5-fluorouracil Research Articles

Efficacy and safety of combined fractional ablative CO2 laser and 5 fluorouracil in the treatment of acral vitiligo: An open, uncontrolled study.

Acral lesions of vitiligo are most likely recalcitrant to the known lines of treatment. Ablative fractional CO2 has shown efficacy in treatment of vitiligo in combination with other modalities. Thirty non-segmental vitiligo patients with acral lesion were included in the study. Each patient was subjected to fractional Carbon Dioxide Laser Treatment followed by application of 5 fluorouracil (5FU) cream for five consecutive days. Evaluation was done 3 weeks from the start of treatment and 12 weeks after the last treatment session using VESTA score, evaluation of patients' photos by blinded investigation in addition to patients' satisfaction scores. Patients showed significant improvement of Vitiligo extent score for a target area (VESTA) score and developed considerable degree of repigmentation as assessed by blinded investigators. The combination of fractional ablative CO2 and 5FU is an effective and safe procedure for the treatment of acral vitiligo with promising results offering patients a new therapeutic window.

Effects of Semecarpus anacardium L.f. ethanol extract on serum biochemical parameters and antioxidant activity of DAL induced mice

Semecarpus anacardium L.f. nuts is one of the best, versatile and most commonly used herbs as a household remedy, distributed in sub-Himalayan region, Tropical region, Bihar, Bengal, Orissa and central and south parts of India. In this work, the anticancer efficacy of ethanol extract of Semecarpus anacardium nuts (EESA) was tested in Swiss albino mice with induced Dalton's Ascites Lymphoma (DAL). Ethanol extract of S. anacardium nuts was given daily for 14 days at doses of 200 mg/kg and 400 mg/kg body weight, after 24 hrs of tumor inoculation. After receiving the final dose and fasting for 18 hrs, the mice were euthanized. Serum biochemical and antioxidant characteristics were measured to determine antitumor activity. 5-Fluoro Uracil, a typical medication, was employed as a positive control. In comparison to the control group, ethanol extract-treated mice restored biochemical and antioxidant parameters to near-normal levels. Biochemical and antioxidant parameters in the Dalton's Ascited Lymphoma (DAL) animal model treated with EESA exhibited similar effects as the positive control drug 5-fluorouracil. Overall, the active ingredients present in ethanol extract of Semecarpus anacardium nuts, modulate serum biochemical and antioxidant parameters and bring about anti-tumor activity against Dalton's Ascites Lymphoma (DAL) in mice.

Downregulation of KRAB zinc finger proteins in 5-fluorouracil resistant colorectal cancer cells

Radio-chemotherapy with 5-flu orouracil (5-FU) is the standard of care treatment for patients with colorectal cancer, but it is only effective for a third of them. Despite our understanding of the mechanism of action of 5-FU, drug resistance remains a significant limitation to the clinical use of 5-FU, as both intrinsic and acquired chemoresistance represents the major obstacles for the success of 5-FU-based chemotherapy. In order to identify the mechanism of acquired resistance, 5-FU chemoresistance was induced in CRC cell lines by passaging cells with increasing concentrations of 5-FU. To study global molecular changes, quantitative proteomics and transcriptomics analyses were performed on these cell lines, comparing the resistant cells as well as the effect of chemo and radiotherapy. Interestingly, a very high proportion of downregulated genes were annotated as transcription factors coding for Krüppel-associated box (KRAB) domain-containing zinc-finger proteins (KZFPs), the largest family of transcriptional repressors. Among nearly 350 KRAB-ZFPs, almost a quarter were downregulated after the induction of a 5-FU-resistance including a common one between the three CRC cell lines, ZNF649, whose role is still unknown. To confirm the observations of the proteomic and transcriptomic approaches, the abundance of 20 different KZFPs and control mRNAs was validated by RT-qPCR. In fact, several KZFPs were no longer detectable using qPCR in cell lines resistant to 5-FU, and the KZFPs that were downregulated only in one or two cell lines showed similar pattern of expression as measured by the omics approaches. This proteomic, transcriptomic and genomic analysis of intrinsic and acquired resistance highlights a possible new mechanism involved in the cellular adaptation to 5-FU and therefore identifies potential new therapeutic targets to overcome this resistance.

Gemcitabine Combined with Cisplatin Has a Better Effect in the Treatment of Recurrent/Metastatic Advanced Nasopharyngeal Carcinoma.

ObjectiveTo explore the efficacy and safety of gemcitabine (GEM) combined with cisplatin (DDP) in the treatment of recurrent/metastatic nasopharyngeal carcinoma (NPC).MethodsA total of 100 patients with recurrent/metastatic NPC treated in the First Affiliated Hospital, Hengyang Medical School, University of South China from January 2018 to March 2020 were retrospectively enrolled. Based on different chemotherapy schemes, they were assigned to an observation (Obs) group (DDP + GEM, n = 55) and a control (Con) group [DDP + FU (fluorouracil), n = 45]. The two groups were compared regarding the following items: therapeutic efficacy; serum levels of platelet-derived growth factor-BB (PDGF-BB), soluble epithelial cadherin (SE-CAD), and inflammation-related factors before and after treatment; toxic and side effects; 1-year survival rate; and quality of life (QOL) 6 months after treatment.ResultsThe Obs group outperformed the Con group in therapeutic efficacy (P < 0.05). There were no significant differences in the levels of PDGF-BB, SE-CAD, interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-α between the two groups before treatment (P > 0.05). After treatment, better improvements in PDGF-BB, SE-CAD and inflammatory factors were observed in the Obs group (P < 0.05). The toxic and side effects were significantly lower and the 1-year survival rate and patients’ QOL after 6 months of treatment were significantly higher in the Obs group compared with the Con group (P < 0.05).ConclusionGEM combined with DDP can provide more clinical benefits for patients with recurrent/metastatic advanced NPC, with less side effects, high tolerance and significant efficacy, which can be further promoted in clinical use.

First principles calculations of the adsorption of fluorouracil and nitrosourea on CTF-0; organic frameworks as drug delivery systems for cancer treatment

2D sheet like materials such graphene are superior drug delivery systems compared to the conventional macro systems due to good adsorption and reasonable bioavailability. The adsorption and bioavailability can be further improved with periodic cavity containing 2D materials which can bind with drug molecules with moderate binding energies. Therefore, we have studied for the first time the potential of 2-dimensional porous covalent triazine framework (CTF-0) for the delivery of anticancer drugs fluorouracil (FU) and nitrosourea (NU). Adsorption energy analysis shows that the drug molecules bind with CTF-0 with moderate interaction energies which is prime requirement of a good drug delivery system. However, FU@CTF-0 complex (−17.45 kcal/mol) is more stable than NU@CTF-0 (−14.83 kcal/mol), and that the dipole moment of surface increases after adsorption of drugs. The increase in dipole moment after complex formation helps to improve the solubility, which is necessary for drug delivery in biological systems. Symmetry adapted perturbation theory confirms the stability of drug-loaded complexes, where the contribution from dispersion interactions is the highest. The HOMO-LUMO energy gap (EH-L) of CTF-0 decreases from 4.5 eV to 4.1 eV and 4.0 eV after loading of FU and NU respectively. The pH in cancerous tissues is typically low, which can lead to protonation of a drug and hence aid its delivery to target cells. The nature of the attraction between the CTF-0 surface and different drugs has been evaluated on the bases of noncovalent interactions (NCI) and also the quantum theory of atoms in molecules (QTAIM). QTAIM results confirm that FU has a stronger affinity towards CTF-0 than NU. Based on all our calculated results, CTF-0 appears to be a viable candidate for the delivery of the anticancer drug FU. Previously reported surface for FU and NU drugs has much higher interaction energy which is problematic for the release of drug from the carrier in the biological system. This study provides useful information that may assist the experimental formulation of a CTF-0-based DDS for FU.

Impact of 5-fluorouracil on anaerobic digestion using sewage sludge

The role of bacterial interaction is vital to control bacterial functions; however, it has not been fully understood in microbial consortia (including anaerobic digestion). In this study, fluorouracil (FU), which is an anticancer agent and a quorum sensing (QS) inhibitor to some of the Gram-negative bacteria was found to inhibit methane production from sewage sludge under anaerobic conditions, as shown in a result where methane production in the presence of FU was eight times lower than the control (sewage sludge without FU). Whereas FU did not influence the hydrolysis process, in the acidogenesis/acetogenesis process, butyrate, and acetate accumulated in samples with FU. Also, in the methanogenesis process, FU remarkably inhibited methane production by acetoclastic methanogens rather than by the hydrogenotrophic ones. This result agreed with the result that growth and methane production of Methanosarcina acetivorans C2A was inhibited in the presence of FU. However, the inhibitory effect of FU was high in the condition that both bacteria and archaea were active. It indicates that FU influences methanogens and bacteria in the process of methane fermentation. The analyses of microbial communities (bacteria and archaea) showed that the abundance ratio of the Firmicutes phyla is high, and hydrogenotrophic methanogens become dominant in the presence of FU. Conversely, the abundance of Spirochaetes significantly decreased under FU. The inhibition of methane production by FU was due to the growth inhibition of methanogenic archaea and the changes in the composition of the bacterial population.

Abstract P5-05-03: Adipocyte associated methionine domain containing (AAMDC): A nuclear envelope protein with predictive and prognostic potential in luminal breast cancer

Abstract Background Estrogen receptor (ER) positive breast cancers (BCs) are less likely to relapse than other types, due to a lower propensity to disseminate and to sensitivity to anti-estrogen drugs in the adjuvant setting. However, combined analysis of DNA mutation and mRNA expression profiles in BC identifies a number of Integrative Clusters (IntClus), one of which, IntClus2, is characterized by ER positivity but high relpase and mortality. A hallmark of IntClus2 tumours is an amplification of chromosome 11, at the center of which lies the gene for the protein AAMDC. Pre-clinical research shows this protein to drive proliferation, migration, colony formation, switching between glucose and lipid metabolism, folate metabolism and anti-estrogen resistance. We postulated that resultant clinical behaviours could include; high relapse and mortality, anti-estrogen resistance, an interaction with the protective effect on relapse from statins and sensitivity to fluorouracil (FU)-based therapies. Methods The retrospective study cohort comprised 1766 ER positive early BC patients treated 1994-2014. Patient and tumour demographic, statin prescription and treatment data were collated. Primary tumour tissue was available with AAMDC expression data on 419 patients. On noting nuclear (N), cytoplasmic (C) and nuclear envelope (NE) expression, separate intensity scores were attributed to each localization. Intensity score cut-points were based on providing statistically useable sub-group sizes for comparison. Results No significant correlations between BC biology and patterns of AAMDC expression were seen. Cytoplasmic AAMDC weakly linked to some aggressive features, including high grade, luminal B sub-type and progesterone receptor negativity, although less lymph node spread. In contrast, nuclear AAMDC associated with some less aggressive features, being less in high grade and luminal B cancers. Nuclear envelope AAMDC was rarer in the HER2 positive sub-type without other correlates. A trend to higher distant relapse was seen for NE +ive BCs (20 v 14%, p=0.09). Overall mortality was statistically higher for NE expression (54 v 44% mortality, p=0.04) and cytoplasmic expression (56 v 47% mortality, p=0.04) and a trend to lower mortality for nuclear expression (46 v 54%, p=0.06). Looking at combinatorial expression, BC deaths were significantly lower in the nuclear +ive/NE -ive phenotype (4.7%) than the nuclear -ive/NE -ive (19.5%, p=0.013), nuclear -ive/NE +ive (17.6%, p=0.017) or nuclear +ive/NE +ive phenotypes (19.3%, p=0.011).Considering the effects of statins on early BC outcome, overall our patients on statins had notably lower BC return rates (HR 0.31, p=0.004). Considering interactions with AAMDC, in high-risk NE +ive cancers statin protection was high (HR for relapse 0.33, p=0.032), compared to no protection in already low risk NE -ive tumours (HR 0.90, p=0.41). The hypothesis that AAMDC confers sensitivity to FU-based agents was confirmed with a correlation observed for longer responses to FU-based chemotherapy for increasing NE AAMDC expression (R=0.334), whereas no link was seen for other agents or other AAMDC expression sub-locations. The mean times on FU-based therapy for low, moderate and high NE expression were 2.0, 5.7 and 12.2 months respectively (p=0.02). This work indicates that AAMDC expression can BC affect outcome, identifying nuclear envelope located AAMDC as both associating with higher mortality and correlating with superior protection from statins as well as response to FU-based chemotherapies. This could guide metastatic chemotherapy selection for affected patients, implies NE positive BCs might preferentially benefit from adjuvant statins and suggests that AAMDC and NE-associated AAMDC partners may be future therapeutic targets. Citation Format: Indunil Weerasena, Lisa Spalding, Benjamin F Dessauvagie, Emily Golden, Eleanor Woodward, Pilar Blancafort, Andrew Redfern. Adipocyte associated methionine domain containing (AAMDC): A nuclear envelope protein with predictive and prognostic potential in luminal breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-05-03.

Resistant Plane Warts Treated by 40% Salicylic Acid and 16% Lactic Acid Combination on the Face

Human papillomaviruses (HPV) cause warts, which are the benign epithelial proliferation of the mucous membrane and skin. HPV-3 and HPV-10 commonly cause plane warts. Multiple treatment options must be used as no specific treatment option is available. We have a lot of limitations for the face as treatment can cause permanent scarring on the face. We report a case of 41 years immunocompetent male presenting with many plane warts on the face who was successfully treated with topical application of 40% Salicylic acid cream and 16% lactic acid cream made up of 44% of bees wax on lesions after a failure of many other treatment options, a) Topical zinc oxide twice per day for 3 months, b) Topical 5% salicylic acid dispensing cream made in 95% bees wax, c) Topical 5% fluorouracil cream, d) Topical imiquimod cream, e) Topical retinoids cream only at night for one month, f) Oral Isotretinoin 20mg twice per day for 2 months, and 3 sessions of cryotherapy. The patient's last treatment was oral isotretinoin 20 mg twice per day for the last 2 months. In general, doctors avoid using more than 5% salicylic acid, but after a detailed discussion with the patient, we decided to try this combination and succeeded.

Does the Computed Tomography Hounsfield Units Change Predict Response to Perioperative Chemotherapy in Patients with Gastric Adenocarcinoma.

Purpose: We aimed to investigate whether Computed Tomography (CT) attenuation change is predictive of poor pathological response in patients with gastric cancer (GC) and gastroesophageal junction (GEJ) adenocarcinoma who received perioperative fluorouracil (FU), leucovorin (LV), oxaliplatin, and docetaxel (FLOT) regimen.Methods: This trial was planned as a retrospective single-center study. In the neoadjuvant setting, patients received a regimen that includes docetaxel (50 mg/m2), oxaliplatin (85 mg/m2), and LV (200 mg/m2) with short-term infusional FU (2600 mg/m2 as a 24-hour infusion), on day 1 and administered every two weeks for four cycles. Patients were classified as response rates according to the CAP-TRG system (0-1 response or 2-3 response) after completing four cycles of the FLOT regimen.Results: In total, 108 patients with GC and GEJ adenocarcinoma were included in the study. In a univariate analysis, age, histologic grade, T stage, N stage, and change in attenuation were found to be the statistically significant factors (p = 0.034, p =0.038, p = 0.001, p =0.029, and p = 0.022, respectively). In a multivariate analysis, T4 tumors and a higher change in attenuation were found to be important factors associated with poor pathologic response (p = 0.027 and p = 0.038, respectively).Conclusion: Our results demonstrate that a higher decrease in CT attenuation and T4 tumors is associated with a poor response to perioperative FLOT chemotherapy in patients with GC and GEJ adenocarcinoma.

The Overall Number of Actinic Keratosis Lesions Is Not Predictable by the Number of Visible Lesions: Consequences for Field-Directed Therapies

Actinic keratoses are keratotic lesions occurring on skin areas extensively damaged by sunlight. Using data from a previously published Phase III randomized, controlled clinical trial in patients with at least 5 actinic keratoses, we explored the potential link between the number of visible actinic keratosis lesions before any treatment and the total number of lesions of the field cancerization as revealed by 5-fluorouracil cream. Our analysis suggests that the baseline number of visible actinic keratoses is a poor indicator of the real number of lesions in the field of cancerization, reinforcing the need to explain the field cancerization concept to patients. (Curr Ther Res Clin Exp. 2022; 82:XXX–XXX) © 2022 Elsevier HS Journals, Inc.

A DFT study on the Ag-decorated AlP nanosheets as chemical sensor for recognition of adrucil drug

We employed density functional B3LYP to inspect the impact of Ag-decoration on an AlP nanosheet (AlPNS) sensing performance in detection of adrucil (AR) drug. The interaction of the pristine AlPNS with the AR was found to be weak, and the sensing response is about 2.3. Decorating an Ag atom into the AlPNS surface increases the adsorption energy (Ead) of AR from −5.8 to −23.6 kcal/mol. The sensing response significantly rises to 91.7 by Ag-decoration. A short recovery time of 15.7 s is found for the AR desorption from the Ag-decorated AlPNS surface at 298 K. The water solvent reduces Ead of AR to −19.6 kcal/mol. Finally, we found that Ag-decorated AlPNS may be promising and highly sensitive AR sensor.

Antifungal Activity of Essential Oils Vapors Against Fungi Isolated from Car Air- Conditioner Filters

Background/A car air conditioner AC filter is a suitable place for microbial growth. Fungal structures or/ andtheir by-products are pollutants of car air space. They are transmitted via air current forward passengers. Mostisolates were reported as allergens and mycotoxins producers. Chemical and less nonchemical treatmentswere followed to solve this problem. The current study aims to isolate and identify fungi associated withCAC filters and discuss the relationship between the fungal community with car age and the types of seatcoats. Also, we inspected the antifungal activity of the vapor and liquid phases of five essential oils invitro. Methods/ A cross-section study was followed, a swap samples were collected during one week. Theywere cultured on Sabouroad’s dextrose agar and Typha pollens agar. Plates were incubated at (25oC ±2).The highest occurrence% were Penicillium sp. &gt; Alternaria sp. &gt; Aspergillus (3sp.), while Acremoniumsp.,Rhizopus sp., Rodotorula sp. and Stachybotrys sp., showed low O% as well as yellow yeast and sterilemycelia. The crude oils of Hacinathus sp., Cymbopogon citratus, Myrtus communis, Eucalyptus sp.,and Cyperus rotundus were extracted and examined. ANOVA test showed that C.citratus oil vapor phasesignificantly affects the dominant isolate. Conclusion/ Car AC filter is a source of fungal structures withhealth impact. Liquid and vapor phases of EOs are probably practical alternatives to control fungal ACcontamination

Penerapan Teknologi Mesin AC Mobil Bagi Siswa Jurusan Teknik Otomotif Di SMK Negeri 1 Losarang

Completeness praktikun learning tool in achieving competence automotive field would be a necessity that must be met. Seeing the large number of students at SMKN 1 Losarang, majoring in Automotive engineering, having practicum facilities that are still relatively minimal, with the limited practical facilities, additional practical facilities are needed in the form of car AC machine trainers to improve student competence at SMK N 1 Losarang. Increased competence by providing trainer AC Drives and conducted training and workshops and provide free test and post-test were conducted before and after the training. With the application of AC engine technology competence of students majoring in Automotive cars increased by 20.5%. This is based on comparison of the value of the free test to post-test value that has been done. PKM activity carried out has an impact enough for both students and the school's own department.

Porokeratoma treated with topical 5% 5-fluorouracil cream.

What is known about this subject in regard to women and their families? • Porokeratoma is a rare lesion with distinct pathologic features that make diagnosis challenging. • Porokeratoma has historically been treated with excision. • In those who are cosmetically sensitive, particularly women, excision may not be a desirable treatment option. What is new from this article as messages for women and their families? • Porokeratoma can be successfully treated with topical 5% 5-fluorouracil (5-FU) cream. • Topical 5-FU is a safe and practical alternative to surgical intervention, especially in patients who are cosmetically sensitive. It is also useful in sites, such as the hands, where excision can compromise daily functioning and occupational activities.

Concomitant Use of Proton Pump Inhibitors With Capecitabine Based Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: Is it Safe?

Capecitabine (Cape) is routinely used for the neoadjuvant chemoradiation treatment (NACRT) of locally advanced rectal cancers (LARCs). Previous reports have suggested that the concomitant use of proton pump inhibitors (PPIs) may affect the efficacy of Cape, although the true effect of PPIs when used with Cape as a radiosensitizer for neoadjuvant radiation is unclear. The aim of our study was to evaluate the impact of concurrent PPI use along with fluorouracil (FU) and Cape based NACRT in terms of pathologic and oncological outcomes, in patients with LARC. LARC patients treated at our center with NACRT from 2010 to 2016 were identified. Postoperative pathology and follow-up outcomes were examined for any differences with relation to the use of PPIs concurrently with FU and Cape based NACRT and adjuvant chemotherapy regimens. Three hundred four and 204 patients received treatment with FU and Cape based NACRT. No difference in pathologic complete response rate was noted between the 2 arms with the concurrent use of PPIs (25.8% and 25%, respectively, P=0.633); or with and without the use of PPIs in the Cape-NACRT arm specifically (20% and 20.7%, P=0.945). At a median follow-up of 5 years, no statistical difference in local or distant control was noted in the Cape-NACRT patients, with and without concomitant PPI use (P=0.411 and 0.264, respectively).Multivariate analysis showed no association of PPI use and NACRT with Cape, in terms of local control (hazard ratio=0.001, P=0.988) or overall survival (hazard ratio=1.179, confidence interval=0.249-5.579, P=0.835). Our study revealed that there was no adverse pathologic or oncological outcome with the concurrent use of PPIs along with Cape-NACRT in the treatment of LARC. We report that it may be safe to use PPIs if essential, in this clinical setting, although it would be wise to exercise caution.

Neoplasia-related spiny keratoderma: Dermoscopic findings of two cases and a literature review.

Neoplasia-related spiny keratoderma: Dermoscopic findings of two cases and a literature review.

Randomized phase II study of modified FOLFIRINOX versus gemcitabine plus nab-paclitaxel combination therapy for locally advanced pancreatic cancer (JCOG1407).

4017 Background: FOLFIRINOX, consisting of leucovorin (LV), fluorouracil (FU), irinotecan (IRI) and oxaliplatin (L-OHP), and GnP, consisting of gemcitabine (GEM) plus nab-paclitaxel (nPTX), have shown superior efficacy over GEM in patients (pts) with metastatic pancreatic cancer. Although several studies have reported the efficacy of FOLFIRINOX or GnP for pts with locally advanced pancreatic cancer (LAPC), no randomized controlled trial to compare the two regimens has been conducted in those pts. To select the most promising chemotherapy for LAPC, a randomized phase II selection design trial (JCOG1407) was conducted to compare between modified FOLFIRINOX (FOLFIRINOX with dose reduction of IRI and without bolus FU; Arm A) and GnP (Arm B) for pts with LAPC. Methods: In Arm A, 85 mg/m2 of L-OHP, 200 mg/m2 of l-LV, 150 mg/m2 of IRI, followed by 2,400 mg/m2 of continuous FU over 46 hours are infused every 2 weeks. In Arm B, 125 mg/m2 of nPTX followed by 1,000 mg/m2 of GEM are infused on days 1, 8, and 15 every 4 weeks. The primary endpoint was overall survival (the proportion of 1-year OS), and secondary endpoints included progression-free survival (PFS), distant metastasis-free survival (MFS) and response rate in pts with target lesions. The planned sample size was 124 pts to select more effective regimen in 1-year OS with a probability of at least 0.85 and to test the null hypothesis of 53% in 1-year OS with a one-sided alpha of 5% and 80% Results: From 2015 to 2019, a total of 126 pts was enrolled from 29 Japanese institutions, and were allocated to Arm A (n = 62) or Arm B (n = 64). The median (range) age was 66 (44-75) years and 58.7% were male. At the analysis, after a median (range) follow-up of 1.52 (0.55-3.99) years, 75 (59.5%) pts died. The proportion of 1-year OS was better in Arm B, 77.4% [95% CI 64.9–86.0] vs. 82.5% [95% CI 70.7–89.9], but 2-year OS was better in Arm A, 48.2% [95% CI 33.3–61.7] vs. 39.7% [95% CI 28.6–52.5]. Median OS was 2.0 years [95% CI 1.6-2.7] in Arm A and 1.8 years [95% CI 1.5-2.0] in Arm B. 1-year PFS for Arm A/B was 47.5 % [95% CI 34.5-59.4]/40.2% [95% CI 27.8-52.3], and 1-year MFS was 64.2 % [95% CI 50.9-74.8]/57.3% [95% CI 43.9-68.6]. Arm A was better OS in pts with CA19-9 &lt;1000 U/mL and the opposite trend was observed in pts with CA19-9&gt;1000 U/mL. Response rate was 30.9% [95% CI 19.1-44.8] in Arm A, and 41.4% [95% CI 28.6-55.1]) in Arm B. Incidences of grade 3-4 non-hematological toxicities for Arm A and Arm B were 66.1% and 67.2%, respectively. There was no treatment-related death. Conclusions: This study was the first randomized trial comparing the two regimens. The 1-year OS of the primary endpoint in GnP was better than mFOLFIRINOX, but mFOLFIRINOX achieved longer survival in 2-year OS. It is required to confirm longer OS and safety profiles which regimen should be selected as a standard regimen in LAPC. Clinical trial information: jRCTs031180085.

High-Potency Topical Steroid Treatment of Multiple Keratoacanthomas Associated With Prurigo Nodularis.

Patients who present with multiple keratoacanthomas (KAs) associated with prurigo nodularis often pose a treatment challenge. These lesions often require aggressive treatment, such as Mohs micrographic surgery, surgical excision, electrodesiccation and curettage, intralesional steroid injection, and long-term acitretin. 5-Fluorouracil (5-FU) cream 5% has been shown to be effective; however, topical options are limited when 5-FU fails. We have found success using a high-potency topical steroid under occlusion, resulting in resolution of KAs and prurigo nodules.

Inhibition of Human Uracil DNA Glycosylase Sensitizes a Large Fraction of Colorectal Cancer Cells to 5-Fluorodeoxyuridine and Raltitrexed but Not Fluorouracil.

Previous short-hairpin RNA knockdown studies have established that depletion of human uracil DNA glycosylase (hUNG) sensitizes some cell lines to 5-fluorodeoxyuridine (FdU). Here, we selectively inhibit the catalytic activity of hUNG by lentiviral transduction of uracil DNA glycosylase inhibitor protein into a large panel of cancer cell lines under control of a doxycycline-inducible promoter. This induced inhibition strategy better assesses the therapeutic potential of small-molecule targeting of hUNG. In total, 6 of 11 colorectal lines showed 6- to 70-fold increases in FdU potency upon hUNG inhibition ("responsive"). This hUNG-dependent response was not observed with fluorouracil (FU), indicating that FU does not operate through the same DNA repair mechanism as FdU in vitro. Potency of the thymidylate synthase inhibitor raltitrexed (RTX), which elevates deoxyuridine triphosphate levels, was only incrementally enhanced upon hUNG inhibition (<40%), suggesting that responsiveness is associated with incorporation and persistence of FdU in DNA rather than deoxyuridine. The importance of FU/A and FU/G lesions in the toxicity of FdU is supported by the observation that dT supplementation completely rescued the toxic effects of U/A lesions resulting from RTX, but dT only increased the IC50 for FdU, which forms both FU/A and FU/G mismatches. Contrary to previous reports, cellular responsiveness to hUNG inhibition did not correlate with p53 status or thymine DNA glycosylase expression. A model is suggested in which the persistence of FU/A and FU/G base pairs in the absence of hUNG activity elicits an apoptotic DNA damage response in both responsive and nonresponsive colorectal lines. SIGNIFICANCE STATEMENT: The pyrimidine base 5-fluorouracil is a mainstay chemotherapeutic for treatment of advanced colorectal cancer. Here, this study shows that its deoxynucleoside form, 5-fluorodeoxyuridine (FdU), operates by a distinct DNA incorporation mechanism that is strongly potentiated by inhibition of the DNA repair enzyme human uracil DNA glycosylase. The hUNG-dependent mechanism was present in over 50% of colorectal cell lines tested, suggesting that a significant fraction of human cancers may be sensitized to FdU in the presence of a small-molecule hUNG inhibitor.

FeC19 cage vehicle for fluorouracil anticancer drug delivery: DFT approach

This work was performed by the importance of applications of nanostructures in drug delivery processes especially for anticancer consumption. Fluorouracil (FU) is a known anticancer drug, in which its loading at the surface of FeC19 cage vehicle was investigated by performing density functional theory (DFT) calculations. The employed cage was indeed an iron-doped model of C20 cage to provide surface interacting with FU. Seven starting positions (S1 to S7) were predefined for FU to participate in interaction with the cage to provide S1 to S7 complex formations. Optimized structures of six of them were achieved properly, but that of S5 was not achieved even by performing long-hour optimization processes. High strength of obtained complexes approved the complex formation of models and indicating possible role of such metal nanoparticle (MNP) for external filed conducting targeted drug delivery processes. Moreover, the complexes themselves were categorized by the strength level, in which S2 and S4 were introduced as the strongest and the weakest models respectively. Analyses of energies also approved such achievements in addition to confirming results obtained by the atomic scale quadrupole coupling constant (QCC) parameters. Based on such obtained features of detailed information, FU@FeC19 complexes were proposed for drug delivery process.