Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gastrointestinal tract is very infrequently involved by malignant lymphoma. Primary lymphoma accounts for 1-4% of all gastrointestinal tumors. The stomach is the most common site of primary non-Hodgkin lymphoma. Esophagus is least likely site of lymphoma of the gastrointestinal tract. Hodgkin disease is almost exclusively a nodal disease, and the involvement of gastrointestinal tract usually is the result of disseminated disease that began in nodal sites. Gastrointestinal lymphomas have a wide array of appearances, which can be explained by the nature of lymphocytes and the variety of ways in which their malignant counterparts can develop and spread. The radiographic appearance of gastrointestinal lymphoma varies. Frequently, an appearance is indistinguishable from a primary adenocarcinoma, from other primary mural masses, such as smooth muscle tumors. The radiograph double-contrast barium study remains the screening procedure. Computed tomography plays a pivotal role in management of the process of staging in patient with lymphoma. CT is comparable in its ability to detect retroperitoneal and pelvic lymph nodes. Also 99mTc-MIBI scintigraphy and 99mTc-MIBI uptake within the lymphomatous tumors are helpful. During 1991-2000, 63 patients with suspected lymphoma of gastrointestinal tract were examined in Clinic of Radiology of Kaunas University Hospital. Contrast-enhanced CT had shown 79.3 percent involvement in mesenterial lymph nodes, X-ray double-barium study--14.2 percent in stomach, 3 percent in small intestine, 1.5 percent in colon.
 ...
PMID:[Radiographic diagnosis of gastrointestinal lymphoma]. 1247 34

Although Notch receptor expression on malignant B cells is widespread, the effect of Notch signaling in these cells is poorly understood. To investigate Notch signaling in B-cell malignancy, we assayed the effect of Notch activation in multiple murine and human B-cell tumors, representing both immature and mature subtypes. Expression of constitutively active, truncated forms of the 4 mammalian Notch receptors (ICN1-4) inhibited growth and induced apoptosis in both murine and human B-cell lines but not T-cell lines. Similar results were obtained in human precursor B-cell acute lymphoblastic leukemia lines when Notch activation was achieved by coculture with fibroblasts expressing the Notch ligands Jagged1 or Jagged2. All 4 truncated Notch receptors, as well as the Jagged ligands, induced Hes1 transcription. Retroviral expression of Hairy/Enhancer of Split-1 (Hes1) recapitulated the Notch effects, suggesting that Hes1 is an important mediator of Notch-induced growth arrest and apoptosis in B cells. Among the B-cell malignancies that were susceptible to Notch-mediated growth inhibition/apoptosis were mature B-cell and therapy-resistant B-cell malignancies, including Hodgkin, myeloma, and mixed-lineage leukemia (MLL)-translocated cell lines. These results suggest that therapies capable of activating Notch/Hes1 signaling may have therapeutic potential in a wide range of human B-cell malignancies.
 ...
PMID:Notch signaling is a potent inducer of growth arrest and apoptosis in a wide range of B-cell malignancies. 1611 16

Gastrointestinal lymphoma is an uncommon disease but is the most frequently occurring extranodal lymphoma and is almost exclusively of non-Hodgkin type. Primary gastrointestinal lymphoma most commonly involves the stomach but can involve any part of the gastrointestinal tract from the esophagus to the rectum. Risk factors for the development of gastrointestinal lymphoma include Helicobacter pylori infection, immunosuppression after solid organ transplantation, celiac disease, inflammatory bowel disease, and human immunodeficiency virus infection. Although gastrointestinal lymphoma has a wide variety of imaging appearances and definitive diagnosis relies on histopathologic analysis, certain findings (eg, a bulky mass or diffuse infiltration with preservation of fat planes and no obstruction, multiple site involvement, associated bulky lymphadenopathy) can strongly suggest the diagnosis. Imaging also plays an important role in the detection of complications such as perforation, obstruction, and fistulization. The most commonly used imaging modalities are barium examination and computed tomography (CT). These modalities are complementary, although CT provides a better overall assessment of the disease stage.
 ...
PMID:Primary gastrointestinal lymphoma: spectrum of imaging findings with pathologic correlation. 1784 97

Notch-signalling has been implicated as a pathogenetic factor and a therapeutical target in T-cell leukaemias and in some lymphomas of B-cell origin. Our aim was to investigate the role of Notch-signalling in apoptosis regulation in human non-Hodgkin B-cell lymphoma (B-NHL) cell lines and in primary chronic lymhocytic leukaemia (CLL) cells using Delta-like 4 (Dll4) ligand mediated Notch activation and gamma-secretase inhibitor (GSI) mediated Notch inhibition in vitro. The potential cross-talk of Notch with the transforming growth factor-beta (TGFb) pathway in apoptosis induction was also explored, and the effect of GSI on drug-induced apoptosis was assessed. Modulation of Notch-signalling by itself did not change the rate of apoptosis in B-NHL cell lines and in CLL cells. TGFb-induced apoptosis was decreased - but not completely abolished - by GSI in TGFb-sensitive cell lines, but resistance to the apoptotic effects of TGFb were not reversed by Notch activation or inhibition. Drug-induced apoptosis was not modified by GSI. We identified Hairy/Enhancer of Split (HES)-1 as a TGFb target gene in selected - TGFb-sensitive - B-NHL cell lines. TGFb-induced HES-1 was only partially Notch-dependent in later phases. Apoptosis regulation by TGFb and GSI was not dependent on the transcriptional regulation of c-myc. In conclusion, our data does not support a unifying role of Notch in regulating apoptosis in B-NHL, but warns that gamma-secretase inhibitors may actually counteract apoptosis in some cases.
 ...
PMID:Notch-regulation upon Dll4-stimulation of TGFb-induced apoptosis and gene expression in human B-cell non-Hodgkin lymphomas. 2001 7

We describe a patient who presented with dysphagia after radiation therapy for Hodgkin's lymphoma secondary to wide-mouthed sacculation of the upper esophagus on barium esophagography, most likely resulting from localized radiation necrosis of the muscular layer of the esophageal wall. Despite its rarity, radiologists should be aware of this finding as a potential cause of dysphagia after radiation therapy to the neck or chest. Unlike radiation strictures, radiation-induced sacculation of the esophagus probably can be managed conservatively without need for endoscopic dilatation procedures.
 ...
PMID:Wide-mouthed sacculation of the esophagus: a cause of dysphagia after radiation therapy. 2020 13

Chronic intussusception is defined as intussusception with a history of more than 14 days and is generally associated with a predisposing factor. We are reporting a rare case of chronic intussusception due to Non Hodgkin lymphoma of ileum, appendix, caecum and ascending colon presented as acute intestinal obstruction in emergency. Chronic Intussusception is rare in childhood due to Non Hodgkin lymphoma. A five year male child presented with fever, pain abdomen, vomiting, diarrhoea and mass in right flank. Ultrasonography of the abdomen revealed a mass in ileao-caecal region with chronic intussusception which was confirmed on surgery. X ray of the abdomen showed dilated bowel loops. It is very difficult to make diagnosis of intestinal lymphoma on pre-operative investigations. Patient presented with obstruction should be explored as surgery is the treatment of the choice. Diagnosis can be confirmed by histopathologically. In conclusion, a high index of suspicion and appropriate investigations (USS, Barium enema and CT scan) can result in prompt diagnosis. In majority of children the diagnosis is made at laparotomy and surgery plays a pivotal role in the management.
 ...
PMID:A rare case of chronic intussusception due to non Hodgkin lymphoma. 2256 46

The histone methyltransferase Enhancer of Zeste Homolog 2 (EZH2) is frequently dysregulated in cancers, and gain-of-function (GOF) EZH2 mutations have been identified in non-Hodgkin lymphomas. Small-molecule inhibitors against EZH2 demonstrated anti-tumor activity in EZH2-mutated lymphomas and entered clinical trials. Here, we developed models of acquired resistance to EZH2 inhibitor EI1 with EZH2-mutated lymphoma cells. Resistance was generated by secondary mutations in both wild-type (WT) and GOF Y641N EZH2 alleles. These EZH2 mutants retained the substrate specificity of their predecessor complexes but became refractory to biochemical inhibition by EZH2 inhibitors. Resistant cells were able to maintain a high level of H3K27Me3 in the presence of inhibitors. Interestingly, mutation of EZH2 WT alone generated an intermediate resistance phenotype, which is consistent with a previously proposed model of cooperation between EZH2 WT and Y641N mutants to promote tumorigenesis. In addition, the findings presented here have implications for the clinical translation of EZH2 inhibitors and underscore the need to develop novel EZH2 inhibitors to target potential resistance emerging in clinical settings.
...
PMID:Development of secondary mutations in wild-type and mutant EZH2 alleles cooperates to confer resistance to EZH2 inhibitors. 2589 94

Epigenetic alterations contributing to malignancy have become a more prominent field of investigation over the past several years, as several hallmarks of cancer are substantially altered by changes in the epigenome. Enhancer of zeste homologue 2 (EZH2), an enzyme involved in silencing the transcription of various genes, is overexpressed or mutated in multiple cancers and can lead to proliferation of dedifferentiated cells. Both gain-of-function and loss-of-function mutations have been noted in hematologic cancers, with gain-of-function mutations prevalent among non-Hodgkin lymphomas. Tazemetostat is a first-in-class EZH2 inhibitor developed to target this overexpression. Phase I trials have shown it is generally well tolerated and efficacious in solid tumors as well as hematological malignancies. Tazemetostat was approved by the U.S. Food and Drug Administration (FDA) for use in epithelioid sarcoma in January 2020 on the basis of the results of a recent phase II trial, but with several clinical trials ongoing, the use of tazemetostat for hematological malignancies is a promising avenue for treatment.
 ...
PMID:Tazemetostat for the treatment of multiple types of hematological malignancies and solid tumors. 3252 36


<< Previous 1 2 3