An injectable magnesium-loaded hydrogel releases hydrogen to promote osteoporotic bone repair via ROS scavenging and immunomodulation.

Background: The repair of osteoporotic bone defects remains challenging due to excessive reactive oxygen species (ROS), persistent inflammation, and an imbalance between osteogenesis and osteoclastogenesis. Methods: Here, an injectable H2-releasing hydrogel (magnesium@polyethylene glycol-poly(lactic-co-glycolic acid), Mg@PEG-PLGA) was developed to remodel the challenging bone environment and accelerate the repair of osteoporotic bone defects. Results: This Mg@PEG-PLGA gel shows excellent injectability, shape adaptability, and phase-transition ability, can fill irregular bone defect areas via minimally invasive injection, and can transform into a porous scaffold in situ to provide mechanical support. With the appropriate release of H2 and magnesium ions, the 2Mg@PEG-PLGA gel (loaded with 2 mg of Mg) displayed significant immunomodulatory effects through reducing intracellular ROS, guiding macrophage polarization toward the M2 phenotype, and inhibiting the IκB/NF-κB signaling pathway. Moreover, in vitro experiments showed that the 2Mg@PEG-PLGA gel inhibited osteoclastogenesis while promoting osteogenesis. Most notably, in animal experiments, the 2Mg@PEG-PLGA gel significantly promoted the repair of osteoporotic bone defects in vivo by scavenging ROS and inhibiting inflammation and osteoclastogenesis. Conclusions: Overall, our study provides critical insight into the design and development of H2-releasing magnesium-based hydrogels as potential implants for repairing osteoporotic bone defects.

Bronchial oncocytic carcinoma in an adult: a case report and literature review.

BACKGROUND: Lung salivary-type tumors originating from bronchial submucosal glands are rare, only four types of salivary gland-type tumors are listed in 2015 WHO classification of lung tumors. Here, we report a rare case of oncocytic carcinoma (OC) in the right main bronchus. CASE PRESENTATION: A 34-year-old man presented to our hospital with a two-month history of recurrent hemoptysis and with one month of inspiratory dyspnea. Pulmonary function tests showed mild restrictive ventilatory dysfunction and severe diffusion dysfunction. Furthermore, the flow volume loop showed a variable extra-thoracic obstruction. Computed tomography (CT) of the chest revealed that a polypiform nodule of 13 mm in diameter was at the proximal right main bronchus. Testing for purified protein derivative was positive (category 2). The nodule was resected under bronchoscopy. The bronchial aspirate was negative for mycobacterium tuberculosis and tumor cells. The biopsy sample showed a solid and acinar predominant pattern with abundant eosinophilic cytoplasm. The bronchial mucosa was destroyed and replaced by tumor cells. The loose edematous stromal reaction could be seen in a local area. Immunohistochemically, tumor cells were positive for CK, EMA, Vimentin, CD117, CK7, S100, Mammaglobin and SOX10. Only scattered tumor cells were stained by basal cell markers, including CK5/6, P40 and P63. Electron microscopy revealed numerous swelling mitochondria with lacking mitochondrial cristae in tumor cells. Fluorescence in situ hybridization (FISH) testing for MAML2 and ETV6 rearrangement were negative. Next-generation sequencing analysis of 520 genes in the tissue biopsy specimen showed no somatic mutation. The diagnosis of OC was made. Subsequently, the patient underwent a right upper lobectomy with sleeve resection of the main bronchus and lymph dissection. No recurrent evidence was seen during two years of chest CT follow-up. CONCLUSIONS: To our knowledge, this is the first case of primary OC in the bronchus. This patient has no recurrence during two years of follow-up, indicating that primary OC in the bronchus has the same favorable prognosis as in salivary glands. Moreover, complete excision and thorough sampling to know the invasive growth pattern is important to reach the correct diagnosis.

Engineering a triple-functional magnetic gel driving mutually-synergistic mild hyperthermia-starvation therapy for osteosarcoma treatment and augmented bone regeneration.

Malignant bone tumors result in high rates of disability and death and are difficult to treat in terms of killing tumors and repairing bone defects. Compared with other hyperthermia strategies, magnetic hyperthermia has become an effective therapy for treating malignant bone tumors due to its lack of depth limitations. However, tumor cells express heat shock protein (HSP) to resist hyperthermia, which reduces its curative effect. Competitive ATP consumption can reduce HSP production; fortunately, the basic principle of starvation therapy by glucose oxidase (GOx) is consuming glucose to control ATP production, thereby restricting HSP generation. We developed a triple-functional magnetic gel (Fe3O4/GOx/MgCO3@PLGA) as a magnetic bone repair hydrogels (MBRs) with liquid‒solid phase transition capability to drive magneto-thermal effects to simultaneously trigger GOx release and inhibit ATP production, reducing HSP expression and thereby achieving synergistic therapy for osteosarcoma treatment. Moreover, magnetic hyperthermia improves the effect of starvation therapy on the hypoxic microenvironment and achieves a reciprocal strengthening therapeutic effect. We further demonstrated that in situ MBRs injection effectively suppressed tumor growth in 143B osteosarcoma tumor-bearing mice and an in-situ bone tumor model in the rabbit tibial plateau. More importantly, our study also showed that liquid MBRs could effectively match bone defects and accelerate their reconstruction via magnesium ion release and enhanced osteogenic differentiation to augment the regeneration of bone defects caused by bone tumors, which generates fresh insight into malignant bone tumor treatment and the acceleration of bone defect repair.

Erratum: BMP4 augments the survival of hepatocellular carcinoma (HCC) cells under hypoxia and hypoglycemia conditions by promoting the glycolysis pathway.

[This corrects the article on p. 793 in vol. 11, PMID: 33791154.].

p53 downregulates PD-L1 expression via miR-34a to inhibit the growth of triple-negative breast cancer cells: a potential clinical immunotherapeutic target.

BACKGROUND: Compared with other breast cancer subtypes, triple-negative breast cancer (TNBC) has poorer responses to therapy and lower overall survival rates. The use of an inhibitor of immune checkpoint programmed cell death ligand 1 (PD-L1) is a promising treatment strategy and is approved for malignant tumors, especially for TNBC. p53 regulates various biological processes, but the association between p53 and immune evasion remains unknown. miR-34a is a known tumor suppressor and p53-regulated miRNA that is downregulated in several cancers; however, it has not been reported in TNBC. Herein, we aimed to explore the regulatory signaling axis among p53, miR-34a and PD-L1 in TNBC cells in vivo and in tissue and to improve our understanding of immunotherapy for TNBC. METHODS AND RESULTS: p53-EGFP, p53-siRNA and miR-34a mimics were transfected into TNBC cell lines, and the interaction between miR-34a and PD-L1 was analyzed via dual-luciferase reporter assays. We found that p53 could inhibit the expression of PD-L1 via miR-34a and that miR-34a could inhibit both cell activity and migration and promoted apoptosis and cytotoxicity in TNBC. Furthermore, miR-34a agomir was injected into MDA-MB-231 tumors of nude mice. The results showed that miR-34a could inhibit tumor growth and downregulate the expression of PD-L1 in vivo. A total of 133 TNBC tissue samples were analyzed by immunochemistry; the proportion of positive expression of PD-L1 was 57.14% (76/133), and the proportion of samples with negative expression of PD-L1 was 42.86% (57/133). CONCLUSION: Our research may provide a novel potential target for TNBC.

Injectable versatile liquid-solid transformation implants alliance checkpoint blockade for magnetothermal dynamic-immunotherapy.

The ongoing circulating energy loss, low reactive oxygen species (ROS) accumulation and poor immunogenicity of tumors make it difficult to induce sufficient immunogenic cell death (ICD) in the tumor immunosuppressive microenvironment (TIME), resulting in unsatisfactory immunotherapy efficacy. Furthermore, for highly malignant tumors, simply enhancing ICD is insufficient for exhaustively eliminating the tumor and inhibiting metastasis. Herein, we propose a unique magnetothermal-dynamic immunotherapy strategy based on liquid-solid transformation porous versatile implants (Fe3O4/AIPH@PLGA) that takes advantage of less energy loss and avoids ongoing circulating losses by minimally invasive injection into tumors. In addition, the magnetothermal effect regresses and eliminates tumors that are not limited by penetration to simultaneously trigger 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) decomposition and generate a large amount of oxygen-irrelevant free radicals and heat shock protein (HSP) accumulation by heating, evoking both intracellular oxidative stress and endoplasmic reticulum (ER) stress to induce large-scale ICD and enhance tumor immunogenicity. More importantly, in orthotopic bilateral breast tumor models, a significant therapeutic effect was obtained after combining amplified ICD with CTLA4 checkpoint blockade. The 21-day primary and distant tumor inhibition rates reached 90%, and the underlying mechanism of the effective synergetic strategy of inducing the T-cell-related response, the immune memory effect and TIME reprogramming in vivo was verified by immune cell analyses. This remarkable therapeutic effect provides a new direction for antitumor immunotherapy based on magnetothermally controlled oxygen-independent free radical release.

Prognostic Biomarker NUMB Is Inhibited by Breast Cancer Cell Exosomes to Promote Breast Cancer Progression.

Objective: To clarify the regulation of breast cancer cell-derived exosomes on breast cancer and the expression of the NUMB endocytic adaptor protein (NUMB) protein. Methods: The exosomes of breast cancer cell line MDA-MB-231 were isolated. The exosomes were subsequently labeled with PKH67 and added to breast cancer MDA-MB-231 cells cultured in vitro. Transwell and clone formation assays were performed to detect cell migration, invasion, and clone formation. Meanwhile, Western blot and qPCR were conducted to determine the regulation of NUMB expression by exosomes in breast cancer cells. Furthermore, NUMB overexpressed lentivirus was supplemented to validate the recovery. Results: The number of migrating and invasive breast cancer cells in the exosome-treated group was significantly increased compared with the control group. Moreover, the number of breast cancer cell clones in the exosome-treated group was increased than in the control group. However, the NUMB expression in breast cancer cells treated with exosomes revealed a substantial decrease, indicating that the exosomes of breast cancer cells could inhibit NUMB expression. NUMB overexpressed lentivirus supplementation markedly suppressed cell migration, invasion, and proliferation of breast cancer cells compared with exosome group. Conclusion: Taken together, the exosomes of breast cancer cells could inhibit the expression of NUMB and promote the migration, invasion, and cell clone formation of breast cancer cells.

Mitochondrial Glutathione Depletion Nanoshuttles for Oxygen-Irrelevant Free Radicals Generation: A Cascaded Hierarchical Targeting and Theranostic Strategy Against Hypoxic Tumor.

An oxygen-irrelevant free radicals generation strategy has shown great potential in hypoxic tumor therapy. However, insufficient tumor accumulation, nonspecific intracellular localization, and the presence of highly reductive mitochondrial glutathione (GSH) dramatically hamper the free radicals therapeutic efficacy. Herein, a hierarchical targeting system was constructed by Fe-doped polydiaminopyridine nanoshuttles, indocyanine green (ICG), and an oxygen-irrelevant radicals generator (AIPH) to possess a negative charge. An acid-specific charge-reverse capability of the shuttles was achieved to enhance cell uptake in the tumor microenvironment (TME). In addition, the iron release occurs only in the acidic TME, which can be used as acidity enhancers to strengthen the charge-reverse process, thereby leading to more efficient tumor internalization and deep penetration. Moreover, such a nanosystem has significantly improved the delivery efficiency of nanoshuttles (16.06%) in the tumor tissues at 24 h postinjection, much higher than that of naked Fe-doped polydiaminopyridine (6.59%). More importantly, the nanoshuttles enable simultaneously mitochondria targeting and corresponding GSH depleting capability to show advantages in free radicals-based therapy after charge reversion, leading to a powerful tumor inhibition rate (>95%). The prescence of iron could allow for magnetic resonance imaging, while ICG allowed for photoacoustic imaging and fluorescence imaging to guide the therapeutic process. The remarkable features of the nanoshuttles may open a new avenue to explore an oxygen-irrelevant free radicals generating system for accurate cancer theranostics.

Qualitative Histopathological Classification of Primary Bone Tumors Using Deep Learning: A Pilot Study.

BACKGROUND: Histopathological diagnosis of bone tumors is challenging for pathologists. We aim to classify bone tumors histopathologically in terms of aggressiveness using deep learning (DL) and compare performance with pathologists. METHODS: A total of 427 pathological slides of bone tumors were produced and scanned as whole slide imaging (WSI). Tumor area of WSI was annotated by pathologists and cropped into 716,838 image patches of 256 × 256 pixels for training. After six DL models were trained and validated in patch level, performance was evaluated on testing dataset for binary classification (benign vs. non-benign) and ternary classification (benign vs. intermediate vs. malignant) in patch-level and slide-level prediction. The performance of four pathologists with different experiences was compared to the best-performing models. The gradient-weighted class activation mapping was used to visualize patch's important area. RESULTS: VGG-16 and Inception V3 performed better than other models in patch-level binary and ternary classification. For slide-level prediction, VGG-16 and Inception V3 had area under curve of 0.962 and 0.971 for binary classification and Cohen's kappa score (CKS) of 0.731 and 0.802 for ternary classification. The senior pathologist had CKS of 0.685 comparable to both models (p = 0.688 and p = 0.287) while attending and junior pathologists showed lower CKS than the best model (each p < 0.05). Visualization showed that the DL model depended on pathological features to make predictions. CONCLUSION: DL can effectively classify bone tumors histopathologically in terms of aggressiveness with performance similar to senior pathologists. Our results are promising and would help expedite the future application of DL-assisted histopathological diagnosis for bone tumors.

BMP4 augments the survival of hepatocellular carcinoma (HCC) cells under hypoxia and hypoglycemia conditions by promoting the glycolysis pathway.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide although its pathogenic mechanism remains to be fully understood. Unlike normal cells, most cancer cells rely on aerobic glycolysis and are more adaptable to the microenvironment of hypoxia and hypoglycemia. Bone Morphogenetic Protein 4 (BMP4) plays important roles in regulating proliferation, differentiation, invasion and migration of HCC cells. We have recently shown that BMP4 plays an important role in regulating glucose metabolism although the effect of BMP4 on glucose metabolic reprogramming of HCC is poorly understood. In this study, we found that BMP4 was highly expressed in HCC tumor tissues, as well as HCC cell lines that were tolerant to hypoxia and hypoglycemia. Mechanistically, we demonstrated that BMP4 protected HCC cells from hypoxia and hypoglycemia by promoting glycolysis since BMP4 up-regulated glucose uptake, the lactic acid production, the ATP level, and the activities of rate limiting enzymes of glycolysis (including HK2, PFK and PK). Furthermore, we demonstrated that BMP4 up-regulated HK2, PFKFB3 and PKM2 through the canonical Smad signal pathway as SMAD5 directly bound to the promoter of PKM. Collectively, our findings shown that BMP4 may play an important role in regulating glycolysis of HCC cells under hypoxia and hypoglycemia condition, indicating that novel therapeutics may be developed to target BMP4-regulated glucose metabolic reprogramming in HCC.

Pigmentibacter ruber gen. nov., sp. nov., a novel bacterium of the family Silvanigrellaceae isolated from human blood.

A Gram-negative, aerobic, non-motile, pleomorphic, red-pigmented bacterium, designated HNSRY-1T, was isolated from the blood sample of a near drowning patient in Republic of China. Strain HNSRY-1T grew at 15-37 °C (optimum, 35 °C), with pH 6.0-8.0 (optimum, pH 7.0) and 0-1.5% (W/V) NaCl (optimum, 1%). The predominant fatty acids (> 5%) in HNSRY-1T cells are iso-C15:0, C17:0, C17:1 ω8c, C16:0, and C16:1 ω6c/C16:1 ω7c. The major respiratory quinone is MK-8. The polar lipids are phosphatidylglycerol, phosphatidylethanolamine, three unidentified lipids and four unidentified aminolipids. The 16S rRNA gene sequence-based phylogenetic analysis indicated that strain HNSRY-1T belonged to the family Silvanigrellaceae, forming a distinct phylogenetic line distantly related (< 96.4% sequence similarity) to known species of the family. The ANI values of strain HNSRY-1T compared to the closely related species were below the determined genus division threshold limit (92-94% ANI), and AAI values were lower than the determined genus division threshold limit (80% AAI). Whole genome sequencing revealed a genome size of 3.63 Mb with a DNA G + C content at 29.6%. The half-lethal dose of strain HNSRY-1T on KM mice is about 1.12 × 108 CFU/ml. Virulence gene analysis showed that the pathogenicity of HNSRY-1T may be related to tufA, htpB, katA, wbtL, wbtM, pseB, clpP, cheY, cheV3, acpXL, pilB, fliN, ggt, flgG, fliP, nueB, pseA, bioB and flil. Based on these findings from the polyphasic taxonomy studies, a novel genus and species of the family Silvanigrellaceae. Pigmentibacter ruber gen. nov., sp. nov. is proposed, with type strain HNSRY-1T (= KCTC 72920T = CGMCC 1.18525T).

A Rare Case Report of Encephalocele with Numerous Ependymal Components: A Potential Diagnostic Pitfall.

Different cellular constituents of the central nervous system occurring in encephaloceles or neuroglial heterotopias (NGHs) have been reported, but the ependymal morphology has rarely been described in the previous literature, let alone the related histological images. To determine the ependymal morphology in encephaloceles or NGHs, we report a rare case of encephalocele with numerous ependymal components. Radiological examination showed that a 6.2 × 3.1 cm nasal dorsum mass-forming encephalocele in a 24-year-old woman, who had an intracranial connection through a frontal bone defect. This patient underwent a resection of the encephalocele under nasal endoscopy and a reconstruction of the cranial base. The patient had a good prognosis with no postoperative complications during follow-up. Microscopically, the ependymal components entrapped in a collagenized background showed numerous slit-like spaces lined by columnar cells with abundant palely eosinophilic cytoplasm and apical surface microvilli. With immunohistochemistry, in addition to the expression of EMA along with the slit-like spaces, GFAP and S100 were diffusely expressed in the slit-like spaces. In conclusion, the ependymal component in either encephaloceles or NGHs may present slit-like spaces arranged in an anastomosing pattern. The unusual morphology of ependyma continues to be underrecognized by pathologists and is easily misdiagnosed; therefore, an awareness of the morphological change in ependyma is necessary.

Efficacy of Chemiluminescence Immunoassays on VCA-IgA and EBNA1-IgA Antibodies of Epstein-Barr Virus in Diagnosing Nasopharyngeal Carcinoma.

Background: IgA antibodies against Epstein-Barr virus (EBV) capsid antigen (VCA) and nuclear antigen 1 (EBNA1) have been proposed to facilitate the diagnosis and early detection of nasopharyngeal carcinoma (NPC) in high-incidence regions. However, while new methodologies and new platforms for the detection of VCA-IgA and EBNA1-IgA have become available, proper interassay simultaneous comparisons have not been carried out. The study was to compare the performance of the chemiluminescent immunoassays (CLIA) and enzyme-linked immunosorbent assay (ELISA) for VCA-IgA and EBNA1-IgA antibodies, and to evaluate the levels of EBV antibodies in healthy population from different areas of China. Methods: CLIA and ELISA for VCA-IgA and EBNA1-IgA were performed in NPC and healthy populations from high-incidence areas of NPC in South China (N=555), medium-incidence areas of NPC in Central China (N=318) and low-incidence areas of NPC in North China (N=379), and the results were compared and analyzed. Results: (1) The highest sensitivity in total, early and advanced NPC were 91.5% (CLIA for VCA-IgA), 86.4% (CLIA and ELISA-2 for EBNA1-IgA) and 93.6% (CLIA for VCA-IgA). However, the specificity of EBV-IgA measured by CLIA was relatively lower than ELISA. The top three seromarkers with the largest AUC was CLIA for VCA-IgA (AUC: 0.929, 95% CI: 0.905-0.953), ELISA-2 for EBNA1-IgA (AUC: 0.922, 95% CI: 0.896-0.947) and CLIA for EBNA1-IgA (AUC:0.919, 95% CI: 0.893-0.945), respectively. The positive and negative coincidence rates of the two EBNA1-IgA kits were 69.5% and 91.9%, respectively. However, the coincidence rates of VCA-IgA were relatively low. CLIA kits had good repeatability between different laboratories. (2) The positive rates of EBV-IgA antibodies were relatively high in high-incidence areas of NPC (P < 0.017), while there was no significant difference in the antibody positive rates between medium-incidence areas and low-incidence areas of NPC (P > 0.05). Conclusions: The performance of EBV-IgA antibodies measured by CLIA has good repeatability, higher sensitivity and similar specificity. The higher EBV-IgA positive rate in healthy subjects by CLIA raises concern about its suitability for NPC-risk screening and requires further analysis.

A rare case of lung squamous cell carcinoma coexisting with pulmonary MALT lymphoma presenting as a progressive pGGN.

Pulmonary extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) presenting as a progressive pure ground-glass nodule (GGN) coexisting with lung squamous cell carcinoma has not been reported. A 65-year-old male presented with a progressive lung GGN in the left upper lobe identified six and a half years ago but showed no symptoms. The patient had a history of tuberculosis, squamous cell carcinoma, and stomach MALT lymphoma. The patient was diagnosed with lung squamous cell carcinoma coexisting with pulmonary MALT lymphoma through computed tomography (CT)-guided lung biopsy. A progressive lung GGN presenting in a patient with squamous cell carcinoma does not always indicate multiple primary lung adenocarcinoma, especially when given a specific medical history. The development of MALT lymphoma in the lung presenting as GGNs suggests a possible association between these two entities.

Progress in the research of p53 tumour suppressor activity controlled by Numb in triple-negative breast cancer.

Numb is known as a cell fate determinant as it identifies the direction of cell differentiation via asymmetrical partitioning during mitosis. It is considered as a tumour suppressor, and a frequent loss of Numb expression in breast cancer is noted. Numb forms a tri-complex with p53 and E3 ubiquitin ligase HDM2 (also known as MDM2), thereby preventing the ubiquitination and degradation of p53. In this study, we examined Numb expression in 125 patients with triple-negative breast cancer (TNBC). The results showed that 61 (48.8%) patients presented with a deficient or decreased Numb expression. The percentage of Ki67 > 14% in the retained Numb group was significantly lower than that in the decreased and deficient Numb groups (86.00% vs. 98.40%, P = .0171). This study aimed to detect the expression and migration of Numb, HDM2 and p53 in the membrane, cytoplasmic and nuclear fractions of normal mammary epithelial cell line MCF-10A and basal-like TNBC cell line MDA-MB-231. We obtained the cell fractions to identify changes in these three protein levels after the re-expression of NUMB in the MDA-MB-231 cells and the knocking down of NUMB in the MCF-10A cells. Results showed that Numb regulates p53 levels in the nucleus where the protein levels of Numb are positively correlated with p53 levels, regardless if it is re-expressed in the MDA-MB-231 cells or knocked down in the MCF-10A cells. Moreover, HDM2 was remarkably decreased only in the membrane fraction of NUMB knock-down cells; however, its mRNA levels were increased significantly. Our results reveal a previously unknown molecular mechanism that Numb can migrate into the nucleus and interact with HDM2 and p53.

A rare case report of pituicytoma with biphasic pattern and admixed with scattered Herring bodies.

BACKGROUND: Pituicytoma is a rare pituitary non-neuroendocrine tumour. The awareness of pituitary non-neuroendocrine tumours has gradually increased over the past several decades, but the knowledge of some histological variants of the tumours is limited, particularly in clinicopathological significance. Here, we report a rare case of pituicytoma variant. CASE PRESENTATION: A 71-year-old man presented with sudden symptoms of stroke including urinary incontinence, weakness in right lower limb, and trouble speaking. Physical examinations showed a right facial paralysis. The radiological examinations eventually found a 1.7 × 1.4 × 1.3 cm sellar occupied lesion. After symptomatic treatment improved the symptoms, the patient underwent transsphenoidal resection of the pituitary mass. Histologically, the tumour contained hypocellular area and hypercellular area. The hypocellular area showed elongated spindle cells arranged in a fascicular pattern around small vessels and scattered Herring bodies; the hypercellular area showed a large number of pseudorosettes. Immunohistochemistrically, the tumour cells were positive for thyroid transcription factor-1, S100, and neuron-specific enolase. Neurofilament only showed a little positive in the hypocellular area, and silver impregnation was only noted in a perivascular distribution. The patient had no recurrence 4 months after the surgery. CONCLUSIONS: The rare variant of pituicytoma has a favourable prognosis. Moreover, it needs to be distinguished pituicytomas with pseudorosettes from ependymomas because of different prognosis. Lastly, Herring bodies may occasionally be seen in the pituicytoma, which could be a potential diagnostic pitfall.

The first case of gland inclusion in an intrapulmonary lymph node: a mimic of metastasis.

BACKGROUND: Lymph node inclusions are foci of ectopic tissue in lymph nodes, which were reported in different areas of the body. However, inclusions in the mediastinal lymph node are rare. Here, we report the first case of glandular inclusion within the parenchyma of the intrapulmonary lymph node in a patient with primary lung adenocarcinoma. CASE PRESENTATION: A computed tomography (CT) scan showed a solid pulmonary nodule in the right upper lobe in a 44-year-old man. After a fine needle aspiration biopsy diagnosis of adenocarcinoma, lobectomy and lymph dissection were performed. Histological sections of the lung demonstrated a papillary predominant adenocarcinoma and one intrapulmonary lymph node, which displayed glandular inclusion occupying the node parenchyma. The gland inclusion was very similar to metastasis, but was formed by two layers of epithelial cells, and the abluminal cells were positive for P63, P40, and CK5/6. The patient has remained alive without recurrence and metastasis at the last follow-up before publication. CONCLUSIONS: It is very important to correctly diagnose a lymph node inclusion for proper clinical management.

Positive correlation between programmed death ligand-1 and p53 in triple-negative breast cancer.

PURPOSE: Tumors with high mutation load tend to have a stronger immune response in some tumors. The correlation between expression of programmed death ligand-1 (PD-L1), a biomarker of immune response in tumors, and p53, accepted as the most frequently mutated gene in many cancers, in triple-negative breast cancer (TNBC) has not been fully investigated in cancer patients. MATERIALS AND METHODS: 132 cases of TNBC and 32 cases of non-TNBC paraffin-embedded tissue sections were selected to detect the expression of PD-L1 and p53 by immunohistochemistry, and results were correlated with clinical data and survival outcomes. The staining of PD-L1 in tumor cells (TCs) and tumor-associated immune cells (TAICs) was assessed separately. RESULTS: Strong positive correlations were observed between expression of p53 and PD-L1 both in TCs (r=0.338, P=0.000) and TAICs (r=0.186, P=0.033). The same positive correlation was found in the expression of PD-L1 in TCs and TAICs (r=0.764, P=0.000). Like p53 (P=0.024), positive rate of PD-L1 in TCs was significantly higher in TNBC than in non-TNBC (P=0.02). PD-L1 and p53 in TCs staining were significantly associated with histological grade, tumor size and Ki67 index (P<0.05). PD-L1 in TCs staining was also associated with lymphatic metastasis status (P=0.000). However, PD-L1 in TAICs was only related to histological grade in statistically (P=0.012). Kaplan-Meier survival analysis showed that positive groups of p53, PD-L1 in TCs and TAICs had a worse overall survival and a worse progression-free survival as compared with the negative groups, but marginal significance was found only in overall survival of PD-L1 in TCs and TAICs, and progression-free survival of PD-L1 in TAICs (P=0.074, 0.097, 0.068, respectively). CONCLUSION: Our findings suggest that positive correlation between p53 and PD-L1 in TNBC and the higher expression rates are closely correlated with some key prognostic factors and worse survival outcomes. These findings would lay the foundation for further study on the relationship of p53 and PD-L1 and the combination of mutated p53 inhibitors and PD-1/PD-L1 antibodies in TNBC.