Luna Ghosh

Tomato sauce supplementation and prostate cancer: lycopene accumulation and modulation of biomarkers of carcinogenesis.

As part of a randomized placebo-controlled study to evaluate the effect of lycopene supplementation on DNA damage in men with prostate cancer, a nonrandomized 5th arm using tomato sauce was included and reported here. Thirty-two patients with localized prostate adenocarcinoma consumed tomato sauce-based pasta dishes for 3 weeks (30 mg of lycopene/day) before their scheduled radical prostatectomy. Prostate tissue was obtained as biopsies at baseline and as resected tissue at the time of the prostatectomy. Serum and prostate lycopene, serum prostate specific antigen (PSA) concentrations, and leukocyte DNA 8-OH-deoxyguanosine/deoxyguanosine (80HdG) were measured at baseline and at the end of the intervention. Cancer cells in paraffin sections of prostate biopsies and postintervention resected tissue were compared for 80HdG staining and for apoptosis. Adherence to the daily consumption of tomato-based entrees was 81.6% of the intended dose, and serum and prostate lycopene concentrations increased 1.97- and 2.92-fold (P< 0.001), respectively. Mean serum PSA concentrations decreased by 17.5% (P< 0.002) and leukocyte 80HdG decreased by 21.3% (P< 0.005) after tomato sauce consumption. Resected tissues from tomato sauce-supplemented patients had 28.3% lower prostate 80HdG compared with the nonstudy control group (P < 0.03). Cancer cell 80HdG staining of Gleason Score-matched resected prostate sections was reduced by 40.5% in mean nuclear density (P < 0.005) and by 36.4% in mean area (P < 0.018) compared with the presupplementation biopsy. Apoptotic index was higher in hyperplastic and neoplastic cells in the resected tissue after supplementation. These data taken as a whole indicate significant uptake of lycopene into prostate tissue and a reduction in DNA damage in both leukocyte and prostate tissue. Whether reduction in DNA. damage to prostate cancer cells is beneficial awaits further research, although reduction in serum PSA concentrations is promising.

Development of skeletal metastasis by human prostate cancer in athymic nude mice.

The biology of skeletal metastasis is poorly understood. In order to establish an animal model of bone metastasis, cells from a human prostate cancer cell line (PC-3) were injected into the tail veins of athymic nude mice while the inferior vena cava was occluded. This technique was used in order to divert cells into the vertebral venous plexus. A control group of animals received tumor cells without caval occlusion. Bone lesions developed in 3/16 (19 per cent) experimental mice and in none of the control mice. The incidence of lung metastasis was significantly decreased in the experimental mice (5/16) as compared with non-occluded control mice (14/16). Two tumor sublines were established from explant cultures of bone lesions. Injection of these cells resulted in bone metastasis in 19/36 (53 per cent) mice (P=0.03 compared with the parent line). The incidence of lung lesions was also increased. The predominant site of bone metastasis was the lumbar vertebrae; other affected sites were the pelvis and femurs. All bone lesions resulted in extensive bone destruction. The successful development of bone metastasis using the technique of caval occlusion lends support to the hypothesis that entry of cells into the vertebral circulation is an important step in the development of these lesions. This model should be of value in understanding the pathogenesis of bone metastasis, and in studying the effects of various agents on the prevention and control of these lesions.

Effects of Tomato Sauce Consumption on Apoptotic Cell Death in Prostate Benign Hyperplasia and Carcinoma

Population studies have suggested that lycopene, which is mostly found in tomato and tomato products, may reduce the risk of prostate cancer. We previously found that tomato sauce consumption prior to prostatectomy for prostate cancer decreased serum prostate specific antigen, decreased oxidative DNA damage, and increased lycopene concentrations in prostate tissue (Chen et al., 2001). Here, we extended those investigations to determine whether apoptotic cell death and associated Bcl-2 and Bax proteins were modulated by tomato sauce intervention. Thirty-two patients diagnosed by biopsy with prostate carcinoma were given tomato sauce pasta entrees (30 mg lycopene/day) for 3 wk before prostatectomy. Thirty-four patients with prostate cancer who did not consume tomato sauce and underwent prostatectomy served as controls. When tumor areas with the most apoptotic cells were compared in the biopsy (before) and resected prostate tissue (after), tomato sauce consumption increased apoptotic cells in benign prostate hyperplasia (BPH) from 0.66 ± 0.10% to 1.38 ± 0.31% (P = 0.013) and in carcinomas from 0.84 ± 0.13% to 2.76 ± 0.58% (P = 0.0003). When comparable morphological areas were counted, apoptotic cell death in carcinomas increased significantly with treatment, from 0.84 ± 0.13% to 1.17 ± 0.19% (P = 0.028), and apoptotic cell death in BPH showed a tendency toward an increase from 0.66 ± 0.10% to 1.20 ± 0.32% (P = 0.20). When the values of apoptotic cells in BPH and carcinomas of patients who consume tomato sauce were compared with corresponding control lesions of the patients who did not consume tomato sauce in resected prostate tissue, the differences of values were not significant [BPH 1.38 ± 0.31% vs. 1.14 ± 0.32% (P= 0.97); carcinomas 2.76 ± 0.58% vs. 1.91 ± 0.32% (P = 0.24)]. Tomato sauce consumption did not affect Bcl-2 expression but decreased Bax expression in carcinomas. These data provide the first in vivo evidence that tomato sauce consumption may suppress the progression of the disease in a subset of patients with prostate cancer by increasing apoptotic cell death. However, because of the relatively small number of control and tomato sauce-supplemented patients and the variability in the values of apoptotic cells in BPH and carcinomas, a much larger number of patients needs to be examined to support the data generated in this study.

Up-regulation of E-selectin and intercellular adhesion molecule-1 differs between Crohn's disease and ulcerative colitis

In present study, we investigated if inflammatory mediators secreted by the inflamed colonic mucosa from patients with Crohns disease and ulcerative colitis had the ability to up-regulate the expression of two adhesion molecules, E-selectin and intercellular adhesion molecule-1. Organ culture techniques and enzyme-linked immunoassays were used to quantify these up-regulations in human umbilical vein endothelial cells. Our results show that, in Crohns disease patients, the expression of E-selectin was up-regulated 5.5-fold over control values and intercellular adhesion molecule-1 expression was increased 2.4-fold. In ulcerative colitis patients, E-selectin expression was up-regulated twofold over controls with only a 1.5-fold increase in intercellular adhesion molecule-1 expression. Histologically, there was no difference in the degree of inflammation between the two disease groups. Sulfasalazine, in a dose-dependent manner, inhibited E-selectin expression up to 58% and intercellular adhesion molecule-1 up to 62% when stimulated by lipopolysaccharide. The up-regulation of E-selectin and intercellular adhesion molecule-1 may play an important role in mediating the inflammatory process in inflammatory bowel disease. The observed difference between Crohns disease and ulcerative colitis may reflect differences in inflammatory cell infiltrates or the histopathological differences between the two diseases.

Epidermal Growth Factor in the Normal and Neoplastic Kidney and Bladder

Epidermal growth factor (EGF) is a cell-regulating polypeptide that appears important to the maintenance and function of some benign tissues and to the transformation and proliferation of certain malignancies. In humans the highest concentrations of EGF are found in the urine. We investigated possible interactions between EGF and normal and neoplastic tissues of the urinary system with indirect immunohistochemical staining of paraffin-embedded tissue sections. A polyclonal antibody directed against mouse EGF but shown to react with human EGF was used in the assays. Positive staining was granular in nature and confined to the cytoplasm. Staining of the renal parenchyma (N = 5) was observed in the epithelium of the proximal and distal tubules and the collecting ducts. There was staining of clear cell (N = 6) and papillary (N = 3) carcinomas of the kidney. Staining of the normal urothelium (N = 5) was limited to superficial cells. All transitional cell (N = 21) and squamous (N = 2) carcinomas of the bladder stained. Subjectively, the staining intensity of the transitional cell carcinomas correlated inversely with tumor differentiation. In light of evidence that internalized, receptor-bound EGF is rapidly degraded, the striking immunohistochemical demonstration of cytoplasmic EGF suggests active synthesis. EGF synthesized by urothelial and renal carcinomas may be involved in an autocrine mechanism of malignant proliferation.

Effect of unilateral testicular torsion on blood flow and histology of contralateral testes

BACKGROUND/PURPOSE Infertility occurs in 25% of patients after unilateral testicular torsion; hence, the authors examined hemodynamic and histological changes in both testes after acute testicular torsion in neonatal piglets. METHODS The animals were anesthetized, intubated, ventilated, catheterized, and assigned randomly to a sham group or one of three experimental groups undergoing 720 degrees torsion of the left testis for 8 hours after which it was untwisted in group I and removed in group II. In group III, both testes were removed. Data were collected at baseline (T = 0), 4 hours (T = 4), and 8 hours of torsion (T = 8) and at the ninth hour of the experiment (T = 9). Testicular blood flow was determined by using radiolabeled microspheres. The testes also were examined blindly with routine and electron microscopy. RESULTS In group I, testicular blood flow decreased in the affected testis during torsion and increased significantly after detorsion, whereas blood flow to the contralateral testis increased significantly after detorsion. Sham-operated animals showed no histological abnormality in either testis. In all torsion groups, the affected testis showed extensive changes caused by hemorrhagic necrosis. The contralateral testis only showed changes in group I. CONCLUSION Unilateral testicular torsion resulted in ipsilateral damage caused by a decrease and subsequent increase in blood flow while in the contralateral testis; damage was the result of a significant increase in blood flow after detorsion.

Ultrastructural study of stroma in human mammary carcinoma.

This investigation was designed to study the origin of the stromal component of human mammary carcinoma. Tissues from 30 proved breast carcinomas were studied. Under a light microscope with special stains, an increased connective tissue component was seen in carcinoma. Gluteraldehyde-fixed tissue was examined under an electron microscope. The stroma appeared to be composed of fibroblastic, myofibroblastic, histiocytic and primitive mesenchymal cells. Elastic fibers were intimately intermingled with collagen and reticulin and seen in close association with carcinoma cells. In some areas they were seen inside the carcinoma cells with discontinuous cytoplasmic membrane, as if they were formed by the cancer cells. This observation suggests that breast carcinoma cells play an important role in the production of elastic fibers in association with stromal cells and also stimulate the proliferation of the stromal cellular component.

Dysphagia caused by a fetus-in-fetu in a 27-year-old man

Mechanical obstruction of the distal esophagus by a fetus-in-fetu is an extremely rare condition that has not been previously reported. We present the case of a 27-year-old man who presented with dysphagia caused by fetus-in-fetu contained within a retroperitoneal cystic cavity. The tumor, noticed since childhood, did not cause any symptoms until a year before presentation when symptoms of dysphagia developed. We propose including this entity in the differential diagnosis of a retroperitoneal mass.

Hemangiopericytoma arising in a solitary plexiform neurofibroma: Report of a case and review of the literature

A 71-year-old black woman with no known stigmata of neurofibromatosis developed a left buccal mass of 2 years duration. Histologic findings revealed a hemangiopericytoma and a plexiform neurofibroma in the same tumor. Cells with features of both tumor components were demonstrated ultrastructurally.

Congenital embryonal rhabdomyosarcoma of the hand and Apert's syndrome

A unique case of congenital embryonal rhabdomyosarcoma of the hand in a patient with Aperts syndrome is presented. Immediately after birth a 1 cm soft, bluish mass of the right thenar eminence was clinically diagnosed as a hemangioma. Several months later when the lesion started rapidly enlarging the nature of the tumor was identified, and it was treated with a multidisciplinary approach that included surgical resection, chemotherapy, and radiation.