scholarly journals Oral secretory leukocyte protease inhibitor (SLPI): Associations with oropharyngeal cancer and treatment outcome

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0254161
Author(s):  
Brittney L. Dickey ◽  
Bradley Sirak ◽  
Laura Martin-Gomez ◽  
Richard R. Reich ◽  
Martha Abrahamsen ◽  
...  
Keyword(s):  
Protease Inhibitor ◽  
Treatment Response ◽  
Oropharyngeal Cancer ◽  
Secretory Leukocyte Protease Inhibitor ◽  
Response To Treatment ◽  
Hpv Dna ◽  
The Us ◽  
Oral Hpv ◽  
Incomplete Treatment ◽  
Control Study

Background Rates of oropharyngeal cancer (OPC) associated with alcohol & tobacco use have decreased, while human papillomavirus (HPV) associated OPC has increased among men in the US. Secretory leukocyte protease inhibitor (SLPI), detectable in a variety of secretions, has been implicated in cancers of the head and neck, associated with tumor progression and anti-viral activity. Using the recently verified oral gargle specimen, this study aimed to assess the association of salivary SLPI expression with risk of OPC and response to treatment. Methods A case-control study design compared levels of salivary SLPI among OPC cases to age and tobacco smoking matched healthy controls. Oral HPV DNA and SLPI was quantified from oral gargle specimens. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (CI) for associations of oral SLPI and risk of OPC and treatment outcomes. Results In crude and adjusted analyses of 96 OPC cases and 97 age- and smoking-matched controls, OPC was not significantly associated with oral gargle SLPI levels. Among cases, oral SLPI was associated with tonsillectomy (p = 0.018) and among controls oral SLPI was associated with HPV in the oral gargle (p = 0.008). Higher concentrations of SLPI was significantly associated with increased odds of incomplete treatment response (T2: OR: 12.39; 95% CI: 1.44–106.72; T3: OR: 9.86; 95% CI: 1.13–85.90) among all cases, but not among P16+ cases. Conclusions Salivary SLPI was not associated with OPC risk but was associated with higher odds of an incomplete treatment response.

scholarly journals Prospective study evaluating dynamic changes of cell-free HPV DNA in locoregional viral-associated oropharyngeal cancer treated with induction chemotherapy and response-adaptive treatment

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Ari J. Rosenberg ◽  
Evgeny Izumchenko ◽  
Alexander Pearson ◽  
Zhen Gooi ◽  
Elizabeth Blair ◽  
...  
Keyword(s):  
Prospective Study ◽  
Treatment Response ◽  
Induction Chemotherapy ◽  
Oropharyngeal Cancer ◽  
Post Treatment ◽  
Smoking History ◽  
Dynamic Changes ◽  
Hpv Dna ◽  
Adaptive Treatment ◽  
Receive Treatment

Abstract Background Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) has a favorable prognosis which has led to efforts to de-intensify treatment. Response-adaptive de-escalated treatment is promising, however improved biomarkers are needed. Quantitative cell-free HPV-DNA (cfHPV-DNA) in plasma represents an attractive non-invasive biomarker for grading treatment response and post-treatment surveillance. This prospective study evaluates dynamic changes in cfHPV-DNA during induction therapy, definitive (chemo)radiotherapy, and post-treatment surveillance in the context of risk and response-adaptive treatment for HPV + OPC. Methods Patients with locoregional HPV + OPC are stratified into two cohorts: High risk (HR) (T4, N3, $$\ge$$ ≥ 20 pack-year smoking history (PYH), or non-HPV16 subtype); Low risk (LR) (all other patients). All patients receive induction chemotherapy with three cycles of carboplatin and paclitaxel. LR with ≥ 50% response receive treatment on the single-modality arm (minimally-invasive surgery or radiation alone to 50 Gy). HR with ≥ 50% response or LR with ≥ 30% and < 50% response receive treatment on the intermediate de-escalation arm (chemoradiation to 50 Gy with cisplatin). All other patients receive treatment on the regular dose arm with chemoradiation to 70 Gy with concurrent cisplatin. Plasma cfHPV-DNA is assessed during induction, (chemo)radiation, and post-treatment surveillance. The primary endpoint is correlation of quantitative cfHPV-DNA with radiographic response. Discussion A de-escalation treatment paradigm that reduces toxicity without compromising survival outcomes is urgently needed for HPV + OPC. Response to induction chemotherapy is predictive and prognostic and can select candidates for de-escalated definitive therapy. Assessment of quantitative cfHPV-DNA in the context of response-adaptive treatment of represents a promising reliable and convenient biomarker-driven strategy to guide personalized treatment in HPV + OPC. Trial registration This trial is registered with ClinicalTrials.gov on October 1st, 2020 with Identifier: NCT04572100.

Oral HPV infection in HPV-positive oropharyngeal cancer cases and their spouses.

2013 ◽  
Vol 31 (18_suppl) ◽  
pp. CRA6031-CRA6031 ◽  
Author(s):  
Gypsyamber D'Souza ◽  
Neil D. Gross ◽  
Sara I. Pai ◽  
Robert I. Haddad ◽  
Maura L. Gillison ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Oropharyngeal Cancer ◽  
Oral Sex ◽  
Computer Assisted ◽  
Hpv Dna ◽  
Oral Rinse ◽  
History Of ◽  
Oral Hpv ◽  
Never Smokers ◽  
One Year

CRA6031 Background: Incidence of human papillomavirus-positive oropharyngeal cancer (HPV-OPC) is increasing, and spouses of these patients have high anxiety about their own HPV-related cancer risk. Methods: Partner study of 149 HPV-OPC and 81 of their spouse/long-term partners. Data collection included a 30-second rinse and gargle (at diagnosis and again 1 year later for 103 cases and 46 partners), computer-assisted risk factor survey, tumor collection (cases), and visual oral examination (spouses). Oral rinse samples were tested for 36 types of HPV DNA using PGMY09/11 primers and line-blot amplification, and HPV16 copy-number using real-time PCR. Results: Cases were primarily male (89%), white non-Hispanic (92%), had performed oral sex (94%), and never-smokers (51%) with a median age of 56 years. Twelve-month survival was high among never- and ever-smoking HPV-OPC (100% vs 93%, p=0.18). The 81 spouses of HPV-OPC were primarily female (81%), white non-Hispanic (92%), never-smokers (54%), with a median age of 53 years. Spouses were significantly less likely than cases to have >10 lifetime oral sex partners (11% vs 39%, p<0.001). Prevalence of any oral HPV (65%) and oral HPV16 (52%) was high among HPV-OPC at diagnosis. Four (7.7%) of 52 HPV-OPC with HPV16 DNA detectable before therapy, had HPV16 persistently detected one year after diagnosis/therapy. Prevalence of any oral HPV DNA among partners was significantly lower than among HPV-OPC (7.3% vs 65%, p<0.001). Oral HPV prevalence was significantly higher among the 7 male partners than the 74 female partners (29% vs 5%, p=0.025). Oral HPV infections among partners included HPV16 (n=2), HPV62 (n=2), HPV 83 and 51 (1 each). Both partners with oral HPV16 infections were female and no longer had oral HPV16 detected at the one year follow-up. 64% of spouses had a visual oral exam, and no pre-cancers or cancers were identified. However, two (2.5%) enrolled spouses reported a personal history of cervical cancer, and 6 HPV-HNC cases (4.0%) reported a previous spouse who developed cervical or vaginal cancer. Conclusions: Oral HPV16 DNA is common among HPV-OPC, but not among their spouses. Spouses of HPV-OPC may have an elevated risk or history of cervical cancer.

scholarly journals Intralesional measles, mumps, and rubella vaccine for the treatment of recalcitrant warts: A case series and review of literature

2020 ◽  
Vol 0 ◽  
pp. 1-6
Author(s):  
Bini Chandran
Keyword(s):  
Treatment Response ◽  
Adverse Reactions ◽  
Case Series ◽  
Complete Response ◽  
Response To Treatment ◽  
Review Of Literature ◽  
Mmr Vaccine ◽  
Rubella Vaccine ◽  
Intralesional Treatment ◽  
Incomplete Treatment

Objectives: To document the response of recalcitrant warts to intralesional measles, mumps, and rubella (MMR) vaccine. Materials and Methods: This case series reports the treatment response to intralesional MMR vaccine observed in 11 patients who attended the dermatology outpatient department with recalcitrant warts of more than 1 year duration. Only the largest wart was treated in each case. The intralesional treatment was repeated at an interval of 2 weeks. Results: Nine patients (81.9%) showed complete response to treatment. One patient did not return for treatment after two sessions (9.1%). One showed incomplete treatment response (9.1%). The adverse reactions noted among the 11 patients were pain (3/11, 27.3%) and secondary bacterial infection (1/11, 9.1%). Limitations: Results are based on a case series of 11 patients. Conclusion: Intralesional MMR vaccine was found effective and safe in the management of recalcitrant warts.

scholarly journals Oral Human Papillomavirus (HPV) Infection in HPV-Positive Patients With Oropharyngeal Cancer and Their Partners

2014 ◽  
Vol 32 (23) ◽  
pp. 2408-2415 ◽  
Author(s):  
Gypsyamber D'Souza ◽  
Neil D. Gross ◽  
Sara I. Pai ◽  
Robert Haddad ◽  
Karen S. Anderson ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
General Population ◽  
Oropharyngeal Cancer ◽  
Quantitative Polymerase Chain Reaction ◽  
Invasive Cervical Cancer ◽  
Hpv Infection ◽  
Hpv Dna ◽  
Oral Rinse ◽  
Hpv Prevalence ◽  
Oral Hpv

Purpose To better understand oral human papillomavirus (HPV) infection and cancer risk among long-term sexual partners of patients with HPV-positive oropharyngeal cancer (HPV-OPC). Patients and Methods An oral rinse sample, risk factor survey, cancer history, and oral examination (partners only) were collected from patients with HPV-OPC and their partners. Oral rinse samples were evaluated for 36 types of HPV DNA using PGMY 09/11 primers and line-blot hybridization and HPV16 copy number using quantitative polymerase chain reaction. Oral HPV prevalence was compared with infection among those age 45 to 65 years using National Health and Nutrition Examination Survey (NHANES) 2009-2010. Results A total of 164 patients with HPV-OPC and 93 of their partners were enrolled. Patients were primarily men (90%), were never-smokers (51%), and had performed oral sex (97%), with a median age of 56 years; they had a high prevalence of oncogenic oral HPV DNA (61%) and oral HPV16 DNA (54%) at enrollment. Female partners had comparable oncogenic oral HPV prevalence compared with members of the general population of the same age (1.2% v 1.3%). Among the six male partners, no oncogenic oral HPV infections were detected. No precancers or cancers were identified during partner oral cancer screening examinations. However, a history of cervical disease was reported by nine partners (10.3%) and two female patients (11.8%), and three patients (2.0%) reported a previous partner who developed invasive cervical cancer. Conclusion Oral HPV16 DNA is commonly detected among patients with HPV-OPC at diagnosis, but not among their partners. Partners of patients with HPV-OPC do not seem to have elevated oral HPV infection compared with the general population.

scholarly journals Biomarkers predictive of treatment response in psoriasis and psoriatic arthritis: a systematic review

2021 ◽  
Vol 13 ◽  
pp. 1759720X2110140
Author(s):  
Conor Magee ◽  
Hannah Jethwa ◽  
Oliver M. FitzGerald ◽  
Deepak R. Jadon
Keyword(s):  
Systematic Review ◽  
Psoriatic Arthritis ◽  
Treatment Response ◽  
Unmet Need ◽  
Response To Treatment ◽  
Cochrane Library ◽  
Original Research ◽  
Eligibility Criteria ◽  
Psoriatic Disease ◽  
Subsequent Response

Aims: The ability to predict response to treatment remains a key unmet need in psoriatic disease. We conducted a systematic review of studies relating to biomarkers associated with response to treatment in either psoriasis vulgaris (PsV) or psoriatic arthritis (PsA). Methods: A search was conducted in PubMed, Embase and the Cochrane library from their inception to 2 September 2020, and conference proceedings from four major rheumatology conferences. Original research articles studying pre-treatment biomarker levels associated with subsequent response to pharmacologic treatment in either PsV or PsA were included. Results: A total of 765 articles were retrieved and after review, 44 articles (22 relating to PsV and 22 to PsA) met the systematic review’s eligibility criteria. One study examined the response to methotrexate, one the response to tofacitinib and all the other studies to biologic disease-modifying antirheumatic drugs (DMARDs). Whilst several studies examined the HLA-C*06 allele in PsV, the results were conflicting. Interleukin (IL)-12 serum levels and polymorphisms in the IL-12B gene show promise as biomarkers of treatment response in PsV. Most, but not all, studies found that higher baseline levels of C-reactive protein (CRP) were associated with a better clinical response to treatment in patients with PsA. Conclusion: Several studies have identified biomarkers associated with subsequent response to treatment in psoriatic disease. However, due to the different types of biomarkers, treatments and outcome measures used, firm conclusions cannot be drawn. Further validation is needed before any of these biomarkers translate to clinical practice.

scholarly journals Discovering Non-Invasive Biomarkers Predictive of Opioid Use Disorder Treatment Response

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 173-173
Author(s):  
Amir Levine ◽  
Kelly Clemenza ◽  
Shira Weiss ◽  
Adam Bisaga ◽  
Erez Eitan ◽  
...  
Keyword(s):  
Treatment Response ◽  
Mononuclear Cells ◽  
Specific Treatment ◽  
The United States ◽  
Opioid Use Disorder ◽  
Response To Treatment ◽  
Post Translational Modification ◽  
Opioid Use ◽  
Peripheral Blood Mononuclear ◽  
Long Term Treatment

AbstractBackgroundOpioid use disorder (OUD) continues to be the driving force behind drug overdoses in the United States, killing nearly 47,000 people in 2018 alone. The increasing presence of deadlier fentanyl analogues in the heroin drug supply are putting users at a greater risk for overdose than ever before. Admissions to treatment programs for OUD have also nearly doubled since 2006, yet relapse rates remain high. In response to these alarming statistics, developing approaches to reduce overdose deaths has become an area of high priority. As it is not yet known which patients are most likely to benefit from a specific treatment, there is a dire need to utilize new molecular tools to guide precision medicine approaches and improve treatment outcomes. Here we describe a proof-of-concept study evaluating plasma-derived extracellular vesicle (EV) signatures and how they differ in patients who responded to two pharmacologically contrasting treatments for OUD: the μOR agonist methadone, and the μOR antagonist naltrexone.MethodsWe obtained blood samples from patients with OUD who remained abstinent from illicit opioids for at least 3 months during treatment with methadone (n=5) and naltrexone (n=5), as well as matched healthy controls (n=5). EVs were isolated from plasma and histones were isolated from peripheral blood mononuclear cells (PBMCs). EVs were then analyzed for lipid and histone post-translational modification (PTM) content using liquid chromatography-mass spectrometry. EV miRNA cargo was determined by RNA sequencing.ResultsWe found one lipid class and six miRNAs that differed significantly between the naltrexone group and the methadone and control groups. We also found that histone H3acK9acK14 was increasingly acetylated in PMBCs from both the methadone and naltrexone groups compared to controls.DiscussionNaltrexone, which is used in treatment of OUD and other substance use disorders as well as disorders of impulse control, was found to have multiple potential corresponding molecular signatures that can be identified after long-term treatment. It remains to be seen if these markers can also be a good predictor for treatment response. In addition, significant gender differences in EV content are found between men and women with OUD, which supports the importance of examining changes in response to treatment in a gender informed way.

Role of the norepinephrine transporter polymorphisms in atomoxetine treatment: From response to side effects in children with ADHD

2021 ◽  
pp. 026988112110152
Author(s):  
Melike Kevser Gul ◽  
Elif Funda Sener ◽  
Muge Gulcihan Onal ◽  
Esra Demirci
Keyword(s):  
Side Effects ◽  
Treatment Response ◽  
Large Population ◽  
Norepinephrine Transporter ◽  
Response To Treatment ◽  
Nucleotide Polymorphisms ◽  
Children With Adhd ◽  
Real Time Quantitative Pcr ◽  
Treatment Side Effects ◽  
Adhd Treatment

Objective: Atomoxetine (ATX), one of the most commonly used drugs after stimulants in attention deficit hyperactivity disorder (ADHD) treatment, is an inhibitor of the norepinephrine transporter ( NET/SLC6A2), which is also associated with the etiology of ADHD. In this study, we aimed to investigate the effect of NET gene polymorphisms on response to ATX treatment and to find the answers to the questions about whether there is a relationship between the severity of the disorder and the observed side effects in children with ADHD. Method: About 100 children with ADHD and 80 healthy controls (HCs) were included in this study. The dose of ATX was started at 0.5 mg/kg/day and titrated at 1.2 mg/kg/day. Response to treatment of 78 patients was evaluated 2 months after the beginning of the treatment. After whole blood samples were obtained, DNAs were isolated, and samples were stored at −80°C. Two single-nucleotide polymorphisms (SNPs) (rs12708954 and rs3785143) were analyzed by real-time quantitative PCR (qRT-PCR). Results: The patients with both rs12708954 and rs3785143 heterozygous genotype had better treatment response and more side effects than patients with wild type. There was not found any association between any of the investigated NET polymorphisms and ADHD severity. Conclusion: It was, however, found that the NET rs12708954 and rs3785143 genotypes affect the treatment response to ATX in our study; thus, further studies with a large population are needed to understand the effects of NET polymorphisms on treatment, side effects, and also the severity of ADHD.

scholarly journals SLPI is a critical mediator that controls PTH-induced bone formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Akito Morimoto ◽  
Junichi Kikuta ◽  
Keizo Nishikawa ◽  
Takao Sudo ◽  
Maki Uenaka ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Bone Formation ◽  
Protease Inhibitor ◽  
Bone Metabolism ◽  
Serine Protease ◽  
Serine Protease Inhibitor ◽  
Secretory Leukocyte Protease Inhibitor ◽  
Bone Imaging ◽  
Genetic Ablation

AbstractOsteoclastic bone resorption and osteoblastic bone formation/replenishment are closely coupled in bone metabolism. Anabolic parathyroid hormone (PTH), which is commonly used for treating osteoporosis, shifts the balance from osteoclastic to osteoblastic, although it is unclear how these cells are coordinately regulated by PTH. Here, we identify a serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI), as a critical mediator that is involved in the PTH-mediated shift to the osteoblastic phase. Slpi is highly upregulated in osteoblasts by PTH, while genetic ablation of Slpi severely impairs PTH-induced bone formation. Slpi induction in osteoblasts enhances its differentiation, and increases osteoblast–osteoclast contact, thereby suppressing osteoclastic function. Intravital bone imaging reveals that the PTH-mediated association between osteoblasts and osteoclasts is disrupted in the absence of SLPI. Collectively, these results demonstrate that SLPI regulates the communication between osteoblasts and osteoclasts to promote PTH-induced bone anabolism.

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