Frequency of gastrointestinal involvement and its clinical significance in mantle cell lymphoma

BACKGROUND: The reported frequency of gastrointestinal (GI) tract involvement in patients with mantle cell lymphoma (MCL) is 15-30%. However, this figure most likely is an underestimate because most patients with MCL involving the GI tract previously reported were examined endoscopically only if they had GI tract symptoms. The impact of endoscopic assessment on the management of MCL patients is unknown. METHODS: From March 1998 to May 2001 baseline upper and lower endoscopy of the GI tract was performed in consecutive untreated patients with MCL as part of a prospective therapeutic trial. Biopsies were performed on abnormal as well as macroscopically normal mucosa. Endoscopy was repeated during treatment and as part of follow-up evaluations. RESULTS: Only 26% of patients presented with GI symptoms at the time of diagnosis. MCL was present histologically in the lower GI tract of 53 of 60 patient (88%) and in the upper GI tract of 28 of 58 patients (43%). Microscopic evidence of MCL was found in 84% of patients with normal visual (macroscopic) findings by lower endoscopy and in 45% of patients with macroscopically normal findings by upper endoscopy. Despite this high frequency of GI tract involvement, the use of upper and lower endoscopy with biopsies in this group of patients resulted in changes in clinical management in only three (4%) patients. CONCLUSIONS: Gastrointestinal tract involvement was found to be present in most patients with MCL, usually at a microscopic level involving macroscopically normal mucosa. The use of aggressive staging evaluation of the GI tract was found to have little impact on patient management decisions in the current study.     

Cyclophosphamide treatment modifies tumor oxygenation and glycolytic rates of RIF-1 tumors: 13C magnetic resonance spectroscopy, Eppendorf electrode, and redox scanning

The effect of cyclophosphamide (Cp) on the glycolytic rate of radiation-induced fibrosarcomas (RIF-1) was measured in vivo in C3H mice by following the production of [3-(13)C]lactate after tail vein infusion of labeled [1-(13)C]glucose. Cp administered i.p. at a dose of 300 mg/kg caused a significant drop in glycolytic rate 24 h after treatment (P < 0.01). This drop was accompanied by an increase in [C-3]/[C-4] glutamate ratio in perchloric acid extracts of the tumors, indicating an increase in the Kreb's cycle activity. Treatment with Cp led to a significant decrease (P < 0.01) in tissue pO(2), measured in vivo with an oxygen Eppendorf electrode. Increases in NADH levels were also observed in rapidly frozen excised tumors examined by three-dimensional optical redox scanning. A significant decrease in tumor pO(2) and an increase in the NADH levels are suggestive of an increase in oxygen consumption by these tumors after Cp treatment. Overall, these data indicate that the reduction in glycolytic rate of Cp-treated RIF-1 tumors is due to an increase in aerobic metabolism.     

Synthetic and antibacterial studies on some new furanopeptides

A series of new furanopeptides (3) are prepared by the coupling of arylsubstituted furoic acids (1) with amino acid methyl esters, di and tetra-peptide methyl esters using dicyclohexyl carbodiimide (DCC) as coupling agent. Some of the newly synthesized compounds are characterized on the basis of IR, 1H NMR, mass spectral data and elemental analysis. Some of the selected compounds are also tested for their antibacterial properties.     

U(VI) reduction by spores of Clostridium acetobutylicum

Vegetative cells of Clostridium acetobutylicum are known to reduce hexavalent uranium (U(VI)). We investigated the ability of spores of this organism to drive the same reaction. We found that spores were able to remove U(VI) from solution when H₂ was provided as an electron donor and to form a U(IV) precipitate. We tested several environmental conditions and found that spent vegetative cell growth medium was required for the process. Electron microscopy showed the product of reduction to accumulate outside the exosporium. Our results point towards a novel U(VI) reduction mechanism, driven by spores, that is distinct from the thoroughly studied reactions in metal-reducing Proteobacteria.     

Early detection of radiation therapy response in non‐Hodgkin's lymphoma xenografts by in vivo 1H magnetic resonance spectroscopy and imaging

The purpose of the study was to investigate the capability of ¹H MRS and MRI methods for detecting early response to radiation therapy in non‐Hodgkin's lymphoma (NHL). Studies were performed on the WSU‐DLCL2 xenograft model in nude mice of human diffuse large B‐cell lymphoma, the most common form of NHL. Radiation treatment was applied as a single 15 Gy dose to the tumor. Tumor lactate, lipids, total choline, T₂ and apparent diffusion coefficients (ADC) were measured before treatment and at 24 h and 72 h after radiation. A Hadamard‐encoded slice‐selective multiple quantum coherence spectroscopy sequence was used for detecting lactate (Lac) while a stimulated echo acquisition mode sequence was used for detection of total choline (tCho) and lipids. T₂‐ and diffusion‐weighted imaging sequences were used for measuring T₂ and ADC. Within 24 h after radiation, significant changes were observed in the normalized integrated resonance intensities of Lac and the methylenes of lipids. Lac/H₂O decreased by 38 ± 15% (p = 0.03), and lipid (1.3 ppm, CH₂)/H₂O increased by 57 ± 14% (p = 0.01). At 72 h after radiation, tCho/H₂O decreased by 45 ± 14% (p = 0.01), and lipid (2.8 ppm, polyunsaturated fatty acid)/H₂O increased by 970 ± 36% (p = 0.001). ADC increased by 14 ± 2% (p = 0.003), and T₂ did not change significantly. Tumor growth delay and regression were observed thereafter. This study enabled comparison of the relative sensitivities of various ¹H MRS and MRI indices to radiation and suggests that ¹H MRS/MRI measurements detect early responses to radiation that precede tumor volume changes. Copyright © 2010 John Wiley & Sons, Ltd.     

The neem limonoids azadirachtin and nimbolide inhibit cell proliferation and induce apoptosis in an animal model of oral oncogenesis

Limonoids from the neem tree (Azadirachta indica) have attracted considerable research attention for their cytotoxicity against human cancer cell lines. However, the antiproliferative and apoptosis inducing effects of neem limonoids have not been tested in animal tumour models. The present study was therefore designed to evaluate the relative chemopreventive potential of the neem limonoids azadirachtin and nimbolide in the hamster buccal pouch (HBP) carcinogenesis model by analyzing the expression of proliferating cell nuclear antigen (PCNA), p21^waf1, cyclin D1, glutathione S-transferase pi (GST-P), NF-κB, inhibitor of κB (IκB), p53, Fas, Bcl-2, Bax, Bid, Apaf-1, cytochrome C, survivin, caspases-3, −6, −8 and −9, and poly(ADP-ribose) polymerase (PARP) by RT-PCR, immunohistochemical, and Western blot analyses. The results provide compelling evidence that azadirachtin and nimbolide mediate their antiproliferative effects by downregulating proteins involved in cell cycle progression and transduce apoptosis by both the intrinsic and extrinsic pathways. On a comparative basis, nimbolide was found to be a more potent antiproliferative and apoptosis inducing agent and offers promise as a candidate agent in multitargeted prevention and treatment of cancer.