Distant Organ Metastasis Research Articles

Factors associated with prolonged progression-free survival of patients treated with first-line afatinib for advanced epidermal growth factor receptor-mutated non-small cell lung cancer.

This study aimed to investigate the factors associated with prolonged progression-free survival (PFS) (>36 months) of advanced non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations treated with first-line afatinib. We performed a retrospective analysis of data of patients with advanced EGFR-mutated NSCLC receiving first-line afatinib at two tertiary care referral centers, Linkou and Kaohsiung Chang Gung Memorial Hospital, in Taiwan between June 2014 and April 2022. The data of 546 treatment-naïve EGFR-mutated advanced NSCLC patients were analyzed. Median PFS and overall survival were 14.5 months and 27.2 months, respectively. The PFS of 462 patients (84.6%) was less than 36 months and of 84 patients (15.4%) was more than 36 months. The PFS > 36 months group had a significantly higher percentage of patients with uncommon mutations (p = 0.002). The PFS ≤36 months group had significantly higher incidences of bone, liver, and adrenal metastases (all p < 0.05) and a higher rate of multiple distant metastases. Multivariate logistic regression analysis showed that liver metastasis was negatively and independently associated with prolonged PFS (adjusted odds ratio = 0.246 [95% CI: 0.067-0.908], p = 0.035). The median overall survival of the PFS >36 months group was 46.0 months and that of the PFS ≤36 months group was 22.9 months (log-rank test, p < 0.001). We found that EGFR-mutated NSCLC patients receiving first-line afatinib were prone to shorter PFS if they had distant organ metastasis, especially liver metastasis.

Adrenal Ganglioneuroma with Lymph Node Metastasis: A Rare Case Report

Ganglioneuroma (GN) is a rare benign, well-differentiated neoplasia originating from the neural crest. Although it is most commonly seen in the posterior mediastinum, it can be observed in many areas including the adrenal gland. Lesions located in the posterior mediastinum and retroperitoneum are mostly seen in the pediatric population and adrenal ganglioneuromas are more common in the 4-5. decade. GN is a benign neoplasia but very rarely lymph node and distant organ metastases have been reported. In this study, a case of adrenal gland ganglioneuroma showing lymph node metastasis in a 3-year-old male patient is presented.

Current scenario of chalcone hybrids with antibreast cancer therapeutic applications.

Breast cancer, an epithelial malignant tumor that occurs in the terminal ducts of the breast, is the most common female malignancy. Currently, approximately 70%-80% of breast cancer with early-stage, nonmetastatic disorder is curable, but the emergency of drug resistance often leads to treatment failure. Moreover, advanced breast cancer with distant organ metastases is incurable with the available therapeutics, creating an urgent demand to explore novel antibreast cancer agents. Chalcones, the precursors for flavonoids and isoflavonoids, exhibit promising activity against various breast cancer hallmarks, inclusive of proliferation, angiogenesis, invasion, metastasis, inflammation, stemness, and regulation of cancer epigenetics, representing useful scaffolds for the discovery of novel antibreast cancer chemotherapeutic candidates. In particular, chalcone hybrids could act on two or more different biological targets simultaneously with more efficacy, lower toxicity, and less susceptibility to resistance. Accordingly, there is a huge scope for application of chalcone hybrids to tackle the present difficulties in breast cancer therapy. This review outlines the chalcone hybrids with antibreast cancer potential developed from 2018. The structure-activity relationshipsas well as mechanisms of action are also discussed to shed light on the development of more effective and multitargeted chalcone candidates.

Distant organ metastasis patterns and prognosis of lung adenosquamous carcinoma: a SEER database analysis.

Our purpose is to evaluate the patterns of organ metastasis and the prognosis in lung adenosquamous carcinoma patients with organ metastasis. We collected the data from the surveillance epidemiology and end results database, covering the period of 2000-2018. Cox regression, Kaplan-Meier and log-rank analyses were performed. Totally, 2698 patients were enrolled, comprising 851 (31.54%) patients diagnosed with organ metastasis and 2017 (68.46%) patients without organ metastasis. Patients with distant organ metastasis show a significant decrease in median overall survival. In addition to the aforementioned factors, age over 70 years, male, main bronchus, advanced T stage, larger tumour size, absence of primary tumour surgery and lack of radiotherapy have all been identified as prognostic indicators associated with a poorer outcome. In terms of treatment options, patients with organ metastasis can benefit from chemotherapy and primary tumour surgery. Moreover, in patients with organ metastasis, those who received a combination treatment of surgery, chemotherapy and radiotherapy displayed the most favourable prognosis, with a median overall survival of 17 months. We identified the prognostic indicators for organ metastasis in patients with lung adenosquamous carcinoma. Highly selected patients who undergo a combination treatment of surgery, chemotherapy and radiotherapy may experience the greatest survival benefit.

Transanal minimally invasive surgery (TAMIS) for local excision of benign and malignant rectal neoplasia: a 7-year experience

PurposeTransanal minimally invasive surgery (TAMIS) is an advanced transanal platform that can be utilised to perform high-quality local excision (LE) of rectal neoplasia. This study describes clinical and midterm oncological outcomes from a single unit’s 7-year experience with TAMIS.MethodsConsecutive patients who underwent TAMIS LE at our institution between January 1st, 2016, and December 31st, 2022, were identified from a prospectively maintained database. Indication for TAMIS LE was benign lesions not amenable to endoscopic excision or histologically favourable early rectal cancers. The primary endpoints were resection quality, disease recurrence and peri-operative outcomes. The Kaplan–Meier survival analyses were used to describe disease-free survival (DFS) for patients with rectal adenocarcinoma that did not receive immediate salvage proctectomy.ResultsThere were 168 elective TAMIS LE procedures performed for 102 benign and 66 malignant lesions. Overall, a 95.2% negative margin rate was observed, and 96.4% of lesions were submitted without fragmentation. Post-operative morbidity was recorded in 8.3% of patients, with post-operative haemorrhage, being the most common complication encountered. The mean follow-up was 17 months (SD 15). Local recurrence occurred in 1.6%, and distant organ metastasis was noted in 1.6% of patients.ConclusionsFor carefully selected patients, TAMIS for local excision of early rectal neoplasia is a valid option with low morbidity that maintains the advantages of organ preservation.

Distant organ metastasis patterns and prognosis of cervical adenocarcinoma: a population-based retrospective study.

Adenocarcinoma is a common histological subtype of cervical cancer, accounting for 10-15% of all cases. The prognosis of cervical adenocarcinoma with distant organ metastases remains unclear. Therefore, our study aimed to investigate the patterns and prognosis of distant organ metastasis in cervical adenocarcinoma. We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database spanning from 2010 to 2019. Cox regression, Kaplan-Meier, and log-rank analyses were conducted. We observed that adenocarcinoma (AC) of the cervix primarily metastasizes to single organs, with a rate of 73.3%. The lungs are the most common organs of metastasis, followed by the liver and bones. Patients with bone metastases have a median survival period of 12 months, which is slightly longer compared to metastasis in other organs. Distant organ metastasis, age, positive lymph nodes, higher AJCC stages, larger tumor diameter, and higher cell grades are related to poor prognosis (p < 0.001). Furthermore, we have observed that surgical intervention, radiotherapy, and chemotherapy can potentially provide benefits for patients with distant organ metastases. Metastasis is an independent prognostic factor for cervical adenocarcinoma patients. Surgery, radiotherapy, and chemotherapy can provide an overall survival advantage for patients with distant organ metastases.

Downregulation of NEBL promotes migration and invasion of clear cell renal cell carcinoma by inducing epithelial-mesenchymal transition

As a member of the nebulin protein family and a structural protein of cytoskeleton, NEBL plays an important role in cardiac diseases. Recently, literature have reported the involvement of NEBL in the occurrence and development of various cancers except clear cell renal cell carcinoma (ccRCC). In this study, we found that mRNA and protein of NEBL are downregulated remarkably in ccRCC tissues based on both the TCGA database and clinical samples we collected. The areas under curve values of NEBL analyzed based on the TCGA database, qRT-PCR and IHC results were 0.9376, 0.9733 and 0.9807, respectively. The lower mRNA level of NEBL was associated with worse outcomes in ccRCC patients. When overexpressing NEBL in ccRCC cell lines, the proliferation, migration and invasion of ccRCC cells were suppressed significantly, suggesting a tumor suppressor role of NEBL. In addition, we identified that NEBL is closely related to epithelial-mesenchymal transition (EMT), thereby reducing the motility of ccRCC cells. Furthermore, the lower expression of NEBL was correlated with ccRCC patients with distant organ metastasis. In summary, we firstly described the aberrant expression of NEBL and revealed its tumor suppressor role in ccRCC. Our data support that NEBL could serve as a valuable diagnostic and prognostic biomarker in ccRCC, as well as a promising therapeutic target.

The association between sarcopenia, defined by a simplified screening tool, and long-term outcomes.

Sarcopenia and frailty are frequently observed in older adult patients and linked to unfavorable postoperative outcomes. Identifying low muscle mass and function is primary for diagnosing sarcopenia. The simpler screening, which excludes muscle mass measurement, exhibited strong predictive capabilities in identifying sarcopenia. This research explored the association between sarcopenia, as defined by the C3 formula, and long-term outcomes in older adult cancer patients who underwent surgery. Surgical cancer patients aged 60 and older were enrolled. Sarcopenia was identified using the C3 formula, assessing muscle strength through handgrip strength, physical performance via a 6-m walk test, and nutrition status via the Mini Nutritional Assessment-Short Form. Long-term outcomes were evaluated with the Barthel Index for activities of daily living (B-ADL) at 3 months, as well as 1-year mortality rates. The study enrolled 251 patients, with 130 classified as sarcopenic according to the C3 formula. Compared with nonsarcopenic patients, patients with sarcopenia exhibited a higher frequency of moderate to severe disability (B-ADL ≤70) 3 months postdischarge (19.5% vs 5.2%; P = 0.001) and elevated 1-year mortality rates (29.5% vs 14.9%; P = 0.006). No significant differences were observed in infection rates, hospital stay duration, or in-hospital mortality. Distant organ metastasis (HR = 3.99; 95% CI = 2.25-7.07) and sarcopenia defined by the C3 formula (HR = 1.78; 95% CI = 1.01-3.15) were identified as independent risk factors for 1-year mortality. The simplified sarcopenia screening tool was associated with increased rates of moderate to severe disability 3 months postdischarge and higher 1-year mortality rates compared with nonsarcopenic patients.

Efficacy of alectinib in lung adenocarcinoma patients with different anaplastic lymphoma kinase (ALK) rearrangements and co-existing alterations-a retrospective cohort study.

Alectinib significantly improves survival of non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK)-rearrangement. In this study, we analyzed the effects of different ALK rearrangements and co-mutations on the efficacy of alectinib. Using the electronic medical record system, we reviewed in terms of clinical and pathological features patients with advanced (IIIB/IV stage) ALK-rearranged NSCLC at Shanghai Chest Hospital between January 2018 and December 2021 who were treated with alectinib in first or second line and were assessed for objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). A total of 66 patients were enrolled in the study, and 17 types of ALK rearrangements were detected, of which five types of ALK rearrangements responded well to alectinib. We classified ALK-rearrangements into four main types, namely echinoderm microtubule-associated protein-like 4 (EML4)-ALK (E6:A20), EML4-ALK (E13:A20), EML4-ALK (E20:A20), and others. There was no significant difference in ORR and DCR of these types (ORR: 31.3% vs. 13.0% vs. 18.2% vs. 17.6%, P=0.575; DCR: 93.8% vs. 95.6% vs. 100.0% vs. 88.2%, P=0.627). The 3-year PFS rates were 25.0% (4/16) vs. 13.0% (3/23) vs. 27.3% (3/11) vs. 18.8% (3/16) for EML4-ALK (E6:A20), EML4-ALK (E13:A20), EML4-ALK (E20:A20), and others, respectively (P=0.725). The results of co-mutation analysis showed that the median PFS (mPFS) for patients with tumors harboring TP53 mutations was 30.4 months, significantly shorter than that of patients with tumors without co-mutations and whose mPFS was not mature (P=0.026). TSC1 co-mutation was also identified as a detrimental factor in outcome, with a DCR of 60% vs. 100% (P=0.031), mPFS of 30.4 months vs. not applicable (P=0.160) in patients with vs. those without this co-mutation, respectively. The efficacy of alectinib in patients with brain metastases is comparable to that in patients without distant organ metastases. There were two cases with specific fusion types that also responded to alectinib; namely, double ALK-rearrangements: EML4-ALK (E13:A20) and MSH2-ALK (M7:A20), and with a rare fusion partner, SPECC1L-ALK (S8:A20). Their PFS were 8.7 and 38.0 months, respectively. In this study, the efficacy of alectinib in different types of ALK-rearrangements varied slightly. TP53 and TSC1 co-mutations were identified as detrimental factors affecting efficacy. This study provides references for the response to alectinib in patients with different types of ALK rearrangements and co-mutation.

VEGF-C-expressing TAMs rewire the metastatic fate of breast cancer cells

The expression of pro-lymphangiogenic VEGF-C in primary tumors is associated with sentinel lymph node metastasis in most solid cancer types. However, the impact of VEGF-C on distant organ metastasis remains unclear. Perivascular tumor-associated macrophages (TAMs) play a crucial role in guiding hematogenous spread of cancer cells by establishing metastatic pathways within the tumor microenvironment. This process supports breast cancer cell intravasation and metastatic dissemination. We show here that VEGF-C-expressing TAMs reduce the dissemination of mammary cancer cells to the lungs while concurrently increasing lymph node metastasis. These TAMs express podoplanin and interact with normalized tumor blood vessels expressing VEGFR3. Moreover, clinical data suggest inverse association between VEGF-C-expressing TAMs and breast cancer malignancy. Thus, our study elucidates the paradoxical role of VEGF-C-expressing TAMs in redirecting cancer cells to preferentially disseminate to lymph nodes rather than to lungs, partially achieved by normalizing tumor blood vessels and promoting lymphangiogenesis.

Abdominal Incision Metastasis from Squamous Cell Carcinoma Cervix after Wertheim’s Hysterectomy-A Case Report and Review of Literature

Scar site recurrence is a rare phenomenon and is more uncommon in squamous cell carcinoma. We present a special case of scar site recurrence in a 40-year-old patient with carcinoma cervix detected on MRI abdomen and pelvis, 5 months after Wertheim’s hysterectomy. The prognosis is bad in these patients, as they also present with distant organ metastasis.

Significance of Surgery for Resectable M1 Lymph Node Metastases Without Organ Metastasis in Esophageal Carcinoma in the Era of Neoadjuvant Treatment.

M1 esophageal carcinoma goes beyond localized disease and requires treatment with systemic therapy. M1 status is primarily divided into two categories: M1 lymph node metastasis and distant organ metastasis. Oligometastasis is defined as a state of limited metastatic disease, and surgery for oligometastasis of distant organs is reported to be beneficial in limited conditions. The aim of this study was to investigate resected cases of M1 lymph node metastases as the only metastatic site in stage IVB esophageal carcinoma. This study was a single-center retrospective cohort study. Patients with esophageal carcinoma who underwent esophagectomy with curative intent between April 2017 and December 2021 were examined. Neoadjuvant chemotherapy was our standard therapy and administered in almost all cases. We hypothesized that four sites of metastatic M1LN (supraclavicular (no. 104), pretracheal (no. 106pre), posterior thoracic para-aortic (no. 112aoP), and abdominal para-aortic (no. 16a2lat) LNs) were potentially resectable M1LN (rM1LN) metastases with curative intent and compared the prognosis of patients with and without rM1LN metastasis. Six hundred eight-two patients were included in the study. Among these patients, 80 had rM1LN metastasis and received surgery for curative intent. Short-term safety outcomes were equivalent between patients with and without rM1LN metastases. After propensity score matching, there were no significant differences in overall survival between patients with and without rM1LN metastasis. Multivariate analyses revealed that the only independent prognostic factor was ypN status. The present study suggests the feasibility and favorable OS in the patients with resection of rM1LN metastasis.

Tumor Profiles of Late Presentation Uveal Ring Melanoma With Novel Characteristics - A Case Series.

The purpose of this study was to investigate the clinical features, tumor characteristics, including histopathology and cytogenetic analysis, and management of patients with uveal ring melanoma in New Zealand. A retrospective review was conducted on all uveal melanoma cases treated in a single national oncology center in New Zealand. The study period was from January 1, 2013 to December 31, 2022 (10 years). Written consent was obtained from all patients included in this case series. Uveal ring melanoma of ciliary body origin (n = 4) comprised 0.7% of all uveal melanomas (n = 571). Ethnicity distribution was three patients of New Zealand European ancestry and one patient of Chinese/Pasifika ancestry. Three patients (75%) were symptomatic at presentation (spontaneous hyphema, glaucoma, and cataract), whereas one was asymptomatic but subsequently developed painful refractory glaucoma. All eyes underwent enucleation. Three eyes had primary iris biopsies with subsequent enucleation for refractory glaucoma and pain and one eye underwent primary enucleation. All cases demonstrated malignant tumor characteristics including diffuse 270 to 360-degree ciliary body ring growth pattern, epithelioid-cell type and presence of either BAP-1 expression loss or gain of MYC gene. Two cases (50%) developed distant organ metastasis - liver, parotid gland, and breast. Of those, one patient was deceased at the time of follow-up whereas one had completed treatment for metastases. Uveal ring melanoma is a rare tumor that is highly invasive and malignant. When detected, prompt definitive treatment should be advocated, and patient counselling should be given regarding the high risk of developing a painful, blind eye with increased risk of metastasis in the absence of treatment.

MSCT findings of primary Pulmonary mucoepidermoid carcinoma

Objectives To improve diagnostic accuracy of pulmonary mucoepidermoid carcinoma (PMEC) through multi-detector computed tomography (MSCT) findings. Methods MSCT findings of 27 histopathologically confirmed PMEC cases were retrospectively analyzed, including the location, size, margin, density, enhancement of the lesion and accompanying signs. Results Among the 27 PMEC cases, 6 (6/27, 22.2%) were the large airway pattern, 14 were (14/27, 51.9%) the pulmonary hilum pattern, and 7 (7/27, 26.9%) were the peripheral pattern. Among those 20 cases with central pattern(6 large airway and 14 pulmonary hilum patterns), 6 presented mild enhancement, 4 moderate enhancement, 5 severe enhancement, 5 heterogeneous enhancement, and 3 with calcification. 7 cases with peripheral patterns were presented as solid pulmonary nodules and masses, 3 with severe enhancement, 1 with moderate enhancement and 3 with mild enhancement. Four cases accompanied by lymph nodal metastasis, and 7 cases with distant organ metastasis. Age(t = –3.132, p = 0.005), enlarged lymph node (x2 = 9.281, p = 0.005), and distant metastasis(x2 = 7.816, p = 0.008) were statistically significant in the low-grade group and high-grade group. Conclusions MSCT images of PMEC patients demonstrated some characteristic findings, which would help improve the diagnostic accuracy of the disease.

Exploration of a novel prognostic model based on nomogram in non-small cell lung cancer patients with distant organ metastasis: implications for immunotherapy.

Evidence for the effects of immunotherapy in non-small cell lung cancer (NSCLC) patients with distant organ metastasis is insufficient, and the predictive efficacy of established markers in tissue and blood is elusive. Our study aimed to determine the prognostic factors and develop a survival prognosis model for these patients. A total of 100 advanced NSCLC patients with distant organ metastases, who received single or combination immune checkpoint inhibitors (ICIs) in Xijing Hospital between June 2018 and June 2021, were enrolled for retrospective analysis. The major clinicopathological parameters were collected, and associated survival outcomes were followed up by telephone or inpatient follow-up for nearly 3 years to assess prognoses. The survival prognosis model was established based on univariate and multivariate Cox regression analyses to determine the candidate prognostic factors. From the start of immunotherapy to the last follow-up, 77 patients progressed and 42 patients died, with a median follow-up of 18 months [95% confidence interval (CI): 15-19.9]. The median progression-free survival (PFS) and overall survival (OS) were 8 months (95% CI: 5.6-10.4) and 21 months (95% CI: 8.9-33.1), respectively. Multivariate Cox proportional hazards analysis showed Eastern Cooperative Oncology Group performance status (ECOG PS), body mass index (BMI), age-adjusted Charlson comorbidity index (ACCI), lactate dehydrogenase (LDH), and absolute neutrophil count (ANC) were correlated significantly with OS. Based on these five predictive factors, a nomogram and corresponding dynamic web page were constructed with a concordance index (C-index) of 0.81 and a 95% CI of 0.778-0.842. Additionally, the calibration plot and time-receiver operating characteristic (ROC) curve validated the precision of the model at 6-, 12-, and 18-month area under the curves (AUCs) reached 0.934, 0.829, and 0.846, respectively. According to the critical point of the model, patients were further divided into a high-risk total point score (TPS) >258, middle-risk (204< TPS ≤258), and low-risk group (TPS ≤204), and significant OS differences were observed among the three subgroups (median OS: 4.8 vs. 13.0 vs. 32.9 months). A feasible and practical model based on clinical characteristics has been developed to predict the prognosis of NSCLC patients with distant organ metastasis undergoing immunotherapy.

18F-fluorodeoxyglucose positron emission tomography/computed tomography findings of breast cancer with signet ring cell differentiation: A single-center experience

Aim: Due to the low incidence of breast cancer with signet ring cell (SRC) differentiation, which constitutes less than 1% of all breast cancers, little is known about its imaging features. The aim of this study was to evaluate the utility of 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography/Computed Tomography (PET/CT) in staging breast cancer with SRC differentiation.&#x0D; &#x0D; Methods: We conducted a retrospective analysis of 14 patients with histologically confirmed breast cancer with SRC differentiation who underwent 18F-FDG PET/CT at our institution between 2014 and 2023. The imaging findings were analyzed in terms of maximum standardized uptake value (SUVmax), lesion size, and the presence of regional or distant metastases were statistically evaluated.&#x0D; &#x0D; Results: The histological subtypes of SRC differentiated primary tumors were 9 invasive lobular, and 5 invasive ductal carcinoma. More intense 18F-FDG uptake was observed in primary tumoral lesions of the ductal subtype (mean SUVmax: 18.8±9.8; range: 2.6–28.9) compared to the lobular subtype (mean SUVmax: 2.6±1.3; range: 1.5–5.1) (p=0.007, Z=2.600). Among the patients included in the study, axillary lymph node metastasis was present in 64% (n=9) of the cases, with lymph node metastasis identified in five cases classified as ductal carcinoma. Additionally, distant organ metastasis was identified in 21% (n=3) of patients, comprising two patients with ductal carcinoma and one with lobular carcinoma.&#x0D; &#x0D; Conclusion: Despite the general consensus that signet-ring cell tumors have a low affinity for 18F-FDG, our study has observed the possibility of high 18F-FDG uptake in cases of ductal carcinoma. However, in cases of lobular carcinoma, where 18F-FDG uptake tends to be low, considering alternative PET radiopharmaceuticals for imaging could be a viable option.

Abstract PR01: Lymph node colonization promotes distant tumor metastasis through the induction of tumor-specific immune tolerance

Abstract The majority of cancer-associated deaths result from distant organ metastasis, yet the mechanisms that enable this process remain poorly understood. Colonization of regional or distant lymph nodes (LNs) typically precedes the formation of distant organ metastases, yet it has been unclear whether LN metastasis plays a functional role in disease progression. LNs are major sites of anti-tumor lymphocyte education, including in the context of immunotherapy, yet LN metastasis frequently correlates with further disease progression. Here, we find that LN metastasis represents a critical step in tumor progression through the capacity of such metastases to induce tumor-specific immune tolerance in a manner that promotes further dissemination of tumors to distant organs. Using an in vivo passaging approach, we generated 300 unique cell lines exhibiting varying degrees of LN metastatic capacity. We show that the presence of these LN metastases enables distant organ seeding of metastases in a manner that the parental tumor cannot, and this effect is eliminated in mice lacking an adaptive immune response. Furthermore, this promotion of distant seeding by LN metastases is tumor specific. Using flow cytometry and single-cell sequencing to perform comprehensive immune profiling, we identify multiple cellular mediators of tolerance. In particular, we find that LN metastases have the capacity to both resist NK cell cytotoxicity and induce regulatory T cells (Tregs). Furthermore, depletion of NK cells in vivo enables non-metastatic tumors to disseminate to LNs, and ablation of Tregs using FoxP3-DTR mice eliminates the occurrence of lymphatic metastases. Adoptive transfer of Tregs from the LNs of mice bearing LN metastasis to naïve mice facilitates metastasis in a manner that Tregs from mice without LN metastases cannot, and we find that these Tregs are induced in an antigen-specific manner. Whole exome sequencing revealed that neither the metastatic proclivity nor immunosuppression evolve through the acquisition of driver mutations, loss of neoantigens, loss of MHC class I presentation, or decreases in melanoma antigen expression. Rather, by RNA-seq and ATAC-seq, we show that a conserved interferon signaling axis is upregulated in LN metastases and is rendered stable through epigenetic reprogramming of chromatin accessibility resulting from chronic exposure to interferons in vivo. Furthermore, using CRISPR/Cas9, we find that these pathways are required for LN metastatic seeding, and validate their conserved significance in multiple mouse models and HNSCC patients with LN metastatic disease. Together, these findings demonstrate a critical role for LN metastasis in promoting tumor-specific immunosuppression. Citation Format: Nathan E. Reticker-Flynn, Weiruo Zhang, Pamela A. Basto, John B. Sunwoo, Sylvia K. Plevritis, Edgar G. Engleman. Lymph node colonization promotes distant tumor metastasis through the induction of tumor-specific immune tolerance [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PR01.

Lysosome-Specific Coumarin-Based Fluorescent Bioprobes for in Vivo Polarity Sensing and Cancer Treatment.

About 90% of cancer deaths worldwide are caused by the spread of cancer cells from the primary tumor to distant organs (metastasis). Therefore, there is an urgent need for an early diagnosis and treatment before cancer metastasis occurs. Lysosomes have emerged as attractive targets for cancer diagnosis and treatment because polar defects in lysosomes can induce apoptosis and cell death. Coumarin is a known polar-sensitive dye with good biocompatibility; because of this, we constructed two fluorescent probes of coumarin derivatives with the "D-π-A" structure, CouN-1 and CouN-2, through three simple reactions. In molecular design, due to morpholine's prominent lysosomal targeting characteristics, it was used as both lysosomal targeting motifs and an electron donor (D), while coumarin was used as an electron acceptor (A). The experimental results strongly proved that CouN-1 and CouN-2 have a good linear relationship with the polarity change of Δf = 0.209-0.308. In addition, both in vitro and in vivo imaging results have shown that CouN-1 and CouN-2 can specifically identify and monitor tumor sites. In the cell uptake and apoptosis experiments, the two probes also showed a strong antiproliferation effect on cancer cells. All of these characteristics demonstrated the potential of these two polarity-sensitive biological probes, CouN-1 and CouN-2, in the diagnosis and treatment of cancer.

Perioperative radiotherapy on local-advanced gastric cancer--From the perspective of failure pattern

Distant metastasis, peritoneal recurrence and locoregional recurrence are the three major patterns of gastric cancer (GC) recurrence after surgery and the causes of patients'death. Among them, distant organ metastasis or peritoneal recurrence after surgery is more common and occurs earlier, while locoregional failure alone occurs later with a relatively lower incidence. Several studies have confirmed that preoperative radiotherapy can shrink tumors and increase R0 resection rates, and postoperative radiotherapy helps reduce local recurrence. However, whether perioperative radiotherapy can further improve patient survival is still controversial.. We believe that this is partly due to the characteristics of recurrence and metastasis. As a local treatment, radiotherapy is complement to the inadequacy of surgery. Thus, we believe that perioperative radiotherapy is not recommended for patients with standard R0 surgery and adequate lymph node dissection, but rather requires accurate prediction of their recurrence and metastasis patterns based on accurate clinical and pathological staging, and thus screening of those who may benefit from radiotherapy.

Fucoidan/chitosan layered PLGA nanoparticles with melatonin loading for inducing intestinal absorption and addressing triple-negative breast cancer progression

Melatonin and fucoidan are naturally active compounds that have been reported to have therapeutic benefits for patients receiving cancer treatment. However, both compounds face significant challenges, including physical, chemical, and biological metabolisms in the gastrointestinal tract, which limit their ability to achieve therapeutic concentrations at the tumor site. Furthermore, the effectiveness of melatonin and fucoidan as adjuvants in vivo is influenced by the route of administration through the digestive system and their accumulation at the endpoint of the tumor. In this study, we developed an oral administration of nanoparticle, MNPs@C@F, that consisted of PLGA nanoparticles modified with chitosan, to promote intestinal microfold cell transcytosis for the delivery of melatonin and fucoidan into tumors. The experimental results indicated that melatonin and fucoidan in the tumors could regulate the tumor microenvironment by decreasing P-gp, Twist, HIF-1α, and anti-inflammatory immune cell expression, and increasing cytotoxic T cell populations following doxorubicin treatment. This resulted in an increase in chemo-drug sensitivity, inhibition of distant organ metastasis, and promotion of immunogenic cell death. This study demonstrates a favorable co-delivery system of melatonin and fucoidan to directly reduce drug resistance and metastasis in TNBC.