Primary Tumor Research Articles

Osteopontin is a therapeutic target that drives breast cancer recurrence

Recurrent breast cancers often develop resistance to standard-of-care therapies. Identifying targetable factors contributing to cancer recurrence remains the rate-limiting step in improving long-term outcomes. In this study, we identify tumor cell-derived osteopontin as an autocrine and paracrine driver of tumor recurrence. Osteopontin promotes tumor cell proliferation, recruits macrophages, and synergizes with IL-4 to further polarize them into a pro-tumorigenic state. Macrophage depletion and osteopontin inhibition decrease recurrent tumor growth. Furthermore, targeting osteopontin in primary tumor-bearing female mice prevents metastasis, permits T cell infiltration and activation, and improves anti-PD-1 immunotherapy response. Clinically, osteopontin expression is higher in recurrent metastatic tumors versus female patient-matched primary breast tumors. Osteopontin positively correlates with macrophage infiltration, increases with higher tumor grade, and its elevated pathway activity is associated with poor prognosis and long-term recurrence. Our findings suggest clinical implications and an alternative therapeutic strategy based on osteopontin’s multiaxial role in breast cancer progression and recurrence.

Structural and dynamical insights revealed the anti-glioblastoma potential of withanolides from Withania coagulans against vascular endothelial growth factor receptor (VEGFR).

Glioblastoma (GBM), well known as grade 4 tumors due to its progressive malignant features such as vascular proliferation and necrosis, is the most aggressive form of primary brain tumor found in adults. Mutations and amplifications in the vascular endothelial growth factor receptor (VEGFR) contribute to almost 25% of GBM tumors. And thus, VEGFR has been declared the primary target in glioblastoma therapeutic strategies. However, many studies have been previously reported that include GBM as global therapeutics challenge, but they lack the molecular level insights that could help in understanding the biological function of a therapeutically important protein playing a major role in the disease and design the best strategies to develop the potential drugs. Therefore, to the best of our knowledge, the present study is the first time of kind, which involves multi-in silico approaches to predict the inhibition potential of withanolides from Withania coagulan against VEGFR. The study is actually based on determining the mode of action of five isolates: withanolide J, withaperuvin, 27-hydroxywithanolide I, coagule E, and coagule E, along with their respective binding energies. Molecular docking simulations revealed primarily four ligands, withanolide J (- 7.33kJ/mol), 27-withanolide (- 7.01kJ/mol), ajugine, withaperuvin (- 6.89kJ/mol), and ajugine E (- 6.39kJ/mol), to have significant binding potencies against the protein. Ligand binding was found to enhance the confirmational stability of the protein revealed through RMSD analysis, and RMSF assessment revealed the protein residues especially from 900-1000 surrounding the binding of the protein. Structural and dynamics of the protein via dynamics cross-correlation movement (DCCM) and principal component analysis (PCA) in both the unbound form and complexed with most potent ligand, withanolide J, reveal the ligand binding affecting the entire conformational integrity of the protein stabilized by hydrogen bonds and electrostatic attractions. Free energy of binding estimations by means of molecular mechanics Poisson-Boltzmann surface area (MMPBSA) method further revealed the withanolide J to have maximum binding potency of the all ligands. Withanolide J in final was also found to have suitable molecular characterizations to cross the blood-brain barrier (BBB +) and reasonable human intestinal absorption ability determined by ADMET profiling via admetSAR tools.

Drug-Free Mesoporous Silica Nanoparticles Enable Suppression of Cancer Metastasis and Confer Survival Advantages to Mice with Tumor Xenografts.

Despite advancements in nanomedicine for drug delivery, many drug-loaded nanoparticles reduce tumor sizes but often fail to prevent metastasis. Mesoporous silica nanoparticles (MSNs) have attracted attention as promising nanocarriers. Here, we demonstrated that MSN-PEG/TA 25, with proper surface modifications, exhibited unique antimetastatic properties. In vivo studies showed that overall tumor metastasis decreased in 4T1 xenografts mice treated with MSN-PEG/TA 25 with a notable reduction in lung tumor metastasis. In vitro assays, including wound-healing, Boyden chamber, tube-formation, and real-time cell analyses, showed that MSN-PEG/TA 25 could modulate cell migration of 4T1 breast cancer cells and interrupt tube formation by human umbilical vein endothelial cells (HUVECs), key factors in suppressing cancer metastasis. The synergistic effect of MSN-PEG/TA 25 combined with liposomal-encapsulated doxorubicin (Lipo-Dox) significantly boosted mouse survival rates, outperforming Lipo-Dox monotherapy. We attributed the improved survival to the antimetastatic capabilities of MSN-PEG/TA 25. Moreover, Dox-loaded MSN-PEG/TA 25 suppressed primary tumors while retaining the antimetastatic effect, thereby enhancing therapeutic outcomes and overall survival. Western blot and qPCR analyses revealed that MSN-PEG/TA 25 interfered with the phosphorylation of ERK, FAK, and paxillin, thus impacting focal adhesion turnover and inhibiting cell motility. Our findings suggest that drug-free MSN-PEG/TA 25 is highly efficient for cancer treatment via suppressing metastatic activity and angiogenesis.

Safety and risk analysis of total resection surgery for thoracic and lumbar spinal tumors: a decadal analysis of 103 cases

Study designRetrospective cohort study.PurposeTo explore the complications and risk factors for total resection (TR) of primary thoracic and lumbar spinal tumors over the past decade at our institution.MethodsPatients meeting inclusion criteria (primary spinal tumors, thoracic or lumbar location, TR at our center) were included. Demographic characteristics, surgical data, perioperative complications and management results were reviewed. Patients were stratified by tumor site, the number of excised segments, and recurrence status to elucidate distinctive characteristics.ResultsThe cohort comprised 103 patients, with a mean age of 35.8 years. On average, 1.83 vertebral segments were resected per patient. Perioperative complications were substantial, totaling 166 events, with 71 classified as major and 95 as minor, yielding an average of 1.61 complications per patient. No perioperative deaths occurred, but 79 patients (76.7%) experienced at least one complication. Multiple vertebral sections correlated with a higher complication rate (P = 0.031), and lumbar surgeries exhibited elevated risks of large vascular injury (P = 0.001), neurological deterioration, and cerebrospinal fluid leakage compared to thoracic cases. Conversely, thoracic spinal procedures showed a higher rate of pleural effusion (P = 0.004). Binary logistics stepwise regression identified multi-segmental resection as the independent risk factor for major perioperative complications.ConclusionsTR of primary spinal tumors is associated with a high perioperative complication rate, although most events have a favorable prognosis. Complication characteristics vary based on the surgical site, number of excised segments, and surgical history. A nuanced preoperative evaluating approach considering patient age, surgical segments, and extent of resection is crucial.

Comparative Analysis of Concurrent Chemoradiotherapy Versus Chemotherapy Alone as First-Line Palliative Treatments for Advanced Esophageal Squamous Cell Carcinoma

Background: In advanced-stage esophageal squamous cell carcinoma (ESCC), treatment of both the primary tumor and metastatic sites is imperatively required. Consequently, an optimal treatment modality should effectively control both aspects. Therefore, the benefits of concurrent chemoradiotherapy (CCRT) in cases of advanced-stage ESCC should be evaluated. Methods: This retrospective study compared the efficacy and safety of CCRT versus chemotherapy alone for advanced-stage ESCC patients from January 2012 to December 2023 at a university hospital in Southern Thailand. Survival was assessed using the Kaplan–Meier approach, with comparisons being made by the log-rank test. A p-value of <0.05 indicated statistical significance. Results: From a total of 196 patients with stage IV ESCC, 117 (59.7%) received CCRT, while 79 (40.3%) received chemotherapy alone. The median overall survival (OS) time was 9.04 months for CCRT and 5.79 months for chemotherapy (hazard ratio, HR: 0.58 [0.43–0.78]). CCRT significantly improved OS time in stage IVA patients (HR: 0.52 [0.29–0.93]), but not in stage IVB patients (HR: 0.76 [0.51–1.11]). The median progression-free survival (PFS) time was 6.04 months for CCRT and 3.50 months for chemotherapy (HR 0.48 [0.35–0.65]). The objective response rates (ORRs) were 43.6% and 22.8%, respectively (p = 0.003). Hematological toxicities were more common with CCRT, along with mild cases of treatment-associated pneumonitis and dermatitis. Conclusions: Although palliative chemotherapy is the standard treatment for advanced-stage ESCC, CCRT provides significant benefits for patients with stage IVA ESCC, improving OS, PFS, and ORRs, despite there being a higher incidence of adverse events. Thus, CCRT should be considered for patients with stage IVA ESCC with a good performance status.

Low SMARCD3 expression is associated with poor prognosis in patients with prostate cancer.

SWI/SNF complexes represent a family of multi-subunit chromatin remodelers that are affected by alterations in >20% of human tumors. While mutations of SWI/SNF genes are relatively uncommon in prostate cancer (PCa), the literature suggests that deregulation of various subunits plays a role in prostate tumorigenesis. To assess SWI/SNF functions in a clinical context, we studied the mutually exclusive, paralogue accessory subunits SMARCD1, SMARCD2, and SMARCD3 that are included in every known complex and are sought to confer specificity. Performing immunohistochemistry (IHC), the protein levels of the SMARCD family members were measured using a tissue microarray (TMA) comprising malignant samples and matching healthy tissue of non-metastatic PCa patients (n = 168). Moreover, IHC was performed in castration-resistant tumors (n = 9) and lymph node metastases (n = 22). To assess their potential role as molecular biomarkers, SMARCD1 and SMARCD3 protein levels were correlated with clinical parameters such as T stage, Gleason score, biochemical recurrence, and progression-free survival. SMARCD1 protein levels in non-metastatic primary tumors, lymph node metastases, and castration-resistant samples were significantly higher than in benign tissues. Likewise, SMARCD3 protein expression was elevated in tumor tissue and especially lymph node metastases compared to benign samples. While SMARCD1 levels in primary tumors did not exhibit significant associations with any of the tested clinical parameters, SMARCD3 exhibited an inverse correlation with pre-operative PSA levels. Moreover, low SMARCD3 expression was associated with progression to metastasis. In congruence with previous literature, our results implicate that both SMARCD1 and SMARCD3 may exhibit relevant functions in the context of prostate tumorigenesis. Moreover, our approach suggests a potential role of SMARCD3 as a novel prognostic marker in clinically non-metastatic PCa.

Morbidity and Mortality Following Surgery for Pancreatic Cancer in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.

Measuring postoperative outcomes after complex cancer operations such as pancreatectomy is vital to improve cancer surgery in low- and middle-income countries (LMICs); however, such data is often limited. This study aimed to review existing research and obtain baseline estimates for postoperative mortality and morbidity after pancreatic cancer surgery in LMICs. PubMed, Embase, Web of Science Core Collection, and Global Index Medicus were systematically searched for original articles published between January 2005 and May 2022. LMICs based studies reporting postoperative mortality, morbidity, and/or length of stay of patients with primary pancreatic tumors undergoing pancreaticoduodenectomy and/or distal pancreatectomy were included. Of 18 344 unique titles and abstracts retrieved, 114 studies met the inclusion criteria. Of these, 51 "good" quality studies comprising 7528 patients were included in the meta-analyses. Pooled estimates for pancreatic fistula were 16.6% (95% CI 14.0-19.7, p < 0.001); 16.0% (95% CI 11.1-22.5, p < 0.001) for Clavien-Dindo grade 3 and 4 complications; 13.4% (95% CI 9.8-17.9, p < 0.001) for wound infection; and 4.4% (95% CI 3.3-5.7, p < 0.001) for postoperative mortality. This is the first systematic review and meta-analysis examining surgical complications after pancreatic surgery in LMICs. We highlight a lack of data and the need to further evaluate surgical outcomes in LMICs.

CIC/ATXN1-rearranged tumors in the central nervous system are mainly represented by sarcomas: A comprehensive clinicopathological and epigenetic series.

CIC fusions have been described in two different central nervous system (CNS) tumor entities. On one hand, fusions of CIC or ATXN1 genes belonging to the same complex of transcriptional repressors, were reported in the CIC-rearranged, sarcoma (SARC-CIC). The diagnosis of this tumor type, which was recently added to the World Health Organization (WHO) Classification of CNS tumors, is difficult mainly because the data concerning its histopathology (as compared to its soft tissue counterpart), immunoprofile, and clinical as well as radiological characteristics are scarce in the literature. On the other hand, a recent study, based on DNA-methylation profiling, has identified a novel high-grade neuroepithelial tumor characterized by recurrent CIC fusions (HGNET-CIC). The aim of this multicentric study was to characterize a cohort of 15 primary CNS tumors harboring a CIC or ATXN1 fusion in terms of clinical, radiological, histopathological, immunophenotypical, and epigenetic characteristics. According to the integrated diagnoses, 14/15 tumors corresponded to SARC-CIC, and only one to HGNET-CIC. The tumors showed similar clinical (mainly pediatric), radiological (mostly supratentorial, cystic, and contrast enhancing), immunophenotypical (common expression of glioneuronal markers), and genetic (similar spectrum of fusions) profiles but their histopathological appearance was clearly distinct. Moreover, we found a novel fusion transcript (CIC::EWSR1) in a SARC-CIC. Most DNA methylation profiles using the Heidelberg Brain Tumor Classifier (v12.8) annotated the samples to the methylation class "SARC-CIC" (9/14 tumors with available data). By using uniform manifold approximation and projection analysis, four other samples were classified as SARC-CIC and another clustered within the methylation class of HGNET-CIC. Our findings confirm that CNS CIC-fused tumors do not represent a single molecular tumor entity. Further analyses are needed to characterize HGNET-CIC in more detail. These results may help to refine the essential diagnostic criteria for SARC-CIC and their terminology (with a suggested consensual name of sarcoma, CIC/ATXN1-complex rearranged).

Correlation of Pre-Operative Myo-Inositol/Creatine Ratio with Histopathological Grade of Glioma

Background: Introduction: Gliomas are the most frequent primary intracerebral tumors in adults &amp; constitute 35–50% of all intracranial neoplasms. In determining a treatment plan, tumor grade is a key consideration for minimizing the risk of unnecessary morbidity and mortality. Objective: To evaluate Correlation of pre-operative Myo-inositol/Creatine ratio with histopathological grade of glioma. Materials and method: This was a cross sectional experimental study. Total 33 patients consistent with selection criteria were enrolled in this study. Myo-inositol/ Creatine ratio was obtained from MRS. Histopathological grade of glioma was obtained from biopsy (hematoxylin and eosin stain or HE stain) report. The obtained results were then grouped categorically. Result: Out of 33 patients, 22 were male and 11 were female. According to histopathology, 14 gliomas were confirmed as high grade and 19 gliomas were confirmed as low grade. Spearman Rank Correlation Test showed a moderate negative association between Myo-inositol/Creatine ratio with glioma grading with coefficient value of r = -0.611 with a statistically significant p-value (p&lt;0.001). We were able to differentiate between low grade (II) and high grade (III + IV) gliomas using the Myoinositol/ Creatine ratio. The levels of MI/Cr were higher (e”0.48) in patients with lowgrade glioma, and lower (&lt;0.48) in patients high grade glioma Conclusion: This study has shown a significant correlation between pre-operative Myo-inositol/Creatine ratio with histopathological grade of glioma. It may help neurosurgeons in taking clinical decisions about patient management and counselling. Bang. J Neurosurgery 2024; 13(2): 57-63

Olaparib: A Chemosensitizer for the Treatment of Glioblastoma.

Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor. The current treatment for GBM includes adjuvant chemotherapy with temozolomide (TMZ), radiation therapy, and surgical tumor excision. There is still an issue because 50% of patients with GBM who get TMZ have low survival rates due to TMZ resistance. The activation of several DNA repair mechanisms, such as Base Excision Repair (BER), DNA Mismatch Repair (MMR), and O-6- Methylguanine-DNA Methyltransferase (MGMT), is the main mechanism via which TMZ resistance develops. The zinc-finger DNA-binding enzyme poly (ADP-ribose) polymerase-1 (PARP1), which is activated by binding to DNA breaks, affects the activation of the MGMT, BER, and MMR pathway deficiency, which results in TMZ resistance in GBM. PARP inhibitors have been studied recently as sensitizing medications to increase TMZ potency. The first member of the PARP inhibitor family to be identified was Olaparib. It inhibits PARP1 and PARP2, which causes apoptosis in cancer cells and DNA strand break. Olaparib is currently investigated as a radio- and/or chemo-sensitizer in addition to being used as a single agent because it may increase the cytotoxic effects of other treatments. This review addresses Olaparib and its significance in treating TMZ resistance in GBM.

Honokiol inhibits human osteosarcoma MG63 cell migration by upregulating FTO and Smad6 to promote autophagy

BackgroundOsteosarcoma (OS) is a common primary malignant tumor of bone, most commonly seen in children and adolescents, which has a low survival rate and is a serious threat to patients' lives. Honokiol (HKL) is the main active components of Magnolia officinalis, which have significant anti-tumor properties. The aim of this study was to observe the autophagic and migratory effects of HKL on MG63 cells and to investigate whether the mechanism of action was related to FTO and Smad6. MethodsFirstly, we cultured MG63 cells in vitro and intervened with different concentrations of HKL to detect cell activity by CCK8, apoptosis by flow cytometry, cell migration ability by scratch assay, cell invasion ability by transwell assay and MMP2, P62, LC3 I/II, FTO and Smad6 protein expression by Western blot. ResultsHKL inhibited MG63 cells activity and that this effect was dose and time dependent. Although there was no significant effect on apoptosis and invasive ability, HKL could act through effects such as promoting cell autophagy and inhibiting migration. HKL increased the protein expression levels of FTO, Smad6, MMP2, LC3 I/II and P62, and this effect was reduced after silencing of Smad6. ConclusionsHKL induced autophagy and inhibited cell migration in MG63 cells by increasing the expression of FTP and Smad6. It can be seen that HKL may be a promising drug for the treatment of OS.

Factors Influencing the Outcome of Patients with Surgically Managed Intracranial Meningioma

Background: Intracranial Meningiomas are the most common primary brain tumor in adult which are predominantly non-malignant. Surgical intervention is the goldstandard treatment option for intracranial meningiomas but the surgical outcomes are influenced by various epidemiological risk factors. Understanding these factors is essential for a precise decision-making process, application of effective therapeutic intervention and prognostication. Aims: This study aimed to identify the possible predictive factors influencing surgical outcome in patients with intracranial meningioma. Materials and Methods: This Prospective Observational Study included 34 patients of intracranial Meningioma who had surgery in the Department of Neurosurgery, Chittagong Medical College Hospital between February 2022 to August 2023. Outcome measures were the Glasgow Outcome Scale (GOS) and Karnofsky Performance Status (KPS) score at the immediate postoperative period, “0” postoperative day, at the time of discharge, 1 month, 3 months, and 6 months post-surgery. GOS score 1-3 was considered as poor outcome. Results: The mean age of the patients was 46.8±12.6 years and 70.6% were female. Most of the patients were in either ASA class I (35.3%) or Class II (55.9%), and the median KPS score was 80% before surgery. Twenty-eight (82.4%) patients survived at least six months following surgery and the 6-months mortality rate was 17.6%. Twenty-seven (79.4%) patients had a good outcome and 7 (20.6%) patients had a poor outcome. Preoperative KPS score (p=0.024), tumor location (p=0.019), and tumor volume (p=0.003) were found to have a significant association with outcome in univariate analysis. However, none of these factors retained a significant association in multivariate analysis. Conclusions: In conclusion, specific influencing factors for postoperative poor outcomes revealed in univariate analysis in the present study were low preoperative KPS score, skull base meningioma, and large-size tumor Bang. J Neurosurgery 2024; 13(2): 121-129

Expression of TRPS1 in Metastatic Tumors of the Skin: An Immunohistochemical Study of 72 Cases

TRPS1 (Tricho-rhino-phalangeal syndrome 1) is a GATA transcriptional activator gene encoding for a protein used as a sensitive immunohistochemical marker of breast carcinomas. In dermatopathology, TRPS1 is used as a marker of mammary and extramammary Paget’s disease and is also expressed by a variety of primary cutaneous tumors, mostly of adnexal origin. So far, very limited data exist on the expression of TRPS1 in metastatic skin tumors. We studied the immunohistochemical expression of TRPS1 in 72 cutaneous metastatic tumors from the breast (n: 19) and other origins (n: 53) in order to assess its diagnostic usefulness. The intensity of TRPS1 immunostaining was expressed as a histoscore: the product of the percentage of positive cells (scored semi-quantitatively 0–4) and the staining intensity (scored 0–3). In normal skin, nuclear TRPS1 expression was predominantly observed in cells of adnexal structures (pilosebaceous follicles and sweat glands). Eighteen (18/19, 94.7%) metastatic breast carcinomas showed diffuse and strong TRPS1 positivity (histoscore 12). Lower reactivity was found in some other metastases, including from the lung (11/22), the female genital tract (3/4), and the kidney (2/4), whereas most (20/22) metastases from the digestive system and peritoneum, along with a case of metastatic prostate carcinoma, were negative. These results suggest that a high histoscore for TRPS1 is in favor of the mammary origin of metastatic cutaneous carcinoma. Although TRPS1 is not absolutely specific or sensitive to a particular primary, we consider that it can be added to a panel of other markers when investigating the origin of a cutaneous metastasis, namely when this is the first manifestation of the neoplastic disease.

Protocol summary of a randomized phase III study: comparing systemic therapy with and without debulking surgery (primary tumour resection) for clinical stage IVA (cT1-2bN0-1M1a) non-small cell lung cancer with radiologically undetermined pleural dissemination JCOG2103 (DEBULK-LUNG).

In patients with non-small cell lung cancer (NSCLC) who present with radiologically undetermined malignant pleural dissemination or incidental surgical diagnosis of the same, surgery is generally not the preferred option; systemic therapy is favoured. However, there is no consensus on incorporating primary site resection into the treatment plan. Retrospective analyses hint at potential benefits of combining systemic therapy with primary site resection, but prospective studies have yet to confirm these findings. Consequently, we have planned a multicentre, open-label, randomized controlled phase III trial to assess the efficacy of adding primary site resection to standard systemic therapy for stage IVA (cT1-2bN0-1M1a) NSCLC patients with radiologically undetermined pleural dissemination. The primary endpoint is overall survival. We aim to enroll 170 patients from 71 institutions over 5 years. This trial is registered at the Japan Registry of Clinical Trials (jRCT) under study number jRCTs031220666.

Enhanced Tumor Immunotherapy by Triple Amplification Effects of Nanomedicine on the STING Signaling Pathway in Dendritic Cells.

Insufficient activation of stimulator of interferon genes (STING) signaling pathway in tumor-associated dendritic cells limits the efficiency of tumor immunotherapy. Herein, the "three-in-one" IAHA-LaP/siPTPN6 NPs containing lanthanum ions (La3+), cGAMP, and PTPN6 siRNA are developed for triple amplification of the STING pathway. In vitro results demonstrate that La3+ significantly promotes cGAMP-mediated activation of the STING pathway by enhancing the phosphorylation of STING, TBK1, IRF3, and NF-κB p65. Moreover, the IAHA-LaP/siPTPN6 NPs further significantly enhance the phosphorylation of STING and NF-κB p65 and augment K63-linked ubiquitination of STING protein via siPTPN6-mediated downregulation of SHP-1 protein. Furthermore, NPs improve the secretion of IFNβ (2.4-fold), IL-6 (1.5-fold), and TNF-α (1.4-fold), thereby promoting DCs maturation compared to the mixture of La3+ and cGAMP. In vivo results show that the IAHA-LaP/siPTPN6 NPs remarkably inhibit primary tumor growth by increasing the percentage of mature DCs in tumor-draining lymph nodes, polarizing M2/M1 phenotype in TME, and promoting the infiltration of CD8+T cells into tumors. Moreover, these NPs dramatically prevent the growth of distal tumor by inducing systemic anti-tumor immunity and generating a long-term anti-tumor memory for protection against tumor recurrence in mice bearing bilateral B16F10. These IAHA-LaP/siPTPN6 NPs may offer a promising platform for robust anti-tumor immune responses.

Nomogram predicts cervical lymph node metastasis of pathological subtypes of papillary thyroid carcinoma.

Pathological subtypes of papillary thyroid carcinoma (PTC) are important factors in thyroid cancer. Some rare subtypes exhibit extensive lymph node metastasis. These pathological subtypes should receive more attention in clinical practice. Patients with different pathological subtypes of PTC were selected from the SEER database. Logistic regression, random forest, and bootstrap aggregating (bagging) methods were employed to screen for risk factors associated with cervical lymph node metastasis in the training cohort. A nomogram was established based on the model with the largest area under the curve (AUC) and evaluated using calibration curves. Decision curve analysis (DCA) was used to evaluate the clinical benefit to patients. The nomogram was validated in depth by 200 iterations of tenfold cross-validation. A total of 7,882 patients were included in the analysis, with 5,516 patients in the training group and 2,366 patients in the testing group. The logistic regression model achieved the highest AUC of 0.7396. Sex, age, race, extension (extrathyroidal extension), pathological type, and primary tumour size were identified as independent risk factors for cervical lymph node metastasis (p < 0.05). The calibration curve indicated that the model was well calibrated. DCA indicated that the nomogram model had good clinical practicability. In clinical practice, it is important to consider the pathological subtypes of PTC. The established nomogram can serve as a predictive tool for assessing cervical lymph node metastasis.

Photoimmunotherapy using indocyanine green-loaded Codium fragile polysaccharide and chitosan nanoparticles suppresses tumor growth and metastasis

Metastasis and recurrence are the main challenges in cancer treatment. Among various therapeutic approaches, immunotherapy holds promise for preventing metastasis and recurrence. In this study, we evaluated the efficacy of treating primary cancer and blocking metastasis and recurrence with photo-immunotherapeutic nanoparticles, which were synthesized using two types of charged polysaccharides. Codium fragile polysaccharide (CFP), which exhibits immune-stimulating properties and carries a negative charge, was combined with positively charged chitosan to synthesize nanoparticles. Additionally, indocyanine green (ICG), a photosensitizer, was loaded inside these particles and was referred to as chitosan-CFP-ICG (CC-ICG). Murine colon cancer cells (CT-26) internalized CC-ICG, and subsequent 808-nanometer laser irradiation promoted apoptotic/necrotic cell death. Moreover, intratumoral injection of CC-ICG, with 808-nanometer laser irradiation eliminated CT-26 tumors in mice. Rechallenged lung metastases of CT-26 cancer were inhibited by dendritic cell activation-mediated cytotoxic T lymphocyte stimulation in mice cured by CC-ICG. These results demonstrated that CC-ICG is a natural tumor therapeutic with the potential to treat primary tumors and suppress metastasis and recurrence.

Laparoscopic-Assisted, Percutaneous Cryoablation: A Novel Technique for the Treatment of Abdominal Wall Soft Tissue Tumors.

Percutaneous cryoablation is a first-line therapeutic option for primary neoplasms and metastatic lesions of the musculoskeletal system. Treatment of abdominal wall tumors is challenging as surgical resection can be highly morbid and necessitate complex reconstructive surgery; the efficacy of cryoablation for abdominal wall tumors may be limited by inadequate posterior margins owing to the proximity of intra-abdominal organs. With laparoscopy and insufflation, peritoneal structures can be safely mobilized away from the abdominal wall, allowing for adequate deep margin freeze and visualization of the ice ball. We present two patients with abdominal wall soft tissue tumors treated with a novel approach of laparoscopic-assisted, percutaneous ultrasound-guided cryoablation. Patient 1 is a 65-year-old female with metastatic extraskeletal myxoid chondrosarcoma, stable on systemic therapy, who presented with a new soft tissue metastasis to the abdominal wall. Resection would have necessitated a highly morbid complex abdominal wall reconstruction with mesh. Patient 2 is a 35-year-old female with a large abdominal wall desmoid tumor, diagnosed after miscarriage. Resection was relatively contraindicated owing to the morbidity of a complex abdominal wall reconstruction and concerns regarding potential future pregnancies after surgery. Both patients underwent procedures in the outpatient setting after discussion at multidisciplinary sarcoma tumor board. Laparoscopic enterolysis was performed to mobilize the bowel away from the abdominal wall, to allow direct visualization of the peritoneal aspect of the tumor, and to confirm adequacy of the posterior margin freeze of the lesion. Laparoscopic transversus abdominus preperitoneal (TAPP) blocks with local anesthetic were performed for postoperative pain control. Interventional radiology performed an ultrasound-guided cryoablation consisting of two freeze and thaw cycles. Both patients recovered well without complications and were without radiographic evidence of persistent or recurrent disease at 12 and 18 months postoperatively, respectively. We report a novel approach of laparoscopic-assisted cryoablation for the treatment of abdominal wall soft tissue tumors. This allowed for successful minimally invasive local control of these large tumors that would have otherwise required highly morbid resections with complex abdominal wall reconstruction and mesh repair.

Distant Metastases of Breast Cancer Resemble Primary Tumors in Cancer Cell Composition but Differ in Immune Cell Phenotypes.

Breast cancer is the most commonly diagnosed cancer in women, with distant metastasis being the main cause of breast cancer-related deaths. Elucidating the changes in the tumor and immune ecosystems that are associated with metastatic disease is essential to improve understanding and ultimately treatment of metastasis. Here, we developed an in-depth, spatially resolved single-cell atlas of the phenotypic diversity of tumor and immune cells in primary human breast tumors and matched distant metastases, using imaging mass cytometry to analyze a total of 75 unique antibody targets. While the same tumor cell phenotypes were typically present in primary tumors and metastatic sites, suggesting a strong founder effect of the primary tumor, their proportions varied between matched samples. Notably, the metastatic site did not influence tumor phenotype composition, except for the brain. Metastatic sites exhibited a lower number of immune cells overall, but had a higher proportion of myeloid cells as well as exhausted and cytotoxic T cells. Myeloid cells showed distinct tissue-specific compositional signatures and increased presence of potentially matrix remodeling phenotypes in metastatic sites. This analysis of tumor and immune cell phenotypic composition of metastatic breast cancer highlights the heterogeneity of the disease within patients and across distant metastatic sites, indicating myeloid cells as the predominant immune modulators that could potentially be targeted at these sites.

Integrative prognostic modeling for stage III lung adenosquamous carcinoma post-tumor resection: machine learning insights and web-based implementation

IntroductionThe prognostic landscape of stage III Lung Adenosquamous Carcinoma (ASC) following primary tumor resection remains underexplored. A thoughtfully developed prognostic model has the potential to guide clinicians in patient counseling and the formulation of effective therapeutic strategies.MethodsUtilizing data from the Surveillance, Epidemiology, and End Results database spanning 2000 to 2018, this study identified independent prognostic factors influencing Overall Survival (OS) in ASC using Boruta analysis. Employing Gradient Boosting, Random Forest, and Neural Network algorithms, predictive models were constructed. Model performance was assessed through key metrics, including Area Under the Receiver Operating Characteristic Curve (AUC), calibration plot, Brier score, and Decision Curve Analysis (DCA).ResultsAmong 241 eligible patients, seven clinical parameters—age, sex, primary tumor size, N stage, primary tumor site, chemotherapy, and systemic therapy—were identified as significant predictors of OS. Advanced age, male gender, larger tumor size, absence of chemotherapy, and lack of systemic therapy were associated with poorer survival. The Random Forest model outperformed others, achieving 3- and 5-year AUCs of 0.80/0.79 (training) and 0.74/0.65 (validation). It also demonstrated better calibration, lower Brier scores (training: 0.189/0.171; validation: 0.207/0.199), and more favorable DCA. SHAP values enhanced model interpretability by highlighting the impact of each parameter on survival predictions. To facilitate clinical application, the Random Forest model was deployed on a web-based server for accessible prognostic assessments.ConclusionsThis study presents a robust machine learning model and a web-based tool that assist healthcare practitioners in personalized clinical decision-making and treatment optimization for ASC patients following primary tumor resection.