Immunization with an mRNA DTP vaccine protects against pertussis in rats.

is a Gram-negative bacterium that is the causative agent of the respiratory disease known as pertussis. Since the switch to the acellular vaccines of DTaP and Tap, pertussis cases in the US have risen and cyclically fallen. We have observed that mRNA pertussis vaccines are immunogenic and protective in mice.

Intranasal challenge with B. pertussis leads to more severe disease manifestations in mice than aerosol challenge.

The murine Bordetella pertussis challenge model has been utilized in preclinical research for decades. Currently, inconsistent methodologies are employed by researchers across the globe, making it difficult to compare findings. The objective of this work was to utilize the CD-1 mouse model with two routes of challenge, intranasal and aerosol administration of B.

State Marijuana Laws and Marijuana Use Among Sexual and Gender Minority Youth in the United States.

The purpose of this study was to explore the association between state-level marijuana policies and marijuana use among sexual and gender minority (SGM) adolescents. A secondary analysis was conducted using a nonprobability sample, the 2017 , based on 10,027 youth who reported their marijuana use behaviors and state of residence. Random intercept multilevel models were estimated to account for between- and within-state variability.

Substance Use and Healthcare Utilization Across the Pre-Exposure Prophylaxis (PrEP) Care Cascade among Black and Latino Men Who Have Sex with Men.

 Despite the documented efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention, large disparities in uptake and adherence exist among Black and Latino/Hispanic men who have sex with men (BLMSM). Limited data exists among BLMSM on the impact of substance use at different stages of the PrEP Care Cascade. We examined the ways substance (alcohol, cannabis, other drug) use is related to PrEP experiences across the PrEP Care Cascade (PrEP aware/no use; PrEP use/discontinuation; PrEP use/adherent).

Intranasal administration of BReC-CoV-2 COVID-19 vaccine protects K18-hACE2 mice against lethal SARS-CoV-2 challenge.

SARS-CoV-2 is a viral respiratory pathogen responsible for the current global pandemic and the disease that causes COVID-19. All current WHO approved COVID-19 vaccines are administered through the muscular route. We have developed a prototype two-dose vaccine (BReC-CoV-2) by combining the Receptor Binding Domain (RBD) antigen, via conjugation to Diphtheria toxoid (EcoCRM).

LGBTQ state policies: A lever for reducing SGM youth substance use and bullying.

Purpose: Sexual and gender minority youth (SGMY) are more likely than their cisgender and heterosexual peers to use substances and to be bullied, yet it is unknown whether the absence/presence of youth- and LGBTQ-specific equity laws drive these disparities. The purpose of this study was to extend previous research focused on adult- and LGBTQ-specific structural factors (e.g.

Teacher Support, Victimization, and Alcohol Use Among Sexual and Gender Minority Youth: Considering Ethnoracial Identity.

Although scholarship continues to document higher rates of alcohol use for sexual and gender minority (SGM) youth compared with heterosexual and cisgender youth, research identifying factors that mitigate SGM youths' risk is nascent. Youth spend substantial time in schools; therefore, teachers could play significant roles in attenuating these health concerns. We used data from a nationwide survey of 11,189 SGM youth (M = 15.

Population pharmacokinetics of clofarabine and its metabolite 6-ketoclofarabine in adult and pediatric patients with cancer.

Clofarabine for injection is a second-generation nucleoside analog approved in the United States (Clolar(®)) and Europe (Evoltra(®)) for the treatment of pediatric relapsed or refractory acute lymphoblastic leukemia. This report describes the population pharmacokinetics of clofarabine and its metabolite 6-ketoclofarabine in adult and pediatric patients with hematologic malignancies or solid tumors. Clofarabine pharmacokinetics were best described by a 2-compartment model with linear elimination and first-order absorption after oral administration.

Phase II assessment of talabostat and cisplatin in second-line stage IV melanoma.

Background: Metastatic melanoma is an incurable disease with an average survival of less than one year. Talabostat is a novel dipeptidyl peptidase inhibitor with immunostimulatory properties.

Methods: This phase II, open label, single arm study was conducted to evaluate the safety and efficacy of 75-100 mg/m2 cisplatin combined with 300-400 mcg talabostat bid for 6, 21-day cycles.

RLIP76 and Cancer.

RLIP76 is a multifunctional membrane protein that transports glutathione conjugates of electrophilic compounds and other xenobiotics including chemotherapy agents out of cells. The protein is overexpressed in lung carcinomas, ovarian carcinomas, and melanomas. The protein also binds Ral and participates in mitotic spindle function, clathrin-dependent endocytosis, and triggers GTPase-activating protein activity.

Phase 1 study of escalating-dose OncoGel (ReGel/paclitaxel) depot injection, a controlled-release formulation of paclitaxel, for local management of superficial solid tumor lesions.

OncoGel is a novel depot formulation of paclitaxel designed for intralesional injection with a sustained paclitaxel delivery over approximately 6 weeks from a single administration. This phase 1 study was designed to characterize the toxicity, pharmacokinetics and preliminary antitumor activity associated with OncoGel administered directly into solid tumors. OncoGel was injected into 18 superficially accessible advanced solid cancerous lesions among 16 adult patients for whom no curative therapy was available.

Phase I trial of PT-100 (PT-100), a cytokine-inducing small molecule, following chemotherapy for solid tumor malignancy.

PT-100 upregulates cytokine expression competitively inhibiting the dipeptidyl peptidase activity of fibroblast activation protein (FAP) and dipeptidyl peptidase IV (DPP-IV). This dose-escalation study was conducted to evaluate the safety of PT-100 in patients receiving myelosuppressive chemotherapy and to assess its effects on neutrophil recovery.PT-100 was administered orally for 7 days as a 200 microg, 400 microg, 800 microg, or 1,200 microg total daily dose (divided twice daily) to 6, 6, 17, and 5 patients, respectively.

Phase II study of belagenpumatucel-L, a transforming growth factor beta-2 antisense gene-modified allogeneic tumor cell vaccine in non-small-cell lung cancer.

Purpose: Belagenpumatucel-L is a nonviral gene-based allogeneic tumor cell vaccine that demonstrates enhancement of tumor antigen recognition as a result of transforming growth factor beta-2 inhibition.

Patients And Methods: We performed a randomized, dose-variable, phase II trial involving stages II, IIIA, IIIB, and IV non-small-cell lung cancer patients. Each patient received one of three doses (1.

Phase I Trial of sequential administration of recombinant DNA and adenovirus expressing L523S protein in early stage non-small-cell lung cancer.

L523S is an immunogenic lung cancer antigen that has demonstrated preclinical safety when the gene is injected intramuscularly as an expressive plasmid (pVAX/L523S) and when delivered following incorporation into an E1B-deleted adenovirus (Ad/L523S). We performed a phase I clinical trial in 13 stage IB, IIA, and IIB non-small-cell lung cancer patients. pVAX/L523S (8 mg on days 0 and 14 in all cohorts) and Ad/L523S (1, 20, 400 x 10(9) vp on days 28 and 56, cohorts 1, 2, and 3, respectively) were administered to 3 patients in each of three cohorts.

Phase I study of CT-2103, a polymer-conjugated paclitaxel, and carboplatin in patients with advanced solid tumors.

Purpose: The primary objective of this study was to determine the maximum tolerated dose (MTD) of CT-2103 (poly L-glutamic acid-paclitaxel) in combination with carboplatin in patients with histologically proven solid tumors that were either refractory to conventional treatment or for which no conventional therapy was available.

Patients And Methods: Twenty-two adult patients with advanced solid tumors were treated in this dose escalation study. Patients were treated every 21 days with CT-2103 at 175, 210, 225, or 250 mg/m2 (doses expressed as units of conjugated-paclitaxel) via 10-20 minute intravenous (IV) infusion, followed one hour later with carboplatin administered at AUC 5 or 6 via 30 minute IV infusion.

Phase I and pharmacokinetic study of the dolastatin-15 analogue tasidotin (ILX651) administered intravenously on days 1, 3, and 5 every 3 weeks in patients with advanced solid tumors.

Purpose: To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of tasidotin (ILX651), a dolastatin-15 analogue, when administered on days 1, 3, and 5 every 3 weeks in patients with advanced solid tumors.

Patients And Methods: Thirty-two patients were treated with 92 courses of tasidotin through seven dose levels determined by a modified Fibonacci scheme ranging from 3.9 to 45.

Phase I trial of an all-oral combination chemotherapy regimen: topotecan and capecitabine in solid tumor patients.

The objective of this phase I study was to investigate the safety of an all-oral combination chemotherapy regimen: topotecan and capecitabine. Topotecan was administered once a day for 5 consecutive days followed by 2 days of rest and was administered again for 5 consecutive days. The starting dose of topotecan was 0.

TNFerade, an adenovector carrying the transgene for human tumor necrosis factor alpha, for patients with advanced solid tumors: surgical experience and long-term follow-up.

Background: Over the last several years, attempts have been made to use the tumoricidal effects of tumor necrosis factor (TNF)-alpha to treat cancer. Many of these studies demonstrated dose-limiting systemic side effects from high concentrations of TNF-alpha. The recent focus has been on developing a local delivery system for TNF-alpha to minimize the systemic response.

Phase 1 clinical and pharmacokinetics evaluation of oral CI-1033 in patients with refractory cancer.

Purpose: To determine the tolerability and pharmacokinetics of oral CI-1033, a pan-erbB tyrosine kinase inhibitor, administered over 14 consecutive days of a 21-day cycle.

Design: Phase 1, multicenter trial involving patients with solid tumors that are refractory to standard therapy. CI-1033 was administered initially at 300 mg/day to a minimum cohort of three patients.

Phase I study of oral CI-994 in combination with carboplatin and paclitaxel in the treatment of patients with advanced solid tumors.

Purpose: To determine maximum tolerated dose of CI-994, a novel oral histone deacetylase inhibitor, in combination with carboplatin and paclitaxel in patients with advanced solid tumors.

Patients And Methods: Patients with advanced solid tumors who had received two or fewer prior chemotherapy regimens were eligible for trial. Five cohorts of patients were treated with escalating doses (4-6 mg/m2) and alternative schedules (7 days or 14 days) of CI-994.

Intratumoral injection of INGN 241, a nonreplicating adenovector expressing the melanoma-differentiation associated gene-7 (mda-7/IL24): biologic outcome in advanced cancer patients.

The mda-7 gene (approved gene symbol IL24) is a novel tumor suppressor gene with tumor-apoptotic and immune-activating properties. We completed a Phase I dose-escalation clinical trial, in which a nonreplicating adenoviral construct expressing the mda-7 transgene (INGN 241; Ad-mda7) was administered intratumorally to 22 patients with advanced cancer. Excised tumors were evaluated for vector-specific DNA and RNA, transgenic MDA-7 expression, and biological effects.