The microprotein HDSP promotes gastric cancer progression through activating the MECOM-SPINK1-EGFR signaling axis.

The presence of noncanonical open reading frames within lncRNAs (long non-coding RNAs) suggests their potential for translation, yielding various functional peptides or proteins. However, the existence and specific roles of these products in gastric cancer remain largely unclear. Here we identify the HOXA10-HOXA9-derived small protein (HDSP) in gastric cancer through comprehensive analysis and experimental validation, including mass spectrometry and western blotting. HDSP exhibits high expression and oncogenic roles in gastric cancer. Mechanistically, HDSP blocks TRIM25-mediated ubiquitination and degradation by interacting with MECOM, leading to MECOM accumulation and enhanced SPINK1 transcription-a gene promoting cancer via the EGFR signaling pathway. Furthermore, MECOM fosters HOXA10-HOXA9 transcription, establishing a feedback loop activating SPINK1-EGFR signaling. HDSP knockdown inhibits tumor growth in a PDX (patient-derived xenograft) model, and infusion of an artificially synthesized HDSP peptide as a neoantigen enhances immune cell-mediated anti-tumor efficacy against gastric cancer in vitro and in vivo. These findings propose HDSP as a potential therapeutic target or neoantigen candidate for gastric cancer treatment.

Small Cell Lung Cancer-An Update on Chemotherapy Resistance.

OPINION STATEMENT: Compared to other types of lung cancer, small cell lung cancer (SCLC) exhibits aggressive characteristics that promote drug resistance. Despite platinum-etoposide chemotherapy combined with immunotherapy being the current standard treatment, the rapid development of drug resistance has led to unsatisfactory clinical outcomes. This review focuses on the mechanisms contributing to the chemotherapy resistance phenotype in SCLC, such as increased intra-tumoral heterogeneity, alterations in the tumor microenvironment, changes in cellular metabolism, and dysregulation of apoptotic pathways. A comprehensive understanding of these drug resistance mechanisms in SCLC is imperative for ushering in a new era in cancer research, which will promise revolutionary advancements in cancer diagnosis and treatment methodologies.

Single-cell transcriptome sequencing provides insight into multiple chemotherapy resistance in a patient with refractory DLBCL: a case report.

Relapsed and refractory diffuse large B-cell lymphoma (DLBCL) is associated with poor prognosis. As such, a comprehensive analysis of intratumoral components, intratumoral heterogeneity, and the immune microenvironment is essential to elucidate the mechanisms driving the progression of DLBCL and to develop new therapeutics. Here, we used single-cell transcriptome sequencing and conventional bulk next-generation sequencing (NGS) to understand the composite tumor landscape of a single patient who had experienced multiple tumor recurrences following several chemotherapy treatments. NGS revealed several key somatic mutations that are known to contribute to drug resistance. Based on gene expression profiles at the single-cell level, we identified four clusters of malignant B cells with distinct transcriptional signatures, showing high intra-tumoral heterogeneity. Among them, heterogeneity was reflected in activating several key pathways, human leukocyte antigen (HLA)-related molecules' expression, and key oncogenes, which may lead to multi-drug resistance. In addition, FOXP3+ regulatory CD4+ T cells and exhausted cytotoxic CD8+ T cells were identified, accounted for a significant proportion, and showed highly immunosuppressive properties. Finally, cell communication analysis indicated complex interactions between malignant B cells and T cells. In conclusion, this case report demonstrates the value of single-cell RNA sequencing for visualizing the tumor microenvironment and identifying potential therapeutic targets in a patient with treatment-refractory DLBCL. The combination of NGS and single-cell RNA sequencing may facilitate clinical decision-making and drug selection in challenging DLBCL cases.

Tissue-Matched IgH Gene Rearrangement of Circulating Tumor DNA Shows Significant Value in Predicting the Progression of Diffuse Large B Cell Lymphoma.

BACKGROUND: Evidence has demonstrated that monitoring of the variable, diversity, and joining gene segments (VDJ) rearrangement of the immunoglobulin (Ig) genes in the circulating tumor DNA (ctDNA) is of value in predicting the outcomes of diffuse large B cell lymphoma (DLBCL). In this study, we investigated the role of VDJ rearrangement proportion in ctDNA for predicting DLBCL progression. METHODS: Patients diagnosed with newly diagnosed DLBCL were included in this study. The VDJ sequences of IgH were detected using next-generation sequencing (NGS) in formalin-fixed paraffin-embedded tissue and/or peripheral blood. The clonotype of the highest proportion in the peripheral blood was defined as the "dominant circulating clonotype," whilst the clonotype of the highest proportion in matched tissue that is detected in peripheral blood was defined as the "dominant tissue-matched clonotype." The decision tree, a machine learning-based methodology, was used to establish a progression-predicting model through a combination of "dominant tissue-matched clonotype" proportion or "dominant circulating clonotype" proportion, and the clinicopathological information, including age, sex, cell of origin, stage, international prognostic index, lactate dehydrogenase, number of extranodal involvements and ß2-microglobulin. RESULTS: A total of 55 patients with eligible sequencing data were used for prognosis analysis, among which 36 patients had matched tissue samples. The concordance rate of "dominant circulating clonotype" and "dominant tissue-matched clonotype" was 19.44% (7/36). The decision tree model showed that the combination of extranodal involvement event and "dominant circulating clonotype" proportion (≥37%) had a clinical value in predicting the prognosis of DLBCL following combined chemotherapy (sensitivity, 0.63; specificity, 0.81; positive prediction value (PPV), 0.59; negative prediction value, 0.83; kappa value, 0.42). Noticeably, the combination of the "dominant tissue-matched clonotype" and extranodal involvement event showed a higher value in predicting the progression (sensitivity, 0.85; specificity, 0.78; PPV, 0.69; kappa value, 0.64). CONCLUSION: IgH proportion detected in the ctDNA samples traced from tissue samples has a high clinical value in predicting the progression of DLBCL.

Accurate interpretation of p53 immunohistochemical patterns is a surrogate biomarker for TP53 alterations in large B-cell lymphoma.

BACKGROUND: To clarify the relationship between p53 immunohistochemistry (IHC) staining and TP53 alterations (including mutations and deletions) in large B-cell lymphomas (LBCLs) and to explore the possibility of p53 IHC expression patterns as surrogate markers for TP53 alterations. METHODS: A total of 95 patients diagnosed with LBCLs were selected, and paraffin samples were taken for TP53 gene sequencing, fluorescence in situ hybridization and p53 IHC staining. The results were interpreted by experienced pathologists and molecular pathologists. RESULTS: Forty-three nonsynonymous TP53 mutations and p53 deletions were detected in 40 cases, whereas the remaining 55 cases had wild-type TP53 genes. The majority of TP53 mutations (34/43, 79.1%) occurred in exons 4-8, and R248Q was the most common mutation codon (4/43, 9.3%). The highest frequency single nucleotide variant was C > T (43.6%). p53 expression was interpreted as follows: Pattern A: p53 staining was positive in 0%-3% of tumor cells, Pattern B: p53 staining was positive in 4-65% of tumor cells, Pattern C: more than 65% of tumor cells were stained positive for p53. The p53 IHC expression patterns were associated with TP53 alterations. Gain of function variants and wild-type TP53 tended to exhibit type C and B p53 expression patterns, but loss of function variants were exclusively seen in type A cases. Additionally, interpretation of the staining by various observers produced significant reproducibility. CONCLUSIONS: The p53 IHC expression patterns can be used to predict TP53 alterations and are reliable for diverse alteration types, making them possible surrogate biomarkers for TP53 alterations in LBCLs.

Tertiary Lymphoid Structures Are Related to Inflammatory Progression and Bone Loss in Human Apical Periodontitis.

INTRODUCTION: Bone loss is strongly associated with the immunologic milieu in apical periodontitis (AP). Tertiary lymphoid structures (TLSs) are organized lymphoid cell aggregates that form in nonlymphoid tissues under persistent inflammatory circumstances. To date, there has been no relevant report of TLSs in periapical lesions. This work aimed to investigate the formation and potential function of TLSs in AP. METHODS: Tissues from human apical lesions (n = 61) and healthy oral mucosa (n = 5) were collected. Immunohistochemistry and multiplex immunofluorescence were used to detect the formation of TLSs. Correlation analyses were performed between clinical variables and TLSs. In addition, immunohistochemistry was used to evaluate the expression of interleukin-1 beta, interleukin-6, receptor activator of nuclear factor kappa-B ligand, and macrophage subsets in the apical lesions. RESULTS: Periapical granulomas (n = 24) and cysts (n = 37) were identified by histologic evaluation. TLSs, composed of B-cell and T-cell clusters, developed in periapical granulomas and radicular cysts. The CXC-chemokine ligand 13, its receptor CXC-chemokine receptor 5, follicular dendritic cells, and high endothelial venules were localized in TLSs. The quantity and size of TLSs were positively associated with bone loss in AP. Moreover, proinflammatory cytokines and macrophage subsets were also substantially elevated in TLS regions of apical lesions. CONCLUSIONS: The formation of TLSs in periapical granulomas and cysts was closely associated with persistent immune responses and bone loss in apical lesions. TLSs provide an updated insight into the complicated immune response process in AP.

A new prognostic nomogram in patients with mucosa-associated lymphoid tissue lymphoma: a multicenter retrospective study.

Background: The present study sought to understand how clinical factors and inflammatory biomarkers affected the prognosis of mucosa-associated lymphoid tissue (MALT) lymphoma and develop a predictive nomogram to assist in clinical practice. Methods: We conducted a retrospective study on 183 cases of newly diagnosed MALT lymphoma from January 2011 to October 2021, randomly divided into two groups: a training cohort (75%); and a validation cohort (25%). The least absolute shrinkage and selection operator (LASSO) regression analysis was combined with multivariate Cox regression analysis to construct a nomogram for predicting the progression-free survival (PFS) in patients with MALT lymphoma. To evaluate the accuracy of the nomogram model, the area under the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used. Results: The PFS was significantly associated with the Ann Arbor Stage, targeted therapy, radiotherapy, and platelet-to-lymphocyte ratio (PLR) in MALT lymphoma. These four variables were combined to establish a nomogram to predict the PFS rates at three and five years. Importantly, our nomogram yielded good predictive value with area under the ROC curve (AUC) values of 0.841 and 0.763 in the training cohort and 0.860 and 0.879 in the validation cohort for the 3-year and 5-year PFS, respectively. Furthermore, the 3-year and 5-year PFS calibration curves revealed a high degree of consistency between the prediction and the actual probability of relapse. Additionally, DCA demonstrated the net clinical benefit of this nomogram and its ability to identify high-risk patients accurately. Conclusion: The new nomogram model could accurately predict the prognosis of MALT lymphoma patients and assist clinicians in designing individualized treatments.

[Improvement effect of Shegan Mahuang Decoction on rats with cold-induced asthma based on TRPV1/NRF-1/mtTFA pathway].

This study investigated the therapeutic effect of Shegan Mahuang Decoction(SGMHD) on cold-induced asthma in rats and explored its underlying mechanism. Seventy-two healthy male SD rats of specific pathogen free(SPF) grade were randomly divided into a blank group, a model group, a positive control group(dexamethasone, 0.4 mg·kg~(-1)), and low-, medium-, and high-dose SGMHD groups(3.2, 6.4, and 12.8 g·kg~(-1)). The blank group received saline, while the other groups were sensitized by intraperitoneal injection of ovalbumin(OVA) solution. Subsequently, the rats were placed in a cold chamber adjustable to 0-2 ℃, and OVA solution was ultrasonically nebulized to induce cold-induced asthma in rats. After three weeks of treatment, the general behaviors of rats were observed. Hematoxylin-eosin(HE) staining was used to evaluate pathological changes in lung tissues, periodic acid-Schiff(PAS) staining assessed mucin changes, and Masson staining was performed to examine collagen deposition. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of the inflammatory factors interleukin-4(IL-4) and vascular endothelial growth factor(VEGF) in serum and bronchoalveolar lavage fluid(BALF). Real-time quantitative polymerase chain reaction(RT-PCR) was employed to assess the mRNA expression levels of transient receptor potential vanilloid subfamily member 1(TRPV1), nuclear respiratory factor 1(NRF-1), and mitochondrial transcription factor A(mtTFA) in lung tissues. Western blot was used to measure the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues. Compared with the blank group, the model group exhibited signs of rapid respiration, increased frequency of defecation with looser stools, and disheveled and dull fur. Pathological results showed significant infiltration of inflammatory cells in lung tissues, narrowing of bronchial lumens, increased mucin secretion, and enhanced collagen deposition in the model group. Additionally, the levels of IL-4 and VEGF in serum and BALF were significantly elevated, and the mRNA and protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were significantly increased. Compared with the model group, SGMHD improved the behaviors of rats, alleviated pathological changes in lung tissues, mucin production, and collagen deposition, significantly decreased the levels of IL-4 and VEGF in serum and BALF, and reduced the mRNA expression levels of TRPV1, NRF-1, and mtTFA in lung tissues, with the medium-dose SGMHD group showing the most significant effect. Moreover, the protein expression levels of TRPV1, NRF-1, and mtTFA in lung tissues were also reduced, with the medium-dose SGMHD group exhibiting the most significant effect. In conclusion, this study demonstrates that SGMHD can alleviate airway inflammation and inhibit airway remodeling in cold-induced asthma rats. These effects may be associated with the modulation of the TRPV1/NRF-1/mtTFA signaling pathway.

A novel neutrophil extracellular trap signature to predict prognosis and immunotherapy response in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant cancers, and patients with HNSCC possess early metastases and poor prognosis. Systematic therapies (including chemotherapy, targeted therapy, and immunotherapy) are generally applied in the advanced/late stages of HNSCC, but primary and acquired resistance eventually occurs. At present, reliable biomarkers to predict the prognosis of HNSCC have not been completely identified. Recent studies have shown that neutrophil extracellular traps (NETs) are implicated in cancer progression, metastasis and cancer immune response, and NET-related gene signatures are associated with the prognosis of patients with several human cancers. To explore whether NET-related genes play crucial roles in HNSCC, we have performed systematic analysis and reported several findings in the current study. Firstly, we identified seven novel NET-related genes and developed a NET-score signature, which was highly associated with the clinicopathological and immune traits of the HNSCC patients. Then, we, for the first time, found that NIFK was significantly upregulated in HNSCC patient samples, and its levels were significantly linked to tumor malignancy and immune status. Moreover, functional experiments confirmed that NIFK was required for HNSCC cell proliferation and metastasis. Altogether, this study has identified a novel NET-score signature based on seven novel NET-related genes to predict the prognosis of HNSCC and NIFK has also explored a new method for personalized chemo-/immuno-therapy of HNSCC.

Oligonucleotide Discrimination Enabled by Tannic Acid-Coordinated Film-Coated Solid-State Nanopores.

Discrimination of nucleotides serves as the basis for DNA sequencing using solid-state nanopores. However, the translocation of DNA is usually too fast to be detected, not to mention nucleotide discrimination. Here, we utilized polyphenolic TA and Fe3+, an attractive metal-organic thin film, and achieved a fast and robust surface coating for silicon nitride nanopores. The hydrophilic coating layer can greatly reduce the low-frequency noise of an original unstable nanopore, and the nanopore size can be finely tuned in situ at the nanoscale by simply adjusting the relative ratio of Fe3+ and TA monomers. Moreover, the hydrogen bonding interaction formed between the hydroxyl groups provided by TA and the phosphate groups of DNAs significantly increases the residence time of a short double-strand (100 bp) DNA. More importantly, we take advantage of the different strengths of hydrogen bonding interactions between the hydroxyl groups provided by TA and the analytes to discriminate between two oligonucleotide samples (oligodeoxycytidine and oligodeoxyadenosine) with similar sizes and lengths, of which the current signal patterns are significantly different using the coated nanopore. The results shed light on expanding the biochemical functionality of surface coatings on solid-state nanopores for future biomedical applications.

The lncRNA ZFAS1 regulates lipogenesis in colorectal cancer by binding polyadenylate-binding protein 2 to stabilize SREBP1 mRNA.

Colorectal cancer (CRC) is the fourth leading cause of cancer-related mortality globally. Therefore, a better understanding of the early molecular events of this disease is needed. Long noncoding RNAs (lncRNAs) play a critical role in the regulation of tumorigenesis and cancer progression. In this study, we investigated the characteristics of ZFAS1 in CRC. We analyzed three independent microarray datasets of CRC tissues from GEO and found that ZFAS1 expression was remarkably upregulated in all three datasets. Moreover, we validated the overexpression of ZFAS1 in CRC tissues compared with normal tissues and found that ZFAS1 was positively correlated with tumor size and metastasis in CRC. Knockdown of ZFAS1 significantly suppressed the malignant phenotype and lipogenesis of CRC cells. Mechanistically, ZFAS1 binds polyadenylate-binding protein 2 (PABP2) to stabilize SREBP1 mRNA, thereby increasing the expression of SREBP1 and its target genes stearoyl-CoA desaturase (SCD1) and fatty acid synthase (FASN), thus promoting CRC lipid accumulation. These data demonstrated that ZFAS1 could act as an oncogene for CRC and that ZFAS1 reprograms lipid metabolism by binding with PABP2 to stabilize SREBP1 mRNA accumulation, implicating it as a novel and potent target for the treatment of CRC.

LRIG1, a regulator of stem cell quiescence and a pleiotropic feedback tumor suppressor.

LRIG1, leucine-rich repeats and immunoglobulin-like domains protein 1, was discovered more than 20 years ago and has been shown to be downregulated or lost, and to function as a tumor suppressor in several cancers. Another well-reported biological function of LRIG1 is to regulate and help enforce the quiescence of adult stem cells (SCs). In both contexts, LRIG1 regulates SC quiescence and represses tumor growth via, primarily, antagonizing the expression and activities of ERBB and other receptor tyrosine kinases (RTKs). We have recently reported that in treatment-naïve human prostate cancer (PCa), LRIG1 is primarily regulated by androgen receptor (AR) and is prominently overexpressed. In castration-resistant PCa (CRPC), both LRIG1 and AR expression becomes heterogeneous and, frequently, discordant. Importantly, in both androgen-dependent PCa and CRPC models, LRIG1 exhibits tumor-suppressive functions. Moreover, LRIG1 induction inhibits the growth of pre-established AR+ and AR- PCa. Here, upon a brief introduction of the LRIG1 and the LRIG family, we provide an updated overview on LRIG1 functions in regulating SC quiescence and repressing tumor development. We further highlight the expression, regulation and functions of LRIG1 in treatment-naïve PCa and CRPC. We conclude by offering the perspectives of identifying novel cancer-specific LRIG1-interacting signaling partners and developing LRIG1-based anti-cancer therapeutics and diagnostic/prognostic biomarkers.

Case Report: Long-Term Response to Radiotherapy Combined With Targeted Therapy in Histiocytic Sarcoma Harboring Mutations in MAPK and PI3K/AKT Pathways.

BACKGROUND: Histiocytic sarcoma (HS) is a rare hematopoietic malignancy with an aggressive clinical presentation associated with a poor overall survival. To date, surgical resection, radiation therapy, and chemotherapy were often utilized for HS, but curative effects are rather disappointing. CASE PRESENTATION: A 19-year-old female was referred to our hospital with a pathologic diagnosis of HS in December 2017. The patient had a severe airway obstruction resulting from a large mass (6.0 cm × 4.4 cm) arising from the left parapharyngeal space. She did not respond to cyclophosphamide, doxorubicin, vincristine, prednisone, and etoposide (CHOEP) chemotherapy, then she was switched to radiotherapy and crizotinib according to next-generation sequencing (NGS) results (mutations in MET and MAP2K1). The patient got a partial response after radiotherapy and crizotinib, then she switched to imatinib combined with thalidomide treatment. The patient got a long-term complete response from the treatment and is alive 44 months after initial diagnosis without disease progression. Further KEGG pathway enrichment analysis of NGS results from patient's tissue revealed that phosphatidylinositol 3' kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) pathways were activated in this HS patient. We further performed experiments in vitro in a canine histiocytic sarcoma cell line DH82, in order to explore the possible mechanism of imatinib plus thalidomide in HS. Results of cell counting kit-8 (CCK8) assays showed that the proliferation activity of DH82 was significantly inhibited by imatinib but not thalidomide. Combined thalidomide and imatinib treatment did not improve the inhibitory effects of imatinib to DH82. Results of Western blot confirmed the inhibitory effects of imatinib on DH82 by targeting activation of MAPK and PI3K/AKT pathways. CONCLUSION: Radiotherapy combined with targeted therapy guided by NGS may be promising, and further perspective clinical trial is warranted for the localized HS.

Synchronous double primary lymphoma and thyroid cancer: A single-institution retrospective study.

ABSTRACT: Synchronous double primary malignancies of lymphoma and thyroid cancer are rare. In this retrospective study, we investigated the pathology, clinical characteristics, and treatment outcomes of patients with synchronous lymphoma and thyroid cancer.Of the 1156 newly diagnosed lymphoma patients treated in our hospital between January 1, 2016 and February 1, 2021, 8 cases had lymphoma complicated with thyroid cancer. The clinical data and treatment strategies of 8 cases with synchronous lymphoma and thyroid cancer were retrospectively analyzed.The median age of patients was 56 (25-64) years. All the 8 patients were female and papillary thyroid cancer. Only 1 patient had peripheral T-cell lymphoma, and the other 7 were B-cell lymphoma. Seven of 8 patients had normal free triiodothyronine and free thyroxine at the time of diagnosis. Seven thyroid cancer patients received total thyroidectomy and levothyroxine and the remaining 1 patient has a plan for surgery. At the last follow-up, 7 patients with B-cell lymphoma are alive; the patient with peripheral T-cell lymphoma complicated with thyroid cancer died due to lymphoma progression.Synchronous lymphoma and thyroid cancer are more predominant in women. Histologically, B-cell lymphomas and papillary thyroid cancer subtypes are more common. Attention should be paid to the presence of thyroid nodules in the diagnosis of lymphoma. Biopsy or ultrasound-guided fine needle aspiration of the suspicious thyroid nodule should be performed to exclude thyroid malignancy.

Circadian Rhythm Gene PER3 Negatively Regulates Stemness of Prostate Cancer Stem Cells via WNT/ß-Catenin Signaling in Tumor Microenvironment.

Prostate cancer (PCa) cells are heterogeneous, containing a variety of cancer cells with phenotypical and functional discrepancies in the tumor microenvironment, where prostate cancer stem cells (PCSCs) play a vital role in PCa development. Our earlier studies have shown that ALDHhiCD44+ (DP) PCa cells and the corresponding ALDHloCD44- (DN) PCa cells manifest as PCSCs and non-PCSCs, respectively, but the underlying mechanisms regulating stemness of the PCSCs are not completely understood. To tackle this issue, we have performed RNA-Sequencing and bioinformatic analysis in DP (versus DN) cells in this study. We discovered that, PER3 (period circadian regulator 3), a circadian rhythm gene, is significantly downregulated in DP cells. Overexpression of PER3 in DP cells significantly suppressed their sphere- and colony-forming abilities as well as tumorigenicity in immunodeficient hosts. In contrast, knockdown of PER3 in DN cells dramatically promoted their colony-forming and tumor-initiating capacities. Clinically, PER3 is downregulated in human prostate cancer specimens and PER3 expression levels are highly correlated with the prognosis of the PCa patient. Mechanistically, we observed that low levels of PER3 stimulates the expression of BMAL1, leading to the phosphorylation of ß-catenin and the activation of the WNT/ß-catenin pathway. Together, our results indicate that PER3 negatively regulates stemness of PCSCs via WNT/ß-catenin signaling in the tumor microenvironment, providing a novel strategy to treat PCa patients.

Primary central nervous system lymphoma after heart transplantation: A case report and literature review.

RATIONALE: The heart transplantation is the most important treatment for patients with end-stage severe heart disease who failed to conventional therapy. Post-transplant lymphoproliferative disorder is the second most common malignancy in heart transplant recipients. However, primary central nervous system lymphoma (PCNSL) after heart transplantation is an extremely rare condition. PATIENTS CONCERNS: This report described a 53-year-old male who was diagnosed as PCNSL 17 months after heart transplantation. DIAGNOSES: The patient was admitted to the local hospital presenting with dizziness, headache, and reduced left-sided power and sensation for 1 week. He had a medical history of heart transplantation because of the dilated cardiomyopathy 17 months ago and had a 17-month history of immunosuppressive therapy with tacrolimus. A computed tomography scan of the brain revealed a bulky mass in the right temporal lobe. The emergency intracranial mass resection and cerebral decompression were performed in our hospital. The histopathology of the brain lesions showed diffuse large B-cell lymphoma. A further FDG positron emission tomography-computed tomography scan of the whole body showed no significantly increased metabolic activity in other regions. The final diagnosis of this patient was PCNSL after heart transplantation. INTERVENTIONS: Given the poor health condition, with the patient's consent, the whole brain radiotherapy was performed with supportive care. OUTCOMES: The disease deteriorated rapidly during the period of receiving radiotherapy, and he died within 2 months from the diagnosis. LESSONS: PCNSL after heart transplantation is an extremely rare phenomenon with extremely poor prognosis. We should pay close attention to the heart recipients, especially when the patients present with neurological symptoms and signs. The available treatment options for PCNS-post-transplant lymphoproliferative disorder include the reduction of immunosuppressive drugs, immune-chemotherapy, operation, radiotherapy. However, individual treatments for heart transplant recipients with PCNSL should be based on the performance status and tolerance to treatment, combined with the doctor's experience and supportive care.

Long-term outcomes of upfront concurrent chemoradiotherapy followed by P-GDP regimen in newly diagnosed early stage extranodal nasal-type NK/T cell lymphoma: A prospective single-center phase II study.

The optimal treatment strategy of newly diagnosed stage I/II, extranodal nasal-type natural killer/T cell lymphoma (NKTCL) remains unclear. This prospective phase II trial was conducted to explore the short-term and the long-term efficacy and safety of upfront concurrent chemoradiotherapy (CCRT) followed by pegaspargase, gemcitabine, dexamethasone, cisplatin (P-GDP) regimen in patients newly diagnosed with early stage NKTCL.Thirty patients newly diagnosed with stage I/II NKTCL were enrolled from January 2013 to December 2016, and treated as the following strategy: upfront CCRT with cisplatin weekly (25 mg/m) for 5 weeks, followed by 3 cycles of P-GDP regimen chemotherapy (pegaspargase 2500IU/m capped at 3750IU, intramuscular on day 4, gemcitabine 850 mg/m intravenous on days 1 and 8; dexamethasone 40 mg/day intravenous on days 1 to 4; and cisplatin 20 mg/m intravenous on days 1-3) 3 weeks after the completion of CCRT. The objective response rate (ORR) and the complete response (CR) rate were the primary endpoints, and the secondary endpoints were the overall survival (OS), progression-free survival (PFS), and the adverse event (AE).The median follow-up period was 51.5 months (range, 5-78months). The ORR was 93.3% (28/30) and all these 28 patients attained CR at the end of the treatment. Two patients suffered from lymphoma associated hemophagocytic syndrome (LAHS) during the period of consolidation chemotherapy and died within 2 months. The 5-year OS was 93.3%, and the 5-year PFS was 89.4%Mucositis was the most common grades 3/4 nonhematologic AEs (10%, 3/30) of CCRT. During the P-GDP chemotherapy, vomiting (6.7%, 2/30), neutropenia (43.3%, 13/30) and thrombocytopenia (23.3%, 7/30) were the major grades 3/4 toxicities during chemotherapy. No treatment-related deaths occurred.The upfront CCRT followed by P-GDP regimen chemotherapy is an effective and well-tolerated first-line treatment strategy for patients diagnosed with early stage NKTCL. Further investigation of larger sample size is warranted.

Successful Treatment of Chidamide and Cyclosporine for Refractory/Relapsed Angioimmunoblastic T Cell Lymphoma With Evans Syndrome: A Case Report With Long-Term Follow-Up.

BACKGROUND: Refractory/relapsed angioimmunoblastic T cell lymphoma (AITL) with Evans syndrome is a very rare condition with a poor prognosis. There is no evidence-based treatment strategy for refractory/relapsed AITL with Evans syndrome. CASE PRESENTATION: A 51-year-old female was admitted to our hospital with multiple enlarged bilateral cervical lymph nodes, more than 1 week-long chest distress, and night sweats in July 2014. An excision biopsy of the left cervical enlarged lymph node revealed AITL. However, the patient showed resistance to the first-line chemotherapy for AITL and was diagnosed with refractory AITL. Complete remission was achieved after the salvage treatment with the combination of chemotherapy, radiotherapy, and immunomodulatory agent lenalidomide. Unfortunately, 12 months later, the patient suffered from disease progression and was diagnosed as refractory/relapsed AITL with Evans syndrome according to the laboratory findings and imaging. With the diagnosis of refractory/relapsed AITL with Evans syndrome, the patient received the first-line treatment for Evans syndrome including prednisone and intravenous immunoglobulin. The response to the first-line treatment for Evans syndrome was poor. The combination regimen of chidamide (30 mg, po, biw) and cyclosporine were administrated considering the treatment targeting simultaneously both refractory/relapsed AITL and Evans syndrome. The efficacy evaluation was complete remission. The last follow-up of the patient was April 30th, 2020, and no evidence of disease progression was observed. The overall survival of the patient was more than 70 months. CONCLUSION: The treatment for refractory/relapsed AITL combined with Evans syndrome remains challenging to patients and physicians. The combination of chidamide and cyclosporine may be an effective and tolerable regimen for the intractable AITL with Evans syndrome case and more observations are necessary to identify the efficacy and safety in the future.

A Primary Mediastinal Large B-Cell Lymphoma Patient With COVID-19 Infection After Intensive Immunochemotherapy: A Case Report.

Background: The outbreak of coronavirus disease 2019 (COVID-19) had become a global public health event. Lymphoma patients need to be distinguished from the general population because of their deficient immune status and intensive anti-tumor treatment. The impacts of cancer subtypes and treatment on COVID-19 infection are unclear. Case Presentation: We here report the case of a primary mediastinal large B-cell lymphoma patient who was infected with COVID-19 after intensive immunochemotherapy (DA-EPOCH-R). The patient developed a neutropenic fever during chemotherapy, and fever was persistent, although antibiotics were used. Initial chest CT was negative, and the patient received a throat swab test since the second CT showed evidence of pneumonia. With treatment with Arbidol Hydrochloride and LianHuaQingWen capsule, his COVID-19 was cured. Conclusions: To the best of our knowledge, this is the first report focusing on COVID-19 infection in a lymphoma patient undergoing intensive immunochemotherapy. For those patients being treated with immunochemotherapy in epidemic areas, a reduced dose intensity of intensive chemotherapy should be considered, and the effect of immunotherapies such as rituximab on COVID-19 infection should be considered. The impacts of anti-cancer treatment on COVID-19 infection need to be explored further.

Author Correction: LRIG1 is a pleiotropic androgen receptor-regulated feedback tumor suppressor in prostate cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.