Ocular malignancies treated with iodine-125 low dose rate (LDR) brachytherapy at a single high-volume institution: A retrospective review.

The aim of our study is to document our cases of choroidal melanoma treated with low dose rate (LDR) brachytherapy and to correlate the dosimetry and radiobiology with clinical effects and oncologic outcomes. Data from 157 patients treated from 2014 to 2018 with LDR brachytherapy were used for this investigation. Treatments used a collaborative ocular melanoma study eye plaque and Iodine-125 radioactive seeds.

Significance of hematopoietic surface antigen CD34 in neuroblastoma prognosis and the genetic landscape of CD34-expressing neuroblastoma CSCs.

High-risk neuroblastoma (HR-NB) is branded with hematogenous metastasis, relapses, and dismal long-term survival. Intensification of consolidation therapy with tandem/triple autologous stem cell (SC) rescue (with bone marrow [BM]/peripheral blood [PB] CD34 selection) after myeloablative chemotherapy has improved long-term survival. However, the benefit is limited by the indication of NB cells in CD34 PBSCs, CD34 expression in NB cells, and the risk of reinfusing NB cancer stem cells (NB CSCs) that could lead to post-transplant relapse.

MicroRNAs in neuroblastoma tumorigenesis, therapy resistance, and disease evolution.

Neuroblastoma (NB) deriving from neural crest cells is the most common extra-cranial solid cancer at infancy. NB originates within the peripheral sympathetic ganglia in adrenal medulla and along the midline of the body. Clinically, NB exhibits significant heterogeneity stretching from spontaneous regression to rapid progression to therapy resistance.

Cancer stem cells in neuroblastoma therapy resistance.

Neuroblastoma (NB) is the most common cancer of infancy and accounts for nearly one tenth of pediatric cancer deaths. This mortality rate has been attributed to the > 50% frequency of relapse despite intensive, multimodal clinical therapy in patients with progressive NB. Given the disease's heterogeneity and developed resistance, attaining a cure after relapse of progressive NB is highly challenging.

Targeting acquired oncogenic burden in resilient pancreatic cancer: a novel benefit from marine polyphenols.

The upsurge of marine-derived therapeutics for cancer treatment is evident, with many drugs in clinical use and in clinical trials. Seaweeds harbor large amounts of polyphenols and their anti-cancer benefit is linear to their anti-oxidant activity. Our studies identified three superlative anti-cancer seaweed polyphenol drug candidates (SW-PD).

Dosimetric considerations when utilizing Venezia, Capri, Rotte double tandem, and tandem and ring with interstitial needles for the treatment of gynecological cancers with high dose rate brachytherapy.

This work evaluated the difference in dosimetry of high dose rate (HDR) brachytherapy treatments between plans using advanced multichannel applicators and simplified base versions. Eighteen HDR patients treated using Interstitial Ring CT/MR Applicator Set (Elekta Brachytherapy, Netherlands) (TRN) (21 plans), CapriTM Applicator Set (Varian Medical Systems, Inc., Palo Alto, CA) (CC) (19 plans), Rotte Endometrial Applicator Set (Elekta Brachytherapy, Netherlands) (RDT) (18 plans), and the Advanced Gynecological Applicator Venezia (Vz) (Elekta Brachytherapy, Netherlands) (6 plans) were retrospectively reviewed.

Droplet digital PCR as an alternative to FISH for MYCN amplification detection in human neuroblastoma FFPE samples.

Background: MYCN amplification directly correlates with the clinical course of neuroblastoma and poor patient survival, and serves as the most critical negative prognostic marker. Although fluorescence in situ hybridization (FISH) remains the gold standard for clinical diagnosis of MYCN status in neuroblastoma, its limitations warrant the identification of rapid, reliable, less technically challenging, and inexpensive alternate approaches.

Methods: In the present study, we examined the concordance of droplet digital PCR (ddPCR, in combination with immunohistochemistry, IHC) with FISH for MYCN detection in a panel of formalin-fixed paraffin-embedded (FFPE) human neuroblastoma samples.

Radiation treatment to a postresection primary mucoepidermoid carcinoma (MEC) of the conjunctiva with positive margins at the Tenon's fascia-A case study.

The primary occurrence of mucoepidermoid carcinoma (MEC) of the conjunctiva is extremely rare, aggressive, and easily mistaken for squamous cell carcinoma. With fewer than 50 cases reported in the literature, there is no consensus on the most effective treatment. Radiation is an alternative to enucleation or orbital exenteration with the potential of eye preservation.

Retinal Degeneration Protein 3 (RD3) in normal human tissues: Novel insights.

The 195-amino-acid-long human Retinal Degeneration Protein 3 (RD3) is critical in the regulation of guanylate cyclase (GC) signaling and photoreceptor cell survival. Recently, we identified significant loss of RD3 in high-risk neuroblastoma and the influential role of RD3 in tumor progression. However, the functional characterization of RD3 in tumor systems has been hampered by the dearth of information on its localization in normal tissue and by the lack of antibodies suitable for staining FFPE tissue, primarily due to the inaccessibility of the epitopes.

Silencing BMI1 radiosensitizes human breast cancer cells by inducing DNA damage and autophagy.

Overexpression of BMI1 in human cancer cells, a member of the polycomb group of repressive complexes, correlates with advanced stage of disease, aggressive clinico-pathological behavior, poor prognosis, and resistance to radiation and chemotherapy. Studies have shown that experimental reduction of BMI1 protein level in tumor cells results in inhibition of cell proliferation, induction of apoptosis and/or senescence, and increased susceptibility to cytotoxic agents and radiation therapy. Although a role for BMI1 in cancer progression and its importance as a molecular target for cancer therapy has been established, information on the impact of silencing BMI1 in triple-negative breast cancer (TNBC) and its consequence on radiotherapy have not been well studied.

Hormophysa triquerta polyphenol, an elixir that deters CXCR4- and COX2-dependent dissemination destiny of treatment-resistant pancreatic cancer cells.

Therapy-resistant pancreatic cancer (PC) cells play a crucial role in tumor relapse, recurrence, and metastasis. Recently, we showed the anti-PC potential of an array of seaweed polyphenols and identified efficient drug deliverables. Herein, we investigated the benefit of one such deliverable, Hormophysa triquerta polyphenol (HT-EA), in regulating the dissemination physiognomy of therapy-resistant PC cells in vitro,and residual PC in vivo.

Serum-circulating miRNAs predict neuroblastoma progression in mouse model of high-risk metastatic disease.

Background: Circulating miRNAs have momentous clinical relevance as prognostic biomarkers and in the progression of solid tumors. Recognizing novel candidates of neuroblastoma-specific circulating miRNAs would allow us to identify potential prognostic biomarkers that could predict the switch from favorable to high-risk metastatic neuroblastoma (HR-NB).

Results: Utilizing mouse models of favorable and HR-NB and whole miRnome profiling, we identified high serum levels of 34 and low levels of 46 miRNAs in animals with HR-NB.

Polyphenols from marine brown algae target radiotherapy-coordinated EMT and stemness-maintenance in residual pancreatic cancer.

Introduction: Therapy-associated onset of stemness-maintenance in surviving tumor-cells dictates tumor relapse/recurrence. Recently, we recognized the anti-pancreatic cancer (PC) potential of seaweed polyphenol manifolds and narrowed down three superior drug-deliverables that could serve as adjuvants and benefit PC cure. Utilizing the PC- cancer stem cells (PC-CSCs) grown ex vivo and mouse model of residual-PC, we investigated the benefits of seaweed polyphenols in regulating stemness-maintenance.

RD3 loss dictates high-risk aggressive neuroblastoma and poor clinical outcomes.

Clinical outcomes for high-risk neuroblastoma patients remains poor, with only 40-50% 5-Year overall survival (OS) and <10% long-term survival. The ongoing acquisition of genetic/molecular rearrangements in undifferentiated neural crest cells may endorse neuroblastoma progression. This study recognized the loss of Retinal Degeneration protein 3, RD3 in aggressive neuroblastoma, and identified its influence in better clinical outcomes and defined its novel metastasis suppressor function.

Acquired genetic alterations in tumor cells dictate the development of high-risk neuroblastoma and clinical outcomes.

Background: Determining the driving factors and molecular flow-through that define the switch from favorable to aggressive high-risk disease is critical to the betterment of neuroblastoma cure.

Methods: In this study, we examined the cytogenetic and tumorigenic physiognomies of distinct population of metastatic site- derived aggressive cells (MSDACs) from high-risk tumors, and showed the influence of acquired genetic rearrangements on poor patient outcomes.

Results: Karyotyping in SH-SY5Y and MSDACs revealed trisomy of 1q, with additional non-random chromosomal rearrangements on 1q32, 8p23, 9q34, 15q24, 22q13 (additions), and 7q32 (deletion).

Reorganization of metastamiRs in the evolution of metastatic aggressive neuroblastoma cells.

Background: MetastamiRs have momentous clinical relevance and have been correlated with disease progression in many tumors. In this study, we identified neuroblastoma metastamiRs exploiting unique mouse models of favorable and high-risk metastatic human neuroblastoma. Further, we related their deregulation to the modulation of target proteins and established their association with clinical outcomes.

Novel synthetic monoketone transmute radiation-triggered NFκB-dependent TNFα cross-signaling feedback maintained NFκB and favors neuroblastoma regression.

Recently, we demonstrated that radiation (IR) instigates the occurrence of a NFκB-TNFα feedback cycle which sustains persistent NFκB activation in neuroblastoma (NB) cells and favors survival advantage and clonal expansion. Further, we reported that curcumin targets IR-induced survival signaling and NFκB dependent hTERT mediated clonal expansion in human NB cells. Herein, we investigated the efficacy of a novel synthetic monoketone, EF24, a curcumin analog in inhibiting persistent NFκB activation by disrupting the IR-induced NFκB-TNFα-NFκB feedback signaling in NB and subsequent mitigation of survival advantage and clonal expansion.

Anti-pancreatic cancer deliverables from sea: first-hand evidence on the efficacy, molecular targets and mode of action for multifarious polyphenols from five different brown-algae.

Pancreatic cancer (PC) remains the fourth leading cause of cancer death with an unacceptable survival that has remained relatively unchanged over the past 25 years. The presence of occult or clinical metastases at the time of diagnosis together with the lack of effective chemotherapies pose a dire need for designing new and targeted therapeutic deliverables that favors the clinical outcome. Herein, we investigated the anti-tumorigenic potential of polyphenols from five different brown-algae in human PC cells (MiaPaCa-2, Panc-1, BXPC-3 and Panc-3.

Radiation-induced TNFα cross signaling-dependent nuclear import of NFκB favors metastasis in neuroblastoma.

Ascertaining function-specific orchestration of NFκB in response to radiation may reveal a molecular blue-print that dictates induced relapse and metastasis of the neuroblastoma. We recently demonstrated that sustained activation of NFκB caused by ionizing radiation (IR)-initiated TNFα-NFκB feedback signaling leads to radioresistance and recurrence of neuroblastoma. We investigated whether muting IR-triggered or TNFα-dependent second-signaling feedback-dependent NFκB nuclear import results in limiting IR-altered invasion and metastasis.

Molecular basis of 'hypoxic' breast cancer cell radio-sensitization: phytochemicals converge on radiation induced Rel signaling.

Background: Heterogeneously distributed hypoxic areas are a characteristic property of locally advanced breast cancers (BCa) and generally associated with therapeutic resistance, metastases, and poor patient survival. About 50% of locally advanced BCa, where radiotherapy is less effective are suggested to be due to hypoxic regions. In this study, we investigated the potential of bioactive phytochemicals in radio-sensitizing hypoxic BCa cells.

EGFR tyrosine kinase inhibitor pelitinib regulates radiation-induced p65-dependent telomerase activation in squamous cell carcinoma.

Our earlier studies indicated that ionizing radiation (IR) induces NF-κB-dependent clonal expansion of therapy resistant tumor cells. Herein, we investigated whether mitigation of NF-κB-dependent telomerase activation by EGFR tyrosine kinase inhibitor can enhance IR-induced celling killing. SCC-4 and SCC-9 cells exposed to IR with or without Pelitinib were examined for NF-κB and hTERT transcription using luciferase reporter assays.

Impact of curcumin, raspberry extract, and neem leaf extract on rel protein-regulated cell death/radiosensitization in pancreatic cancer cells.

Objectives: Nuclear factor κB (NF-κB) plays an intrinsic role in promoting growth, angiogenesis, and metastasis in pancreatic cancer (PC) and serves as a mechanism underlying therapeutic resistance. Accordingly, we investigated the efficacy of bioactive phytochemicals in inhibiting radiotherapy (RT)-induced NF-κB activity, signaling, and NF-κB-dependent regulation of cell death.

Methods: Panc-1, BxPC-3, and MIA PaCa-2 cells exposed to 10 Gy (single high dose [SDR]) or 2 Gy/d for 5 days (fractionated radiation [FIR]) with or without curcumin (CUR), neem leaf extract (NLE), or black raspberry extract (RSE) were analyzed.

Radiation-triggered tumor necrosis factor (TNF) alpha-NFkappaB cross-signaling favors survival advantage in human neuroblastoma cells.

Induced radioresistance in the surviving cancer cells after radiotherapy could be associated with clonal selection leading to tumor regrowth at the treatment site. Previously we reported that post-translational modification of IκBα activates NFκB in response to ionizing radiation (IR) and plays a key role in regulating apoptotic signaling. Herein, we investigated the orchestration of NFκB after IR in human neuroblastoma.

Neem leaf extract induces radiosensitization in human neuroblastoma xenograft through modulation of apoptotic pathway.

Unlabelled: Induction of apoptosis is directly correlated with the biological effectiveness of ionizing radiation (IR). Accordingly, we investigated the efficacy of neem leaf extract (NLE) on IR-associated apoptotic transcriptional modulation and cell death in neuroblastoma (NB).

Materials And Methods: NB xenografts exposed to single dose (SDR, 10 Gy) or fractionated (FIR, 2 Gy/d×5d) with or without NLE were examined for transcriptional activation of 84 apoptotic pathway genes using quantitative polymerase chain reaction.

Curcumin regulates low-linear energy transfer γ-radiation-induced NFκB-dependent telomerase activity in human neuroblastoma cells.

Purpose: We recently reported that curcumin attenuates ionizing radiation (IR)-induced survival signaling and proliferation in human neuroblastoma cells. Also, in the endothelial system, we have demonstrated that NFκB regulates IR-induced telomerase activity (TA). Accordingly, we investigated the effect of curcumin in inhibiting IR-induced NFκB-dependent hTERT transcription, TA, and cell survival in neuroblastoma cells.