Perioperative Modified FOLFIRINOX for Resectable Pancreatic Cancer: A Nonrandomized Controlled Trial.

Importance: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant tumor, and durable disease control is rare with the current standard of care, even for patients who undergo surgical resection. Objective: To assess whether neoadjuvant modified 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFIRINOX) leads to early control of micrometastasis and improves survival. Design, Setting, and Participants: This open-label, single-arm, phase 2 nonrandomized controlled trial for resectable PDAC was conducted at the Yale Smilow Cancer Hospital from April 3, 2014, to August 16, 2021. Pancreatic protocol computed tomography was performed at diagnosis to assess surgical candidacy. Data were analyzed from January to July 2023. Interventions: Patients received 6 cycles of neoadjuvant mFOLFIRINOX before surgery and 6 cycles of adjuvant mFOLFIRINOX. Whole blood was collected and processed to stored plasma for analysis of circulating tumor DNA (ctDNA) levels. Tumors were evaluated for treatment response and keratin 17 (K17) expression. Main Outcomes and Measures: The primary end point was 12-month progression-free survival (PFS) rate. Additional end points included overall survival (OS), ctDNA level, tumor molecular features, and K17 tumor levels. Survival curves were summarized using Kaplan-Meier estimator. Results: Of 46 patients who received mFOLFIRINOX, 31 (67%) were male, and the median (range) age was 65 (46-80) years. A total of 37 (80%) completed 6 preoperative cycles and 33 (72%) underwent surgery. A total of 27 patients (59%) underwent resection per protocol (25 with R0 disease and 2 with R1 disease); metastatic or unresectable disease was identified in 6 patients during exploration. Ten patients underwent surgery off protocol. The 12-month PFS was 67% (90% CI, 56.9-100); the median PFS and OS were 16.6 months (95% CI, 13.3-40.6) and 37.2 months (95% CI, 17.5-not reached), respectively. Baseline ctDNA levels were detected in 16 of 22 patients (73%) and in 3 of 17 (18%) after 6 cycles of mFOLFIRINOX. Those with detectable ctDNA levels 4 weeks postresection had worse PFS (hazard ratio [HR], 34.0; 95% CI, 2.6-4758.6; P = .006) and OS (HR, 11.7; 95% CI, 1.5-129.9; P = .02) compared with those with undetectable levels. Patients with high K17 expression had nonsignificantly worse PFS (HR, 2.7; 95% CI, 0.7-10.9; P = .09) and OS (HR, 3.2; 95% CI, 0.8-13.6; P = .07). Conclusions and Relevance: This nonrandomized controlled trial met its primary end point, and perioperative mFOLFIRINOX warrants further evaluation in randomized clinical trials. Postoperative ctDNA positivity was strongly associated with recurrence. K17 and ctDNA are promising biomarkers that require additional validation in future prospective studies. Trial Registration: ClinicalTrials.gov Identifier: NCT02047474.

DNA encoding schemes herald a new age in cybersecurity for safeguarding digital assets.

With the urge to secure and protect digital assets, there is a need to emphasize the immediacy of taking measures to ensure robust security due to the enhancement of cyber security. Different advanced methods, like encryption schemes, are vulnerable to putting constraints on attacks. To encode the digital data and utilize the unique properties of DNA, like stability and durability, synthetic DNA sequences are offered as a promising alternative by DNA encoding schemes. This study enlightens the exploration of DNA's potential for encoding in evolving cyber security. Based on the systematic literature review, this paper provides a discussion on the challenges, pros, and directions for future work. We analyzed the current trends and new innovations in methodology, security attacks, the implementation of tools, and different metrics to measure. Various tools, such as Mathematica, MATLAB, NIST test suite, and Coludsim, were employed to evaluate the performance of the proposed method and obtain results. By identifying the strengths and limitations of proposed methods, the study highlights research challenges and offers future scope for investigation.

Growth characteristics of HCT116 xenografts lacking asparagine synthetase vary according to sex.

BACKGROUND: Sex-related differences in colorectal (CRC) incidence and mortality are well-documented. However, the impact of sex on metabolic pathways that drive cancer growth is not well understood. High expression of asparagine synthetase (ASNS) is associated with inferior survival for female CRC patients only. Here, we used a CRISPR/Cas9 technology to generate HCT116 ASNS-/- and HCT 116 ASNS+/+ cancer cell lines. We examine the effects of ASNS deletion on tumor growth and the subsequent rewiring of metabolic pathways in male and female Rag2/IL2RG mice. RESULTS: ASNS loss reduces cancer burden in male and female tumor-bearing mice (40% reduction, q < 0.05), triggers metabolic reprogramming including gluconeogenesis, but confers a survival improvement (30 days median survival, q < 0.05) in female tumor-bearing mice alone. Transcriptomic analyses revealed upregulation of G-protein coupled estrogen receptor (GPER1) in tumors from male and female mice with HCT116 ASNS-/- xenograft. Estradiol activates GPER1 in vitro in the presence of ASNS and suppresses tumor growth. CONCLUSIONS: Our study indicates that inferior survival for female CRC patients with high ASNS may be due to metabolic reprogramming that sustains tumor growth. These findings have translational relevance as ASNS/GPER1 signaling could be a future therapeutic target to improve the survival of female CRC patients.

PROTAC-Mediated Dual Degradation of BCL-xL and BCL-2 Is a Highly Effective Therapeutic Strategy in Small-Cell Lung Cancer.

BCL-xL and BCL-2 are validated therapeutic targets in small-cell lung cancer (SCLC). Targeting these proteins with navitoclax (formerly ABT263, a dual BCL-xL/2 inhibitor) induces dose-limiting thrombocytopenia through on-target BCL-xL inhibition in platelets. Therefore, platelet toxicity poses a barrier in advancing the clinical translation of navitoclax. We have developed a strategy to selectively target BCL-xL in tumors, while sparing platelets, by utilizing proteolysis-targeting chimeras (PROTACs) that hijack the cellular ubiquitin proteasome system for target ubiquitination and subsequent degradation. In our previous study, the first-in-class BCL-xL PROTAC, called DT2216, was shown to have synergistic antitumor activities when combined with venetoclax (formerly ABT199, BCL-2-selective inhibitor) in a BCL-xL/2 co-dependent SCLC cell line, NCI-H146 (hereafter referred to as H146), in vitro and in a xenograft model. Guided by these findings, we evaluated our newly developed BCL-xL/2 dual degrader, called 753b, in three BCL-xL/2 co-dependent SCLC cell lines and the H146 xenograft models. 753b was found to degrade both BCL-xL and BCL-2 in these cell lines. Importantly, it was considerably more potent than DT2216, navitoclax, or DT2216 + venetoclax in reducing the viability of BCL-xL/2 co-dependent SCLC cell lines in cell culture. In vivo, 5 mg/kg weekly dosing of 753b was found to lead to significant tumor growth delay, similar to the DT2216 + venetoclax combination in H146 xenografts, by degrading both BCL-xL and BCL-2. Additionally, 753b administration at 5 mg/kg every four days induced tumor regressions. At this dosage, 753b was well tolerated in mice, without observable induction of severe thrombocytopenia as seen with navitoclax, and no evidence of significant changes in mouse body weights. These results suggest that the BCL-xL/2 dual degrader could be an effective and safe therapeutic for a subset of SCLC patients, warranting clinical trials in future.

SASAN: ground truth for the effective segmentation and classification of skin cancer using biopsy images.

OBJECTIVES: Early skin cancer diagnosis can save lives; however, traditional methods rely on expert knowledge and can be time-consuming. This calls for automated systems using machine learning and deep learning. However, existing datasets often focus on flat skin surfaces, neglecting more complex cases on organs or with nearby lesions. METHODS: This work addresses this gap by proposing a skin cancer diagnosis methodology using a dataset named ASAN that covers diverse skin cancer cases but suffers from noisy features. To overcome the noisy feature problem, a segmentation dataset named SASAN is introduced, focusing on Region of Interest (ROI) extraction-based classification. This allows models to concentrate on critical areas within the images while ignoring learning the noisy features. RESULTS: Various deep learning segmentation models such as UNet, LinkNet, PSPNet, and FPN were trained on the SASAN dataset to perform segmentation-based ROI extraction. Classification was then performed using the dataset with and without ROI extraction. The results demonstrate that ROI extraction significantly improves the performance of these models in classification. This implies that SASAN is effective in evaluating performance metrics for complex skin cancer cases. CONCLUSIONS: This study highlights the importance of expanding datasets to include challenging scenarios and developing better segmentation methods to enhance automated skin cancer diagnosis. The SASAN dataset serves as a valuable tool for researchers aiming to improve such systems and ultimately contribute to better diagnostic outcomes.

PROTAC-mediated dual degradation of BCL-xL and BCL-2 is a highly effective therapeutic strategy in small-cell lung cancer.

BCL-xL and BCL-2 are validated therapeutic targets in small-cell lung cancer (SCLC). Targeting these proteins with navitoclax (formerly ABT263, a dual BCL-xL/2 inhibitor) induces dose-limiting thrombocytopenia through on-target BCL-xL inhibition in platelets. Therefore, platelet toxicity poses a barrier in advancing the clinical translation of navitoclax. We have developed a strategy to selectively target BCL-xL in tumors, while sparing platelets, by utilizing proteolysis-targeting chimeras (PROTACs) that hijack the cellular ubiquitin proteasome system for target ubiquitination and subsequent degradation. In our previous study, the first-in-class BCL-xL PROTAC, called DT2216, was shown to have synergistic antitumor activities when combined with venetoclax (formerly ABT199, BCL-2-selective inhibitor) in a BCL-xL/2 co-dependent SCLC cell line, NCI-H146 (hereafter referred to as H146), in vitro and in a xenograft model. Guided by these findings, we evaluated our newly developed BCL-xL/2 dual degrader, called 753b, in three BCL-xL/2 co-dependent SCLC cell lines and the H146 xenograft models. 753b was found to degrade both BCL-xL and BCL-2 in these cell lines. Importantly, it was considerably more potent than DT2216, navitoclax, or DT2216+venetoclax to reduce the viability of BCL-xL/2 co-dependent SCLC cell lines in cell culture. In vivo, 5 mg/kg weekly dosing of 753b leads to significant tumor growth delay similar to the DT2216+venetoclax combination in H146 xenografts by degrading both BCL-xL and BCL-2. Additionally, 753b administration at 5 mg/kg every four days induced tumor regressions. 753b at this dosage was well tolerated in mice without induction of severe thrombocytopenia as seen with navitoclax nor induced significant changes in mouse body weights. These results suggest that the BCL-xL/2 dual degrader could be an effective and safe therapeutic for a subset of SCLC patients warranting clinical trials in future.

Anaplastic Large Cell Lymphoma of the Spine: Report of a Rare Case.

This abstract discusses a rare case of anaplastic large cell lymphoma (ALCL) involving the cervical and dorsal spine in a 17-year-old female. ALCL is a distinct subtype of lymphoma characterized by abnormal proliferation of lymphocytes and is divided into ALK-positive and ALK-negative subtypes. Spinal involvement in ALCL is uncommon, particularly in the cervical and dorsal regions. The patient presented with persistent fever, weakness, and delayed onset of severe neck pain. Diagnosis involved imaging, bone marrow biopsy, and lymph node biopsy. Treatment strategies for ALCL typically involve a multimodal approach, including chemotherapy, radiotherapy, and targeted therapy. However, due to the rarity of spinal involvement, treatment decisions are based on extrapolation from other ALCL cases. Prognosis is influenced by disease stage and ALK status, but specific outcomes for spinal involvement remain poorly established. This case emphasizes the need for considering lymphoma in patients with unexplained symptoms and abnormal imaging findings. It highlights the importance of further research to improve the understanding and management of ALCL with spinal involvement.

Digital spatial proteomic profiling reveals immune checkpoints as biomarkers in lymphoid aggregates and tumor microenvironment of desmoplastic melanoma.

BACKGROUND: Desmoplastic melanoma (DM) is a rare melanoma subtype characterized by dense fibrous stroma, a propensity for local recurrence, and a high response rate to programmed cell death protein 1 (PD-1) blockade. Occult sentinel lymph node positivity is significantly lower in both pure and mixed DM than in conventional melanoma, underscoring the need for better prognostic biomarkers to inform therapeutic strategies. METHODS: We assembled a tissue microarray comprising various cores of tumor, stroma, and lymphoid aggregates from 45 patients with histologically confirmed DM diagnosed between 1989 and 2018. Using a panel of 62 validated immune-oncology markers, we performed digital spatial profiling using the NanoString GeoMx platform and quantified expression in three tissue compartments defined by fluorescence colocalization (tumor (S100+/PMEL+/SYTO+), leukocytes (CD45+/SYTO+), and non-immune stroma (S100-/PMEL-/CD45-/SYTO+)). RESULTS: We observed higher expression of immune checkpoints (lymphocyte-activation gene 3 [LAG-3] and cytotoxic T-lymphocyte associated protein-4 [CTLA-4]) and cancer-associated fibroblast (CAF) markers (smooth muscle actin (SMA)) in the tumor compartments of pure DMs than mixed DMs. When comparing lymphoid aggregates (LA) to non-LA tumor cores, LAs were more enriched with CD20+B cells, but non-LA intratumoral leukocytes were more enriched with macrophage/monocytic markers (CD163, CD68, CD14) and had higher LAG-3 and CTLA-4 expression levels. Higher intratumoral PD-1 and LA-based LAG-3 expression appear to be associated with worse survival. CONCLUSIONS: Our proteomic analysis reveals an intra-tumoral population of SMA+CAFs enriched in pure DM. Additionally, increased expressions of immune checkpoints (LAG-3 and PD-1) in LA and within tumor were associated with poorer prognosis. These findings might have therapeutic implications and help guide treatment selection in addition to informing potential prognostic significance.

Precision Oncology in Gastrointestinal and Colorectal Cancer Surgery.

Precision medicine is used to treat gastrointestinal malignancies including esophageal, gastric, small bowel, colorectal, and pancreatic cancers. Cutting-edge assays to detect and treat these cancers are active areas of research and will soon become standard of care. Colorectal cancer is a prime example of precision oncology as disease site is no longer the final determinate of treatment. Here, the authors describe how leveraging an understanding of tumor biology translates to individualized patient care using evidence-based practices.

Immunotherapy utilization in stage IIIA melanoma: less may be more.

Background: Immunotherapy agents are approved for adjuvant treatment of stage III melanoma; however, evidence for survival benefit in early stage III disease is lacking. Current guidelines for adjuvant immunotherapy utilization in stage IIIA rely on clinician judgment, creating an opportunity for significant variation in prescribing patterns. This study aimed to characterize current immunotherapy practice variations and to compare patient outcomes for different prescribing practices in stage IIIA melanoma. Study design: Patients with melanoma diagnosed from 2015-2019 that met American Joint Committee on Cancer 8th edition criteria for stage IIIA and underwent resection were identified in the National Cancer Database. Multiple imputation by chained equations replaced missing values. Factors associated with receipt of adjuvant immunotherapy were identified. Multivariable Cox proportional hazards regression compared overall survival across groups. Results: Of 4,432 patients included in the study, 34% received adjuvant immunotherapy. Patients had lower risk-adjusted odds of receiving immunotherapy if they were treated at an academic center (OR=0.48, 95%CI=0.33-0.72, p<0.001 vs. community facility) or at a high-volume center (OR=0.69, 0.56-0.84, p<0.001 vs. low-volume). Immunotherapy receipt was not associated with risk-adjusted survival (p=0.095). Moreover, patients treated at high-volume centers experienced longer overall risk-adjusted survival than those treated at low-volume centers (HR=0.52, 0.29-0.93, p=0.030). Risk-adjusted survival trended toward being longer at academic centers than at community centers, but the difference was not statistically significant. Conclusion: Academic and high-volume centers utilize significantly less adjuvant immunotherapy in stage IIIA melanoma than community and low-volume centers without compromise in overall survival. These findings suggest that this population may benefit from more judicious immunotherapy utilization.

Immunotherapy Initiation at the End of Life in Patients With Metastatic Cancer in the US.

Importance: While immunotherapy is being used in an expanding range of clinical scenarios, the incidence of immunotherapy initiation at the end of life (EOL) is unknown. Objective: To describe patient characteristics, practice patterns, and risk factors concerning EOL-initiated (EOL-I) immunotherapy over time. Design, Setting, and Participants: Retrospective cohort study using a US national clinical database of patients with metastatic melanoma, non-small cell lung cancer (NSCLC), or kidney cell carcinoma (KCC) diagnosed after US Food and Drug Administration approval of immune checkpoint inhibitors for the treatment of each disease through December 2019. Mean follow-up was 13.7 months. Data analysis was performed from December 2022 to May 2023. Exposures: Age, sex, race and ethnicity, insurance, location, facility type, hospital volume, Charlson-Deyo Comorbidity Index, and location of metastases. Main Outcomes and Measures: Main outcomes were EOL-I immunotherapy, defined as immunotherapy initiated within 1 month of death, and characteristics of the cohort receiving EOL-I immunotherapy and factors associated with its use. Results: Overall, data for 242 371 patients were analyzed. The study included 20 415 patients with stage IV melanoma, 197 331 patients with stage IV NSCLC, and 24 625 patients with stage IV KCC. Mean (SD) age was 67.9 (11.4) years, 42.5% were older than 70 years, 56.0% were male, and 29.3% received immunotherapy. The percentage of patients who received EOL-I immunotherapy increased over time for all cancers. More than 1 in 14 immunotherapy treatments in 2019 were initiated within 1 month of death. Risk-adjusted patients with 3 or more organs involved in metastatic disease were 3.8-fold more likely (95% CI, 3.1-4.7; P < .001) to die within 1 month of immunotherapy initiation than those with lymph node involvement only. Treatment at an academic or high-volume center rather than a nonacademic or very low-volume center was associated with a 31% (odds ratio, 0.69; 95% CI, 0.65-0.74; P < .001) and 30% (odds ratio, 0.70; 95% CI, 0.65-0.76; P < .001) decrease in odds of death within a month of initiating immunotherapy, respectively. Conclusions and Relevance: Findings of this cohort study show that the initiation of immunotherapy at the EOL is increasing over time. Patients with higher metastatic burden and who were treated at nonacademic or low-volume facilities had higher odds of receiving EOL-I immunotherapy. Tracking EOL-I immunotherapy can offer insights into national prescribing patterns and serve as a harbinger for shifts in the clinical approach to patients with advanced cancer.

Identifying novel inhibitors targeting Exportin-1 for the potential treatment of COVID-19.

The nuclear export protein 1 (XPO1) mediates the nucleocytoplasmic transport of proteins and ribonucleic acids (RNAs) and plays a prominent role in maintaining cellular homeostasis. XPO1 has emerged as a promising therapeutic approach to interfere with the lifecycle of many viruses. In our earlier study, we proved the inhibition of XPO1 as a therapeutic strategy for managing SARS-COV-2 and its variants. In this study, we have utilized pharmacophore-assisted computational methods to identify prominent XPO1 inhibitors. After several layers of screening, a few molecules were shortlisted for further experimental validation on the in vitro SARS-CoV-2 cell infection model. It was observed that these compounds reduced spike positivity, suggesting inhibition of SARS-COV-2 infection. The outcome of this study could be considered further for developing novel antiviral therapeutic strategies against SARS-CoV-2.

Cell surface RNAs control neutrophil recruitment.

RNAs localizing to the outer cell surface have been recently identified in mammalian cells, including RNAs with glycan modifications known as glycoRNAs. However, the functional significance of cell surface RNAs and their production are poorly known. We report that cell surface RNAs are critical for neutrophil recruitment and that the mammalian homologs of the sid-1 RNA transporter are required for glycoRNA expression. Cell surface RNAs can be readily detected in murine neutrophils, the elimination of which substantially impairs neutrophil recruitment to inflammatory sites in vivo and reduces neutrophils' adhesion to and migration through endothelial cells. Neutrophil glycoRNAs are predominantly on cell surface, important for neutrophil-endothelial interactions, and can be recognized by P-selectin (Selp). Knockdown of the murine Sidt genes abolishes neutrophil glycoRNAs and functionally mimics the loss of cell surface RNAs. Our data demonstrate the biological importance of cell surface glycoRNAs and highlight a noncanonical dimension of RNA-mediated cellular functions.

Perfluorooctanesulfonic Acid and Perfluorooctanoic Acid Promote Migration of Three-Dimensional Colorectal Cancer Spheroids.

Perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are persistent environmental contaminants that are of increasing public concern worldwide. However, their relationship with colorectal cancer (CRC) is poorly understood. This study aims to comprehensively investigate the effect of PFOS and PFOA on the development and progression of CRC in vitro using a series of biological techniques and metabolic profiling. Herein, the migration of three-dimensional (3D) spheroids of two CRC cell lines, SW48 KRAS wide-type (WT) and SW48 KRAS G12A, were observed after exposure to PFOS and PFOA at 2 µM and 10 µM for 7 days. The time and dose-dependent migration phenotype induced by 10 µM PFOS and PFOA was further confirmed by wound healing and trans-well migration assays. To investigate the mechanism of action, derivatization-mass spectrometry-based metabolic profiles were examined from 3D spheroids of SW48 cell lines exposed to PFOS and PFOA (2 µM and 10 µM). Our findings revealed this exposure altered epithelial-mesenchymal transition related metabolic pathways, including fatty acid ß-oxidation and synthesis of proteins, nucleotides, and lipids. Furthermore, this phenotype was confirmed by the downregulation of E-cadherin and upregulation of N-cadherin and vimentin. These findings show novel insight into the relationship between PFOS, PFOA, and CRC.

Role of colectomy in the management of appendiceal tumors: a retrospective cohort study.

BACKGROUND: Appendiceal tumors represent a range of histologies that vary in behavior. Recommendations for treatment with appendectomy versus right hemicolectomy (RHC) for different tumor types are evolving and sometimes conflicting. This study sought to characterize variation in the United States around surgical treatment of major appendiceal tumor types over time and describe differences in outcomes based on procedure. METHODS: Patients diagnosed with appendiceal goblet cell adenocarcinoma (GCA), mucinous adenocarcinoma, neuroendocrine neoplasm (NEN), or non-mucinous adenocarcinoma from 2004-2017 were identified in the National Cancer Database. Trends in RHC over time and predictors of RHC were identified. Surgical outcomes for each histologic type and stage were compared. RESULTS: Of 18,216 patients, 11% had GCAs, 34% mucinous adenocarcinoma, 31% NENs, and 24% non-mucinous adenocarcinoma. Rate of RHC for NEN decreased from 68% in 2004 to 40% in 2017 (p = 0.008) but remained constant around 60-75% for other tumor types. Higher stage was associated with increased odds of RHC for all tumor types. RHC was associated with higher rate of unplanned readmission (5% vs. 3%, p < 0.001) and longer postoperative hospital stay (median 5 days vs. 3 days, p < 0.001). On risk-adjusted analysis, RHC was significantly associated with increased survival versus appendectomy for stage 2 disease of all tumor types (HRs 0.43 to 0.63) and for stage 1 non-mucinous adenocarcinoma (HR = 0.56). CONCLUSIONS: Most patients with appendiceal tumors undergo RHC, which is associated with increased readmission, longer length of stay, and improved survival for stage 2 disease of all types. RHC should be offered selectively for appendiceal tumors.

Tobramycin-loaded nanoparticles of thiolated chitosan for ocular drug delivery: Preparation, mucoadhesion and pharmacokinetic evaluation.

The present work aimed to develop nanoparticles of tobramycin (TRM) using thiolated chitosan (TCS) in order to improve the mucoadhesion, antibacterial effect and pharmacokinetics. The nanoparticles were evaluated for their compatibility, thermal stability, particle size, zeta potential, mucoadhesion, drug release, kinetics of TRM release, corneal permeation, toxicity and ocular irritation. The thiolation of chitosan was confirmed by 1H NMR and FTIR, which showed peaks at 6.6 ppm and 1230 cm-1, respectively. The nanoparticles had a diameter of 73 nm, a negative zeta potential (-21 mV) and a polydispersity index of 0.15. The optimized formulation, NT8, exhibited the highest values of mucoadhesion (7.8 ± 0.541h), drug loading (87.45 ± 1.309%), entrapment efficiency (92.34 ± 2.671%), TRM release (>90%) and corneal permeation (85.56%). The release pattern of TRM from the developed formulations was fickian diffusion. TRM-loaded nanoparticles showed good antibacterial activity against Pseudomonas aeruginosa. The optimized formulation NT8 (0.1% TRM) greatly increased the AUC(0-∞) (1.5-fold) while significantly reducing the clearance (5-fold) compared to 0.3% TRM. Pharmacokinetic parameters indicated improved ocular retention and bioavailability of TRM loaded nanoparticles. Our study demonstrated that the TRM-loaded nanoparticles had improved mucoadhesion and pharmacokinetics and a suitable candidate for effective treatment of ocular bacterial infections.

Multi-omic analysis reveals metabolic pathways that characterize right-sided colon cancer liver metastasis.

There are well demonstrated differences in tumor cell metabolism between right sided (RCC) and left sided (LCC) colon cancer, which could underlie the robust differences observed in their clinical behavior, particularly in metastatic disease. As such, we utilized liquid chromatography-mass spectrometry to perform an untargeted metabolomics analysis comparing frozen liver metastasis (LM) biobank samples derived from patients with RCC (N = 32) and LCC (N = 58) to further elucidate the unique biology of each. We also performed an untargeted RNA-seq and subsequent network analysis on samples derived from an overlapping subset of patients (RCC: N = 10; LCC: N = 18). Our biobank redemonstrates the inferior survival of patients with RCC-derived LM (P = 0.04), a well-established finding. Our metabolomic results demonstrate increased reactive oxygen species associated metabolites and bile acids in RCC. Conversely, carnitines, indicators of fatty acid oxidation, are relatively increased in LCC. The transcriptomic analysis implicates increased MEK-ERK, PI3K-AKT and Transcription Growth Factor Beta signaling in RCC LM. Our multi-omic analysis reveals several key differences in cellular physiology which taken together may be relevant to clinical differences in tumor behavior between RCC and LCC liver metastasis.

Impact of COVID-19 on the gastrointestinal surgical oncology patient population.

Background: The onset of the COVID-19 pandemic led to substantial alterations in healthcare delivery and access. In this study, we aimed to evaluate the impact of COVID-19 on the presentation and surgical care of patients with gastrointestinal (GI) cancers. Methods: All patients who underwent GI cancer surgery at a large, tertiary referral center between March 15, 2019 and March 15, 2021 were included. March 15, 2020 was considered the start of the COVID-19 pandemic. Changes in patient, tumor, and treatment characteristics before the pandemic compared to during the pandemic were evaluated. Results: Of 522 patients that met study criteria, 252 (48.3%) were treated before the COVID-19 pandemic. During the first COVID-19 wave, weekly volume of GI cancer cases was one-third lower than baseline (p = 0.041); during the second wave, case volume remained at baseline levels (p = 0.519). There were no demographic or tumor characteristic differences between patients receiving GI cancer surgery before versus during COVID-19 (p > 0.05 for all), and no difference in rate of emergency surgery (p > 0.9). Patients were more likely to receive preoperative chemotherapy during the first six months of the pandemic compared to the subsequent six months (35.6% vs. 15.5%, p < 0.001). Telemedicine was rapidly adopted at the start of the pandemic, rising from 0% to 47% of GI surgical oncology visits within two months. Conclusions: The COVID-19 pandemic caused an initial disruption to the surgical care of GI cancers, but did not compromise stage at presentation. Preoperative chemotherapy and telemedicine were utilized to mitigate the impact of a high COVID-19 burden on cancer care.