Primary lymphoma of mucosa associated lymphoid tissue (MALT lymphoma) in the urinary bladder mimicking recurrent urinary tract infection: a case report and literature review.

We report the case of a 79-year-old woman with primary lymphoma of mucosa-associated lymphoid tissue (MALT) in the urinary bladder. The patient, with urinary frequency, urgency and suprapubic pain had several emergency room visits due to recurrent urinary tract infection. Both sonogram and cystoscopy identified bladder tumors near the bladder neck. An abdominal contrast-enhanced computed tomography scan revealed a polypoid lesion on the anterior bladder wall without enlarged lymph nodes. Transurethral resection of the bladder tumor was conducted. The pathology report confirmed extranodal marginal zone MALT lymphoma. The clinical stage was IEA. Follow-up imaging reported residual bladder tumors, prompting adjuvant radiotherapy. The patient was treated successfully and was disease-free at the 9-month follow-up visit. Primary lymphoma is an uncommon pathological subtype. Its clinical and radiological differentiation from urothelial carcinoma (UC) can be challenging, but treatment strategies differ significantly. A definitive diagnosis relies on histopathology and immunohistochemistry. Typically, bladder lymphoma has a favorable prognosis, but further research is required to identify the optimal treatment.

Immunoglobulin M-based local production in skin-associated lymphoid tissue of flounder (Paralichthys olivaceus) initiated by immersion with inactivated Edwardsiella tarda.

Fish skin, the mucosal site most exposed to external antigens, requires protection by an efficient local mucosal immune system. The mucosal reserve of IgM is recognized as an immune strategy that blocks pathogen invasion to maintain homeostasis, whereas the mechanism of skin-associated local IgM production induced by mucosal antigens is not well know. In this study, we found that the skin of flounder (Paralichthys olivaceus) was equipped with the immune cellular and molecular basis for processing mucosal antigens and triggering local specific responses, i.e., CD4+ Zap-70+ T cells, CD4- Zap-70+ T/NK cells, IgM+ MHCII+ B cells, PNA+ MHCII+ antigen-presenting cells, UEA-1+ WGA+ and UEA-1+ WGA- antigen-sampling cells, as well as secreted IgM and pIgR, as demonstrated by indirect immunofluorescence assay using different antibodies and lectins. After immersion immunization with inactivated Edwardsiella tarda, qPCR assay displayed up-regulation of immune-related genes in flounder skin. Flow cytometry analysis and EdU labeling demonstrated that the mucosal inactivated vaccine induced local proliferation and increased amounts of cutaneous IgM+ B cells. Skin explant culture proved the local production of specific IgM in the skin, which could bind to the surface of E. tarda. ELISA, laser scanning confocal microscopy, and western blot revealed that, in addition to the elevated IgM levels, pIgR protein level was significantly up-regulated in skin tissue and surface mucus containing the pIgR (secretory component, SC)-tetrameric IgM complex, indicating that mucosal vaccine stimulated up-regulation of IgM and pIgR, which were secreted as a complex into skin mucus to exert the protective effects as secretory IgM. These findings deepen the understanding of IgM-based local responses in the mucosal immunity of teleosts, which will be critical for subsequent investigation into the protective mechanism of mucosal vaccines for fish health.

Feeding docosahexaenoic acid and arachidonic acid during suckling and weaning contributes to oral tolerance development by beneficially modulating the intestinal cytokine and immunoglobulin levels in an allergy-prone Brown Norway rat model.

BACKGROUND: Suckling and weaning arachidonic acid (ARA)+docosahexaenoic acid (DHA) supplementation promoted oral tolerance (OT) development in pups, however, the effect of it on the intestine to promote OT development remains unknown. OBJECTIVE: We aimed to explore the impact of this supplementation on intestinal fatty acid composition, structure, and indicators that are supportive of OT development. METHODS: Allergy-prone Brown Norway dams were randomized to a control (0%ARA, 0%DHA) or ARA+DHA diet (0.45%ARA, 0.8%DHA) during suckling (0-3wks). At weaning (3-8wks), offspring were randomized to a control (0%ARA, 0%DHA) or ARA+DHA diet (0.5% ARA, 0.5%DHA). At 3wks, offspring in each group received an oral gavage of sucrose or ovalbumin (OVA) solution for 5 consecutive days. At 7wks, all offspring received an intraperitoneal OVA injection. At 8wks, offspring were terminated to evaluate jejunum morphology and measure mucosal food allergy-related sIgA and cytokines, ileum phospholipid and triglyceride fatty acid compositions and fecal calprotectin. RESULTS: Weaning ARA+DHA resulted in a higher percentage of DHA in ileum phospholipids and triglycerides (both P <0.001), without affecting the percentage of ARA. Despite no lasting effect of suckling ARA+DHA on the DHA content in ileum phospholipids, a programming effect was found on the allergy-related intestinal immune profile (higher levels of mucosal IL-2 (P =0.049) and sIgA (P =0.033)). OVA treatment resulted in a lower level of mucosal IL-6 (P =0.026) regardless of dietary interventions. Offspring fed ARA+DHA during suckling and/or weaning had a higher level of mucosal TGF-ß after OVA treatment but this was not observed in offspring fed control diets during suckling and weaning (P =0.04). CONCLUSIONS: Early-life dietary ARA+DHA supplementation to allergy-prone rats enhanced the DHA level in intestinal phospholipids (weaning period) and increased the mucosal sIgA, IL-2 and TGF-ß levels (suckling and weaning period), indicating its ability to create a tolerogenic intestinal environment to support OT development.

Epidemiology and tumor microenvironment of ocular surface and orbital tumors on growth and malignant transformation.

The ocular surface and orbit constitute unique microenvironments in the human body. Current advances in molecular research have deepened our understanding of tumor development in these regions. Tumors exhibit greater heterogeneity compared to normal tissues, as revealed by pathological and histological examinations. The tumor microenvironment (TME) plays a crucial role in the proliferation and progression of cancer cells. Factors from the external environment or the body's own inflammation and microcirculation interact within the TME, maintaining a delicate balance. Disruption of this balance, through uncontrolled signal pathway activation, can transform normal or benign tissues into malignant ones. In recent years, various systemic immunotherapies have been developed for cancer treatment. This study reviews the epidemiology of ocular surface and orbital tumors include squamous cell carcinoma, basal cell carcinoma, sebaceous carcinoma and lymphoma in conjunction with their occurrence, growth, and underlying mechanisms. We propose that by examining clinical histopathological images, we can identify specific and shared microscopic features of tumors. By collecting, classifying, and analyzing data from these clinical histopathological images, we can pinpoint independent diagnostic factors characteristic of tumors. We hope this study provides a basis for future exploration of the mechanisms underlying different ocular diseases.

Gut-associated lymphoid tissue carcinoma analyzed using next-generation sequencing: A case report.

Tumors related to the gut-associated lymphoid tissue (GALT) have been recently described. GALT carcinomas (GCs) have a characteristic appearance: macroscopically, they appear as a "dome-type" lesion, whereas microscopically, they show dilated cystic glands in the submucosa, differentiated adenocarcinoma without goblet cells, and stromal lymphocytes with germinal centers. However, their origin and pathogenesis remain controversial. Here, we present the case of a 54-year-old man that presented with a protruding lesion in the upper rectum during colonoscopy and had no family or past medical history. Low anterior resection was performed, and the tumor was diagnosed as GC based on its typical morphology. The tumor cells were negative for Mucin 2 and other mucins and CD10. p53 showed null-type. The tumor was associated with rich lymphocyte infiltration and germinal centers. Next-generation sequencing detected EGFR missense and TP53 nonsense mutations. Although GCs are known as conventional colorectal carcinomas that invade the submucosa, this case showed no neoplastic lesion in the mucosal epithelium in situ. Moreover, we detected EGFR and TP53 mutations (no pathogenic APC or KRAS mutations), which are not conventional adenoma-carcinoma mutations. Further studies are warranted to confirm whether GC is a sporadic carcinoma that invades the GALT submucosa.

Higher Microbial Abundance and Diversity in Bronchus-Associated Lymphoid Tissue (BALT) Lymphomas than in Non-Cancerous Lung Tissues.

Purpose: It is well known that the majority of the extranodal marginal zone lymphomas of mucosa-associated lymphoid tissues (MALT lymphomas) are associated with microbiota, e.g., gastric MALT lymphoma with Helicobacter pylori. In general, they are very sensitive to low-dose radiotherapy and chemotherapeutic agents. The microbiota profile is not clearly elucidated in bronchus-associated lymphoid tissue (BALT) lymphoma, a rare type of MALT lymphoma in the lung. Thus, this study aimed to clarify the intratumor microbiome in BALT lymphoma using the third-generation NGS method. Materials and Methods: DNAs were extracted from 12 formalin-fixed paraffin-embedded (FFPE) tumor tissues obtained from BALT lymphoma patients diagnosed between 1990 and 2016. 16S rRNA gene was amplified by polymerase chain reaction. Amplicons were sequenced using a Nanopore platform. Next-generation sequencing analysis was performed to assess microbial profiles. For comparison, FFPE specimens from nine non-cancerous lung tissues were also analyzed. Results: Specific bacterial families including Burkholderiaceae, Bacillaceae, and Microbacteriaceae were associated with BALT lymphoma by a linear discriminant analysis effect size approach. Although the number of specimens was limited, BALT lymphomas exhibited significantly higher microbial abundance and diversity with distinct microbial composition patterns and correlation networks than non-cancerous lung tissues. Conclusion: This study provides the first insight into intratumor microbiome in BALT lymphoma using the third-generation NGS method. A distinct microbial composition suggests the presence of a unique tumor microenvironment of BALT lymphoma.

Chemokine receptors in primary and secondary lymphoid tissues.

Chemokine receptors are a complex superfamily of surface G protein-coupled receptors present mostly in leukocytes. In this chapter, we review the presence and functions of chemokine receptors in the immune cells of the primary and secondary lymphoid organs. Those include bone marrow, thymus, spleen, lymph nodes, and Peyer's patches as the main components of the gut-associated lymphoid tissue. There are general groups of chemokine receptors: conventional and atypical. We will mostly cover the role of conventional chemokine receptors, which are divided into four classes (CC, CXC, CX3C, and XC). Some relevant members are CXCR4, CXCR5, CCR4 and CCR7. For example, CXCR4 is a key chemokine receptor in the bone marrow controlling from the homing of progenitor cells into the bone marrow, the development of B cells, to the homing of long-lived plasma cells to this primary lymphoid organ. CCR7 and CCR4 are two of the main players in the thymus. CCR7 along with CCR9 control the traffic of thymic seed progenitors into the thymus, while CCR4 and CCR7 are critical for the entry of thymocytes into the medulla and as controllers of the central tolerance in the thymus. CXCR4 and CXCR5 have major roles in the spleen, guiding the maturation and class-switching of B cells in the different areas of the germinal center. In the T-cell zone, CCR7 guides the differentiation of naïve T cells. CCR7 also controls and directs the entry of T cells, B cells, and dendritic cells into secondary lymphoid tissues, including the spleen and lymph nodes. As new technologies emerge, techniques such as high dimensional spectral flow cytometry or single-cell sequencing allow a more comprehensive knowledge of the chemokine receptor network and their ligands, as well as the discovery of new interactions mediating unknown and overlooked mechanisms in health and disease.

The Dilemma for Early-Stage Conjunctival Mucosa-Associated Lymphoid Tissue Lymphoma: To Treat or Not to Treat?

BACKGROUND: Primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (MALToma) is typically treated with radiotherapy. Some studies suggested a "wait and watch" approach due to the adverse effects of radiotherapy. However, the benefits of observation for localized conjunctival MALToma remain unclear. Therefore, we aimed to explore the clinical course of early-stage conjunctival MALToma, distinguish heterogeneity between T1 and T2 patients, and identify prognostic factors. METHODS: This retrospective study involved patients with stage T1-T2 conjunctival MALToma and lasted >6 months. Clinical characteristics were compared between T1 and T2 subjects. Prognostic factors were examined with Cox regression. RESULTS: The research comprised 32 subjects with early-stage conjunctival MALToma, of whom 25% underwent observation. No individuals expired regardless of choosing observation or radiotherapy. The T1 patients were younger (p = 0.002) and more inclined towards observation only (p = 0.035) than the T2 subjects. Despite more of the T1 patients undergoing watchful waiting than the T2 subjects, the T1 patients seemed to have longer systemic relapse-free survival than the T2 subjects (17 vs. 13 years, p = 0.343). CD43 may imply poor prognosis (p = 0.049). CONCLUSIONS: Careful observation may be suggested for early-stage conjunctival MALToma. While more of the T1 individuals were younger and chose observation than the T2 patients, survival seemed longer in the T1 subjects without significance. CD43 may indicate shorter survival in early-stage cases.

Bisphenol A triggers activation of ocular immune system and aggravates allergic airway inflammation.

Bisphenol A (BPA) is widely used in manufacturing plastic products, and it has been reported that exposure through the airway or orally aggravates allergic airway inflammation. Because BPA is detected in the atmosphere and indoor environments, the eyes can also be exposed to BPA. After ocular exposure to BPA and antigen via eye drops, we observed enhanced antigen uptake of antigen-presenting cells (APCs) in tear duct-associated lymphoid tissue (TALT). Additionally, we observed the formation of germinal center (GC) B cells in TALT and induction of allergic airway inflammation in mice sensitized with BPA and antigen via eye drops, followed by airway antigen exposure. We also found that DNAX-activating protein of 12 kDa (DAP12)-deficient mice displayed impaired activation of APCs enhanced by ocular exposure to BPA. These results indicate that ocular sensitization to BPA and allergen triggers allergic inflammation via TALT activation, and that DAP12 might be a key molecule for modulating the ocular immune system.

Harnessing the potential of the NALT and BALT as targets for immunomodulation using engineering strategies to enhance mucosal uptake.

Mucosal barrier tissues and their mucosal associated lymphoid tissues (MALT) are attractive targets for vaccines and immunotherapies due to their roles in both priming and regulating adaptive immune responses. The upper and lower respiratory mucosae, in particular, possess unique properties: a vast surface area responsible for frontline protection against inhaled pathogens but also simultaneous tight regulation of homeostasis against a continuous backdrop of non-pathogenic antigen exposure. Within the upper and lower respiratory tract, the nasal and bronchial associated lymphoid tissues (NALT and BALT, respectively) are key sites where antigen-specific immune responses are orchestrated against inhaled antigens, serving as critical training grounds for adaptive immunity. Many infectious diseases are transmitted via respiratory mucosal sites, highlighting the need for vaccines that can activate resident frontline immune protection in these tissues to block infection. While traditional parenteral vaccines that are injected tend to elicit weak immunity in mucosal tissues, mucosal vaccines (i.e., that are administered intranasally) are capable of eliciting both systemic and mucosal immunity in tandem by initiating immune responses in the MALT. In contrast, administering antigen to mucosal tissues in the absence of adjuvant or costimulatory signals can instead induce antigen-specific tolerance by exploiting regulatory mechanisms inherent to MALT, holding potential for mucosal immunotherapies to treat autoimmunity. Yet despite being well motivated by mucosal biology, development of both mucosal subunit vaccines and immunotherapies has historically been plagued by poor drug delivery across mucosal barriers, resulting in weak efficacy, short-lived responses, and to-date a lack of clinical translation. Development of engineering strategies that can overcome barriers to mucosal delivery are thus critical for translation of mucosal subunit vaccines and immunotherapies. This review covers engineering strategies to enhance mucosal uptake via active targeting and passive transport mechanisms, with a parallel focus on mechanisms of immune activation and regulation in the respiratory mucosa. By combining engineering strategies for enhanced mucosal delivery with a better understanding of immune mechanisms in the NALT and BALT, we hope to illustrate the potential of these mucosal sites as targets for immunomodulation.

Epidemiological and pathomorphologic investigation of peste des petits ruminants in Western Algeria: A comprehensive study of clinical and histopathological findings.

Background: This study delves into the epidemiology and pathomorphologic characteristics of peste des petits ruminants (PPR) in western Algeria, a viral disease that constantly threatens small animals in Africa, the Middle East, and Asia. Aim: The purpose of this investigation was to evaluate the epidemiology of PPR in western Algeria and to understand the pathomorphological lesions in naturally infected small ruminants. Methods: An online survey conducted via google forms and shared with veterinarians in the wilaya of Tiaret, provided insights into the prevalence and clinical manifestations of PPR.A comprehensive examination of organs was conducted and representative tissue samples from the lungs, trachea, thymus, spleen, liver, kidney, heart, tongue, stomach, different parts of the small and large intestine, and mesenteric lymph nodes were collected and the specimen was fixed in a 10% neutral buffer formalin solution. Results: Among 2,200 small ruminants managed by expert veterinarians, 192 small ruminants exhibited clinical signs compatible with PPR, and 79 dead animals. Among the 31 sick young small ruminants, eight were confirmed to be infected with the PPR virus. Necropsies of affected animals revealed significant gross lesions in organs such as the lungs, intestines, spleen, and lymph nodes. Histopathological analysis further illuminated the severity of lesions, including interstitial pneumonia, syncytial cell formation, and severe gastroenteritis. Conclusion: The study's comprehensive approach, encompassing epidemiological data, necropsy findings, and histopathological insights, contributes valuable knowledge for understanding and managing PPR outbreaks.The pathological lesions observed in this study exhibited consistency with those previously documented in experimental studies, thereby providing support for the diagnosis based on clinical signs and disease history.

Novel AHR ligand AGT-5 ameliorates type 1 diabetes in mice through regulatory cell activation in the early phase of the disease.

Type 1 diabetes (T1D) is an autoimmune disease with a strong chronic inflammatory component. One possible strategy for the treatment of T1D is to stimulate the regulatory arm of the immune response, i.e. to promote the function of tolerogenic dendritic cells (tolDC) and regulatory T cells (Treg). Since both cell types have been shown to be responsive to the aryl hydrocarbon receptor (AHR) activation, we used a recently characterized member of a new class of fluorescent AHR ligands, AGT-5, to modulate streptozotocin-induced T1D in C57BL/6 mice. Prophylactic oral administration of AGT-5 reduced hyperglycemia and insulitis in these mice. Phenotypic and functional analysis of cells in the pancreatic infiltrates of AGT-5-treated mice (at the early phase of T1D) revealed a predominantly anti-inflammatory environment, as evidenced by the upregulation of tolDC and Treg frequency, while CD8+ cell, Th1 and Th17 cells were significantly reduced. Similarly, AGT-5 enhanced the proportion of Treg and tolDC in small intestine lamina propria and suppressed the activation status of antigen-presenting cells through down-regulation of co-stimulatory molecules CD40, CD80 and CD86. The expression levels of Cyp1a1, controlled by the AHR, were increased in CD4+, CD8+ and Treg, confirming the AHR-mediated effect of AGT-5 in these cells. Finally, AGT-5 stimulated the function of regulatory cells in the pancreatic islets and lamina propria by upregulating indoleamine 2,3-dioxigenase 1 (IDO1) in tolDC. These findings were supported by the abrogation of AGT-5-mediated in vitro effects on DC in the presence of IDO1 inhibitor. AGT-5 also increased the expression of CD39 or CD73 ATP-degrading ectoenzymes by Treg. The increase in Treg is further supported by the upregulated frequency of IL-2-producing type 3 innate lymphoid cells (ILC3) in the lamina propria. Anti-inflammatory effects of AGT-5 were also validated on human tonsil cells, where in vitro exposure to AGT-5 increased the proportion of immunosuppressive dendritic cells and ILC3. These results suggest that AGT-5, by stimulating AHR, may promote a general immunosuppressive environment in the pancreas and small intestine lamina propria at the early phase of disease, and thereby inhibit the severity of T1D in mice.

Acute Kidney Injury Results in Long-term Alterations of Kidney Lymphatics in Mice.

The long-term effects of a single episode of acute kidney injury (AKI) induced by bilateral ischemia-reperfusion injury (BIRI) on kidney lymphatic dynamics are not known. The purpose of this study was to determine if alterations in kidney lymphatics are sustained in the long-term and how they relate to inflammation and injury. Mice underwent BIRI as a model of AKI and were followed up to 9 months. While kidney function markers initially normalized, histological analysis revealed sustained tissue damage and inflammation for up to 9 months. Transcriptional analysis showed both acute and late-stage lymphangiogenesis, supported by increased expression of lymphatic markers, with unique signatures at each phase. Expression of Ccl21a was distinctly upregulated during late-stage lymphangiogenesis. Three-dimensional tissue cytometry confirmed increased lymphatic vessel abundance, particularly in the renal cortex, at early and late timepoints post-injury. Additionally, the study identified the formation of tertiary lymphoid structures composed of CCR7+ lymphocytes and observed changes in immune cell composition over time, suggesting a complex and dynamic response to AKI involving tissue remodeling and immune cell involvement. These studies provide new insights into the role of lymphatics in the progression of AKI to chronic kidney disease.

Steatotic liver disease in the context of hematological malignancies and anti-neoplastic chemotherapy.

The rising prevalence of obesity-related illnesses, such as metabolic steatotic liver disease (MASLD), represents a significant global public health concern. This disease affects approximately 30 % of the adult population and is the result of metabolic abnormalities rather than alcohol consumption. Additionally, MASLD is associated with an increased risk of cardiovascular disease (CVD), chronic liver disease, and a variety of cancers, particularly gastrointestinal cancers. Clonal hematopoiesis (CH) is a biological state characterized by the expansion of a population of blood cells derived from a single mutated hematopoietic stem cell. The presence of CH in the absence of a diagnosed blood disorder or cytopenia is known as clonal hematopoiesis of indeterminate potential (CHIP), which itself increases the risk of hematological malignancies and CVD. Steatotic liver disease may also complicate the clinical course of cancer patients receiving antineoplastic agents, a condition referred to as chemotherapy induced steatohepatitis (CASH). This review will present an outline of the various aspects of MASLD, including complications. Furthermore, it will summarize the existing knowledge on the emerging association between CHIP and MASLD and present the available data on patient cases with concurrent MASLD and hematological neoplasms. Finally, it will provide a brief overview of the chemotherapeutic drugs associated with CASH, the underlying pathophysiologic mechanisms and their clinical implications.

Serial regression of primary gastric diffuse large B cell lymphoma after Helicobacter pylori eradication therapy: A case report.

Key Clinical Message: Primary gastric diffuse large B-cell lymphoma (DLBCL), a rare malignancy linked to Helicobacter pylori (HP) infection, in this case regressed to low-grade lymphoma and then achieved complete remission after HP eradication (HPE), highlighting this unique interim change and the potential of HPE as an effective treatment for early-stage cases. Abstract: Primary gastric diffuse large B-cell lymphoma (DLBCL) is a rare malignancy. Like gastric mucosa-associated lymphoid tissue (MALT) lymphoma, HP infection is implicated in lymphomagenesis and has thus emerged as a therapeutic target. Studies have demonstrated the sustained efficacy of HP eradication alone for limited-stage primary gastric DLBCL. This report presents the case of a 53-year-old woman with stage IE gastric DLBCL who received triple therapy for HP eradication and experienced an interim histological transformation to MALT lymphoma, ultimately achieving complete pathologic remission. HP eradication therapy may represent a viable treatment option for patients with early-stage primary gastric DLBCL.

Mucosa­associated lymphoid tissue lymphoma translocation protein 1 inhibitor, MI­2, attenuates non­small cell lung cancer cell proliferation, migration and invasion, and promotes apoptosis by suppressing the JNK/c­JUN pathway.

Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitors are effective in attenuating the progression of several types of cancer. However, their role in lung cancer requires further investigation. Therefore, the present study aimed to explore the effect of the MALT1 inhibitor, MI-2, on the behavior of non-small cell lung cancer (NSCLC) cells and to uncover their possible underlying mechanism of action. The mRNA and protein expression levels of MALT1 were detected in the human normal lung epithelial cell line BEAS-2B, and the NSCLC cell lines, NCI-H1299, NCI-H1650, HCC827, A549 and NCI-H23. Subsequently, NCI-H1650 and A549 cells were treated with MI-2. Additionally, NCI-H1650 and A549 cells were co-treated with anisomycin, a c-JUN N-terminal kinase (JNK) pathway activator, with or without MI-2. The results illustrated that the mRNA and protein expression levels of MALT1 were significantly increased in NCI-H1299, NCI-H1650, A549 and NCI-H23 cells compared with those in BEAS-2B cells. Treatment of NCI-H1650 and A549 cells with MI-2 for 72 h reduced the optical density value as determined using the Cell Counting Kit-8 assay. Consistently, the 5-ethynyl-2'-deoxyuridine assay also showed that proliferation was reduced in MI-2-treated NSCLC cells. In addition, MI-2 downregulated B-cell lymphoma 2 (BCL2), and enhanced BCL2-associated X-protein expression and apoptotic rate in NCI-H1650 and A549 cells. These findings indicated that MI-2 could inhibit NCI-H1650 and A549 cell proliferation and promote apoptosis. Furthermore, treatment of cells with MI-2 only attenuated the migration and invasion of NCI-H1650 cells. Notably, MI-2 decreased the expression levels of phosphorylated (p)-JNK and p-c-JUN in NCI-H1650 and A549 cells, thus suggesting that MI-2 could suppress the JNK/c-JUN signaling pathway. However, NSCLC cell co-treatment with anisomycin (JNK pathway activator) reversed the effect of MI-2 on the proliferation, apoptosis and activation of the JNK/c-JUN pathway in NCI-H1650 and A549 cells. In conclusion, the present study demonstrated that the MALT1 inhibitor, MI-2, could suppress NSCLC cell proliferation, migration and invasion, and induce apoptosis via inactivating the JNK/c-JUN pathway.

A Case of Primary Hepatic Mucosa-Associated Lymphoid Tissue Lymphoma in a Patient With Primary Biliary Cholangitis and Hashimoto's Thyroiditis.

Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade malignant lymphoproliferative disease, representing a low percentage of newly diagnosed lymphoma cases. Although its exact cause is still unclear, it is commonly associated with infections or autoimmune diseases. The stomach is the most frequent site for MALT lymphoma, with primary hepatic MALT lymphoma being exceptionally rare. Cases of primary hepatic MALT lymphoma often coincide with viral hepatitis. In this report, we present a case of primary hepatic MALT lymphoma in a patient with no history of hepatitis but complicated by primary biliary cholangitis (PBC) and Hashimoto's thyroiditis.

Remission With Radiation Therapy in Primary Tongue Mucosa-Associated Lymphoid Tissue Lymphoma: A Case Report.

Mucosa-associated lymphoid tissue (MALT) lymphoma arising from the tongue is a rare pathologic condition for which a standard treatment mode has not been established. This disease represents a low-grade lymphoma frequently found in the stomach but rarely in the lymphoid tissue of the tongue. Only six cases that have been reported could be retrieved. We present the case of a 79-year-old woman who manifested with a mass on her tongue. A biopsy of the mass confirmed a diagnosis of MALT lymphoma. Radiation therapy of 30.6 Gy in 17 fractions was performed, and a complete metabolic response was achieved.

Blood MALT1 serves as a potential biomarker reflecting the response and survival of immune­checkpoint­inhibitor therapy in advanced hepatocellular carcinoma.

Treatment modalities involving an immune-checkpoint-inhibitor (ICI) have emerged as therapeutic options in advanced hepatocellular carcinoma (HCC). Nonetheless, auxiliary biomarkers are required to evaluate their efficacy. The present study aimed to assess the potential of blood mucosa-associated lymphoid tissue 1 (MALT1) in reflecting clinical response and prognosis in patients with advanced HCC who received ICI therapy. Peripheral blood was collected from 51 patients with advanced HCC who were about to receive ICI or ICI-based treatment. Blood MALT1 levels were determined using reverse transcription-quantitative PCR, and the blood MALT1 levels in 50 healthy controls (HCs) were also assessed. Besides, the treatment response and survival data were collected. The Wilcoxon rank-sum test was used for comparison analysis and the Spearman's rank correlation coefficient test was used for correlation analysis. The prognostic value of MALT1 was determined by Kaplan-Meier curve analysis with the log-rank test. Univariate and multivariate Cox regression models were used to identify factors associated with progression-free survival (PFS) and overall survival (OS). The results demonstrated that blood MALT1 levels were significantly increased in patients with advanced HCC compared with that in HCs (P<0.001). Blood MALT1 levels were increased in patients with portal vein invasion (vs. without portal vein invasion; P=0.010), extrahepatic disease (vs. without extrahepatic disease; P=0.026) and α-fetoprotein (AFP) ≥200 ng/ml (vs. AFP <200 ng/ml; P=0.040). After 4 cycles of ICI therapy, the objective response rate (ORR) and disease control rate (DCR) was 29.4 and 68.6%, respectively. Blood MALT1 levels were also significantly and negatively associated with the ORR (P=0.043) and DCR (P=0.004). Furthermore, PFS and OS were shortened in patients with high blood MALT1 levels (cut-off by the median) compared to those with low blood MALT1 levels. After adjusting using multivariate Cox regression models, high blood MALT1 levels were demonstrated to be a significant independent risk factor for shortened PFS [hazard ratio (HR)=2.419; P=0.009] and OS (HR=2.706, P=0.018) in patients with advanced HCC who received ICI therapy. In summary, blood MALT1 levels serve as a potential biomarker to reflect treatment response and survival in patients with advanced HCC who receive ICI therapy.