 'architecture of language' (Baines and Haslam, 2005) - they ...build narratives, and create inquisitive interpretive spaces through which the reader experiences meaning. Typography and letterforms can possibly be perceived and defined in two ways - functional (legibility) and visual (formal). The utilitarian domain of typography is a prerequisite for effective communication, but letterforms have also been an unsolved quest for designers to explore and qualify various other more ephemeral dimensions of communication. Unique to letterforms is the distinctive manner in which they can be used to occupy space, convey characteristics, portray personality and physique, and situate dimensionally or even be associated with variety of emotions. Type is an art form, providing immense pleasure to the everyday observer, reader and speculator.
The quality of public space, as manifest in the city, is one of the closest measures of the state of the public sphere and as succinctly described by Low and Smith (2006), ‘…An understanding of ...public space is an imperative for understanding the public sphere.’ With the burgeoning interest in the urban, the focus on people along with form and space, there is an increasing relevance of public space. As a result, urban designers, planners and managing agencies that have to plan, design, deliver and manage public space are confronted with an important pragmatic question: how to measure and evaluate the performance of public space? Scholars have been trying to address this explicitly and several very good measures of public space have emerged in the recent past.
Purpose: The objective of this study is to determine if there is a significant correlation between race/ethnicity and total thyroid volume among patients with benign thyroid disease. Our hypothesis ...is that patients of racial and ethnic minorities may present with enlarged, non-cancerous thyroids more frequently than white patients.
Methods: This is a retrospective cohort study of 457 patients diagnosed with benign thyroid disease between 2008 and 2020 at Montefiore Medical Center. Data were taken from an existing database and the electronic health record. The primary outcome was total thyroid volume (cm3/mL) calculated from ultrasound measurements. The secondary outcome was the maximum dimension (cm) of the largest thyroid nodule.
Results: Black patients had a mean thyroid volume (± standard deviation) of 142.7±131.1 cm3/mL and a mean maximum nodule dimension of 4.3±1.9 cm. White patients had a mean thyroid volume of 74.7±128.0 cm3/mL and a mean maximum nodule size of 3.0±1.5 cm. Race was significantly correlated with total thyroid volume (P=0.0007). Black race specifically was significantly correlated with total thyroid volume (95% confidence interval CI, 0.209 to 0.794; P=0.0008) and maximum nodule dimension (95% CI, 0.006 to 1.278; P=0.05).
Conclusion: Black patients had significantly larger total thyroid volumes and nodules compared to white patients. Thyroid volume was not associated with measures of socioeconomic status such as insurance type or estimated income. Although these findings illustrate an important relationship between race and thyroid volume, further research is required to determine the etiology of this discrepancy. KCI Citation Count: 0
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