Showing papers by "Bo Lu published in 2021"

NBTXR3 Radiotherapy-Activated Functionalized Hafnium Oxide Nanoparticles Show Efficient Antitumor Effects Across a Large Panel of Human Cancer Models.

Abstract: Purpose The side effects of radiotherapy induced on healthy tissue limit its use. To overcome this issue and fully exploit the potential of radiotherapy to treat cancers, the first-in-class radioenhancer NBTXR3 (functionalized hafnium oxide nanoparticles) has been designed to amplify the effects of radiotherapy. Patients and methods Thanks to its physical mode of action, NBTXR3 has the potential to be used to treat any type of solid tumor. Here we demonstrate that NBTXR3 can be used to treat a wide variety of solid cancers. For this, we evaluated different parameters on a large panel of human cancer models, such as nanoparticle endocytosis, in vitro cell death induction, dispersion, and retention of NBTXR3 in the tumor tissue and tumor growth control. Results Whatever the model considered, we show that NBTXR3 was internalized by cancer cells and persisted within the tumors throughout radiotherapy treatment. NBTXR3 activated by radiotherapy was also more effective in destroying cancer cells and in controlling tumor growth than radiotherapy alone. Beyond the effects of NBTXR3 as single agent, we show that the antitumor efficacy of cisplatin-based chemoradiotherapy treatment was improved when combined with NBTXR3. Conclusion These data support that NBTXR3 could be universally used to treat solid cancers when radiotherapy is indicated, opening promising new therapeutic perspectives of treatment for the benefit of many patients.

Targeting SIRT1 to inhibit the proliferation of multiple myeloma cells

Abstract: Multiple myeloma (MM) is the second most common hematopoietic malignancy and remains an incurable disease. Thus, novel drugs and therapeutic methods are required for patients with MM. The present study aimed to investigate the effect of sirtuin 1 (SIRT1) inhibitor cambinol on the proliferation and apoptosis of myeloma cell lines, RPMI8226 and U266. Moreover, the present study evaluated the underlying molecular mechanisms of proliferation inhibition and apoptosis induced by cambinol. A Cell Counting Kit-8 assay was used to measure the viability of RPMI8226 and U266 cells treated with cambinol. Apoptosis and the cell cycle were analyzed via flow cytometry. The expression levels of caspase-3, poly(ADP-ribose) polymerase 1 (PARP), p53, acetylated p53 (Ac-p53), Bcl-2, cyclin D1 and p21 were detected in cells treated with cambinol using western blot analysis. The results demonstrated that cambinol inhibited the proliferation of RPMI8226 and U266 cells in a time- and dose-dependent manner. Increased apoptosis and G1 cell cycle arrest, together with enhanced procaspase-3 degradation and PARP cleavage were identified in cambinol-treated cells compared with controls. Western blotting results also revealed the upregulation of p53 acetylation and p21, as well as the downregulation of Bcl-2 and cyclin D1 in cells treated with cambinol. In conclusion, the present results suggest that cambinol inhibits the proliferation and induces apoptosis in RPMI8226 and U266 cells by regulating acetylation of p53 via the targeting of SIRT1.

Association Between Patient-Clinician Relationships and Adherence to Antihypertensive Medications Among Black Adults: An Observational Study Design.

Abstract: Background We assessed the associations between patient‐clinician relationships (communication and involvement in shared decision‐making [SDM]) and adherence to antihypertensive medications. Method...

Triplet Matching for Estimating Causal Effects With Three Treatment Arms: A Comparative Study of Mortality by Trauma Center Level

Abstract: Comparing outcomes across different levels of trauma centers is vital in evaluating regionalized trauma care. With observational data, it is critical to adjust for patient characteristics to render...

Tyrosine Kinase ROR1 as a Target for Anti-Cancer Therapies.

Abstract: Receptor tyrosine kinase ROR1 plays an essential role in embryogenesis and is overexpressed in many types of malignant tumors. Studies have demonstrated that it plays an important role in oncogenesis by activating cell survival signaling events, particularly the non-canonical WNT signaling pathway. Antibody-based immunotherapies targeting ROR1 have been developed and evaluated in preclinical and clinical studies with promising outcomes. However, small molecule inhibitors targeting ROR1 are underappreciated because of the initial characterization of ROR1 as a peusdokinase. The function of ROR1 as a tyrosine kinase remains poorly understood, although accumulating evidence have demonstrated its intrinsic tyrosine kinase activity. In this review, we analyzed the structural and functional features of ROR1 and discussed therapeutic strategies targeting this kinase.

JMJD3-regulated expression of IL-6 is involved in the proliferation and chemosensitivity of acute myeloid leukemia cells.

Abstract: Emerging evidence shows that histone modification and its related regulators are involved in the progression and chemoresistance of multiple tumors including acute myeloid leukemia cells (AML). Our present study found that the expression of histone lysine demethylase Jumonji domain containing-3 (JMJD3) was increased in AML cells as compared with that in human primary bone marrow (HPBM) cells. Knockdown of JMJD3 can decrease the proliferation of AML cells and increase the chemosensitivity of daunorubicin (DNR) and cytarabine (Ara-C). By screening the expression of cytokines involved in AML progression, we found that knockdown of JMJD3 can inhibit the expression of interleukin-6 (IL-6). Recombinant IL-6 (rIL-6) can attenuate si-JMJD3-suppressed proliferation of AML cells. Mechanistically, JMJD3 can positively regulate the promoter activity and transcription of IL-6 mRNA, while had no effect on its mRNA stability. Further, JMJD3 can regulate the expression of p65, which can directly bind with promoter of IL-6 to increase its transcription. Over expression of p65 significantly attenuated si-JMJD3-suppressed expression of IL-6. Collectively, we revealed that JMJD3 can regulate the proliferation and chemosensitivity of AML cells via upregulation of IL-6. It suggested that JMJD3 might be a potential therapy target for AML treatment.

Associations between neighborhood disinvestment and breast cancer outcomes within a populous state registry

Abstract: Background Breast cancer (BrCa) outcomes vary by social environmental factors, but the role of built-environment factors is understudied. The authors investigated associations between environmental physical disorder-indicators of residential disrepair and disinvestment-and BrCa tumor prognostic factors (stage at diagnosis, tumor grade, triple-negative [negative for estrogen receptor, progesterone receptor, and HER2 receptor] BrCa) and survival within a large state cancer registry linkage. Methods Data on sociodemographic, tumor, and vital status were derived from adult women who had invasive BrCa diagnosed from 2008 to 2017 ascertained from the New Jersey State Cancer Registry. Physical disorder was assessed through virtual neighborhood audits of 23,276 locations across New Jersey, and a personalized measure for the residential address of each woman with BrCa was estimated using universal kriging. Continuous covariates were z scored (mean ± standard deviation [SD], 0 ± 1) to reduce collinearity. Logistic regression models of tumor factors and accelerated failure time models of survival time to BrCa-specific death were built to investigate associations with physical disorder adjusted for covariates (with follow-up through 2019). Results There were 3637 BrCa-specific deaths among 40,963 women with a median follow-up of 5.3 years. In adjusted models, a 1-SD increase in physical disorder was associated with higher odds of late-stage BrCa (odds ratio, 1.09; 95% confidence interval, 1.02-1.15). Physical disorder was not associated with tumor grade or triple-negative tumors. A 1-SD increase in physical disorder was associated with a 10.5% shorter survival time (95% confidence interval, 6.1%-14.6%) only among women who had early stage BrCa. Conclusions Physical disorder is associated with worse tumor prognostic factors and survival among women who have BrCa diagnosed at an early stage.

Stereotactic body radiation therapy (SBRT) for patients with stage I non-small cell lung cancer is applicable to more tumors than sublobar resection.

Abstract: Background Virtually all patients with medically inoperable stage I non-small cell lung cancer (NSCLC) can receive stereotactic body radiation therapy. However, the percentage of such patients in whom sublobar resection is technically feasible is unknown. This discrepancy can confound clinical trial eligibility and designs comparing stereotactic body radiation therapy vs. sublobar resection. Methods A total of 137 patients treated with stereotactic body radiation therapy for lung lesions (3/2013-11/2017) underwent retrospective review. Diagnostic CT chest and PET/CT images, stereotactic body radiation therapy dates, and demographic data were collected on 100 of 137 patients. Two experienced board-certified thoracic surgeons independently reviewed anonymized patients' pre-stereotactic body radiation therapy diagnostic imaging and completed a custom survey about the technical feasibility of sublobar resection for each patient. Interrater agreement was measured using Cohen's kappa coefficient by bootstrap methodology. Summary statistics were performed for baseline demographics and tumor characteristics. Results Of the 100 patients, 57% were female, with median age of 75 years (range, 52-95 years) and Karnofsky Performance Status of 80 (range, 40-100). Most patients (61%) had Stage IA1, T1a tumors. For interrater agreement analysis, one patient was removed from each cohort due to inability to locate tumor on images, leaving 98 patients analyzed. Comparing Surgeon #1 vs. Surgeon #2, 64 (65.3%) vs. 69 (70.3%) of tumors were thought eligible for sublobar resection, respectively (κ=0.414). Conclusions Stereotactic body radiation therapy for stage I NSCLC is applicable to more tumors than sublobar resection, with ~30-35% of stereotactic body radiation therapy patients unable to undergo sublobar resection assessed by pretreatment diagnostic imaging based on technical grounds. This study illustrates that clinical trials comparing stereotactic body radiation therapy vs. sublobar resection are limited to only a subpopulation of patients with stage I NSCLC.

Associations between Cognitive and Affective Responses to Tobacco Advertisements and Tobacco Use Incidence: A Four-Year Prospective Study among Adolescent Boys.

Abstract: Exposure to tobacco advertisements is associated with initiation of tobacco use among youth. The mechanisms underlying this association are less clear. We estimated longitudinal associations between youths' cognitive and affective responses to advertisements for cigarettes, e-cigarettes, and smokeless tobacco (SLT) and initiation of these products. N = 1220 Ohio-residing boys of ages 11-16 were recruited into a cohort in 2015 and 2016. Participants completed surveys every six months for four years. Surveys assessed cognitive and affective responses to tobacco advertisements (which included health warnings) and tobacco use after an advertisement viewing activity. We used mixed-effects Poisson regression models with robust standard errors to estimate risk of initiating use of each tobacco product according to participants' cognitive (i.e., memorability of health risks) and affective (i.e., likability of advertisement) responses to advertisements for that product. No associations between affective responses to advertisements and tobacco use outcomes were detected in adjusted models. However, finding health risks memorable was associated with reduced risk of ever smoking initiation (aRR = 0.57; 95% CI: 0.34, 0.95) and a reduced risk of ever SLT initiation that approached statistical significance (aRR = 0.61; 95% CI: 0.36, 1.05). Measures to increase saliency of health risks on cigarette and SLT advertisements might reduce use among youth.

Reconstruction of volume averaging effect-free continuous photon beam profiles from discrete ionization chamber array measurements using a machine learning technique.

Abstract: PURPOSE The use of the ionization chamber array ICProfiler (ICP) is limited by its relatively poor detector spatial resolution and the inherent volume averaging effect (VAE). The purpose of this work is to study the feasibility of reconstructing VAE-free continuous photon beam profiles from ICP measurements with a machine learning technique. METHODS In- and cross-plane photon beam profiles of a 6 MV beam from an Elekta linear accelerator, ranging from 2 × 2 to 10 × 10 cm2 at 1.5 cm, 5 cm, and 10 cm depth, were measured with an ICP. The discrete measurements were interpolated with a Makima method to obtain continuous beam profiles. Artificial neural networks (ANNs) were trained to restore the penumbra of the beam profiles. Plane-specific (in- and cr-plane) ANNs and a combined ANN were separately trained. The performance of the ANNs was evaluated using the penumbra width difference (PWD, the difference between the penumbra widths of the reconstructed and the reference profile). The plane-specific and the combined ANNs were compared to study the feasibility of using a single ANN for both in- and cross-plane. RESULTS The profiles reconstructed with all the ANNs had excellent agreement with the reference. For in-plane, the ANNs reduced the PWD from 1.6 ± 0.7 mm at 1.5 cm depth to 0.1 ± 0.1 mm, from 1.8 ± 0.6 mm at 5.0 cm depth to 0.1 ± 0.1 mm, and from 2.4 ± 0.1 mm at 10.0 cm depth to 0.0 ± 0.0 mm; for cross-plane, the ANNs reduced the PWD from 1.2 ± 0.4 mm at 1.5 cm depth, 1.2 ± 0.3 mm at 5.0 cm depth, and 1.6 ± 0.1 mm at 10.0 cm depth, to 0.1 ± 0.1 mm. CONCLUSIONS This study demonstrated the feasibility of using simple ANNs to reconstruct VAE-free continuous photon beam profiles from discrete ICP measurements. A combined ANN can restore the penumbra of in- and cross-plane beam profiles of various fields at different depths.