Chemotherapy For Treatment Of Cancer Research Articles

Short duration treadmill exercise improves physical function and skeletal muscle mitochondria protein expression after recovery from FOLFOX chemotherapy in male mice.

FOLFOX (5-FU, leucovorin, oxaliplatin) is a chemotherapy treatment for colorectal cancer which induces toxic side effects involving fatigue, weakness, and skeletal muscle dysfunction. There is a limited understanding of the recovery from these toxicities after treatment cessation. Exercise training can improve chemotherapy-related toxicities. However, how exercise accelerates recovery and the dose required for these benefits are not well examined. The purpose of this study was to examine the effect of exercise duration on physical function, muscle mass, and mitochondria protein expression during the recovery from FOLFOX chemotherapy. 12-week-old male mice were administered four cycles of either PBS or FOLFOX over 8-weeks. Outcomes were assessed after the fourth cycle and after either 4 (short-term; STR) or 10 weeks (long-term; LTR) recovery. Subsets of mice performed 14 sessions (6 d/wk, 18 m/min, 5% grade) of 60 min/d (long) or 15 min/d (short duration) treadmill exercise during STR. Red and white gastrocnemius mRNA and protein expression were examined. FOLFOX treatment decreased run time (RT) (-53%) and grip strength (GS) (-9%) compared to PBS. FOLFOX also reduced muscle OXPHOS complexes, COXIV, and VDAC protein expression. At LTR, FOLFOX RT (-36%) and GS (-16%) remained reduced. Long- and short-duration treadmill exercise improved RT (+58% and +56%) without restoring GS in FOLFOX mice. Both exercise durations increased muscle VDAC and COXIV expression in FOLFOX mice. These data provide evidence that FOLFOX chemotherapy induces persistent deficits in physical function that can be partially reversed by short-duration aerobic exercise.

Lipid-coated albumin-paclitaxel nanoparticles loaded with sorcin-siRNA reverse cancer chemoresistance via restoring intracellular calcium ion homeostasis

Chemoresistance is often a cause of the failure of chemotherapy in cancer treatment. Sorcin (SRI) is a soluble resistance-related calcium-binding protein involved in chemoresistant processes and is overexpressed in many chemoresistant cancer cells, including paclitaxel (PTX)-resistant ovarian cancer. Increased SRI can reduce the concentration of calcium ions in the cytosol and mitochondria and the decrease of calcium ion concentration prevents the occurrence of apoptosis. Here we examined the SRI expression in multiple cancers using a human TissueArray and found that SRI expression was significantly higher in malignant tumor tissues. Furthermore, SRI was overexpressed, while intracellular calcium concentration was decreased, in chemoresistant cancer cells. To restore intracellular calcium homeostasis and overcome chemoresistance, we developed lipid-coated albumin-PTX nanoparticles loaded with SRI-siRNA (LANP-PTX-siSRI) for PTX and SRI-siRNA co-delivery. LANP-PTX-siSRI had dual-target roles in the regulation of SRI and the delivery of PTX into chemoresistant cells. The LANP-PTX-siSRI inhibited the expression of SRI and enhanced intracellular calcium, leading to the induction of apoptosis and the inhibition of the growth of PTX-resistant cancer cells in vitro and in vivo. In addition, the mechanism study revealed that the overexpression of SRI was associated with an impaired TGF-β signaling pathway. The administration of TGF-β1 inhibited two calcium-binding proteins SRI and S100A14. In conclusion, our data unveil that restoring intracellular calcium ion homeostasis via reducing SRI expression can reverse chemoresistance. Thus, the fabricated LANP-PTX-siSRI has a potentially therapeutical application.

Tooth Formation as Experimental Model to Study Chemotherapy on Tissue Development: Effect of a Specific Dose of Temozolomide/Veliparib.

Background: Chemotherapy treatment of cancer in children can influence formation of normal tissues, leading to irreversible changes in their structure and function. Tooth formation is susceptible to several types of chemotherapy that induce irreversible changes in the structure of enamel, dentin and dental root morphology. These changes can make the teeth more prone to fracture or to caries when they have erupted. Recent studies report successful treatment of brain tumors with the alkylating drug temozolomide (TMZ) in combination with veliparib (VLP) in a glioblastoma in vivo mouse model. Whether these drugs also affect tooth formation is unknown. Aim: In this study the effect of TMZ/VLP on incisor formation was investigated in tissue sections of jaws from mice and compared with mice not treated with these drugs. Materials and method: The following aspects were studied using immunohistochemistry of specific protein markers including: (1) proliferation (by protein expression of proliferation marker Ki67) (2) a protein involved in paracellular ion transport (expression of tight junction (TJ) protein claudin-1) and (3) in transcellular passage of ions across the dental epithelium (expression of Na+, K+ 2Cl- cotransporter/NKCC1). Results: Chemotherapy with TMZ/VLP strongly reduced immunostaining for claudin-1 in distal parts of maturation ameloblasts. No gross changes were found in the treated mice, either in cell proliferation in the dental epithelium at the cervical loop or in the immunostaining pattern for NKCC1 in (non-ameloblastic) dental epithelium. The salivary glands in the treated mice contained strongly reduced immunostaining for NKCC1 in the basolateral membranes of acinar cells. Discussion/Conclusions: Based on the reduction of claudin-1 immunostaining in ameloblasts, TMZ/VLP may potentially influence forming enamel by changes in the structure of TJs structures in maturation ameloblasts, structures that are crucial for the selective passage of ions through the intercellular space between neighboring ameloblasts. The strongly reduced basolateral NKCC1 staining seen in fully-grown salivary glands of TMZ/VLP-treated mice suggests that TMZ/VLF could also influence ion transport in adult saliva by the salivary gland epithelium. This may cause treated children to be more susceptible to caries.

Device-assisted intravesical chemotherapy treatment for nonmuscle invasive bladder cancer: 2022 update.

To critically analyze the oncological outcomes and safety profile of device-assisted intravesical chemotherapy studies reported in 2021. Studies were considered eligible if they included patients with nonmuscle invasive blood cancer (NMIBC), had a prospective or retrospective design, included at least 10 patients, were published in 2021, and assessed the oncological impact of device-assisted intravesical chemotherapy and/or reported standardized adverse effects (AEs). Eight new studies reported oncological outcomes after hyperthermic intravesical chemotherapy (HIVEC). In Bacillus Calmette-Guérin (BCG) naive patients, the reported 2-yr. recurrence-free survival (RFS) ranged from 70.7% to 82.4%, with one study reporting 2 yr. progression free survival (PFS) of 92%. In both BCG naive and BCG refractory patients, the reported 1-yr. RFS ranged from 60.5% to 70% and PFS was 94% in one study. For radiofrequency-induced HIVEC, the reported 5-yr. estimates were 38%for RFS and 91.5%for PFS. Regarding AEs, 10.2% of patients had severe AEs. Six studies reported AEs after HIVEC; the majorities were grade 1-2 AEs. Data coming from the studies published in the last years provides support for a consolidating role of device-assisted intravesical chemotherapy as a safe and effective alternative first- or second-line adjuvant treatment of patients with NMIBC.

Construction of Nursing Practice Model in Case Management of Concurrent Chemotherapy and Radiochemotherapy Treatment in Cervical Cancer.

Objective To construct a case management model of synchronous radiotherapy and concurrent chemotherapy and radiochemotherapy (CRR) for cervical cancer led by nurses and carry out preliminary implementation and evaluation, so as to explore a new model of nursing practice. Methods Totally 80 cervical cancer patients were included in this study, 43 patients were in the experimental group, and 37 patients were in the control group. The clinical data, side effects, psychological reactions, and nutritional indexes were collected before and after the intervention. Results The results of Hospital Anxiety and Depression Scale (HADs) showed that anxiety and depression scores decreased after intervention in the experimental group, and the difference between two groups had significant after intervention (P < 0.05). Serum fatty acids, albumin, and cholesterol in the experimental group were decreased after the intervention. Moreover, the incidence of radiation vaginitis and radiation dermatitis had significant differences between the two groups (P < 0.05). Conclusion The case management nursing practice mode of concurrent radiotherapy and chemotherapy for cervical cancer can effectively promote the self-management of risk factors, reduce the occurrence of complications, and improve the ability of self-care.

Abstract 4171: Treatment of canine soft tissue sarcomas and melanomas with intratumoral collagen-anchored IL-2 and IL-12 is safe and effective

Abstract Introduction: Successful translation of novel cancer immunotherapies could be accelerated by using tumor models that recapitulate human disease and receive relevant standard-of-care treatments. Some cancers that naturally arise in pet dogs share critical features with human disease including tumor heterogeneity (immune infiltration, mutational burden, metastatic progression) and patient characteristics (outbred population, immunocompetence, age, microbiome). Investigating novel immunotherapies alongside radiation, chemotherapy, or surgical treatment of spontaneous canine cancers meaningfully informs their clinical translation. Methods: We have developed interleukin -2 and -12 cytokine fusion proteins that bind and anchor to collagen after intratumoral administration and have shown their superior activity and tolerability in murine tumor models (Momin 2019). Here in pet dogs, we test these cytokines for safety and efficacy in two cancer types. Soft tissue sarcomas (n=10) were treated with intratumoral IL-2 and -12 using different dose schedules prior to surgical resection with subsequent tumor tissues assessed by histology for immune infiltrates and by Nanostring for whole tumor transcriptomics. Oral malignant melanomas (n=10) were treated with 9 Gy radiation at day 0, and on day 1 treated with intratumoral injection of the cytokines Q2W for 6 total doses, with dose escalation performed in cohorts of 3. Plasma was collected for PK/PD analysis of drug and IFN-g post-injection, with serial CBC/chemistry profiles and CT scans for assessment of safety and radiologic response, respectively. Results: Intratumoral dosing of collagen binding cytokines was well tolerated by 19/20 dogs, with transient body temperature elevation observed 24-72 hours post-injection and 1 episode of grade 3 transaminase elevation. Magnitude of fever did not correlate with peak serum IFN-g or cytokine dose level. At the lowest dose level (17 ug/kg IL-2, 40 ug/m2 IL-12), 1/3 pet dogs with oral melanomas achieved CR by RECIST criteria, and 3/3 pet dogs achieved near CR at the 2x dose level. Transcriptomic analysis of treated sarcomas revealed enrichment for antigen processing and T cell function two days after treatment. Moreover, IDO1 was upregulated in treated tumors, which suggests its systemic inhibitors combined with the locally-delivered cytokines may potentiate stronger responses. Conclusions: This data supports the safety and efficacy of intratumorally delivered IL-2 and IL-12 collagen binding cytokines and the ability to combine with standard-of-care resection or radiation therapy. We are continuing to enroll dogs to evaluate safety and efficacy at higher dose levels, including response at metastatic sites. Canine cancers bridge the gap between murine and human disease, accelerating the build-test-learn design cycle for novel immunotherapies and treatment combinations. Citation Format: Jordan Stinson, Allison Sheen, Jordan Hampel, Noor Momin, Rebecca Bernstein, Rebecca Kamerer, Timothy M. Fan, K. Dane Wittrup. Treatment of canine soft tissue sarcomas and melanomas with intratumoral collagen-anchored IL-2 and IL-12 is safe and effective [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4171.

Abstract 2772: A novel bio-physical based CDA approach for evaluating lung cancer therapeutic responses

Abstract Background: Lung cancer is the world's highest mortality and incidence rate of malignancy, and the prognosis survival rate is significantly lower than other tumors. A novel bio-physics based multi (pan)-cancer test technology named Cancer Differentiation Analysis Technology (CDA) has been developed and investigated for evaluating and monitoring lung cancer therapeutic responses. Methods: A total of 686 patients diagnosed with different sub-types of lung cancer were included in this study. CDA levels were concurrently measured in peripheral blood obtained from 686 patients during the treatment. According to the response evaluation criteria in solid tumors (RECIST) 1.1 standard, the efficacy of 686 patients after treatment was evaluated, and the diagnostic efficacy of CDA technology was evaluated by receiver operating characteristic (ROC) curve. Results: Clinical pathological parameters of the patients are listed in Table 1. The higher the CDA value, the worse the curative effect. CDA value of lung cancer in CR (complete response) group was significantly lower than that in other 3 groups (p&amp;lt;0.05). CDA value of adenocarcinoma lung cancer in CR group were significantly lower than that in SD (stable disease) group (p&amp;lt;0.05). For non - metastatic lung cancer, CDA value in CR group was significantly lower than that in SD group (p&amp;lt;0.05) The receiver ROC analysis showed that the area under curve (AUC) of lung cancer group, NSCLC group, adenocarcinoma lung cancer group, were 0.756, 0.772, and 0.792, respectively. The AUC of early lung cancer group, and non - metastatic lung cancer group were 0.794, and 0.851. Conclusions: CDA appears to have the ability to predict and monitor therapeutic responses to lung cancer surgery and chemotherapy treatments. In most cases, the CDA of CR patients is low, and there is a good correlation between CDA and curative effect in early lung cancer. CDA could be a potential candidate for evaluating lung cancer, especially for early stage lung cancer therapeutic response. Citation Format: Junjie Wu, Zixiu Zou, Xuedong Du, Yue Lin, Xing Tang, Jie Chen, Lan Peng, Chris Yu. A novel bio-physical based CDA approach for evaluating lung cancer therapeutic responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2772.

Cytotoxic effects of bioactive extracts from Andrographis echioides (L.) Nees: An In vitro approach

In the global search for alternative drugs for various ailments, products from medicinal plants are given much attention. Attempts are being made to identify bioactive compounds from natural products to develop anticancer agents. In the present study exposes the cytotoxic activity of the extracts of the leaves of the plant Andrographis echioides on cancer cell lines. A. echioides leaf extract was taken with polar grade solvents, and methanol was selected based on the best activity. The fractions, obtained by column chromatography separation, rich in bioactive compounds were further screened for anticancer studies, using cancer cell lines, MCF-7, A- 549, and normal Vero cells. Cell proliferation assay, Western blotting, flow cytometry, DNA fingerprinting, and apoptosis assessment were used to identify the anticancer potential of the chosen methanol extract fractions of A. echioides. The IC50 values of the 3′-O-β-D-xylosyl-quercetin (AEMR-1) isolated from A. echioides were 1.25, 1.98 µg/mL, and 4.54 µg/mL for the MCF-7, A-549, and Vero cell lines, respectively. The normal Vero cell line remained unchanged on AEMR-1 exposure. The study's outcome will help to find out the lead compounds in the plant A. echioides useful for chemotherapy in cancer treatment.

Mechanistic Approach of Nano Carriers for Targeted in Cancer Chemotherapy: A Newer Strategy for Novel Drug Delivery System.

The application of nanomedicine represents an innovative approach for the treatment in the modern field of cancer chemotherapy. In the present research work, tamoxifen citrate loaded nanolipid vesicles were prepared conjugated with phosphoethanolamine as the linker molecule, and the specific antibody was tagged with the linker molecule on the bilayer surface of the vesicles. The main objective of this study is to determine the efficacy and biological behavior of antibody conjugated nanoliposome in breast cancer cell lines. Percentage of drug loading and loading efficiency was done and their results were compared to theoretical drug loading. The average diameter of those vesicles was within the 100 nm range, which is revealed in FESEM and TEM images and their lamellarity was observed in cryo-TEM images. The hydrodynamic diameter was done by particle size analysis and the surface charge was determined by the zeta potential parameter. Predominant cellular uptake was observed for antibody conjugated nanolipid vesicles in MCF-7 and MDA-MB-453 human breast cancer cell lines. A cellular apoptosis assay was conducted by flow cytometer (FACS). All experimental data would be more beneficial for the treatment of breast cancer chemotherapy. Further studies are warranted to investigate the efficacy and safety of antibody conjugated nanolipid vesicles in vivo for breast cancer animal model.

Immediate increase in perceived energy after exercise during the course of chemotherapy treatment for breast cancer.

Exercise during chemotherapy has beneficial long-term effects on women with breast cancer, but short-term beneficial changes have been less investigated. Though short-term changes may be important as a encouraging factor, this study aimed to investigate immediate changes in self-reported energy, stress, nausea and pain following a single exercise session during chemotherapy. Forty-six women who were exercising while undergoing adjuvant chemotherapy for breast cancer were included between October 2016 and April 2018. Self-reported energy and stress were assessed before, immediately after and 3h after exercise sessions by the Stress-Energy Questionnaire. On the same questionnaire nausea and pain were assessed by a Visual Analog Scale. The measurements were completed at four time points during cycles 2 and 5 of the 6-cycle chemotherapy course. Energy level increased immediately after a single exercise session for three out of four periods during the chemotherapy course (p<0.01), with a larger increase when energy was lower before the session (p<0.01). Three hours after the exercise session, the energy was about the same level as before the exercise session. Stress decreased immediately after the session during cycle two (p<0.01) but not cycle five. There were no changes in nausea or pain. Patients undergoing chemotherapy should be informed not only about the long-term advantages of exercise, but also immediate benefits in terms of increased energy. The energy increase both while exercise in the beginning and toward the end of the chemotherapy course, this short-term advantageous consequence may strengthen patients' motivation to exercise. Clinicians should also inform patients that exercise does not seem to worsen nausea and pain.

Role of dipeptidyl peptidase 3 (DPP3) in cardiomyocyte toxicity induced by cancer cells and/or chemotherapy treatment

Cardiotoxicity is an important side effect of chemotherapy such as Doxorubicin (Dox). Developing new biomarkers of cardiotoxicity is important to improve the cardiologic monitoring of cancer patients. Dipeptidyl peptidase 3 (DPP3), a zinc-dependent metallopeptidase, has emerged as a new biomarker and therapeutic target of acute cardiac dysfunction. Considering DPP3′ effects on cardiac function, and its increased expression in some types of cancer, we aimed to investigate a possible implication of DPP3 in cancer and/or chemotherapy induced cardiotoxicity. To evaluate DPP3 expression in cancer and in cardiomyocytes cell lines, the effect of DPP3 inhibition on cardiomyocytes survival and the effect of cancer cells secretome, in the presence or absence of DPP3, on cardiomyocytes survival. Our study was conducted, in vitro, in two cell lines: rat cardiomyocytes (H9C2) and murine ovarian cancer cells (ID8). Different treatments were applied; Dox (0.5 μM), DPP3 (0.62 or 6.2 μg/mL) alone or in combination with Dox, in addition to a treatment with anti-DPP3 antibody, procizumab PCZ (4 ng/mL). To investigate the direct effect of cancer on cardiomyocytes, the effect of ID8 secretome (non-treated, treated with Dox 0.5 μM, or with Dox 0.5 μM + PCZ 40 ng/mL), on cardiomyocytes was studied. Cell survival was evaluated after 24 h treatment. Finally, DPP3 protein expression was assessed by Western blot. Our results showed a significant decrease of H9C2 survival when treated with Dox 0.5 μM (×0.32, P < 0.05), reflecting its cardiotoxicity. DPP3 protein expression increased in both ID8 (×19, P < 0.05) and H9C2 (×3.5, P < 0.05) when treated with Dox. Treating ID8 with DPP3 0.62 μg/mL increased their survival when no treatment was applied (×1.52, P < 0.05), however, this increase was not significant with the higher concentration of DPP3. In the presence of Dox treatment, an increase of H9C2 survival was induced by DPP3, in both concentrations; 0.62 μg/mL (×1.68, P < 0.05), 62 μg/mL (×1.83, P < 0.05), in comparison to Dox alone. When blocking DPP3 by PCZ, the survival of H9C2, treated with Dox or with ID8 secretome treated with Dox, has increased (×1.71, P < 0.05) and (×1. 86, P < 0.05), respectively. The effect of PCZ on cardiotoxicity along aside with the increased expression of DPP3 induced by Dox may reflect a possible implication of DPP3 in Dox-induced cardiotoxicity.

Take charge during treatment: A planned exercise protocol to evaluate disparities and cardiovascular outcomes in Black and White patients with breast cancer undergoing treatment.

TPS12138 Background : Cardiotoxicity is a significant challenge associated with common first-line breast cancer (BC) chemotherapy (CTx) treatments including anthracyclines (AC) and targeted therapies, such as anti-Her-2 therapy. For targeted therapies, cardiac complications typically resolve once treatment is completed or stopped. For ACs, treatment may lead to permanent long term cardiac damage, and elevated risk for major adverse cardiovascular events (MACE). Black/African American (B/AA) women are at higher risk for AC-based cardiotoxicity compared to Non-Hispanic White (NHW) women. To date, most efforts have targeted managing and defining mechanisms of large vessels and cardiac damage. However, impaired microvascular function, a powerful but clinically underused predictor of future MACE, may also be implicated. Extensive evidence shows that exercise interventions reduce systemic inflammation and possibly MACE. However, few cardio-oncology studies have utilized exercise to mitigate cardiotoxicity, and none have quantified microvascular endothelial function. A further gap in cardio-oncology research is a paucity of studies focused on understanding and addressing disparities. This research project aims to 1) test the feasibility and efficacy of an exercise intervention designed to mitigate the effects of CTx, Take Charge during Treatment (TCT) and 2) examine the influence of socio-ecological factors on endothelial function in response to an exercise intervention. Methods: B/AA (n=50) and NHW (n=50) women diagnosed with non-metastatic BC, scheduled to receive AC and/or anti-HER-2 therapy, will be recruited and randomized to participate in the TCT intervention or usual care (NCT05223322). TCT is a virtual exercise coaching program with weekly coaching sessions, six of which include supervised exercise. Assessments to assess socio-ecologic and vascular outcomes are presented in the Table. Assessments will be completed prior to treatment (T1), after treatment completion (18-24 weeks, T2), and 12-months post treatment (T3). Clinical trial information: NCT05223322. [Table: see text]

Assessment of a rationally-designed experimental microbial consortium to reduce systemic inflammation in a murine model of chemotherapy-induced mucositis.

e15062 Background: Gastrointestinal (GI) mucositis is a frequent complication of chemotherapy for cancer treatment and conditioning regimens for hematopoietic stem cell transplant (HSCT). Clinical and preclinical data suggest that disruption of the gut microbiome may be implicated in GI mucositis pathophysiology by affecting GI barrier integrity, immune homeostasis, and colonization resistance to pathogens. Here, we evaluated the ability of a rationally-designed microbial consortium, DE486, to reduce systemic inflammation and toxicity in a chemotherapy-induced murine mucositis model. Methods: Germ-free mice were used to evaluate the impact of the microbiome in a 5-fluorouracil-induced (5-FU) mucositis model. Mice were colonized with either DE486 or an inflammatory composition (INFL2). DE486 was rationally designed as a consortium of strains for experimental investigation to restore colonization resistance, improve GI barrier integrity, and reduce inflammatory responses. After 4-5 weeks of colonization, mice were intraperitoneally injected with 5-FU or vehicle control on three consecutive days (days 0-2) to initiate mucositis. The degree of 5-FU-induced toxicity was assessed by daily body weight measurements from the start of 5-FU treatment (day 0) until study end (day 8) and expressed as the mean body weight loss ± SD. Serum levels of pro-inflammatory cytokines were assessed on days 5 and 8 by mouse cytokine/chemokine immunoassays (Luminex xMAP). Data reported are the group mean pg/mL and the statistical significance of group mean differences was analyzed using one-way ANOVA. Results: In the 5-FU-induced mucositis model, mice colonized with DE486 or INFL2 exhibited a mean body weight loss of 10% ± 2% by day 4. However, on day 5, mice colonized with DE486 began to recover body weight and by day 8 returned to their body weight before 5-FU treatment. In contrast, mice colonized with INFL2 continued to lose body weight and by day 8 had a mean body weight loss of 18% ± 4%. Serum analyses showed that on day 5 cytokine levels in mice colonized with DE486 or INFL2 remained low and did not differ significantly between the two groups. However, on day 8, mice colonized with INFL2 developed significantly higher proinflammatory cytokine levels than mice colonized with DE486 (TNFα: 21.68 vs. 2.26, P = 0.018, IL-6: 1860.55 vs. 2.15, P = 0.007, IFN-γ: 177.37 vs. 0.37, P &lt; 0.001). Conclusions: Preclinical assessments in a murine model of chemotherapy-induced mucositis showed that colonization with DE486 promoted body weight recovery and protected against increased levels of key pro-inflammatory cytokines, as compared to colonization with an inflammatory microbiome. These data support the ability of a rationally-designed microbial consortium to ameliorate systemic inflammation following chemotherapy as a strategy to prevent or manage GI mucositis.

Photocatalytic and photothermal bismuthene nanosheets as drug carrier capable of generating CO to improve drug sensitivity and reduce inflammation for enhanced cancer therapy

Bismuthene nanosheet is a nontoxic and low-cost two-dimensional material, and has been reported with very limited biomedical applications. In this report, for the first time, we reported the utilization of bismuthene nanosheet for combined photothermal, photocatalytic and chemotherapy for cancer treatment. Partially oxidized bismuthene nanosheet was modified with polyethylene glycol (POBNS-PEG) and used as a drug delivery vehicle for the first time (antitumor drug doxorubicin (DOX) was used as a model drug, POBNS-PEG/DOX). POBNS-PEG itself shows a photothermal treatment ability under the near infrared light and this treatment can additionally promote better cellular uptake of POBNS-PEG and DOX. More importantly, POBNS-PEG was found to be able to reduce CO2 in cancer cells to CO through photocatalytic pathways under red light irradiation for the first time. The generated CO could obviously reduce the inflammation caused by photothermal treatment and drug resistance of tumor cells caused by chemotherapy. These three combined functions bring the three-in-one multifunctional bismuthene nanosheets not only have a significant antitumor effect but also reduce the side effects, making it with high clinical potentials.

Role of the Microbiota in Lung Cancer: Insights on Prevention and Treatment.

The microbiota is increasingly recognized as a critical player in cancer onset and progression and response to cancer chemotherapy treatment. In recent years, several preclinical and clinical studies have evidenced the involvement of microbiota in lung cancer, one of the world’s deadliest cancers. However, the mechanisms by which the microbiota can impact this type of cancer and patient survival and response to treatments remain poorly investigated. In this review, the peculiarities of the gut and lung microbial ecosystems have been highlighted, and recent findings illustrating the possible mechanisms underlying the microbiota–lung cancer interaction and the host immune response have been discussed. In addition, the mucosal immune system has been identified as a crucial communication frame to ease interactive dynamics between the immune system and the microbiota. Finally, the use of specific next-generation intestinal probiotic strains in counteracting airway diseases has been evaluated. We believe that restoring homeostasis and the balance of bacterial microflora should become part of the routine of integrated cancer interventions, using probiotics, prebiotics, and postbiotics, and promoting a healthy diet and lifestyle.

Socio-demographic and psychological factors associated with quality of life of women undergoing chemotherapy treatment for gynecological cancer

PurposeThis research aimed to investigate the socio-demographic, clinical, and psychological variables predictive of a greater functioning and quality of life in patients with gynecological cancer after their first cycle of carboplatin and taxol-based chemotherapy.MethodsThe sample of the present research consisted of 104 patients. The European Organization on Research and Treatment of Cancer QLQ-C30, the State-Trait Anxiety Inventory-Form Y, and the Multidimensional Scale of Perceived Social Support were administered to each participant.ResultsThe analyses showed that higher state anxiety levels predicted a lower role, emotional, and social functioning and a lower general quality of life. Higher trait anxiety levels and social support perceived from one’s friends predicted a greater role functioning. Similarly, having a relationship predicted a greater physical, cognitive, and social functioning. On the contrary, the presence of relapsed cancer was negatively associated with these patients’ quality of life.ConclusionsThe present study highlighted the importance of identifying patients at higher risk of experiencing lower levels of functioning and worse general quality of life to implement tailored interventions from the beginning of treatment, thus improving the quality of life of these patients throughout the chemotherapy treatment.

Lumiflavin Reduces Cisplatin Resistance in Cancer Stem-Like Cells of OVCAR-3 Cell Line by Inducing Differentiation.

Ovarian cancer stem-like cells (CSCs) play a vital role in drug resistance and recurrence of ovarian cancer. Inducing phenotypic differentiation is an important strategy to enhance the effects of chemotherapy and reduce the drug resistance of CSCs. This study found that lumiflavin, a riboflavin decomposition product, reduced the development of CSC resistance and enhanced the chemotherapy effect of cisplatin (DDP) on CSCs in DDP-resistant ovarian cancer OVCAR-3 cell line (CSCs/DDP) and was related to the induction of CSC phenotypic differentiation. Results showed that the development of DDP-resistant OVCAR-3 cells was related to the increase in the proportion of CSCs/DDP, and the treatment with lumiflavin reduced the DDP-resistance levels of OVCAR-3 cells and proportion of CSCs/DDP. Further investigation found that lumiflavin synergistic with DDP increased apoptosis, decreased mitochondrial membrane potential, and inhibited the clonal formation of CSCs/DDP. Meanwhile, in vivo experiments showed that lumiflavin dose-dependently enhanced the chemotherapy effect of DDP on tumor-bearing nude mice inoculated by CSCs/DDP. Lumiflavin treatment also reduced the ratio of CD133+/CD177+ to CD44+/CD24 cells, which is the identification of CSCs, in CSCs/DDP. In addition, transcriptome sequencing results suggested that the role of lumiflavin was related to the notch and stem cell pathway, and Western blot analysis showed that lumiflavin inhibited the protein expression of notch signaling pathway in CSCs/DDP. In conclusion, lumiflavin reduces the development of the drug resistance of OVCAR-3 cell and increases the sensitivity of CSCs/DDP to DDP by inducing phenotypic differentiation, which may have a potential role in the chemotherapy treatment of ovarian cancer.

Reversing radiation-induced immunosuppression using a new therapeutic modality

Radiation-induced immune suppression poses significant health challenges for millions of patients undergoing cancer chemotherapy and radiotherapy treatment, and astronauts and space tourists travelling to outer space. While a limited number of recombinant protein therapies, such a Sargramostim, are approved for accelerating hematologic recovery, the pronounced role of granulocyte-macrophage colony-stimulating factor (GM-CSF or CSF2) as a proinflammatory cytokine poses additional challenges in creating immune dysfunction towards pathogenic autoimmune diseases. Here we present an approach to high-throughput drug-discovery, target validation, and lead molecule identification using nucleic acid-based molecules. These Nanoligomer™ molecules are rationally designed using a bioinformatics and an artificial intelligence (AI)-based ranking method and synthesized as a single-modality combining 6-different design elements to up- or downregulate gene expression of target gene, resulting in elevated or diminished protein expression of intended target. This method additionally alters related gene network targets ultimately resulting in pathway modulation. This approach was used to perturb and identify the most effective upstream regulators and canonical pathways for therapeutic intervention to reverse radiation-induced immunosuppression. The lead Nanoligomer™ identified in a screen of human donor derived peripheral blood mononuclear cells (PBMCs) upregulated Erythropoietin (EPO) and showed the greatest reversal of radiation induced cytokine changes. It was further tested in vivo in a mouse radiation-model with low-dose (3 mg/kg) intraperitoneal administration and was shown to regulate gene expression of epo in lung tissue as well as counter immune suppression. These results point to the broader applicability of our approach towards drug-discovery, and potential for further investigation of our lead molecule as reversible gene therapy to treat adverse health outcomes induced by radiation exposure.

PO-1327 Fractal-based radiomic approach to tailor the chemotherapy treatment in rectal cancer

PO-1327 Fractal-based radiomic approach to tailor the chemotherapy treatment in rectal cancer

Swallowing Kinematics in Rats Treated with Low Dose Chemotherapy Concurrently with Fractionated Radiation

Dysphagia is a common consequence of chemotherapy and radiation treatment for oropharyngeal cancer. Injury is thought to occur due to damage to the muscle and/or nerves. This can severely impair swallowing function, leading to serious negative outcomes such as aspiration related pneumonia or tube feeding placement to maintain nutrition. Currently, there are only strategies to prevent swallowing dysfunction; however, the development of chronic radiation associated dysphagia persists effecting ~25% of head and neck cancer survivors. Therefore, there is a need to study the mechanisms associated with radiation associated dysphagia to help guide new treatments to improve swallowing outcomes. The present study investigated the effects of concurrent chemoradiation on swallowing function. We tested the hypothesis that fractionated radiation with low doses of chemotherapy alters swallowing kinematics and bolus transit compared to radiation alone or normal controls. We monitored the functional extent of chemoradiation or radiation treatment using videofluoroscopy swallow study in self feeding rats (n=16) at four weeks post treatment. Twelve rats underwent 48Gy of fractionated radiation to the submental muscles using a clinical linear accelerator given in 12 fractions of 4Gy. Irradiated rats received either cisplatin 1mg/kg or saline IP once per week for four weeks during radiation treatment. Four rats received no treatment. During videofluoroscopy, thin liquids and puree consistencies mixed with 40% w/v barium sulfate were given ad libitum. The movement trajectories of the tongue, mandible, and hyoid bone were quantitatively tracked from video data. Changes in the speed of the jaw and hyoid during swallowing were observed between treated and control rats. No differences were observed in bolus flow parameters i.e. pharyngeal transit speed, inter‐swallow interval, and swallow frequency between treatment groups. The average size of the bolus in vallecula decreased by ~4% prior to initiating pharyngeal swallow with chemoradiated rats (p &lt; 0.05). Results suggest that low doses of chemotherapy in conjunction with radiation appear to have minimal differences in swallowing kinematics compared to radiation alone. Higher doses of chemotherapy may be needed to induce similar abnormalities in swallowing as seen clinically.