Pattern Of Invasion Research Articles

Prognostic Role of Tumor Budding and Worst Pattern of Invasion in Lymph Node Metastasis and Disease-Free Survival in Oral Squamous Cell Cancer Patients: Result from Central India's Regional Cancer Centre.

To study the role of pattern of invasion, tumor budding and other clinicopathological parameters in determining the risk of nodal metastases and disease-free survival in oral squamous cell cancer patients. The data of 90 patients with oral squamous cell carcinoma who underwent surgery as their primary modality of treatment were retrospectively analysed. Predictive significance of clinicopathological parameters was assessed with Univariate analysis with Fisher exact test and unpaired t-test. The factors which were significant on Univariate analysis were then analysed with multivariate analysis using logistic regression model to find independent predictors. P value < 0.05 was considered significant. Disease free survival analysis was performed using Kaplan-Meier method and comparison done using the log-rank test for each group. The age of the patients ranged from 22yrs to 72 years with male predominance (81.1%). The most common site of involvement was buccal mucosa. Significant factors predicting nodal metastases on univariate analysis were site (p = 0.031), grade (p = 0.012), T stage (p = < 0.001), Depth of invasion (p = < 0.001), perineural invasion (p = < 0.001), lymphovascular emboli (p = 0.018), tumor budding (p = < 0.001), pattern of invasion (p = < 0.001) and stroma (p = 0.037). On multivariate analysis tumor budding (p = 0.016), depth of invasion (p = 0.016) and perineural invasion (p = 0.044) were predictive of nodal metastasis. A statistically significant difference in 3year disease free survival was seen in infiltrative pattern of invasion and tumor budding which showed a p-value of 0.0372 and 0.0489 respectively. Based on the findings of the present study and review of previous articles tumor budding, worst pattern of invasion, host lymphocyte response should also be included in routine histopathology reporting of OSCC.

Spatio-temporal brain invasion pattern of Streptococcus pneumoniae and dynamic changes in the cellular environment in bacteremia-derived meningitis

Streptococcus pneumoniae (the pneumococcus) is the major cause of bacterial meningitis globally, and pneumococcal meningitis is associated with increased risk of long-term neurological sequelae. These include several sensorimotor functions that are controlled by specific brain regions which, during bacterial meningitis, are damaged by a neuroinflammatory response and the deleterious action of bacterial toxins in the brain. However, little is known about the invasion pattern of the pneumococcus into the brain. Using a bacteremia-derived meningitis mouse model, we combined 3D whole brain imaging with brain microdissection to show that all brain regions were equally affected during disease progression, with the presence of pneumococci closely associated to the microvasculature. In the hippocampus, the invasion provoked microglial activation, while the neurogenic niche showed increased proliferation and migration of neuroblasts. Our results indicate that, even before the outbreak of symptoms, the bacterial load throughout the brain is high and causes neuroinflammation and cell death, a pathological scenario which ultimately leads to a failing regeneration of new neurons.

Risk stratification of submandibular salivary gland involvement in oral squamous cell carcinoma based on histopathological parameters: A 15-year retrospective study.

Squamous cell carcinoma (SCC) represents about 90% of all oral malignancies. The study aimed to assess the involvement of the submandibular salivary gland (SMG) in oral SCC (OSCC) patients and the need for SMG excision. Demographics, clinical information and staging of the 210 patients undergoing surgery for OSCC were obtained from the department records. The histopathological slides were retrospectively reviewed. The nodal status was also verified with the histopathology reports. Frequency distribution, Chi-square association, ordinal logistic regression analysis and Kaplan-Meier analysis were performed. SMG was excised in 171 patients. Five patients had SMG involvement. Buccal mucosa (BM) and gingivobuccal sulcus had a greater risk of level IB metastases (P < 0.01). Pattern 3 and pattern 4 of invasion had a higher risk of level IB metastases (P = 0.04). Depth of invasion (DOI) >4 mm was associated with level IB lymph node (LN) involvement (P = 0.0001). DOI >4 mm to 8 mm had 3.7 times the risk and a DOI >8 mm to 12 mm had 5 times the risk of level IB metastases. Pattern of invasion (POI), tumour budding and DOI >4 mm were significant prognosticators for patient survival. Histologically, patients may be categorised as 'high risk': those with an increased risk of level IB LN involvement and 'low risk': those at low risk for level IB involvement with the help of POI, tumour budding and DOI as risk factors. In low-risk patients, SMG may be spared and the level IB LNs are dissected. High-risk patients may be chosen as candidates for SMG transfer or excision based on the extent of LN involvement.

Grasslands are more vulnerable to plant invasions than forests in south-central Nepal

Understanding the patterns of plant invasions across vegetation types and identifying the underlying drivers for such patterns is essential to prioritize sites for the effective management of invasive species. We sampled three forest types (Shorea robusta, Dalbergia sissoo, and Tropical deciduous riverine forest) and two grasslands in south-central Nepal to evaluate the richness of naturalized and invasive alien plant species (IAPS). Species richness of naturalized species and the IAPS among vegetation types within each physiographic region was compared using analysis of variance and t-test, and the ordination was used to analyze species-environment relations. Of the total 327 species of vascular plants recorded, 14 % were naturalized, and over a third of the naturalized species were invasive. Grasslands had the highest richness of naturalized species and the IAPS. In contrast, S. robusta forest had the lowest naturalized and IAPS richness. Naturalized species richness increased with native species richness. Ordination revealed that a high number of IAPS were associated with areas exposed to frequent fire and livestock grazing and close to human settlements. The results suggest that the grasslands closer to the human settlements and exposed to frequent disturbance are vulnerable to the establishment of IAPS. Early detection and control of IAPS in such frequently disturbed grasslands would prevent their spread into the surrounding landscapes.

Breast Hemangiomas: Imaging Features With Histopathology Correlation.

Breast hemangiomas are rare benign vascular lesions. In a previously performed review of approximately 10,000 breast surgical pathology results, roughly 0.15% (15/~10 000) were hemangiomas. Hemangiomas are more frequent in women and have a documented age distribution of 1.5 to 82 years. They are most often subcutaneous or subdermal and anterior to the anterior mammary fascia but may rarely be seen in the pectoralis muscles or chest wall. On imaging, breast hemangiomas typically present as oval or round masses, often measuring less than 2.5 cm, with circumscribed or mostly circumscribed, focally microlobulated margins, equal or high density on mammography, and variable echogenicity on US. Calcifications, including phleboliths, can be seen. Color Doppler US often shows hypovascularity or avascularity. MRI appearance can vary, although hemangiomas are generally T2 hyperintense and T1 hypointense with variable enhancement. Pathologic findings vary by subtype, which include perilobular, capillary, cavernous, and venous hemangiomas. If core biopsy pathology results are benign, without atypia, and concordant with imaging and clinical findings, surgical excision is not routinely indicated. Because of histopathologic overlap with well-differentiated or low-grade angiosarcomas, surgical excision may be necessary for definitive diagnosis. Findings that are more common with angiosarcomas include size greater than 2 cm, hypervascularity on Doppler US, irregular shape, and invasive growth pattern.

Evaluation of the significance of tumor stromal patterns and peri-tumoral inflammation in head and neck squamous cell carcinoma with special reference to the Yamamoto-Kohama classification.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with 878,348 new cases. Cancer-associated fibroblasts (CAFs) are the predominant cell type in tumor stroma and are important promoters of tumor progression. The aim of the study was to evaluate the pattern of desmoplastic stromal reaction and peri-tumoral inflammatory infiltrate with the histological grade and clinical data. A total of 60 cases of HNSCC were included in the study. The hematoxylin and eosin (H and E)-stained sections from all cases were examined by two experienced pathologists for the grade, nature of stomal reaction (SR), peri-tumoral inflammatory infiltration, Yamamoto-Kohama classification grade, worst pattern of invasion (WPOI), depth of invasion (DOI), and other histopathological parameters. Correlation analysis was conducted using the Chi-square test. P- value less than 0.05 was considered statistically significant. Immature SR was not observed in any of the well-differentiated squamous cell carcinoma (SCC) cases. However, one (3.7%) case of moderately differentiated SCC and two (28.6%) cases of poorly differentiated SCC showed signs of immature SR. In the case of the higher grades of the YK classification, specifically grades 4C and 4D, a more profound depth of tumor cell invasion, equal to or exceeding 10 mm, was evident in six (66.67%) and two (28.57%) cases, respectively. Additionally, among the seven (11.7%) cases classified as poorly differentiated carcinoma, three (42.85%) displayed a WPOI score of 5. SR and the tumor invasive pattern in HNSCC are related to prognosis and may indicate tumor aggressiveness.

Molecular diversity in isocitrate dehydrogenase-wild-type glioblastoma.

In the dynamic landscape of glioblastoma, the 2021 World Health Organization Classification of Central Nervous System tumours endeavoured to establish biological homogeneity, yet isocitrate dehydrogenase-wild-type (IDH-wt) glioblastoma persists as a tapestry of clinical and molecular diversity. Intertumoural heterogeneity in IDH-wt glioblastoma presents a formidable challenge in treatment strategies. Recent strides in genetics and molecular biology have enhanced diagnostic precision, revealing distinct subtypes and invasive patterns that influence survival in patients with IDH-wt glioblastoma. Genetic and molecular biomarkers, such as the overexpression of neurofibromin 1, phosphatase and tensin homolog and/or cyclin-dependent kinase inhibitor 2A, along with specific immune cell abundance and neurotransmitters, correlate with favourable outcomes. Conversely, increased expression of epidermal growth factor receptor tyrosine kinase, platelet-derived growth factor receptor alpha and/or vascular endothelial growth factor receptor, coupled with the prevalence of glioma stem cells, tumour-associated myeloid cells, regulatory T cells and exhausted effector cells, signifies an unfavourable prognosis. The methylation status of O6-methylguanine-DNA methyltransferase and the influence of microenvironmental factors and neurotransmitters further shape treatment responses. Understanding intertumoural heterogeneity is complemented by insights into intratumoural dynamics and cellular interactions within the tumour microenvironment. Glioma stem cells and immune cell composition significantly impact progression and outcomes, emphasizing the need for personalized therapies targeting pro-tumoural signalling pathways and resistance mechanisms. A successful glioblastoma management demands biomarker identification, combination therapies and a nuanced approach considering intratumoural variability. These advancements herald a transformative era in glioblastoma comprehension and treatment.

The distribution of hrHPV genotypes among cervical cancer cases diagnosed across Ghana: a cross-sectional study

BackgroundThe burden of cervical cancer in Ghana is high due to a lack of a national screening and vaccination program. Geographical variations in high-risk Human Papilloma Virus incidence and type should be considered for vaccine improvement and screening in LMICs.MethodsA descriptive, multi-center cross-sectional study with purposive sampling of cases with cervical cancer diagnosed from January 2012 through to December 2018 was employed relying on archived Formalin Fixed Paraffin Embedded (FFPE) tissues from four (4) Teaching Hospitals. Cervical cancers were assessed for histopathological features following WHO guidelines. In addition, the novel Tumour Budding and Nest Size Grade (TBNS) for SCC, SILVA pattern of invasion for EAC and Tumour Infiltrating Lymphocytes (TILs) were assessed. High Risk HPV testing was performed using an isothermal, multiplex nucleic acid amplification method from ATILA biosystem (Mountain View California, USA). The FFPE blocks were tested for 15 hrHPV genotypes. Results were analyzed using SPSS v.26.0, with descriptive statistics and cross-tabulation and chi-square tests done with significance established at p < 0.05.ResultsA total of 297 cases were identified for the study with ages ranging from 20 to 95 years. The peak age group for cervical cancer was 46 to 55 years. For those tested, hrHPV positivity rate was 85.4% [EAC (84.6%) and SCC (85.6%)]. The top five hrHPV serotypes for both histological cancers were 59 (40.0%), 35 (32.0%), 18 (30.0%), 16 (15.0%), and 33 (10.0%) respectively. Approximately, 58.2% of infections were multiple. Single hrHPV infections were mostly caused by hrHPV 59 (28.9%), and 16 (26.3%). TBNS grade for SCC, SILVA pattern of invasion for EAC and TILs did not show any statistically significant relationship with hrHPV.ConclusionWe affirm reported differences in hrHPV types associated with cervical cancer in Ghana with hrHPV types such as 59, 35, and 33 forming a significant proportion of hrHPV types associated with cervical cancer. This difference in hrHPV types should guide vaccine improvement and triaging of hrHPV positives. Though multiple infections are more common, some hrHPV types such as hrHPV 16 and 59 are responsible for most single infections associated with cervical cancer. Simple haematoxylin and eosin-based morphological assessments can improve the prognostication of patients with cervical cancer.

Abstract 6273: GGCT expression is a useful marker for the diagnosis of follicular thyroid carcinoma

Abstract Background: Follicular thyroid carcinoma (FTC) and follicular adenoma (FA) have similar histological findings. FTC is distinct from FA based on the presence of capsular or vascular invasion in the tissues, but it is difficult to confirm the diagnosis in some cases. In this study, we aimed to establish useful molecular maker for differential diagnosis between FTC and FA. Methods: This study included FTC (n = 32), FA (n = 64), and follicular tumors of uncertain malignant potential (FT-UMP, n = 5). Invasive front tissue and tumor center tissue from 3 cases of FTC were collected using a laser microdissection system; RNA was extracted, followed by microarray analysis to examine molecules that were commonly highly expressed in the invasive front. Subsequently, immunohistochemical staining of gamma-glutamyl cyclotransferase (GGCT) was performed. For assessment of GGCT expression, the intensity of the nuclear staining was stratified using a four-tiered scale (0 to 3) and percentage of positive cells (0-100%) in the hotspot. Multiplying intensity score and percent of positive cells, an expression score ranging from 0 to 300 was calculated. The Ki-67 labeling index was examined in 20 cases of FTC, 25 cases of FA, and 4 cases of FT-UMP from the same cohort. We counted at least 2,000 tumor cells in the hot spot for the assessment of Ki-67 labeling index. Results: Microarray analysis revealed GGCT exhibited high expression levels at the invasive front of FTC. In immunohistochemical assessment, GGCT expression scores were significantly higher in FTC than in FA (118.5 ± 51.4 vs. 57.3 ± 34.7, p &amp;lt; 0.0001). The median Ki-67 labeling index were 3.9% (range 0.2 - 16.1) for FTC and 2.4% (range 0.3 - 7.0) for FA. FTC showed a higher Ki-67 index than FA (Wilcoxon rank sum test, p = 0.0444). With GGCT expression score, applying a cutoff value of 101.1, the distinction between FTC and FA resulted in a sensitivity of 68.8% and a specificity of 87.5% (AUC: 0.832). With Ki-67 labeling index, applying a cutoff value of 4.0%, the distinction between FTC and FA resulted in a sensitivity of 50.0% and a specificity of 80.0% (AUC: 0.677). The GGCT expression score was positively related with the Ki-67 labeling index in the FTC cases. (Spearman's ρ = 0.5293, p = 0.0164). There were no significant associations between GGCT expression scores and clinicopathological parameters, including age, gender, tumor diameter, pT stage, pN stage, pattern of capsular invasion, number of foci of vascular invasion, and the presence of distant metastasis. Conclusions: GGCT is a potential marker for differentiating FTC from FA. The GGCT expression of FTC may contribute to estimating the invasive activity and proliferative activity. Citation Format: Toshiyuki Mitsuhashi, Sachiko Ogasawara, Masamichi Nakayama, Reiichiro Kondo, Jun Akiba, Kenta Murotani, Takeharu Ono, Fumihiko Sato, Hirohito Umeno, Hirohisa Yano. GGCT expression is a useful marker for the diagnosis of follicular thyroid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6273.

Abstract 1505: Unraveling diepafitaxis: Investigating ECM stiffness and microarchitecture in tumor spheroid migration

Abstract Background: Metastasis, accounting for up to 90% of cancer-related deaths, remains one of the least understood aspects of cancer progression. Recent research has shifted focus from solely biological hallmarks to the physical characteristics of cancer, such as the stiffness and microarchitecture of the extracellular matrix (ECM), which play pivotal roles in metastatic advancement. We previously introduced the concept of 'diepafitaxis' to describe a unique mechanism driving the interface-mediated tropism of tumor spheroids at matrix-surface boundaries. This phenomenon suggests that cancer cells preferentially migrate along a 2D 'interfacial' track formed by heterogeneous 3D ECM structures, facilitating invasion and dispersion. However, the exact mechanisms by which interfacial components, stiffness, and structural attributes influence cell movement remain debated. To investigate this, we have developed a microfluidic chip with a precisely controlled stiffness of the hydrogel matrix-matrix interface (MMI), aiming to shed light on specific diepafitatic behaviors. Method: We developed a polydimethylsiloxane (PDMS)-based microfluidic chip using a traditional photolithographic process. This chip features three channels, with the center channel designed to precisely control various MMI stiffness combinations: stiff vs soft (t-o), stiff vs stiff (t-t) and soft vs soft (o-o). MDA-MB-231 breast cancer spheroids (BCS), representing an in vitro tumor model, were embedded in the top gel. We observed the dynamic behavior of these cancer spheroids over a 24-h period using differential interference contrast (DIC) microscopy. Result: The study revealed that BCS exhibited more pronounced dispersion in a soft homogeneous ECM compared to a stiff ECM in 3D environments. Interestingly, when BCS were near an MMI, a stiffer MMI (t-t) significantly enhanced BCS invasiveness and single-cell migration, more so than t-o, and notably more than o-o. We previously described this phenomenon as '2.5D migration,' where cells migrate in a ventral 2D manner within a sandwiched 3D gel structure. This diepafitatic behavior was further analyzed for its response to gravitational effects and the influence of chemotaxis, induced by introducing VEGF on one side of the microfluidic channel. Conclusion: Conclusively, our study demonstrates that the stiffness and structure of the ECM, particularly at MMI, significantly influence the invasive behavior and migration patterns of BCS, underscoring the critical role of mechanical microenvironments in cancer metastasis. Citation Format: Hsiang-Pei Chen, Ya-Chu Tsai, Ting-Yuan Tu. Unraveling diepafitaxis: Investigating ECM stiffness and microarchitecture in tumor spheroid migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1505.

Invasion Patterns and Long-Term Clinical Outcomes of Diffuse Tenosynovial Giant Cell Tumor of the Ankle Joint.

The invasion patterns and long-term outcomes ofdiffuse tenosynovial giant cell tumor (D-TSGCT) of the ankle joint remain unclear. Seven patients who visited our department between 2011 and 2023 and were diagnosed withD-TSGCT of the ankle joint by contrast-enhanced MRI and a pathological diagnosis were included. The invasion patterns of ankle D-TSGCT on MRI were investigated. The recurrence rate and clinical symptoms were examined in five patients followed up for more than seven years after total resection. In seven patients (1 male/6 females, mean age 37.0±16.6 years, range 15-57 years) with D-TSGCT of the ankle joint, contrast-enhanced MRI at the initial presentation showed invasion within the ankle joint, extending along the tendon sheath, within the talocalcaneal joint, and in the tarsal sinus in 100% of cases, around the deltoid ligament in 86%, within the plantar surface in 43%, invasion of the interosseous membrane in 57%, around the Achilles tendon in 29%, and scalloping on the talocrural joint in 43%. The mean time from mass awareness to the first visit was 51.9±80.0 months (range 1-240 months). Gross total resection, defined as the removal of all tumors as gauged by MRI, was initially performed on 6/7 patients. One patient underwent partial resection of only the anterior part of the tumor. Of the six cases in which gross total resection was performed, 5 had long-term follow-up of more than seven years post-operatively, and one case is still only one year post-operatively. The long-term results offive patients followed for more than seven years after total resection were as follows: a mean follow-up period of 125 months (range 89-171 months), a 100% recurrence rate, a mean time to recurrence of 27.5±19.2 months (range 7-60 months), and a 16% reoperation rate. In the last follow-up, osteoarthritic changes were observed radiographically in 2/5 patients (40%), both of whom had scalloping of the talocrural joint on MRI at the time of the initial diagnosis. Four of the five patients (80%) had no clinical symptoms in the last follow-up. Ankle D-TSGCT presents with a strong local infiltrative pattern inside and outside the ankle joint along the tendon sheath, radical resection may be difficult, and the recurrence rate may be higher than previously reported. On the other hand, there are many cases that remain free of clinical symptoms in the long term after recurrence, and surgical indications for ankle D-TSGCT need to consider function preservation as well as recurrence rates.

Prognostic Value of P63 Expression in Muscle-Invasive Bladder Cancer and Association with Molecular Subtypes-Preliminary Report.

There is an ongoing need for biomarkers that could reliably predict the outcome of BC and that could guide the management of this disease. In this setting, we aimed to explore the prognostic value of the transcription factor P63 in patients with muscle-invasive bladder cancer (MIBC) having undergone radical cystectomy. The correlation between P63 expression and clinicopathological features (tumor stage, nodes involvement, patterns of muscularis propria invasion, papillary architecture, anaplasia, concomitant carcinoma in situ, lymphovascular invasion, perineural invasion, necrosis) and molecular subtyping (basal and luminal type tumors) was tested in 65 radical cystectomy specimens and matched with cancer-specific survival (CSS) and overall survival (OS). P63-negative tumors displayed significantly higher rates of pattern 2 of muscularis propria invasion (50% vs. 14%, p = 0.002) and variant histology (45% vs. 19%, p = 0.022) compared to P63-positive ones. According to the combined expression of CK5/6 and CK20 (Algorithm #1), P63-positive and P63-negative tumors were mostly basal-like and double-negative, respectively (p = 0.004). Using Algorithm #2, based on the combined expression of CK5/6 and GATA3, the vast majority of tumors were luminal overall and in each group (p = 0.003). There was no significant difference in CSS and OS between P63-positive and P63-negative tumors, but the former featured a trend towards longer OS. Though associated with pathological features harboring negative prognostic potential, P63 status as such failed to predict CSS and OS. That said, it may contribute to better molecular subtyping of MIBC.

Prognostic value of micrometric substaging in pT1 bladder cancer patients treated with en-bloc transurethral resection.

We aimed to assess the oncological impact of micrometric extent of invasion in patients with pT1 bladder cancer (BCa) who underwent en-bloc resection for bladder tumour (ERBT). We retrospectively analysed the records and specimens of 106 pT1 high-grade BCa patients who underwent ERBT. The extent of invasion, such as depth from basal membrane, number of invasive foci, maximum width of invasive focus, muscularis mucosae invasion and infiltration pattern (pattern A: solid sheet-like, nodular or nested growth, pattern B: trabecular, small cluster or single-cell pattern) were evaluated by a single genitourinary pathologist. The end-points were recurrence-free (RFS) and progression-free survival (PFS). Within a median follow-up of 23 months, overall, 36 patients experienced recurrence and 13 patients experienced disease progression. The 2-year PFS differed significantly depending on depth from basal membrane (< 1.3 mm: 94.8% versus ≧ 1.3 mm: 65.2%, P = 0.005), maximum width of invasive focus (< 4 mm: 91.7% versus ≧ 4 mm: 62.3%, P < 0.001), muscularis mucosae (MM) invasion (above MM = 96.1% versus into or beyond MM = 64.8%, P = 0.002) and infiltration pattern (pattern A: 100% versus pattern B: 83.3%, P = 0.037). In a multivariable analysis, MM invasion [hazard ratio (HR) = 4.54, 95% confidence interval (CI) = 1.25-16.5] and maximum width of invasive focus ≧ 4 mm (HR = 4.79, 95% CI = 1.25-16.5) were independent prognostic factors of progression. En-bloc resection facilitates the evaluation of pathologic variables that might be useful in predicting disease recurrence and progression. In particular, not only the MM invasion but also the maximum width of invasion focus, reflecting the invasive volume, appear to be reliable prognosticators for disease progression.

The demise of enemy release associated with the invasion of specialist folivores on an invasive tree

There is a long history of humans either intentionally or accidentally moving plant species to areas outside of their native ranges. In novel environments, populations of many of these plant species exhibit explosive population growth and spread, in part due to the absence of coevolved enemies such as herbivorous insects. However, over time such enemies can ‘catch up' with their host and re‐establish host–herbivore relationships. Though this phenomenon has been documented in several systems, little evidence exists on how this re‐assembly of enemies results in increased levels of herbivory. In this study we focus on the case of black locust Robinia pseudoacacia, a sparsely populated tree species when growing on undisturbed sites in its limited native range in the eastern USA but a highly invasive species, especially in disturbed environments, in most temperate world regions. We recorded folivore damage on invasive populations in five continents, including both native and invaded portions of North America. Here, we investigated 1) how total foliage damage and damage caused by different groups of folivores differs among regions; 2) how seasonal development of folivore damage differs among regions; 3) how folivory varies with distance from the native range within North America; and 4) how the number of recorded specialist folivores correlates with the amount of folivory. We observed strong differences among regions in the amount and type of folivore damage, with the native range experiencing the highest damage, especially that caused by the native chrysomelid beetle Odontota dorsalis, which is limited to the native and invaded North American range of R. pseudoacacia. Among world regions, total folivory is negatively associated with the distance from the native range and positively associated with the number of established R. pseudoacacia specialist folivore species, supporting the hypothesis that global patterns of herbivore invasions are associated with diminished enemy release.

Time since first naturalization is key to explaining non‐native plant invasions on islands

AbstractAimInvestigating the extent of insular invasions by non‐native species (i.e., the number of islands they occupy) is central to island conservation. However, interrelationships among plant life history traits, naturalization histories, and island characteristics in determining island occupancy by non‐native plant species are poorly understood. We investigated whether island occupancy by different non‐native plant species declines in relation to their year of first naturalization and whether periods of first naturalization differ among growth forms, dispersal modes, and biogeographic origins. Then, we asked if non‐native plants that naturalized more recently occur more frequently on islands that are large, less isolated, and close to urban areas. We contrasted trends across growth forms, dispersal modes, and biogeographic origins.Location264 offshore islands in northern Aotearoa New Zealand.TaxaVascular plant species.MethodsWe combined field surveys and published data for 767 non‐native plant species on the islands. We categorized each species according to its growth form (n = 3), dispersal mode (n = 4) and biogeographic origin (n = 5) and identified its year of first naturalization in Aotearoa New Zealand. We tested our hypotheses using ANCOVA and generalized linear models (GLMs).ResultsThere were similar declines in island occupancy in relation to the year of first naturalization in Aotearoa New Zealand across all trait and biogeographic origin categories. First naturalization times of herbaceous species, those with unspecialized dispersal modes, and those originating from Eurasia and the Mediterranean basin were disproportionately earlier than other categories. Non‐native plants with more recent first naturalization occur more frequently on large islands close to urban areas, but not on less isolated ones. Relationships with island characteristics did not differ among trait and biogeographic origin categories.Main ConclusionsOverall, time of first naturalization was more important than trait and biogeographic origin categories in explaining non‐native plant invasion patterns on islands. Since there were similar relationships between island occupancy and the year of first naturalization in Aotearoa New Zealand for all categories, management bodies should focus on non‐native plant species of trait and biogeographic origin categories that have naturalized recently (e.g., woody species from other regions within Oceania), and on large islands close to urban areas. Introduction and naturalization histories provide essential context for interpreting the role of plant traits and biogeographic origin in understanding plant invasions on islands.

Abstract B030: Synergistic antitumor effects of cold atmospheric plasma and temozolomide in glioblastoma: multimodal approaches integrating in-vitro, in vivo, and in silico investigations for novel and enhanced therapeutic advancements

Abstract Glioblastoma multiforme (GBM) is a common and aggressive brain cancer with a median survival rate of 12 to 18 months after diagnosis. Despite standard treatments, including surgery, radiotherapy, and Temozolomide (TMZ), GBM remains highly resistant to therapy due to its infiltrative pattern of invasion, rapid growth, and propensity to relapse [1]. While overall mortality rates remain high, there is a crucial need for a better understanding of the molecular mechanisms and gene mutations involved in GBM and the development of more effective and adaptive therapeutic approaches. Modulating reactive oxygen species (ROS) levels has been suggested as a therapeutic strategy to selectively target the destruction of cancer cells. To address this, we propose a combination therapy utilizing multi-operational plasma devices, including using cold atmospheric plasma (CAP) jet and plasma discharge tube (PDT) in conjunction with TMZ for GBM treatment. CAP functions by elevating reactive oxygen and nitrogen species (RONS) levels and specifically targeting tumor spread. We investigated various plasma devices and their characteristics using optical emission spectroscopy (OES) and measured the electromagnetic potential and emissions of the PDT. The OES of PDT displayed a similar spectrum as the CAP jet, indicating the presence of ROS. In this study, we performed transcriptomic analysis of glioblastoma cells using high throughput deep RNA-Seq with next-generation sequencing (NGS) to quantify genome-wide gene expression changes. Additionally, we examined signaling pathways and predicted structural changes in consequential proteins caused by gene spectrum up or down-regulation. Our results demonstrate that the combination treatment of CAP and TMZ downregulated vital genes involved in MAPK, P53, DNA repair, and cell cycle pathways. The combination of CAP &amp; TMZ showed a significant antitumor effect, inducing apoptosis and damaging essential proteins in GBM cells. In vitro and microscopic studies verified these results, showing nuclear and cell membrane disruption in cancer cells post-plasma treatment. Our findings demonstrate that the combination of CAP/PDT and TMZ effectively sensitizes GBM cells to TMZ, leading to apoptosis. We have previously shown a non-invasive application of CAP jet on the skull of tumor-bearing mice causing ~78% tumor inhibition [2]. Our current study highlights the potential of PDT for non-invasive treatment in vitro, offering a modality for intracranial delivery in in-vivo models. In conclusion, we propose CAP/PDT and TMZ combination therapy as novel non-invasive treatments for GBM in murine models. This approach offers a promising avenue for addressing the dire need for more effective treatments with minimal impact on normal cells. Further investigations and validation in clinical settings are warranted to significantly improve GBM management and patient outcomes.

Significance of Spread Through Air Spaces and Vascular Invasion in Early-stage Adenocarcinoma Survival: A Comprehensive Clinicopathologic Study of 427 Patients for Precision Management.

Spread through air spaces (STAS) is a novel invasive pattern of lung cancer associated with poor prognosis in non-small cell cancer (NSCLC). We aimed to investigate the incidence of STAS in a surgical series of adenocarcinomas (ADCs) resected in our thoracic surgery unit and to identify the association of STAS with other clinicopathological characteristics. We retrospectively enrolled patients with stage cT1a-cT2b who underwent resection between 2016 and 2022. For each case, a comprehensive pathologic report was accessible which included histotype, mitoses, pleural invasion, fibrosis, tumor infiltrating lymphocytes, necrosis, inflammation, vascular and perineural invasion, as well as STAS. PD-L1 expression was also investigated. A total of 427 patients with ADCs underwent surgery. Regarding overall survival (OS), no significant difference was observed between the STAS positive (STAS+) and STAS negative (STAS-) groups ( P =0.44). However, vascular invasion (VI) was associated with a poorer survival probability ( P =0.018). STAS+/VI+ patients had tendentially worse survival compared with STAS+/VI- ( P =0.089). ADCs with pathologic evidence of immune system (IS) activation (TILs>10% and PD-L1≥1) demonstrated significantly increased OS compared with ADCs with no IS and VI. In terms of recurrence rate, no statistical differences were found between the STAS+ and STAS- samples ( P =0.2). VI was also linked to a significantly elevated risk of recurrence ( P =0.0048). Our study suggests that in resected early-stage ADCs, STAS+ does not seem to influence recurrence or mortality. VI was instead an adverse pathologic prognostic factor for both survival and recurrence, whereas IS seemed to be protective.

Immiscible invasion of granular suspension by high-viscosity liquid

We investigate the morphology and dynamics of the pattern of immiscible invasion by injecting a high-viscosity liquid into a granular suspension consisting of movable solid grains in a low-viscosity liquid. Laboratory experiments conducted in a Hele–Shaw cell shed light on how the frictional forces of the grains and the viscous forces of the liquids affect the instability of the liquid–liquid interface and the formation of viscous fingers. The frictional force increases with an increase in either the volume fraction or the size of the grains, leading to higher resistance to the invading pattern. Upon changing the grain shape from spherical to irregular, both the frictional force and the rotational energy of the grains increase, resulting in more numerous but narrower fingers. Increasing either the injection rate or the viscosity of the injected liquid increases the viscous pressure within the fingers, promoting the splitting of the pattern. Although the defending liquid always has a lower viscosity than the invading liquid in this study, the former's viscous force becomes non-negligible as the viscosity ratio of the invading liquid to the defending liquid decreases to near unity, which destabilizes the fluid–fluid interface and causes a transition to an asymmetric pattern.

An Experimental Investigation on the Energy Signature Associated With Multiphase Flow in Porous Media Displacement Regimes

AbstractThis study investigates the energy signature associated with multiphase flow in porous media displacement regimes. We proposed that net efficiency, as the conversion of external work applied to surface energy generated, provides new insights into the transition of flow regimes. The combined effects of wettability and flow rates on immiscible fluid‐fluid displacement is experimentally investigated using high‐resolution imaging in microfluidic flow cells, which allows for tracking the evolution of interfacial area under applied external work. Our study focuses on the morphology of invasion patterns and the efficiency of conversion of external work to surface energy. The results show that the morphology of invasion patterns under unfavorable displacement condition is sharper than that under favorable displacement condition with larger ratios of length and width for fingers. The efficiency of conversion of external work to surface energy decreases with the increase of contact angles and reduces greatly with the increase of Capillary numbers. With favorable displacement conditions, the efficiency of conversion is consistently higher than that for unfavorable displacement. The trends of external work and surface energy serve as a signature of the transition between different flow regimes, which exhibits alteration especially at low Capillary numbers. The findings highlight the importance of wettability and flow rates in determining the efficiency of fluid‐fluid displacement in porous media. Understanding the energy signature associated with multiphase flow can have implications for various geoscience applications, such as oil/gas recovery, groundwater remediation, and underground energy storage.

Superior orbital fissure narrowing and tumor-associated pain in spheno-orbital meningiomas.

Spheno-orbital meningiomas (SOMs) represent a distinct subtype of meningioma characterized by their unique multi-compartmental invasion pattern. Previous studies have investigated correlations between SOMs and visual manifestations. However, our comprehension of pain associated with SOMs remains limited. This study aims to provide insight into the pathophysiology underlying SOM-related pain through measurements of tumor volume and superior orbital fissure (SOF) narrowing. This retrospective study included patients who underwent surgical resection of a SOM between 2000 and 2022. Preoperative CT and/or MRI scans were analyzed, and the tumor volume of each segment was measured. Bony 3D reconstructions were used to measure the area of the SOF, and SOF narrowing was calculated. The study cohort included 66 patients diagnosed with SOMs, among which 25.8% (n = 17) presented with pain. Postoperatively, 14/17 (82.4%) of patients reported pain improvement. There was no significant correlation between the total volume or the volume of tumor within each compartment and the presence of pain on presentation (p > 0.05). The median SOF narrowing was significantly different between patients presenting with and without tumor-associated pain with median of 11 mm2 (IQR 2.8-22.3) and 2 mm2 (IQR 0-6), respectively (p = 0.005). Using logistic regression, a significant correlation between the degree of SOF narrowing and the presence of SOM-associated pain on presentation was identified, with an aOR of 1.2 (95% CI 1.12-1.3, p = 0.02). While the exact cause of tumor-associated pain remains unclear, SOF narrowing seems to play a role in pain among SOM patients. Based on the radiological characteristics, SOF neurovascular decompression is recommended in SOM patients.