Tumor Site Research Articles

Recent Advances in Chemistry, Mechanism, and Applications of Quantum Dots in Photodynamic and Photothermal Therapy.

Semiconductor quantum dots (QD) are a kind of nanoparticle with unique optical properties that have attracted a lot of attention in recent years. In this paper, the characteristics of these nanoparticles and their applications in nanophototherapy have been reviewed. Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has gained special importance because of its high accuracy and local treatment due to the activation of the drug at the tumor site. PDT is a new way of cancer treatment that is performed by activating light-sensitive compounds named photosensitizers (PS) by light. PSs cause the destruction of diseased tissue through the production of singlet oxygen. PTT is another non-invasive method that induces cell death through the conversion of near-infrared light (NIR) into heat in the tumor situation by the photothermal agent (PA). Through using energy transfer via the FRET (Förster resonance energy transfer) process, QDs provide light absorption wavelength for both methods and cover the optical weaknesses of phototherapy agents.

Hyperthermia/glutathione-triggered ferritin nanoparticles amplify the ferroptosis for synergistic tumor therapy

Breast cancer is the most diagnosed malignancy in women globally, and drug resistance is among the major obstacles to effective breast cancer treatment. Emerging evidence indicates that photothermal therapy and ferroptosis are both promising therapeutic techniques for the treatment of drug-resistant breast tumors. In this study, we proposed a thermal/ferroptosis/magnetic resonance imaging (MRI) triple functional nanoparticle (I@P-ss-FRT) in which ferritin, an iron storage material with excellent cellular uptake capacity, was attached via disulfide bonds onto polydopamine coated iron oxide nanoparticle (I@P) as photothermal transduction agent and MRI probe. I@P-ss-FRT converted the near-infrared light (NIR) into localized heat which accelerated the release of ferrous ions from ferritin accomplished by glutathione reduction and subsequently induced ferroptosis. The drug-resistant cancer cell lines exhibited a more significant uptake of I@P-ss-FRT and sensitivity to PTT/ferroptosis compared with normal cancer cell lines. In vivo, I@P-ss-FRT plus NIR displayed the best tumor-killing potential with inhibitory rate of 83.46%, along with a decline in GSH/GPX-4 content and an increase in lipid peroxides generation at tumor sites. Therefore, I@P-ss-FRT can be applied to combat drug-resistant breast cancer.

Chronic Phenotypes Underlying Radiation-Induced Salivary Gland Dysfunction.

Head and neck cancer (HNC) is the sixth most diagnosed cancer, and treatment typically consists of surgical removal of the tumor followed by ionizing radiation (IR). While excellent at controlling tumor growth, IR often damages salivary glands due to their proximity to common tumor sites. Radiation damage to salivary glands results in loss of secretory function, causing severe and chronic reductions in salivary flow. This leads to the patient-reported sensation of dry mouth, termed xerostomia, which significantly reduces quality of life for HNC patients and survivors. The mechanisms underlying salivary gland damage remain elusive, and therefore, treatment options are scarce. Available therapies provide temporary symptom relief, but there is no standard of care for permanent restoration of function. There is a significant gap in understanding the chronic mechanistic responses to radiation as well as treatments that can be given in the months to years following cessation of treatment. HNC cases are steadily rising; particularly, the number of young patients diagnosed with nonfatal human papillomavirus + HNC continues to increase. The growing number of HNC diagnoses and improved prognoses results in more people living with xerostomia, which highlights the mounting need for restorative treatments. Mechanisms underlying chronic damage include decreases in acinar differentiation markers, increases in acinar cell proliferation, immune and inflammatory dysregulation, and metabolic changes including increases in amino acids and reductions in glycolysis and oxidative phosphorylation, fibrosis, and dysregulated neuronal responses. Currently, promising treatment options include adenoviral gene transfers and stem cell therapy. Thus, this review describes in depth known mechanisms contributing to chronic damage and discusses therapeutic advances in treating chronically damaged glands. Understanding the chronic response to radiation offers potential in development of new therapeutics to reverse salivary gland damage and improve the quality of life of HNC survivors.

In Situ Colonization of Trojan‐Yeast for Targeted Glucose Starvation and Reconstruction of Tumor Immune Environment

AbstractGlucose is an important energy source for living cells. Particularly, most tumor cells use glycolysis to harness energy for their fast growth, invasion and metastasis even under aerobic conditions. Thus, reduction of the glucose level in cancer can lead to suppression of tumor growth. Here, macrophage membrane dressed yeast, Trojan M‐yeast, is developed, via coating the surface of yeast with macrophage membrane, for targeted accumulation and suppression of tumor by glucose starvation. Due to the inflammatory homing effects of macrophage membrane, M‐yeast efficiently target and colonize in the inflammatory tumor site, where they compete with tumor cells for glucose consumption, thereby disrupting glycolysis of cancer cells, resulting in the reduction of lactate accumulation and reversal of the acidosis of tumor microenvironment. Subsequently, the apoptotic tumor cells and yeast promote dendritic cell maturation, increase tumor‐infiltrating cytotoxic T lymphocytes. Meanwhile, ethanol and acetaldehyde produced by yeast metabolism of glucose can re‐polarize tumor associated macrophages (TAMs) to the anti‐tumor phenotype (M1), thus reprogramming the tumor immunosuppressive microenvironment, leading to synergistic tumor suppression together with glucose starvation, which is different from traditional chemotherapy and immunotherapy. M‐yeast exhibits promising targeted cancer therapy with a decent safety profile. This work may provide new insights as well as a new paradigm for yeast‐based cancer therapy.

Impact of neoadjuvant immunotherapy on postoperative complications after surgery for rectal cancer.

Despite the increasing use of immunotherapy in treating various cancer types, there is still limited understanding of its impact on surgical complications. We used a national database to examine the difference in surgical outcomes for rectal cancer patients who received standard neoadjuvant chemoradiation plus neoadjuvant immunotherapy and patients who received neoadjuvant chemoradiation only. This retrospective cohort study used the National Cancer Database (NCDB). We selected patients aged 18-90 with T1-3, N1-2, and M0 rectal cancer who underwent curative-intent surgery between 2010 and 2020. We performed a 1:1 propensity match to control for patient age, sex, Charlson-Deyo comorbidity index, surgical approach, and tumor site. Our primary outcome was difference in surgical outcomes (hospital length of stay, unplanned 30-day readmission, 30-day mortality) between the two groups. Secondary outcomes included days from diagnosis to surgery and pathologic outcomes. Our study included 26 229 patients, of which 126 received immunotherapy in addition to chemoradiation and 26 103 received only chemoradiation. In our matched population of 125 pairs of patients, patients who received immunotherapy and chemoradiation underwent surgery later compared to patients who only received chemoradiation (median 245 vs. 144 days, p < 0.001). There were no significant differences in median length of stay (5 vs. 5 days, p = 0.202), unplanned 30-day readmission (7 vs. 9, p = 0.617), and 30-day mortality (0 vs. 1, p = 1.000) between the two groups. Neoadjuvant immunotherapy for rectal cancer is not associated with adverse surgical outcomes. This work can help clinicians optimize treatment protocols and move closer toward strategies tailored to specific patient profiles.

Rural-Urban Cancer Incidence and Trends in the United States, 2000-2019.

Background Despite consistent improvements in cancer prevention and care, rural and urban disparities in cancer incidence persist in the United States. Our objective was to further examine rural-urban differences in cancer incidence and trends. Methods We used the North American Association of Central Cancer Registries (NAACCR) dataset to investigate rural-urban differences in 5-year age-adjusted cancer incidence (2015-2019) and trends (2000-2019), also examining differences by region, sex, race/ethnicity, and tumor site. Age-adjusted rates were calculated using SEER*Stat 8.4.1, and trend analysis was done using Joinpoint, reporting annual percent changes (APCs). Results We observed higher all cancer combined 5-year incidence rates in rural areas (457.6 per 100,000) compared to urban a (447.9), with the largest rural-urban difference in the South (464.4 vs 449.3). Rural populations also exhibited higher rates of tobacco-associated, HPV-associated, and colorectal cancer, including early-onset. Tobacco-associated cancer incidence trends widened between rural and urban from 2000-2019, with significant, but varying, decreases in urban areas throughout the study period, while significant rural decreases only occurred between 2016 and 2019 (APC=-0.96). HPV-associated cancer rates increased in both populations until recently with urban rates plateauing while rural rates continued to rise (e.g., APC =1.56, 2002-2019). Conclusions Rural populations had higher overall cancer incidence rates and higher rates of cancers with preventive opportunities compared to urban. Improvements in these rates were typically slower in rural populations. Impact Our findings underscore the complex nature of rural-urban disparities, emphasizing the need for targeted interventions and policies to reduce disparities and achieve equitable health outcomes.

Odontogenic Tumors in Children and Adolescents: A Retrospective Analysis at a Tertiary-Level Health Care Facility in Bangladesh

Introduction: This study presents the oral and maxillofacial pathological features of several types of odontogenic tumors in children and adolescents less than 18 years of age from a Bangladeshi tertiary-level healthcare facility. Materials and Methods: In this retrospective cross-sectional study, the World Health Organization (WHO) categorization for head and neck tumors in 2022 was used to assess the frequency of odontogenic tumors in children and adolescents. Data relating to sex, age, and tumor site were retrieved and presented. The Chi-square test was implemented to study the association between gender, age, and site with different types of odontogenic tumors. Results: A total of 106 cases were found, and all the cases were benign. Ameloblatoma (75.47%) was the most common tumor, followed by odontogenic myxoma (9.44%), cemento-ossifying fibroma (5.66%), and odontoma (4.72%). A male (60.38%) predominance was observed in the gender distribution, but no statistically noteworthy (P = 0.43) relationship was found. Most of the cases were found in the 13–18 age group (63.21%), with a mean age (standard deviation) of 13.01 (2.29) years. There was no statistical significance found between age group and tumor type (P = 0.78). The mandibular (95.28%) predominance was found over the maxilla (4.72%) (Mandible: Maxilla = 20.2:1) and was statistically significant (P= 0.002). In the mandible, the posterior region (88.68%) was mostly affected. Conclusions: Early detection of odontogenic tumors is rare, and as people aged, they become more common. Ameloblatoma was the most prevalent odontogenic tumor in the jaws, followed by odontogenic myxoma, cemento-ossifying fibroma, and odontoma. Adolescents experience odontogenic tumors more frequently than children do. The mandible was observed to predominate over the maxilla in terms of site distribution. The mandible's posterior portion was primarily affected. Update Dent. Coll. j: 2024; 14(1):19-23

Nano-revolution in hepatocellular carcinoma: A multidisciplinary odyssey - Are we there yet?

In this editorial we comment on the review by Zhou et al reviewing the landscape of nanomedicine in the treatment of hepatocellular carcinoma (HCC). We focus on the immense potential of nanotechnology, particularly ligand-receptor mediated nanotherapy, in revolutionizing the treatment landscape of HCC. Despite advancements in multidisciplinary treatment, HCC remains a significant global health challenge. Ligand-mediated nanotherapy offers the opportunity for precise drug delivery to tumor sites, targeting specific receptors overexpressed in HCC cells, thereby enhancing efficacy and minimizing side effects. Overcoming drug resistance and aggressive tumor biology is facilitated by nanomedicine, bypassing traditional hurdles encountered in chemotherapy. Examples include targeting glypican-3, asialoglycoprotein, transferrin receptor or folic acid receptors, capitalizing on their over-expression in tumor cells. The ability for multi-receptor targeting through dual-ligand nanoparticle modification holds the prospect of further enhancement in specificity and efficacy of directed therapy. However, challenges including immune responses, reproducibility in nanoparticle synthesis, and production scalability remain. Future directions involve refining targeting strategies, improving drug release mechanisms, and streamlining production processes to enable personalized and multifunctional nanotherapies. Overall, the integration of nanotherapy in HCC treatment holds immense promise, but continued partnership and effort are needed in offering hope for more effective, precise, and accessible clinical care in the management of HCC.

Predictors and surgical outcome of hemorrhagic metastatic brain malignancies.

Intracerebral metastases present a substantial risk of tumor-associated intracerebral hemorrhage (ICH). This study aimed to investigate the risk of hemorrhagic events in brain metastases (BM) from various primary tumor sites and evaluate the safety and outcomes of surgical tumor removal. A retrospective, single-center review of medical records was conducted for patients who underwent BM removal between January 2016 and December 2017. Patients with hemorrhagic BM were compared to those with non-hemorrhagic BM. Data on preoperative predictors, perioperative management, and postoperative outcomes were collected and analyzed. A total of 229 patients met the inclusion criteria. Melanoma metastases were significantly associated with preoperative hemorrhage, even after adjusting for confounding factors (p = 0.001). Poor clinical status (p = 0.001), larger tumor volume (p = 0.020), and unfavorable prognosis (p = 0.001) independently predicted spontaneous hemorrhage. Importantly, preoperative use of anticoagulant medications was not linked to increased hemorrhagic risk (p = 0.592). Surgical removal of hemorrhagic BM, following cessation of blood-thinning medication, did not significantly affect intraoperative blood loss, surgical duration, or postoperative rebleeding risk (p > 0.096). However, intra-tumoral hemorrhage was associated with reduced overall survival (p = 0.001). This study emphasizes the safety of anticoagulation in patients with BM and highlights the safety of neurosurgical treatment in patients with hemorrhagic BM when blood-thinning medication is temporarily paused. The presence of intra-tumoral hemorrhage negatively impacts survival, highlighting its prognostic significance in BM patients. Further research with larger cohorts is warranted to validate these findings and elucidate underlying mechanisms.

Emergency department involvement in the diagnosis of cancer among older adults: a SEER-Medicare study.

Internationally, 20-50% of cancer is diagnosed through emergency presentation, which is associated with lower survival, poor patient experience, and socioeconomic disparities, but population-based evidence about emergency diagnosis in the U.S. is limited. We estimated Emergency Department (ED) involvement in the diagnosis of cancer in a nationally representative population of older US adults, and associations with sociodemographic, clinical, and tumor characteristics. We analyzed SEER-Medicare data for Medicare beneficiaries (≥66 years old) diagnosed with female breast, colorectal, lung and prostate cancers (2008-2017), defining their earliest cancer-related claim as their index date, and patients who visited the ED 0-30 days before their index date to have "ED involvement" in their diagnosis, with stratification as 0-7 or 8-30 days. We estimated covariate-adjusted associations of patient age, sex, race/ethnicity, marital status, comorbidity score, tumor stage, diagnosis year, rurality, and census tract poverty with ED involvement using modified Poisson regression. Among 614,748 patients, 23% had ED involvement with 18% visiting the ED in the 0-7 days before their index date. This varied greatly by tumor site: breast 8%, colorectal 39%, lung 40%, prostate 7%. In adjusted models, older age, female sex, non-Hispanic Black and Native Hawaiian/Other Pacific Islander race, being unmarried, recent diagnosis year, later-stage disease, comorbidities, and poverty were associated with ED involvement. The ED may be involved in the initial identification of cancer for 1 in 5 patients. Earlier, system-level identification of cancer in non-ED settings should be prioritized, especially among underserved populations.

Cardiac tumors with life threatening arrhythmia, an eight year single centre experience

Abstract Background Cardiac tumors are rare cardiac disorders which occur either as primary or secondary tumors. They have a wide variety of clinical presentations from accidental discovery till sudden cardiac death. Manifestations are mainly due to mass effect, local invasion, embolization, or constitutional symptoms. (1) Cardiac tumor related arrhythmias are more often incessant, especially in younger children, and the mechanism can be reentry or triggered automaticity. (2) Arrhythmia management depends on its clinical impact as well as tumor size, site, and nature. Surgical resection is preferred in life threating arrhythmias however, the decision should be tailored. Purpose To describe our institution’s tailored approach in treatment of cardiac tumors presenting with life threatening ventricular arrhythmias (VAs), including surgical resection, coiling of feeding vessels or even ICD implantation with long term rhythm monitoring. Methods We reviewed patients with primary cardiac tumors presenting to our center from 2015 to 2023 with emphasis on those with life threatening VAs. Patient records were examined for clinical presentation, ECGs, imaging modalities, histopathological analysis of the resected tumors and interrogation data for those with cardiac implantable electronic devices (CIEDS). Results Over 8 years, 64 patients were diagnosed to have primary cardiac tumors. Of those, 3.8% (6 patients) presented with life threatening monomorphic VT, half of them were pediatrics. Tissue characterization by CMR and histopathological analysis for the resected tumors revealed: 4 fibromas, one lipoma and one hemangioma. Surface ECGs during VT showed exit at, or close to, the site of the tumor (Table). Total surgical resection was performed in four cases (3 fibromas and one lipoma), one of them (the youngest, 6 months old) died during the postoperative period due to refractory heart failure. Partial resection was done in one patient with fibroma as the tumor involved the majority of RV free wall while the patient with hemangioma underwent coiling of the feeding vessels twice with marked decrease in the tumor size however he had one further episode of VT, so ICD was implanted. Over a mean follow up period of 3 years, four patients had no recurrence of tachycardia as confirmed with implantable loop recorders (ILRs) while the patient with ICD had infrequent episodes. Conclusion Total surgical resection, albeit risky, is highly effective in eliminating life threatening VAs caused by cardiac tumors. Other modalities like partial resection or coiling of the feeding vessels could be effective in high-risk patients. Devascularization, in our hemangioma case was not totally protective. Finally, ILRs were highly beneficial in confirming long-term freedom of arrhythmia after resection.Table: VT exit, tumor site and typeECG, CMR, angiogram&amp; surgical view

Intratumoral antigen signaling traps CD8+ T cells to confine exhaustion to the tumor site.

Immunotherapy advances have been hindered by difficulties in tracking the behaviors of lymphocytes after antigen signaling. Here, we assessed the behavior of T cells active within tumors through the development of the antigen receptor signaling reporter (AgRSR) mouse, fate-mapping lymphocytes responding to antigens at specific times and locations. Contrary to reports describing the ready egress of T cells out of the tumor, we find that intratumoral antigen signaling traps CD8+ T cells in the tumor. These clonal populations expand and become increasingly exhausted over time. By contrast, antigen-signaled regulatory T cell (Treg) clonal populations readily recirculate out of the tumor. Consequently, intratumoral antigen signaling acts as a gatekeeper to compartmentalize CD8+ T cell responses, even within the same clonotype, thus enabling exhausted T cells to remain confined to a specific tumor tissue site.

Dual Approach: Micellar Delivery of Chlorambucil Prodrug with Concurrent Glutathione Depletion and GST Inhibition for Enhanced Anticancer Activity.

Although chlorambucil (CHL) is a long-established anticancer drug, the drug failure of CHL, mediated by the intracellular defense system consisting of glutathione (GSH) and glutathione S-transferase pi (GST-pi), has significantly limited the application of CHL. To overcome this issue, we first designed a GSH-responsive small-molecule prodrug (EA-SS-CHL) by combining CHL and ethacrynic acid (EA). Subsequently, drug-loaded nanoparticles (ECPP) were formed by the self-assembly between EA-SS-CHL and amphiphilic PEG-PDLLA to improve the water solubility of the prodrug and its ability to target tumor sites. Upon exposure to high intracellular GSH concentration, EA-SS-CHL gradually degrades, leading to the release of EA and CHL. The presence of EA facilitates the depletion of GSH and inhibition of GST-pi, ultimately attenuating the detoxification of the intracellular defense system to CHL. Cytotoxicity studies and apoptosis assays demonstrate that ECPP exhibits higher therapeutic efficiency than CHL. Additionally, in vivo tumor suppression effects and biocompatibility provide further evidence for the superiority of ECPP. This work presents a promising strategy to enhance the efficacy of CHL in cancer therapy.

Predictive Nomogram and Propensity Score Matching in Neuroendocrine Carcinoma of the Tubular Gastrointestinal Tract: A US Population-Based Clinical Outcome Study

Background: Neuroendocrine carcinomas (NECs) of the tubular gastrointestinal tract (GI-NECs) are rare and associated with worse clinical outcomes. This population-based study aims to highlight key demographics, clinicopathological factors, and survival outcomes in the US population. Methods: Data from 10,387 patients with GI-NECs were extracted from the Surveillance, Epidemiology, and End Result (SEER) database from 2000 to 2020. Results: Most patients were &gt;40 years old at the time of presentation with a median age of 63 years old, with almost equal ethnic distribution per US population data. The most common primary tumor site was the small intestine (33.6%). The metastatic spread was localized in 34.8%, regional in 27.8%, and distant in 37.3% of cases, and the liver was the most common site of metastasis (19.9%) in known cases of metastases. Most NEC patients underwent surgery, presenting the highest 5-year overall survival of 73.2% with a 95% confidence interval (CI) (95% CI 72.0–74.4%), while chemotherapy alone had the lowest 5-year survival of 8.0% (95% CI 6.4–10.0%). Compared to men, women had a superior 5-year survival rate of 59.0% (95% CI 57.6–60.5%). On multivariate analysis, age &gt; 65 (HR 2.49, 95% CI 2.36–2.54%, p ≤ 0.001), distant metastasis (HR 2.57, 95% CI 2.52–2.62%, p ≤ 0.001), tumor size &gt; 4 mm (HR 1.98, 95%, CI 1.70–2.31%, p ≤ 0.001), esophageal (HR 1.49, 95% CI 0.86–2.58%, p ≤ 0.001), transverse colon (HR 1.95, 95% CI 1.15–3.33%, p ≤ 0.01), descending colon (HR 2.12, 95% CI 1.12, 3.97%, p = 0.02) anorectal sites, and liver or lung metastases were associated with worse survival. Surgical intervention and tumors located in the small intestine or appendix showed a better prognosis. Conclusion: GI-NECs are a group of rare malignancies associated with a poor prognosis. Therefore, epidemiological studies analyzing national databases may be the best alternative to have a more comprehensive understanding of this condition, assess the impact of current practices, and generate prognosis tools.

Changes in expression of breast cancer tumor biomarkers between primary tumors and corresponding metastatic sites: common patterns and relationships with survival.

In metastatic breast cancer, differences in expression patterns of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) between the primary tumor (PT) and metastatic site (MET) have been reported. However, there is limited understanding of the relationship of tumor subtype discordance and overall survival (OS). We evaluated patterns of ER/PR/HER2 in PTs and corresponding METs and assessed the relationship between these patterns and OS. Patients diagnosed at our center with metastatic breast cancer (2011-2020) were included. ER/PR were stratified as < 1%/1-10%/ > 10% by immunohistochemistry and HER2 as positive/negative by immunohistochemistry/FISH. Tumor subtypes were classified as ER or PR + /HER2-, HER2+ , or triple-negative. Biomarker discordance data from PTs to METs were analyzed for expression patterns. OS was assessed. Of 254 patients, 41 (16.1%) had synchronous and 213 (83.9%) had metachronous METs. Category change of ER/PR/HER2 expression was observed in 56 (22.0%), 117 (40.5%), and 30 (11.8%) patients, respectively. Tumor subtype changed in 56 (22.0%) patients. We identified a difference between PT and MET from ER > 10% to ER < 1% (n = 28,16.2% p < 0.01); PR > 10% to PR < 1% (n = 54,48.2%, p < 0.001); PR > 10% to PR 1-10% (n = 18,16.1%, p < 0.001), and ER or PR+/HER2-to triple-negative (n = 19,13.0%, p = 0.03). In log-rank analysis, change from an ER or PR+/HER2-(5-year OS 88.6%) PT to a HER2+(67.5%) or triple-negative (54.6%) MET was associated with decreased survival (p < 0.01); however, in multivariate analysis, discordant biomarker expression was not associated with decreased survival (p > 0.05). Tumor expression of ER/PR/HER2 can differ between the PT and MET. Loss of ER/PR expression is common and may be related to worse survival. Routine assessment of MET tumor markers could inform prognosis and therapeutic decision-making.

Energy-storing DNA-based hydrogel remodels tumor microenvironments for laser-free photodynamic immunotherapy

Photodynamic therapy (PDT) is a promising modality for cancer treatment. However, limited tissue penetration of external radiation and complicated tumor microenvironments (TMEs) restrict the antitumor efficiency of PDT. Herein, we report an energy-storing DNA-based hydrogel, which enables tumor-selective PDT without external radiation and regulates TMEs to achieve boosted PDT-mediated tumor immunotherapy. The system is constructed with two ultralong single-stranded DNA chains, which programmed partial complementary sequences and repeated G-quadruplex forming AS1411 aptamer for photosensitizer loading via hydrophobic interactions and π-π stacking. Then, energy-storing persistent luminescent nanoparticles are incorporated to sensitize PDT selectively at tumor site without external irradiation, generating tumor antigen to agitate antitumor immune response. The system catalytically generates O2 to alleviate hypoxia and releases inhibitors to reverse the IDO-related immunosuppression, synergistically remodeling the TMEs. In the mouse model of breast cancer, this hydrogel shows a remarkable tumor suppression rate of 78.3 %. Our study represents a new paradigm of photodynamic immunotherapy against cancer by combining laser-free fashion and TMEs remodeling.

Tracheostomy stomal seeding following tongue cancer resection: A case report

AbstractBackgroundThe tracheostomy site seeding following oral cancer surgery is extremely rare and carries poor prognosis.Case PresentationWe present the case of the 62‐year‐old man with clinical T4bN2bM0 tongue squamous cell carcinoma (SCC). The tracheostomy was planned before cancer resection under general anesthesia, but oral intubation was not possible because of bleeding from tongue cancer. Thus, tracheostomy was performed under local anesthesia. He underwent a total glossectomy with segmental mandibulotomy, bilateral neck dissection with rectus abdominis muscle free flap reconstruction and postoperative radiotherapy. The pathological diagnosis was SCC (pT4bN0M0) with close margin. He underwent adjuvant radiotherapy of 66 Gy that targeted the primary tumor site and upper neck. The mass at the tracheostomy site from seeding was detected 4 months after surgery and treated with 60 Gy of radiotherapy. The patient was died from bleeding and airway obstruction about 7 months from detection of the seeding of tracheostomy site.ConclusionTracheostomy site seeding after temporally tracheostomy for oral cancer is very rare. The pathological mechanisms suspected the tumor seeding. The prognosis of the seeding of tracheostomy site was extremely poor. Possible method to prevent these includes awake tracheostomy without oral intubation for predicting bleeding from bulky tumor with trismus.

Neutral Cyanine: Ultra-Stable NIR-II Merocyanines for Highly Efficient Bioimaging and Tumor-Targeted Phototheranostics.

Fluorescence imaging-guided phototheranostics using emission from the second near-infrared (NIR-II) window show significant potential for cancer diagnosis and treatment. Clinical imaging-used polymethine ionic indocyanine green (ICG) dye is widely adopted for NIR fluorescence imaging-guided photothermal therapy research due to its exceptional photophysical properties. However, ICG has limitations such as poor photostability, low photothermal conversion efficiency (PCE), short-wavelength emission peak, and liver-targeting issues, which restrict its wider use. In this study, we transformed two ionic ICG derivatives into neutral merocyanines (mCy) to achieve much enhanced performance for NIR-II cancer phototheranostics. Initial designs of two ionic dyes showed similar drawbacks as ICG in terms of poor photostability and low photothermal performance. One of the modified neutral molecules, mCy890, shows significantly improved stability, an emission peak over 1000nm, and a high photothermal PCE of 51%, all considerably outperform ICG. In vivo studies demonstrated that nanoparticles of the mCy890 can effectively accumulate at the tumor sites for cancer photothermal therapy guided by NIR-II fluorescence imaging. This research provides valuable insights into the development of neutral merocyanines for enhanced cancer phototheranostics. This article is protected by copyright. All rights reserved.

Facile Synthesis of a Multifunctional Porous Organic Polymer Nanosonosensitizer (mHM@HMME) for Enhanced Cancer Sonodynamic Therapy.

Sonodynamic therapy (SDT), which involves the activation of sonosensitizers to generate cytotoxic reactive oxygen species under ultrasound irradiation, is a promising noninvasive modality for cancer treatment. However, the clinical translational application of SDT is impeded by the lack of efficient sonosensitizers, the inefficient accumulation of sonosensitizers at tumor sites, and the complicated immunosuppressive tumor microenvironment. Herein, we developed a facilely synthesized multifunctional porous organic polymer nanosonosensitizer (mHM@HMME) for enhanced SDT. Specifically, mHM@HMME nanosonosensitizers were prepared by incorporating chemotherapeutic mitoxantrone into the one-step synthesis process of disulfide bond containing porous organic polymers, followed by loading with organic sonosensitizer (HMME) and camouflaging with a cancer cell membrane. Due to the cancer cell membrane camouflage, this multifunctional mHM@HMME nanosonosensitizer showed prolonged blood circulation and tumor targeting aggregation. Under ultrasound irradiation, the mHM@HMME nanosonosensitizer exhibited a satisfactory SDT performance both in vitro and in vivo. Moreover, the potent SDT combined with glutathione-responsive drug release in tumor cells induced robust immunogenic cell death to enhance the antitumor effect of SDT in turn. Overall, this facilely synthesized multifunctional mHM@HMME nanosonosensitizer shows great potential application in enhanced SDT.

Personalized Nanovaccines Enhance Lymph Node Accumulation and Reprogram the Tumor Microenvironment for Improved Photodynamic Immunotherapy.

Tumor immunotherapy has emerged as an efficacious therapeutic approach that mobilizes the patient's immune system to achieve durable tumor suppression. Here, we design a photodynamic therapy-motivated nanovaccine (Dex-HDL/ALA-Fe3O4) co-delivering 5-aminolevulinic acid and Fe3O4 nanozyme that demonstrate a long-term durable immunotherapy strategy. After vaccination, the nanovaccine exhibits obvious tumor site accumulation, lymph node homing, and specific and memory antitumor immunity evocation. Upon laser irradiation, Dex-HDL/ALA-Fe3O4 effectively generates reactive oxygen species at the tumor site not only to induce the immunogenic cell death-cascade but also to trigger the on-demand release of full types of tumor antigens. Intriguingly, Fe3O4 nanozyme-catalyzed hydrogen peroxide generated oxygen for alleviating tumor hypoxia and modifying the inhibitory tumor microenvironment, thereby exhibiting remarkable potential as a sensitizer. The intravenous administration of nanovaccines in diverse preclinical cancer models has demonstrated remarkable tumor regression and inhibition of postoperative tumor recurrence and metastasis, thereby enabling personalized treatment strategies against highly heterogeneous tumors.