Sleeve lobectomy versus pneumonectomy following neoadjuvant therapy in patients with non-small cell lung cancer.

OBJECTIVES: Neoadjuvant therapy has gained widespread acceptance as the standard modality for locally advanced non-small cell lung cancer. However, the clinical benefit of sleeve lobectomy (SL) or pneumonectomy (PN) following neoadjuvant therapy remains controversial. METHODS: The clinical and pathological characteristics of non-small cell lung cancer patients who underwent SL or PN after neoadjuvant therapy at a high-volume single centre between December 2019 and March 2023 were retrospectively collected. The SL group was matched 4:1 with the PN group by propensity score matching. The surgical outcomes were systematically collected and analysed. RESULTS: During a 5-year study period, the majority of patients (175 of 215, 81.4%) underwent the SL procedure, while 40 patients (18.6%) underwent PN. Following propensity score matching, the SL group exhibited lower postoperative arrythmia (4.8% vs 26.9%, P < 0.001), lower 30-day mortality (1.0% vs 7.7%, P = 0.046) and a shorter length of postoperative hospital stay (6.0 days vs 10.0 days, P < 0.001), compared with the PN group. In addition, no significant difference was observed between the two groups in terms of disease-free survival or overall survival (P = 0.977 and P = 0.913, respectively). CONCLUSIONS: SL stands as a safe and feasible option for patients with centrally located non-small-cell lung cancer who have undergone neoadjuvant therapy, in comparison to PN. This finding suggests that SL remains the preferable choice when feasible in the context of the widespread utilization of neoadjuvant therapy.

Current advance of nanotechnology in diagnosis and treatment for malignant tumors.

Cancer remains a significant risk to human health. Nanomedicine is a new multidisciplinary field that is garnering a lot of interest and investigation. Nanomedicine shows great potential for cancer diagnosis and treatment. Specifically engineered nanoparticles can be employed as contrast agents in cancer diagnostics to enable high sensitivity and high-resolution tumor detection by imaging examinations. Novel approaches for tumor labeling and detection are also made possible by the use of nanoprobes and nanobiosensors. The achievement of targeted medication delivery in cancer therapy can be accomplished through the rational design and manufacture of nanodrug carriers. Nanoparticles have the capability to effectively transport medications or gene fragments to tumor tissues via passive or active targeting processes, thus enhancing treatment outcomes while minimizing harm to healthy tissues. Simultaneously, nanoparticles can be employed in the context of radiation sensitization and photothermal therapy to enhance the therapeutic efficacy of malignant tumors. This review presents a literature overview and summary of how nanotechnology is used in the diagnosis and treatment of malignant tumors. According to oncological diseases originating from different systems of the body and combining the pathophysiological features of cancers at different sites, we review the most recent developments in nanotechnology applications. Finally, we briefly discuss the prospects and challenges of nanotechnology in cancer.

Optimizing cell therapy by sorting cells with high extracellular vesicle secretion.

Critical challenges remain in clinical translation of extracellular vesicle (EV)-based therapeutics due to the absence of methods to enrich cells with high EV secretion. Current cell sorting methods are limited to surface markers that are uncorrelated to EV secretion or therapeutic potential. Here, we utilize a nanovial technology for enrichment of millions of single cells based on EV secretion. This approach is applied to select mesenchymal stem cells (MSCs) with high EV secretion as therapeutic cells for improving treatment. The selected MSCs exhibit distinct transcriptional profiles associated with EV biogenesis and vascular regeneration and maintain high levels of EV secretion after sorting and regrowth. In a mouse model of myocardial infarction, treatment with high-secreting MSCs improves heart functions compared to treatment with low-secreting MSCs. These findings highlight the therapeutic importance of EV secretion in regenerative cell therapies and suggest that selecting cells based on EV secretion could enhance therapeutic efficacy.

Identifying optimal surgical approach among T1N2-3M0 non-small cell lung cancer patients: a population-based analysis.

Background: Whether stage T1N2-3M0 non-small cell lung cancer (NSCLC) patients could benefit from surgery and the optimal surgical procedure have remained controversial and unclear. This study aimed to investigate whether stage T1N2-3M0 NSCLC can benefit from different surgery types and develop a tool for survival prediction. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients diagnosed with stage T1N2-3M0 NSCLC between 2000 and 2015. A 1:1 propensity score-matched (PSM) analysis was used to balance the distribution of clinical characteristics. Survival analyses were performed by using the Kaplan-Meier (KM) curves and Cox proportional hazards regression. All patients were randomly split at a ratio of 7:3 into training and validation cohorts. The nomogram was constructed by integrating all independent predictors for overall survival (OS) and cancer-specific survival (CSS). The model's performance was evaluated by discrimination, calibration ability, and risk stratification ability. Results: A total of 4,671 patients were enrolled. After 1:1 PSM, the distribution proportions of clinical characteristics in 1,146 patients were balanced (all P>0.05). The non-surgical approach was associated with worse survival compared with sublobectomy and lobectomy in the unmatched and matched cohorts. The multivariate Cox analysis showed that sublobectomy and lobectomy were both related to better OS and CSS rates compared with no surgery (P<0.001). Moreover, the results of subgroup analyses based on age, N stage, and radiotherapy or chemotherapy strategy were consistent. A total of 801 patients were included in the training cohort and 345 cases constituted the validation cohort. The nomogram constructed for the 1-, 3-, and 5-year OS and CSS prediction showed good discrimination, performance, and calibration both in the training and validation sets. Significant distinctions in survival curves between different risk groups stratified by prognostic scores were also observed (all P<0.001). Conclusions: Stage T1N2-3M0 NSCLC patients could benefit from sublobectomy or lobectomy, and lobectomy provides better survival benefits. We developed and validated nomograms, which could offer clinicians instructions for strategy making.

The Prevalence and Risk Factors of Blepharoptosis in an Elderly Asian Population.

BACKGROUND: Age-related blepharoptosis, or ptosis, affects vision and appearance. Associations with age, gender, BMI, and diabetes have been explored, but the link to blood lipids remains unclear. The impact on refraction also lacks consensus. This study addresses gaps by investigating ptosis prevalence and factors in a representative Chinese population, aiming for a comprehensive understanding. METHODS: A cross-sectional study was conducted among individuals aged 50 and above who were willing to participate in comprehensive systemic check-ups, behavioral questionnaires, and ophthalmic examinations at Yaoxi Community Health Center in Wenzhou City, Zhejiang Province. RESULTS: The prevalence of blepharoptosis among the elderly participants at this health center was 27.16%. Individuals with blepharoptosis tended to be older, male, exhibited slightly higher body mass index, wider waist circumference, engaged in lower exercise frequency, and had a higher prevalence of hypertension, diabetes, and with-the-rule astigmatism compared to their counterparts without these conditions. Adjusting for all other confounding variables, older age, being male, higher fasting plasma glucose (FPG), and lower exercise frequency displayed statistically significant relationships with blepharoptosis. After examining the distribution of blepharoptosis degrees within relevant factor subgroups, we noted a higher prevalence of severe ptosis in subgroups associated with older age, male gender, higher FPG, and against-the-rule astigmatism. CONCLUSION: The notable associations with age, gender, FPG, and exercise level suggest a multifactorial etiology for blepharoptosis. The observed link between with-the-rule astigmatism and blepharoptosis implies a potential contributory role in the refractive aspect of blepharoptosis. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Spread Through Air Spaces in Stage I Pulmonary Large Cell Neuroendocrine Carcinoma.

BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) represents an exceptionally aggressive and infrequent variant within the realm of non-small cell lung cancer, necessitating surgical intervention as the primary therapeutic approach. However, the postoperative management strategy for early-stage patients continues to be a subject of intense debate and uncertainty. METHODS: A retrospective analysis was conducted on a cohort of patients diagnosed with LCNEC who underwent surgical resection at Shanghai Pulmonary Hospital between July 2018 and June 2022. Comprehensive assessments, encompassing univariate and multivariate analyses, were performed to evaluate the prognostic significance of these indicators in patient clinical profiles, overall survival (OS), and disease-free survival (DFS). RESULTS: A comprehensive screening effort identified 171 patients with LCNEC, with 70 stage I patients meeting the criteria for inclusion in the final cohort. Of these, 11 patients (15.7%) presented with combined LCNEC, and 59 (84.3%) exhibited pure LCNEC. Univariate and multivariate analyses both unveiled that spread through air spaces (STAS) status emerged as an independent prognostic determinant for both DFS (P = .003) and OS (P = .013), whereas histologic subtype independently predicted OS (P = .011). Subgroup survival analyses further underscored that the advantageous effects of postoperative chemotherapy were significantly pronounced exclusively among STAS-positive patients, showcasing a statistically significant enhancement in DFS (P = .047) and OS (P = .018). CONCLUSIONS: STAS may serve as an adverse prognostic factor in stage I LCNEC patients, potentially offering guidance for postoperative chemotherapy decisions.

Inhalable extracellular vesicle delivery of IL-12 mRNA to treat lung cancer and promote systemic immunity.

Lung carcinoma is one of the most common cancers and has one of the lowest survival rates in the world. Cytokines such as interleukin-12 (IL-12) have demonstrated considerable potential as robust tumour suppressors. However, their applications are limited due to off-target toxicity. Here we report on a strategy involving the inhalation of IL-12 messenger RNA, encapsulated within extracellular vesicles. Inhalation and preferential uptake by cancer cells results in targeted delivery and fewer systemic side effects. The IL-12 messenger RNA generates interferon-γ production in both innate and adaptive immune-cell populations. This activation consequently incites an intense activation state in the tumour microenvironment and augments its immunogenicity. The increased immune response results in the expansion of tumour cytotoxic immune effector cells, the formation of immune memory, improved antigen presentation and tumour-specific T cell priming. The strategy is demonstrated against primary neoplastic lesions and provides profound protection against subsequent tumour rechallenge. This shows the potential for locally delivered cytokine-based immunotherapies to address orthotopic and metastatic lung tumours.

Effect of Socioeconomic Disparities on Suicide Risk in Patients With Prostate Cancer During 2005 to 2020: A Population Study.

PURPOSE: To determine whether socioeconomic disparities have an impact on the likelihood of suicide among prostate cancer patients. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with malignant prostate cancer between 2005 and 2020. The socioeconomic disparities of the patients were evaluated by median household income (MHI) and ethnicity. Ethnicity included Spanish-Hispanic-Latino and non-Spanish-Hispanic-Latino. A Cox proportional risk model was utilized. Using the Kaplan-Meier approach, the cumulative incidence of suicide mortality was measured. RESULTS: A total of 857,418 US population with prostate cancer were included. In the multivariate analysis, individuals with MHI over $75,000 had a lower risk of suicide mortality than those with MHI between $54,999 and $74,999 in all patients (aHRs: 0.693, 95 CI%: 0.603-0.797). Spanish-Hispanic-Latino displayed lower overall suicide mortality in all patients (aHRs: 0.426, 95% CI: 0.323-0.561). In the subgroup analysis of different ages, individuals with MHI over $75,000 had a lower risk of suicide than those with MHI between $54,999 and $74,999 in patients 60 to 79 years (aHRs: 0.668, 95% CI: 0.562-0.794) and individuals with MHI below $54,999 had higher suicide risk than those with MHI between $54,999 and $74,999 in patients 80+ years (aHRs: 1.786, 95% CI: 1.100-2.902). Hispanic-Latino individuals had lower overall suicide mortality in 00 to 59 years (aHRs: 0.420, 95% CI: 0.240-0.734), 60 to 79 years (aHRs: 0.445, 95% CI: 0.319-0.621), 80+ years (aHRs: 0.363, 95% CI: 0.133-0.988). CONCLUSION: Socioeconomic disparities, including MHI and ethnicity, are important factors strongly related to suicide risk in prostate cancer patients. The lower MHI individuals and non-Spanish-Hispanic-Latino individuals were associated with higher suicide risk.

Dosimetric predictors of radiation pneumonitis in patients with prior immunotherapy exposure: A multi-institutional analysis.

BACKGROUND AND PURPOSE: Combining immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) may magnify the radiation pneumonitis (RP) risk. Dosimetric parameters can predict RP, but dosimetric data in context of immunotherapy are very scarce. To address this knowledge gap, we performed a large multicenter investigation to identify dosimetric predictors of RP in this under-studied population. MATERIALS AND METHODS: All lung cancer patients from five institutions who underwent conventionally-fractionated thoracic intensity-modulated radiotherapy with prior ICI receipt were retrospectively compiled. RP was defined per CTCAE v5.0. Statistics utilized logistic regression modeling and receiver operating characteristic (ROC) analysis. RESULTS: The vast majority of the 192 patients (median follow-up 14.7 months) had non-small cell lung cancer, received PD-1 inhibitors, and did not receive concurrent systemic therapy with TRT. Grades 1-5 RP occurred in 21.9%, 25.0%, 8.3%, 1.6%, and 1.0%, respectively. The mean MLD for patients with grades 1-5 RP was 10.7, 11.6, 12.6, 14.7, and 12.8 Gy, respectively. On multivariable analysis, tumor location and mean lung dose (MLD) significantly predicted for any-grade and grade ≥ 2 pneumonitis. Only MLD significantly predicted for grade ≥ 3 RP. ROC analysis was able to pictorially model RP risk probabilities for a variety of MLD thresholds, which can be an assistive tool during TRT treatment planning. CONCLUSION: This study, by far the largest to date of dosimetric predictors of RP in the immunotherapy era, illustrates that MLD is the most critical dose-volume parameter influencing RP risk. These data may provide a basis for revising lung dose constraints in efforts to better prevent RP in this rapidly expanding ICI/TRT population.

A novel anoikis-related prognostic signature associated with prognosis and immune infiltration landscape in lung adenocarcinoma.

BACKGROUND: One of the most prevalent malignancies in the world is lung adenocarcinoma (LUAD), with a large number of people dying from lung cancer each year. Anoikis has a crucial function in tumor metastasis, promoting cancer cell shedding and survival from the primary tumor site. However, the role of anoikis in LUAD is still unclear. METHODS: The GeneCard database (https://www.genecards.org/) was utilized to obtain anoikis-related genes with correlation greater than 0.4. Differential analysis was employed to acquire differential genes. Univariate, multifactorial Cox analyses and the least absolute shrinkage and selection operator were then utilized to capture genes connected to overall survival time. These genes were used to build prognostic models. The predictive model was analyzed and visualized. Survival analysis was conducted on the model and risk scores were calculated. The TCGA samples were split into groups of low and high risk depending on risk scores. A Gene Expression Omnibus database sample was used for external verification. Immunization estimates were performed using ESTIMATE, CiberSort and single sample gene set enrichment analysis. The connection between the prognostic gene model and immune cells was analyzed. Drug susceptibility prediction analysis was performed. The clinical information for samples was extracted and analyzed. RESULTS: We selected six genes related to anoikis in LUAD to construct a prognosis model (CDC25C, ITPRIP, SLCO1B3, CDX2, CSPG4 and PIK3CG). Compared with cases of high-risk scores, the overall survival of those with low risk was significantly elevated based on Kaplan-Meier survival analysis. Immune function analysis exhibited that different risk groups had different immune states. The results of ESTIMATE, CiberSort and single sample gene set enrichment analysis showed great gaps in immunization between patients in the two groups. The normogram of the risk score and the LUAD clinicopathological features was constructed. Principal component analysis showed that this model could effectively distinguish the two groups of LUAD patients. CONCLUSIONS: We integrated multiple anoikis-related genes to build a prognostic model. This investigation demonstrates that anoikis-related genes can be used as a stratification element for fine therapy of individuals with LUAD.

Chemokine- and chemokine receptor-based signature predicts immunotherapy response in female colorectal adenocarcinoma patients.

The clinical significance and comprehensive characteristics of chemokines and chemokine receptors in female patients with advanced colorectal adenocarcinoma have not ever been reported. Our study explored the expression profiles of chemokines and chemokine receptors and constructed a chemokine- and chemokine receptor-based signature in female patients with advanced colorectal adenocarcinoma. Four independent cohorts containing 1335 patients were enrolled in our study. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were performed to construct the signature. CIBERSORT was used to evaluate the landscape of immune cell infiltration. Thirty-two pairs of tissue specimens of female advanced colorectal cancer (CRC) patients and two CRC cell lines were used to validate the signature in vitro. Quantitative real-time PCR and western blotting were performed to validate the mRNA and protein expression levels of signature genes. EdU and colony formation assays were performed to examine proliferative ability. Transwell and wound healing assays were used to evaluate cell invasion and migration capacity. During the signature construction and validation process, we found that the signature was more applicable to female patients with advanced colorectal adenocarcinoma. Hence, the subsequent study mainly focused on the particular subgroup. Enrichment analyses revealed that the signature was closely related to immunity. The landscape of immune cell infiltration presented that the signature was significantly associated with T cells CD8 and neutrophils. Gene set enrichment analysis (GSEA) confirmed that the high-risk group was chiefly enriched in the tumor-promoting related pathways and biological processes, whereas the low-risk group was mainly enriched in anti-tumor immune response pathways and biological processes. The signature was closely correlated with CTLA4, PDL1, PDL2, TMB, MSI, and TIDE, indicating that our signature could serve as a robust biomarker for immunotherapy and chemotherapy response. ROC curves verified that our signature had more robust prognostic power than all immune checkpoints and immunotherapy-related biomarkers. Finally, we used 32 pairs of tissue specimens and 2 CRC cell lines to validate our signature in vitro. We first provided a robust prognostic chemokine- and chemokine receptor-based signature, which could serve as a novel biomarker for immunotherapy and chemotherapy response to guide individualized treatment for female patients with advanced colorectal adenocarcinoma.

The impact of oncogenic driver mutations on neoadjuvant immunotherapy outcomes in patients with resectable non-small cell lung cancer.

BACKGROUND: Neoadjuvant immunotherapy has been demonstrated to be effective and safe in resectable non-small cell lung cancer (NSCLC) patients. However, the presence of different oncogenic driver mutations may affect the tumor microenvironment and consequently influence the clinical benefit from immunotherapy. METHODS: This retrospective study included consecutive NSCLC patients (stage IIA to IIIB) who underwent radical surgery after receiving neoadjuvant immunotherapy at a single high-volume center between December 2019 and August 2022. Pathological response and long-term outcomes were compared based on the driver oncogene status, and RNA sequencing analysis was conducted to investigate the transcriptomic characteristics before and after treatment. RESULTS: Of the 167 patients included in this study, 47 had oncogenic driver mutations. KRAS driver mutations were identified in 28 patients, representing 59.6% of oncogenic driver mutations. Of these, 17 patients had a major pathological response, which was significantly higher than in the non-KRAS driver mutation group (60.7% vs. 31.6%, P = 0.049). Multivariate Cox regression analysis further revealed that the KRAS driver mutation group was an independent prognostic factor for prolonged disease-free survival (hazard ratio: 0.10, P = 0.032). The median proportion of CD8+ T cells was significantly higher in the KRAS driver mutation NSCLCs than in the non-driver mutation group (18% vs. 13%, P = 0.030). Furthermore, immune-related pathways were enriched in the KRAS driver mutation NSCLCs and activated after immunotherapy. CONCLUSION: Our study suggests that NSCLC patients with KRAS driver mutations have a superior response to neoadjuvant immunotherapy, possibly due to their higher immunogenicity. The findings highlight the importance of considering oncogenic driver mutations in selecting neoadjuvant treatment strategies for NSCLC patients.

Insulin-like Growth Factor 2 (IGF2)-Fused Lysosomal Targeting Chimeras for Degradation of Extracellular and Membrane Proteins.

Targeted degradation of the cell-surface and extracellular proteins via the endogenous lysosomal degradation pathways, such as lysosome-targeting chimeras (LYTACs), has recently emerged as an attractive tool to expand the scope of extracellular chemical biology. Herein, we report a series of recombinant proteins genetically fused to insulin-like growth factor 2 (IGF2), which we termed iLYTACs, that can be conveniently obtained in high yield by standard cloning and bacterial expression in a matter of days. We showed that both type-I iLYTACs, in which IGF2 was fused to a suitable affibody or nanobody capable of binding to a specific protein target, and type-II iLYTAC (or IGF2-Z), in which IGF2 was fused to the IgG-binding Z domain that served as a universal antibody-binding adaptor, could be used for effective lysosomal targeting and degradation of various extracellular and membrane-bound proteins-of-interest. These heterobifunctional iLYTACs are fully genetically encoded and can be produced on a large scale from conventional E. coli expression systems without any form of chemical modification. In the current study, we showed that iLYTACs successfully facilitated the cell uptake, lysosomal localization, and efficient lysosomal degradation of various disease-relevant protein targets from different mammalian cell lines, including EGFR, PD-L1, CD20, and α-synuclein. The antitumor properties of iLYTACs were further validated in a mouse xenograft model. Overall, iLYTACs represent a general and modular strategy for convenient and selective targeted protein degradation, thus expanding the potential applications of current LYTACs and related techniques.

[Deep Learning-Based Identification of Common Complication Features of Surgical Incisions].

Objective: In recent years, due to the development of accelerated recovery after surgery and day surgery in the field of surgery, the average length-of-stay of patients has been shortened and patients stay at home for post-surgical recovery and healing of the surgical incisions. In order to identify, in a timely manner, the problems that may appear at the incision site and help patients prevent or reduce the anxiety they may experience after discharge, we used deep learning method in this study to classify the features of common complications of surgical incisions, hoping to realize patient-directed early identification of complications common to surgical incisions. Methods: A total of 1 224 postoperative photographs of patients' surgical incisions were taken and collected at a tertiary-care hospital between June 2021 and March 2022. The photographs were collated and categorized according to different features of complications of the surgical incisions. Then, the photographs were divided into training, validation, and test sets at the ratio of 8∶1∶1 and 4 types of convolutional neural networks were applied in the training and testing of the models. Results: Through the training of multiple convolutional neural networks and the testing of the model performance on the basis of a test set of 300 surgical incision images, the average accuracy of the four ResNet classification network models, SE-ResNet101, ResNet50, ResNet101, and SE-ResNet50, for surgical incision classification was 0.941, 0.903, 0.896, and 0.918, respectively, the precision was 0.939, 0.898, 0.868, and 0.903, respectively, and the recall rate was 0.930, 0.880, 0.850, and 0.894, respectively, with the SE-Resnet101 network model showing the highest average accuracy of 0.941 for incision feature classification. Conclusion: Through the combined use of deep learning technology and images of surgical incisions, problematic features of surgical incisions can be effectively identified by examining surgical incision images. It is expected that patients will eventually be able to perform self-examination of surgical incisions on smart terminals.

Socioeconomic status on survival outcomes in patients with colorectal cancer: a cross-sectional study.

BACKGROUND: Colorectal cancer (CRC) is widely acknowledged as a prevalent malignancy and the second most common cause of cancer-related mortality worldwide. The aim of this study was to examine the independent impact of Median Household Income (MHI) on prognosis and survival outcomes in patients with CRC. METHODS: Data from 17 cancer registries of the United States Surveillance, Epidemiology, and End Results program, with follow-up extended until November 2022 was analyzed. A Cox proportional hazards regression analysis was conducted to evaluate the influence of different levels of MHI on survival outcomes among patients with CRC. A total of 761,697 CRC patient records were retrieved from the SEER database. RESULTS: The Cox regression analysis results indicated that patients with higher MHI exhibited improved overall survival outcomes when compared to those with lower MHI (MMHI: P < 0.001; HMHI: P < 0.001). Regardless of the specific tumor location, gender, stage of CRC, or treatment method, higher MHI is consistently linked to improved survival outcomes. However, this association was not found to be statistically significant among American Indian/Alaska Native (MMHI: P = 0.017; HMHI: P = 0.081), Asian or Pacific Islander (MMHI: P = 0.223; HMHI: P = 0.002) and unmarried or domestic partner patients (MMHI: P = 0.311; HMHI: P = 0.011). CONCLUSION: These results emphasize the importance of considering socioeconomic factors, such as income level, in understanding and addressing disparities in survival outcomes of CRC patients.

Recurrent choriocarcinoma complicated with leprosy during chemotherapy: A case report and literature review.

RATIONALE: The global prevalence of leprosy has decreased substantially, and cases of leprosy infection are extremely rare in China. In this report, we present a case of recurrent choriocarcinoma complicated by leprosy infection during chemotherapy. PATIENT CONCERNS: A 24-year-old Chinese woman (gravida 3, para 2) presented to a local hospital with vaginal bleeding. Her medical history included a previous diagnosis of hydatidiform mole. DIAGNOSES, INTERVENTIONS AND OUTCOMES: The patient was diagnosed with choriocarcinoma and received chemotherapy in 6 cycles. Shortly after the initial treatment was completed, the disease recurred twice with resistance to multiple chemotherapeutic agents. In her second recurrence of choriocarcinoma, she was diagnosed with leprosy with many cutaneous nodules throughout her entire body. The patient was administered chemical treatment for leprosy with the multidrug therapy regimen after being diagnosed. To prevent exacerbating the infection, no immunotherapy was utilized to treat cancer, and the infection was well-controlled at the conclusion of anticancer therapy. LESSONS: Because of immunological reduction, cancer patients are susceptible to a variety of infections. For patients with cancer, prevention and early detection of rare infectious diseases should receive special attention. Immunotherapy must be used with caution when treating patients with cancer and infections.

Microneedle Patch Delivery of PROTACs for Anti-Cancer Therapy.

Proteolysis-targeting chimera (PROTAC) is an emerging technique for degrading disease-related proteins. However, the current PROTACs suffer from inadequate solubility and lack of organ targeting, which has hampered their druggability. Herein, we report direct and sustained delivery of PROTACs using microneedle patches to the diseased tissues. In this study, we use an estrogen receptor alpha (ERα)-degrading PROTAC, ERD308, to treat ER-positive breast cancer. A pH-sensitive micelle, MPEG-poly(ß-amino ester) (MPEG-PAE), is used to encapsulate ERD308 along with an FDA-approved CDK4/6 inhibitor, Palbociclib (Pal), before loading into biodegradable microneedle patches. These patches enable prolonged drug release into deep tumors, maintaining therapeutic levels for at least 4 days, with an excellent drug retention rate of over 87% in tumors. ERD308 released from the microneedle patches can sufficiently degrade ERα in MCF7 cells. Co-administration of ERD308 and Palbociclib exhibits excellent efficacy by over 80% tumor reduction as well as a good safety profile. Our work demonstrates the feasibility and proof-of-concept therapeutic potential of using microneedle patches to directly deliver PROTACs into tumors.

Palliative care for cancer patients during the COVID-19 pandemic: A narrative synthesis from 36 studies of 16 countries.

BACKGROUND: During the COVID-19 epidemic, palliative care has become even more indispensable for cancer patients. AIM: To identify the changes in palliative care for cancer patients and improvements in palliative care quality during the COVID-19 pandemic. DESIGN: A systematic review and narrative synthesis was conducted in PubMed, Embase and Web of Science. An evaluation tool using mixed methods was used to assess the quality of the study. The main relevant themes identified were used to group qualitative and quantitative findings. RESULTS: A total of 36 studies were identified, primarily from different countries, with a total of 14,427 patients, 238 caregivers and 354 health care providers. Cancer palliative care has been experiencing several difficulties following the COVID-19 pandemic, including increased mortality and infection rates as well as delays in patient treatment that have resulted in poorer prognoses. Treatment providers are seeking solutions such as electronic management of patients and integration of resources to care for the mental health of patients and staff. Telemedicine plays an important role in many ways but cannot completely replace traditional treatment. Clinicians strive to meet patients' palliative care needs during special times and improve their quality of life. CONCLUSIONS: Palliative care faces unique challenges during the COVID-19 epidemic. With adequate support to alleviate care-related challenges, patients in the home versus hospital setting will be able to receive better palliative care. In addition, this review highlights the importance of multiparty collaboration to achieve personal and societal benefits of palliative care. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Liquid biopsy using cell-free DNA in the early diagnosis of hepatocellular carcinoma.

Hepatocellular carcinoma ranks fourth in cancer-related causes of death worldwide and second in China. Patients with hepatocellular carcinoma (HCC) at the early stage have a better prognosis compared to HCC patients at the late stage. Therefore, early screening for HCC is critical for clinical treatment decisions and improving the prognosis of patients. Ultrasound (US), computed tomography (CT), and serum alpha fetoprotein (AFP) have been used to screen HCC, but HCC is still difficult to be diagnosed in the early stage due to the low sensitivity of the above methods. It is urgent to find a method with high sensitivity and specificity for the early diagnosis of HCC. Liquid biopsy is a noninvasive detection method using blood or other bodily fluids. Cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA) are important biomarkers for liquid biopsy. Recently, HCC screening methods using the application of cfDNA and ctDNA have become the hot spot of early HCC diagnostics. In this mini review, we summarize the latest research progress of liquid biopsy based on blood cfDNA in early screening of HCC.

Ugi reaction-assisted assembly of covalent PROTACs against glutathione peroxidase 4.

Inducing cell ferroptosis by inactivating glutathione peroxidase 4 (GPX4) is a popular cancer treatment strategy. However, only few GPX4 inhibitors have been developed to date. PROteolysis Targeting Chimera (PROTAC) is a promising approach to provide new opportunities to overcome limitations of traditional therapeutics. Herein, a PROTAC-like activity-based probe PD-Q2 was first assembled using Ugi reaction, consisting of a known GPX4 inhibitor ML-162 homolog to the E3 ligase cereblon ligand-pomalidomide. Pull-down and immunoblotting analysis revealed that GPX4 was a covalent target of PD-Q2, but the degradation efficiency was weak. Therefore, a series of degraders was further synthesized by varying the linkers of heterofunctional PROTACs. Among these degraders, PD-4 and PD-P2 were found to promote effective GPX4 degradation via the ubiquitin-proteasome system and cause lipid ROS accumulation. PD-4 and PD-P2 showed potent inhibitory of colony formation and cell growth. Furthermore, we found that with pomalidomide, the degraders exhibit a high fluorescent signal that is mostly localized in the lysosome, which may affect the effectiveness of anti-cell proliferation. Overall, we provide GPX4 degraders for further exploring therapeutic potential of regulating ferroptosis.