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World Journal of Surgical Oncology Jun 2024The alteration of the immune microenvironment in the axillary metastatic lymph nodes of luminal A breast cancer patients is still unclear.
BACKGROUND
The alteration of the immune microenvironment in the axillary metastatic lymph nodes of luminal A breast cancer patients is still unclear.
METHODS
Postsurgical tissues from the enrolled luminal A BCs were divided into five categories: primary BC lesion at stage N0 (PL1), primary BC lesion at stage N1 (PL2), negative axillary lymph node at stage N0 BC (LN1), negative axillary lymph node at stage N1 BC (LN2), and positive axillary lymph node at stage N1 BC (LN3). The frequencies of positive immune markers (CD4, CD8, PD1, PD-L1, T-cell immunoglobulin and mucin domain 3 (TIM3), and forkhead box protein 3 (Foxp3)) in the above tissues were quantified by AKOYA Opal Polaris 7 Color Manual IHC Detection Kit.
RESULTS
A total of 50 female patients with luminal A BC were enrolled in this study. Among these patients, 23 had stage N1 disease, and 27 had stage N0 disease. Compared with that in the PL2 subgroup, the frequency of PD-1-positive cells was significantly greater in the PL1 subgroup, whether at the stromal or intratumoral level (P value < 0.05). Both the frequency of CD8 + T cells in LN1 and that in LN2 were significantly greater than that in LN3 (P value < 0.05). The frequency of TIM3 + T cells in LN1 was significantly greater than that in PL1 (P value < 0.05). The frequency of CD8 + TIM3 + T cells was significantly greater in both the LN2 and LN3 groups than in the PL2 group (P value < 0.05). The frequency of CD4 + Foxp3 + T cells was significantly greater in LN1 than in PL1 (P value < 0.05), which was the same for both LN3 and PL2 (P value < 0.05).
CONCLUSION
Increased frequencies of CD8 + PD1+, CD8 + TIM3 + and CD4 + Foxp3 + T cells might inhibit the immune microenvironment of axillary metastatic lymph nodes in luminal A breast cancer patients and subsequently promote lymph node metastasis.
Topics: Humans; Female; Breast Neoplasms; Tumor Microenvironment; Middle Aged; Lymphatic Metastasis; Axilla; Lymph Nodes; Adult; Prognosis; Biomarkers, Tumor; Aged; Follow-Up Studies; Neoplasm Staging; Lymphocytes, Tumor-Infiltrating; B7-H1 Antigen; Programmed Cell Death 1 Receptor
PubMed: 38937736
DOI: 10.1186/s12957-024-03454-x -
Journal of the National Cancer Institute Jun 2024Neoadjuvant therapy (NAT) leads to a clinical complete response (cCR) in a significant proportion of patients with locally advanced rectal cancer (LARC), allowing for...
BACKGROUND
Neoadjuvant therapy (NAT) leads to a clinical complete response (cCR) in a significant proportion of patients with locally advanced rectal cancer (LARC), allowing for possible nonoperative management. The presence of mucin on MRI after NAT leads to uncertainty about residual disease and appropriateness of a watch-and-wait (WW) strategy in patients with no evidence of disease on proctoscopy (endoscopic cCR).
METHODS
MRI reports for LARC patients seen between July 2016 and January 2020 at Memorial Sloan Kettering Cancer Center were queried for presence of mucin in the tumor bed on MRI following NAT. Clinicodemographic, pathologic, and outcome data were compiled and analyzed.
RESULTS
Of 71 patients with mucin on post-treatment MRI, 20 had a cCR and 51 had abnormalities on endoscopy and/or physical exam. One patient with a cCR opted out of WW; thus, 19 patients (27%) entered WW and 52 patients (73%) were planned for surgery (Non-WW). Of the 19 WW patients, 15 (79%) have had no local regrowth with median follow-up of 50 months (range, 29-76 months), while 4 (21%) experienced regrowth between 9 and 29 months after neoadjuvant therapy. Of the 52 patients who were planned to have surgery (Non-WW), 49 underwent resection while 3 developed metastatic disease that precluded curative-intent surgery. Five (10%) of the 49 patients who underwent surgery, including the one with an endoscopic cCR, had a pathologic complete response.
CONCLUSIONS
The presence of mucin after NAT for LARC does not preclude WW management in otherwise appropriate candidates who achieve an endoscopic cCR.
PubMed: 38937278
DOI: 10.1093/jnci/djae152 -
Bulletin Du Cancer Jun 2024Benign tumors of the liver and biliary tract are rare entities, and some of them require surgical management to prevent their malignant transformation. Tumors from the... (Review)
Review
Benign tumors of the liver and biliary tract are rare entities, and some of them require surgical management to prevent their malignant transformation. Tumors from the biliary tract with malignant potential are treated either by hepatic resection, for mucinous cystic neoplasm and ciliated hepatic foregut cysts, or by biliary resections, for biliary papillary neoplasm and type I and IV choledochal cysts. The pathologies requiring prophylactic cholecystectomy are polyps larger than 10 mm, porcelain gallbladder and pancreaticobiliary maljunction. Finally, hepatocellular adenoma over 5cm, occurring in male patients, or exon 3 mutated beta-catenin, should lead to prophylactic resection by hepatic segmentectomy. This article describes these different pathologies and their management.
PubMed: 38937178
DOI: 10.1016/j.bulcan.2024.04.015 -
In Vivo (Athens, Greece) 2024Matrix metalloproteinase 13 (MMP13) has been reported to be involved in tumor development and progression, including of colorectal cancer (CRC). This study aimed at...
BACKGROUND/AIM
Matrix metalloproteinase 13 (MMP13) has been reported to be involved in tumor development and progression, including of colorectal cancer (CRC). This study aimed at evaluating whether the MMP13 rs2252070 gene polymorphism is associated with clinicopathological factors and its influence on long-term survival in Swedish patients with CRC.
PATIENTS AND METHODS
A total of 723 patients with CRC were genotyped using TaqMan single nucleotide polymorphism assays based on polymerase chain reaction.
RESULTS
Assessing clinicopathological factors, we demonstrated that having the G/G genotype for MMP13 rs2252070 was significantly associated with poor differentiation, higher serum level of carcinoembryonic antigen and higher lymph node status. Moreover, the presence of a G allele was significantly related to larger tumor size in rectal cancer but had a significantly protective role against mucinous cancer, perineural invasion and lymphovascular invasion. Kaplan-Meier analysis showed no difference between genotypes regarding cancer-specific survival.
CONCLUSION
Our findings highlight the potential of MMP13 rs2252070 polymorphism as a useful predictor of poor differentiation, serum level of carcinoembryonic antigen, lymph node status, tumor size, mucinous cancer, perineural invasion and lymphovascular invasion in patients with CRC.
Topics: Humans; Colorectal Neoplasms; Male; Female; Polymorphism, Single Nucleotide; Sweden; Matrix Metalloproteinase 13; Aged; Middle Aged; Genotype; Genetic Predisposition to Disease; Prognosis; Alleles; Kaplan-Meier Estimate; Aged, 80 and over; Adult; Carcinoembryonic Antigen; Neoplasm Staging; Biomarkers, Tumor; Genetic Association Studies
PubMed: 38936942
DOI: 10.21873/invivo.13628 -
In Vivo (Athens, Greece) 2024Distinguishing ovarian metastasis of usual-type endocervical adenocarcinoma (UEA) from primary ovarian tumors is often challenging because of several overlapping...
Ovarian Metastasis from Human Papillomavirus-associated Usual-type Endocervical Adenocarcinoma: Clinicopathological Characteristics for Distinguishing from Primary Ovarian Mucinous or Endometrioid Tumor.
BACKGROUND/AIM
Distinguishing ovarian metastasis of usual-type endocervical adenocarcinoma (UEA) from primary ovarian tumors is often challenging because of several overlapping features. This study aimed to investigate the clinicopathological characteristics and outcomes of patients with metastatic ovarian UEA.
PATIENTS AND METHODS
Clinicopathological information was collected from eight patients with metastatic ovarian UEA. Immunostaining was also performed.
RESULTS
Most patients presented with adnexal masses that were suspected to be primary ovarian tumors. All examined cases showed block p16 positivity in paired primary and metastatic tumors. Five patients who completed post-operative chemotherapy or concurrent chemoradiotherapy (CCRT) did not experience recurrence. In contrast, one patient who refused further treatment after the first CCRT cycle experienced ovarian and peritoneal metastases. One patient with isolated ovarian metastasis left untreated and developed peritoneal metastasis during follow-up.
CONCLUSION
Patients with UEA who received proper management for ovarian metastases showed favorable outcomes. Given that ovarian metastatic UEA can mimic primary ovarian borderline tumor or carcinoma of the mucinous or endometrioid type, pathologists should be aware of this unusual but distinctive morphology to avoid misdiagnosis and inappropriate treatment.
Topics: Humans; Female; Ovarian Neoplasms; Middle Aged; Uterine Cervical Neoplasms; Adult; Diagnosis, Differential; Carcinoma, Endometrioid; Adenocarcinoma, Mucinous; Papillomavirus Infections; Aged; Adenocarcinoma; Papillomaviridae; Neoplasm Metastasis; Human Papillomavirus Viruses
PubMed: 38936897
DOI: 10.21873/invivo.13654 -
International Journal of Pharmaceutics Jun 2024The complex structure of the eye poses challenges in delivering drugs effectively, which can be circumvented by employing nanotechnologies. The present study aimed to...
The complex structure of the eye poses challenges in delivering drugs effectively, which can be circumvented by employing nanotechnologies. The present study aimed to prepareacetazolamide-loadedleciplex (ACZ - LP) using a simple one-step fabrication approach followed byoptimization employing a 3 Full Factorial Design. The ACZ - LP demonstrated high entrapment efficiency (93.25 ± 2.32 %), average diameter was recorded around 171.03 ± 3.32 with monodisperse size distribution and zeta potential of 41.33 ± 2.10 mV. Invitro release and ex vivo permeation studies of prepared formulation demonstrated an initial burst release in 1 h followed by sustained release pattern as compared to plain acetazolamide solution. Moreover, an ex vivo corneal drug retention (27.05 ± 1.20 %) and in vitro mucoadhesive studies with different concentration of mucin indicated strong electrostatic bonding confirming the mucoadhesive characteristics of the formulation. Additionally, the histopathological studies ensured that the formulation was non-irritant and nontoxic while and HET-CAM ensured substantial tolerability of the formulation. The in vivo pharmacodynamic investigation carried out on a rabbit model demonstrated that treatment with ACZ - LP resulted in a significant and prolonged reduction in intraocular pressure as compared to plain acetazolamide solution, acetazolamide oral tablet, and Brinzox®. In summary, the ACZ - LP is anefficient and versatile drug delivery approach which demonstrates significant potential in controlling glaucoma.
PubMed: 38936444
DOI: 10.1016/j.ijpharm.2024.124391 -
Angewandte Chemie (International Ed. in... Jun 2024Pancreatic cancer is one of the deadliest cancers worldwide, mainly due to late diagnosis. Therefore, there is an urgent need for novel diagnostic approaches to identify...
Pancreatic cancer is one of the deadliest cancers worldwide, mainly due to late diagnosis. Therefore, there is an urgent need for novel diagnostic approaches to identify the disease as early as possible. We have developed a diagnostic assay for pancreatic cancer based on the detection of naturally occurring tumor associated autoantibodies against Mucin-1 (MUC1) using engineered glycopeptides on nanoparticle probes. We used a structure-guided approach to develop unnatural glycopeptides as model antigens for tumor-associated MUC1. We designed a collection of 13 glycopeptides to bind either SM3 or 5E5, two monoclonal antibodies with distinct epitopes known to recognize tumor associated MUC1. Glycopeptide binding to SM3 or 5E5 was confirmed by surface plasmon resonance and rationalized by molecular dynamics simulations. These model antigens were conjugated to gold nanoparticles and used in a dot-blot assay to detect autoantibodies in serum samples from pancreatic cancer patients and healthy volunteers. Nanoparticle probes with glycopeptides displaying the SM3 epitope did not have diagnostic potential. Instead, nanoparticle probes displaying glycopeptides with high affinity for 5E5 could discriminate between cancer patients and healthy controls. Remarkably, the best-discriminating probes show significantly better true and false positive rates than the current clinical biomarkers CA19-9 and carcinoembryonic antigen (CEA).
PubMed: 38935849
DOI: 10.1002/anie.202407131 -
Journal of Surgical Oncology Jun 2024The absolute requirement for a long-term favorable result with cytoreductive surgery for pseudomyxoma peritonei is a complete resection of all visible disease. A...
BACKGROUND
The absolute requirement for a long-term favorable result with cytoreductive surgery for pseudomyxoma peritonei is a complete resection of all visible disease. A combination of parietal peritonectomy procedures and visceral resections is required for this to occur. The cytoreductive surgery is supplemented by hyperthermic intraperitoneal chemotherapy.
METHODS
We searched our database and secured files for patients who required a total gastrectomy and a total colectomy to achieve a complete cytoreductive surgery. Survival of low-grade mucinous neoplasm (LAMN) and mucinous appendiceal adenocarcinoma (MACA) histologies were determined. Clinical and histologic variables were assessed for their impact on survival.
RESULTS
Thirteen of 450 patients (2.9%) with LAMN histology and 14 of 186 patients (7.5%) with MACA histology had these visceral resections. Median survival of these 27 patients was 10 years. LAMN and MACA patients showed the same survival. For LAMN histology, this requirement for extensive visceral resection markedly reduced survival (p < 0.0001). For MACA, there was no adverse impact on survival (p = 0.4359). Class 4 adverse events caused reduced survival (p = 0.0014).
CONCLUSIONS
A 10-year median survival accompanies total gastrectomy plus total colectomy for advanced pseudomyxoma peritonei. Systemic chemotherapy and class 4 adverse events reduced survival.
PubMed: 38935844
DOI: 10.1002/jso.27742 -
American Journal of Respiratory and... Jun 2024The role of IL-13 on the airway epithelium in severe asthma leading to airway remodeling remains poorly understood.
BACKGROUND
The role of IL-13 on the airway epithelium in severe asthma leading to airway remodeling remains poorly understood.
OBJECTIVE
To study IL-13 induced airway remodeling on goblet cells and cilia in the airway epithelium in severe asthma and the impact of an anti-IL4Rα antibody, dupilumab, .
METHODS
Quantitative CT (qCT) lungs and endobronchial biopsies and brushings were obtained in 51 participants (22 severe, 11 non-severe asthma and 18 healthy participants) in the Severe Asthma Research Program (SARPIII) and measured for mucin and cilia related proteins. Epithelial cells were differentiated in air-liquid interphase (ALI) with IL-13 +/-dupilumab and assessed for mucin, cilia, cilia beat frequency (CBF) and epithelial integrity (transepithelial electrical resistance, TEER).
RESULTS
Increased Muc5AC (Δ+263.2±92.7 lums/EpiArea) and decreased ciliated cells (Δ-0.07±0.03 Foxj1+cells/EpiArea) were observed in biopsies from severe asthma when compared to healthy (p<0.01 and p=0.047 respectively). RNAseq of epithelial cell brushes confirmed a increase with a decrease in a 5-gene cilia-related mean in severe asthma compared to healthy (all p<0.05). IL-13 (5 ng/mL) differentiated ALI cultures of healthy and asthmatic (severe and non-severe participants) increased Muc5AC, decreased cilia (α-acytl-tubulin) in healthy (Δ+6.5±1.5%, Δ-14.1±2.7%; all p<0.001 respectively) and asthma (Δ+4.4±2.5%, Δ-13.1±2.7%; p=0.084, p<0.001 respectively); decreased epithelial integrity (TEER) in healthy (-140.9±21.3 [ohms], p<0.001) while decreasing CBF in asthma (Δ-4.4±1.7 [Hz], p<0.01). When dupilumab was added to ALI with IL-13, there was no significant decrease in Mu5AC but there was restoration of cilia in healthy and asthma participants (absolute increase of 67.5% and 32.5% cilia, all p<0.05 respectively) while CBF increased (Δ+3.6±1.1 [Hz], p<0.001) and TEER decreased (only in asthma Δ-37.8±16.2 [ohms] p<0.05).
CONCLUSIONS
IL-13 drives features of airway remodeling in severe asthma which are partially reversed by inhibiting IL-4Rα receptor .
PubMed: 38935626
DOI: 10.1164/rccm.202307-1266OC -
PloS One 2024Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in...
Mucosal-delivered drugs have to pass through the mucus layer before absorption through the epithelial cell membrane. Although there has been increasing interest in polymeric mucins, a major structural component of mucus, potentially acting as important physiological regulators of mucosal drug absorption, there are no reports that have systematically evaluated the interaction between mucins and drugs. In this study, we assessed the potential interaction between human polymeric mucins (MUC2, MUC5B, and MUC5AC) and various drugs with different chemical profiles by simple centrifugal method and fluorescence analysis. We found that paclitaxel, rifampicin, and theophylline likely induce the aggregation of MUC5B and/or MUC2. In addition, we showed that the binding affinity of drugs for polymeric mucins varied, not only between individual drugs but also among mucin subtypes. Furthermore, we demonstrated that deletion of MUC5AC and MUC5B in A549 cells increased the cytotoxic effects of cyclosporin A and paclitaxel, likely due to loss of mucin-drug interaction. In conclusion, our results indicate the necessity to determine the binding of drugs to mucins and their potential impact on the mucin network property.
Topics: Humans; Paclitaxel; Mucin 5AC; A549 Cells; Drug Interactions; Mucin-5B; Mucins; Mucin-2; Rifampin; Cyclosporine; Protein Binding
PubMed: 38935605
DOI: 10.1371/journal.pone.0306058