Philosophiae Doctor - PhD / The incidence of Diffuse large B cell Lymphoma has been increasing lately at an alarming rate especially, in developing countries like Sudan. The standard therapy in Sudan is based solely on the R-CHOP chemotherapy regimen, yet it has been noticed that Diffuse Large B cell Lymphoma prognosis remains unfavorable. The late diagnosis and the consequent side-effects of the therapy directly affected the disease’s poor outcome. There is a scarcity of scientific publications regarding DLBCL in Sudan, but the increased burden necessitates the need for further research.

Objective: Challenging differential diagnosis Background: B cell lymphoma constitutes 80-85% of cases of Non Hodgkin's lymphoma in the Untied States. Metabolic complications may arise from the disease itself or through its end organ involvement. Case Report: We describe a case of a diffuse large B cell lymphoma diagnosed by abdominal computed tomography after it initially presented as hypoglycemia not correctable by dextrose infusion that instead resulted in increased anion gap metabolic acidosis with elevated lactate levels. Conclusions: The case illustrates how lymphomas can present unusually with hypoglycemia and lactic acidosis, the latter being an ominous sign that can occur without liver involvement. In this regard, the case demonstrates the metabolic sequelae of lymphoma that should raise suspicion for an underlying process. This has implications for diagnosis, treatment, and patient survival. Attention should be paid especially in the primary care setting in order to minimize delays in diagnosis.

Objective: Challenging differential diagnosis Background: B cell lymphoma constitutes 80-85% of cases of Non Hodgkin's lymphoma in the Untied States. Metabolic complications may arise from the disease itself or through its end organ involvement. Case Report: We describe a case of a diffuse large B cell lymphoma diagnosed by abdominal computed tomography after it initially presented as hypoglycemia not correctable by dextrose infusion that instead resulted in increased anion gap metabolic acidosis with elevated lactate levels. Conclusions: The case illustrates how lymphomas can present unusually with hypoglycemia and lactic acidosis, the latter being an ominous sign that can occur without liver involvement. In this regard, the case demonstrates the metabolic sequelae of lymphoma that should raise suspicion for an underlying process. This has implications for diagnosis, treatment, and patient survival. Attention should be paid especially in the primary care setting in order to minimize delays in diagnosis.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20260号 / 医博第4219号 / 新制||医||1020(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 前川 平, 教授 木原 正博, 教授 河本 宏 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 新制・課程博士 / 博士(医学) / 甲第24496号 / 医博第4938号 / 新制||医||1064(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 滝田 順子, 教授 上野 英樹, 教授 河本 宏 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Primary gastrointestinal lymphoma is the most common type of extra-nodal lymphoma, representing about 30-50% of all extra-nodal involvement. The stomach is the most common site, with the colon and rectum accounting for a minority of occurrences. Primary colorectal lymphoma is uncommon, representing only 0.3% of all large intestinal malignancies and approximately 3% of GI lymphomas with the majority of these being B-cell non-Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL) being the most common subtype. We present a case of an 85-year-old male who presented with symptoms suggestive of bowel obstruction, who after further evaluation was diagnosed with primary non-Hodgkin lymphoma of the colon, DLBCL subtype.

Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous disease with multiple distinct molecular subtypes. Increased NF-κB activity and expression of the microRNA miR-155 (product of the BIC gene) are associated with one subtype, called the activated B-cell (ABC) subtype. It is shown here that induction of NF-κB activity leads to increased miR-155 expression, the levels of miR-155 in a panel of B-lymphoma cell lines correlate with increased NF-κB activity, and the NF-κB p50/p65 heterodimer binds to a specific DNA site in the BIC promoter. Also described is a regulatory network wherein NF-κB-dependent up-regulation of miR-155 leads to reduced PU.1 transcription factor expression and consequently reduced PU.1-driven expression of B-lymphoma marker CD10 in the human B-lymphoma cell line BJAB. Genetic variation in DLBCL can be used to explain the response of individual patients to chemotherapy. One cancer therapeutic approach currently in clinical trials uses histone deacetylase inhibitors (HDACi's) as a monotherapy or in combination with other vi agents. It is shown here that two pan-HDACi's, trichostatin A and vorinostat, induce apoptosis in seven of eight human DLBCL cell lines. Ectopic over-expression of antiapoptotic proteins BCL-2 and BCL-XL or the pro-apoptotic protein BIM in select DLBCL cell lines can confer further resistance or sensitivity, respectively, to HDACi treatment. Additionally, the BCL-2 family antagonist ABT-737 can increase the sensitivity of several DLBCL cell lines to vorinostat-induced apoptosis, including the HDACi-resistant SUDHL6 cell line. Moreover, one vorinostat-resistant variant of the HDACi-sensitive cell line SUDHL4 has increased expression of anti-apoptotic proteins BCL-XL and MCL-1 and decreased sensitivity to ABT-737, and a second such variant cell line has increased expression of anti-apoptotic protein MCL-1. These results suggest that the balance of anti- to pro-apoptotic BCL-2 family protein expression is important in determining the sensitivity of DLBCL cell lines to HDACi-induced apoptosis. Thus, the sensitivity of DLBCL cell lines to treatment with HDACi's appears to depend on the complex regulation of BCL-2 family members, suggesting that the response of a subset of DLBCL patients to HDACi treatment may benefit from co-treatment with BCL-2 antagonists.

<p dir="ltr">Lymphoma is a prevalent malignancy in dogs. Diffuse large B-cell Lymphoma (DLBCL) is the common subtype that represents about 50% of the clinically seen lymphoma cases. DLBCL diagnosis relies on cytological examination of a fine needle aspirate and histological evaluation by immunohistochemistry (IHC) in most common practices. This workflow is sufficient to confirm the diagnosis; however, it may be challenging to differentiate reactive and neoplastic forms in some controversial cases. In such cases, PCR-based clonality assays and flow cytometry (FC) can help with more conclusive diagnoses. So, finding more biomarkers that can detect and track DLBCL early and over time is a must for a final diagnosis and helps us learn more about how DLBCL starts at the molecular level. MicroRNAs (miRNAs), the small non-coding RNAs, regulate gene expression by binding to the 3'-untranslated region of protein-coding RNAs, leading to either RNA degradation or translational repression. They can switch on and off genes to regulate physiological and pathological processes. MicroRNA stability features and tissue availability make them promising biomarkers for identifying and sub-classifying patients and sequentially evaluating the disease status or the response toward a specific medicine. This dissertation investigates the small RNA sequence analysis, the differentially expressed miRNAs between healthy and DLBCL-affected lymph nodes, and the miRNA profile in DLBCL cases with different outcomes.</p>

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 5 uppsatser.

Das weitaus häufigste aggressive Non-Hodgkin-Lymphom (NHL) ist mit 30-40% aller NHL das diffus großzellige B-Zell-Lymphom. Innerhalb zahlreicher Tumorentitäten, solide sowie hämatologisch, wurde bereits eine kleine Subpopulation von Tumorstammzellen identifiziert. Mit Hilfe des Farbstoffes Hoechst 33342 konnte mittels Durchflusszytometrie eine so genannte “Side Population” in allen 6 untersuchten Zelllinien von aggressiven NHL (BALM-3, Karpass 422, OCI-Ly1, OCI-Ly3, Ramos and SU-DHL-4) sowie in 8 von 11 untersuchten Primärmaterialien erkrankter Patienten nachgewiesen werden. Diese SP-Zellen wiesen ein erhöhtes Klonogenitätspotenzial und eine geringere Chemosuszeptibilität als die Non Side Population auf. Mischkulturen mit GFP-markierten Zellen ergaben Hinweise auf die Existenz eines dynamischen Systems, welches die Entstehung von SP- aus NSP-Zellen nahelegt. Auf molekulargenetischer Ebene ließ sich eine erhöhte ABCA3-Expressions detektieren, und mit Hilfe von Genanalysen konnten einige den SP-Phänotyp potenziell prägende Gene wie CD44,CXCL12 und JAG1 identifiziert werden.