Angioimmunoblastic T-cell lymphoma presenting as giant kidneys: a case report

<p>Abstract</p> <p>Introduction</p> <p>Angioimmunoblastic T-cell lymphoma is a rare form of tumor of the lymph nodes or lymphoid tissue. In this report we describe an unusual presentation of angioimmunoblastic T-cell lymphoma consisting of giant kidneys with no nephrotic syndrome.</p> <p>Case presentation</p> <p>A 46-year-old Arabic man from Gaza was hospitalized in our ward due to abdominal pain and a weight loss of 20 kg during the preceding two months. The results of the physical examination and laboratory tests raised the possibility of neoplastic disease. A computerized tomographic scan of the abdomen showed huge kidneys, and a kidney biopsy showed infiltration by lymphocytes and eosinophils. The genetic examination revealed T-cell lymphoma. Diagnosis was made by a lymph node biopsy, which shows typical findings of angioimmunoblastic T-cell lymphoma.</p> <p>Conclusions</p> <p>Angioimmunoblastic T-cell lymphoma can present with huge kidneys without nephrotic syndrome.</p

Combined acetyl-11-keto-β-boswellic acid and radiation treatment inhibited glioblastoma tumor cells.

Glioblastoma multiforme (GBM) is the most common and most aggressive subtype of malignant gliomas. The current standard of care for newly diagnosed GBM patients involves maximal surgical debulking, followed by radiation therapy and temozolomide chemotherapy. Despite the advances in GBM therapy, its outcome remains poor with a median survival of less than two years. This poor outcome is partly due to the ability of GBM tumors to acquire adaptive resistance to therapy and in particular to radiation. One of the mechanisms contributing to GBM tumor progression and resistance is an aberrant activation of NF-ĸB, a family of inducible transcription factors that play a pivotal role in regulation of many immune, inflammatory and carcinogenic responses. Acetyl-11-keto-β-boswellic acid (AKBA) is a pentacyclic terpenoid extracted from the gum Ayurvedic therapeutic plant Boswellia serrata. AKBA is anti-inflammatory agent that exhibits potent cytotoxic activities against various types of tumors including GBM. One of the mechanisms underlying AKBA anti-tumor activity is its ability to modulate the NF-ĸB signaling pathway. The present study investigated in vitro and in vivo the effect of combining AKBA with ionizing radiation in the treatment of GBM and assessed AKBA anti-tumor activity and radio-enhancing potential. The effect of AKBA and/or radiation on the survival of cultured glioblastoma cancer cells was evaluated by XTT assay. The mode of interaction of treatments tested was calculated using CalcuSyn software. Inducing of apoptosis following AKBA treatment was evaluated using flow cytometry. The effect of combined treatment on the expression of PARP protein was analysed by Western blot assay. Ectopic (subcutaneous) GBM model in nude mice was used for the evaluation of the effect of combined treatment on tumor growth. Immunohistochemical analysis of formalin-fixed paraffin-embedded tumor sections was used to assess treatment-related changes in Ki-67, CD31, p53, Bcl-2 and NF-ĸB-inhibitor IĸB-α. AKBA treatment was found to inhibit the survival of all four tested cell lines in a dose dependent manner. The combined treatment resulted in a more significant inhibitory effect compared to the effect of treatment with radiation alone. A synergistic effect was detected in some of the tested cell lines. Flow cytometric analysis with Annexin V-FITC/PI double staining of AKBA treated cells indicated induction of apoptosis. AKBA apoptotic activity was also confirmed by PARP cleavage detected by Western blot analysis. The combined treatment suppressed tumor growth in vivo compared to no treatment and each treatment alone. Immunohistochemical analysis showed anti-angiogenic and anti-proliferative activity of AKBA in vivo. It also demonstrated a decrease in p53 nuclear staining and in Bcl-2 staining and an increase in IĸB-α staining following AKBA treatment both alone and in combination with radiotherapy. In this study, we demonstrated that AKBA exerts potent anti-proliferative and apoptotic activity, and significantly inhibits both the survival of glioblastoma cells in vitro and the growth of tumors generated by these cells. Combination of AKBA with radiotherapy was found to inhibit factors which involved in cell death regulation, tumor progression and radioresistence, therefore it may serve as a novel approach for GBM patients

Effect of AKBA treatment on p53 and Bcl-2 expression in an ectopic GBM model.

<p>Formalin-fixed paraffin-embedded sections were stained immunohistochemically for p53 and Bcl-2. Representative microphotographs from each treatment group are shown (original magnification x200).</p

Combined acetyl-11-keto-β-boswellic acid and radiation treatment inhibited glioblastoma tumor cells

<div><p>Glioblastoma multiforme (GBM) is the most common and most aggressive subtype of malignant gliomas. The current standard of care for newly diagnosed GBM patients involves maximal surgical debulking, followed by radiation therapy and temozolomide chemotherapy. Despite the advances in GBM therapy, its outcome remains poor with a median survival of less than two years. This poor outcome is partly due to the ability of GBM tumors to acquire adaptive resistance to therapy and in particular to radiation. One of the mechanisms contributing to GBM tumor progression and resistance is an aberrant activation of NF-ĸB, a family of inducible transcription factors that play a pivotal role in regulation of many immune, inflammatory and carcinogenic responses. Acetyl-11-keto-β-boswellic acid (AKBA) is a pentacyclic terpenoid extracted from the gum Ayurvedic therapeutic plant Boswellia serrata. AKBA is anti-inflammatory agent that exhibits potent cytotoxic activities against various types of tumors including GBM. One of the mechanisms underlying AKBA anti-tumor activity is its ability to modulate the NF-ĸB signaling pathway. The present study investigated <i>in vitro</i> and <i>in vivo</i> the effect of combining AKBA with ionizing radiation in the treatment of GBM and assessed AKBA anti-tumor activity and radio-enhancing potential. The effect of AKBA and/or radiation on the survival of cultured glioblastoma cancer cells was evaluated by XTT assay. The mode of interaction of treatments tested was calculated using CalcuSyn software. Inducing of apoptosis following AKBA treatment was evaluated using flow cytometry. The effect of combined treatment on the expression of PARP protein was analysed by Western blot assay. Ectopic (subcutaneous) GBM model in nude mice was used for the evaluation of the effect of combined treatment on tumor growth. Immunohistochemical analysis of formalin-fixed paraffin-embedded tumor sections was used to assess treatment-related changes in Ki-67, CD31, p53, Bcl-2 and NF-ĸB-inhibitor IĸB-α. AKBA treatment was found to inhibit the survival of all four tested cell lines in a dose dependent manner. The combined treatment resulted in a more significant inhibitory effect compared to the effect of treatment with radiation alone. A synergistic effect was detected in some of the tested cell lines. Flow cytometric analysis with Annexin V-FITC/PI double staining of AKBA treated cells indicated induction of apoptosis. AKBA apoptotic activity was also confirmed by PARP cleavage detected by Western blot analysis. The combined treatment suppressed tumor growth <i>in vivo</i> compared to no treatment and each treatment alone. Immunohistochemical analysis showed anti-angiogenic and anti-proliferative activity of AKBA <i>in vivo</i>. It also demonstrated a decrease in p53 nuclear staining and in Bcl-2 staining and an increase in IĸB-α staining following AKBA treatment both alone and in combination with radiotherapy. In this study, we demonstrated that AKBA exerts potent anti-proliferative and apoptotic activity, and significantly inhibits both the survival of glioblastoma cells <i>in vitro</i> and the growth of tumors generated by these cells. Combination of AKBA with radiotherapy was found to inhibit factors which involved in cell death regulation, tumor progression and radioresistence, therefore it may serve as a novel approach for GBM patients.</p></div

Effect of AKBA treatment on NF-ĸB-related protein expression in an ectopic GBM model.

<p>Formalin-fixed paraffin-embedded sections were stained immuno-histochemically for IĸB-α. Representative microphotographs from each treatment group are shown (original magnification x200).</p

Effect of AKBA treatment on proliferation and intra-tumoral microvessel density in an ectopic GBM model.

<p>Formalin-fixed paraffin-embedded sections were stained immunohistochemically for Ki-67 (proliferation marker) and CD31 (endothelial marker). Representative microphotographs from each treatment group are shown (original magnification x400 –Ki-67, x200- CD31).</p

Combined effect of AKBA and ionizing radiation on the survival of glioblastoma cells.

<p>Cells were irradiated with a single dose and then exposed for 72 hrs to different concentrations of AKBA. The survival was evaluated by XTT colorimetric assay. The graph represents the average survival of treated cells relative to the survival of untreated control cells. The data are mean ± SE values from three individual experiments, each performed in triplicates. Statistical significance was determined by one way ANOVA test (*P < 0.05; **P < 0.01; ***P < 0.001). Normalized isobolograms indicated the mode of interaction between AKBA and ionizing radiation. Combination index for each variant of the combined treatment was calculated using Calcusyn software. The line is the line of additivity: interactions below the line are synergistic while interactions above the line are sub-additive.</p