Expression of focal adhesion kinase in normal and pathologic human prostate tissues

BACKGROUND: Focal adhesion kinase (FAK) regulates multiple cellular processes including growth, differentiation, adhesion, motility, and apoptosis. In tumor cells, including prostate adenocarcinoma, FAK overexpression has been linked to cancer progression. METHODS: By using immunohistochemistry, FAK expression was investigated in human prostate specimens. RESULTS: FAK was expressed predominantly in the basal layer of normal prostate epithelium but not in secretory epithelium. FAK was expressed at similar levels in all stages of prostate tumorigenesis, including preinvasive carcinoma and metastatic disease. Elevated FAK expression was observed at the earliest stages of transformation and expression continued during cancer progression. CONCLUSION: Given the established role for FAK in the regulation of integrin signaling, we suggest that the sustained elevated levels of FAK expression during prostate tumor cell progression is consistent with a role for FAK in the development and maintenance of prostate carcinoma.     

Nasal transit time in normal subjects and pathologic conditions

A radionuclide method using Tc-99m was used to measure the nasal transit time in 43 patients, including normal smokers and nonsmokers and those with various nasal or paranasal pathologies. The technique described was slightly modified from that already in use in various centers in order to enable more precise measurement. Measurement of transit time of a droplet of Tc-99m phytate on the nasal mucosa appears to differentiate patients with immotile cilia syndrome from normal controls. A positive test, however, can occur also in smokers and in patients with other nasal and paranasal problems. The test is reproducible, cost-effective, and noninvasive, enabling the clinician to make a more appropriate selection of patients needing further investigation.     

Immunohistochemical localization of cathepsin B in neoplastic human prostate

Cathepsin B (CB) has been shown to degrade extracellular matrix (ECM) proteins, and has been reported to be involved in invasion and metastasis of several types of solid organ tumors in human and animals, but CB has not been studied in human prostate cancer (CAP). Our objective was to determine the CB protein immunostaining pattern in CAP and to correlate the immunostaining with the degree of malignancy as reflected in the Gleason grading system. We used two types of CB antibodies (namely, monospecific, polyclonal antibodies to human liver CB prepared in rabbits, and polyclonal antibody produced in sheep) to establish CB localization patterns in neoplastic prostate. Our analysis showed a heterogeneous CB immunostaining pattern in the neoplastic human prostate. CB immunostaining occurred in many, but not all, of the neoplastic columnar/cuboidal cells of acini and isolated cells, i.e., in small ragged glands and clusters (groups) of invasive cells in the prostatic stroma. We have shown that, in general, there was a positive correlation of the intensity of CB immunostaining with the Gleason histologic score (or Gleason grade sum) tumors, i.e., from the lowest scores through score 8, but many of the tumors with scores 9 and 10 showed little CB immunostaining. Our study indicated that the increased CB immunostaining in the Gleason grade sum 5–8 tumors may be associated with increased degradation of ECM, but not in 9 and 10 despite the fact that the latter tumors are more malignant clinically. In well-differentiated tumors, fewer CB immunostaining cells were present than the moderately-differentiated tumors. In other words, most of the stromal invasion of the prostatic ECM occurred in tumors of Gleason grade sums 5–8. We suggest that CB immunostaining might be a useful method to assess stromal invasion of prostatic carcinoma, especially in the higher grade tumors.     

表皮生长因子在前列腺带性结构中的分布及意义

目的探讨表皮生长因子(EGF)在前列腺移行带和外周带组织中的分布特征。方法RTPCR法半定量分析17例正常前列腺移行带和外周带组织、20例良性前列腺增生(BPH)组织EGFmRNA表达水平,印迹杂交法(Westernblot)检测EGF蛋白表达。结果正常前列腺移行带和外周带EGFmRNA表达量分别为0.96±0.31、0.53±0.27,差异有统计学意义(P<0.05)。BPH组织EGFmRNA表达量为1.67±0.25,显著高于正常移行带组织,差异有统计学意义(P<0.01)。Westernblot方法证实移行带EGF蛋白表达高于外周带,而在BPH组织中表达更强。结论EGF在正常前列腺移行带和外周带组织中的表达存在差异,EGF对移行带生长有重要的促进作用,可能是BPH的发病基础之一。     

Distribution of lactoferrin in the normal and inflamed human prostate: an immunohistochemical study.

A polyclonal rabbit antibody to lactoferrin was used to localize the distribution of lactoferrin within the different zones of the normal human prostate as well as within the inflamed human prostate. Cases of normal central zone, peripheral zone, periurethral glandular tissue, as well as cases in which foci of moderate to severe inflammation, along with varying degrees of inflammation-related atrophy, were studied. In cases with inflammation, the staining pattern of lactoferrin was compared to the staining pattern of prostate-specific antigen. Within the central zone, lactoferrin staining occurred in numerous individual cells peppered throughout the epithelium as well as within multiple intraepithelial lumens (lacunae). These lacunae were often numerous enough to give the central zone epithelium a fenestrated appearance; they were not seen in any of the other regions of the prostate. With the exception of an occasional individual cell or isolated positive gland, normal peripheral zone exhibited very little lactoferrin activity. Staining within the transition zone was similar to that seen in the peripheral zone. Staining within the urethral lining of the epithelium in the periurethral glands showed a distinct pattern of frequent intense staining involving the entire gland; frequent individual positive cells were also often seen. Three patterns of staining were identified in prostatic inflammation. Mild periglandular chronic inflammation produced foci of epithelial lactoferrin positivity that coincided precisely with the areas of inflammation. Severe acute inflammation produced strong staining within luminal secretions while cytoplasmic staining was limited to the luminal surface of the epithelium. Post-inflammatory atrophy showed intense diffuse lactoferrin staining in the scant cytoplasm of the atrophic epithelium. In 12 of the 17 cases of inflammation that were studied, areas of post-inflammatory atrophy or severe inflammation commonly showed absence of prostate specific antigen staining and epithelium that was strongly lactoferrin-positive. Within the normal human prostate, lactoferrin appears to be produced primarily within the epithelium of the central zone, periurethral glands, and lining epithelium of the prostatic urethra. Lactoferrin-filled central zone lacunae appear to be structures unique to the central zone. The distribution of lactoferrin in the periurethral glands and urethral lining epithelium, along with the intense production of lactoferrin in the presence of inflammation, and the preservation of lactoferrin production in severe inflammation or atrophy suggest that lactoferrin may be a key component of the inflammatory response within the human prostate.     

Comparative analysis of growth factors in normal and pathologic human prostates

Growth factors, as detected by DNA synthesis stimulating activity for BALB/c 3T3 cells, in normal, benign hypertrophic and cancerous human prostates were analyzed. The total content (units per gram of tissue) in benign hypertrophic prostate was two to four times higher than those in normal and cancerous prostates. In all the three groups, heparin-binding growth factor, growth factor adsorbed to heparin-Sepharose in the presence of 0.5 NaCl. accounted for about 80-95% of the total growth factor content. Qualitative analysis using a heparin-Sepharose column revealed two types of heparin-binding growth factor in the prostates, one eluted from the column at 1.2-1.3 M NaCl and the other at 1.5-1.8 M NaCl. The latter was the predominant type in all groups. In addition to the growth factors detected with BALB/c 3T3, a growth factor with specific action upon MC3T3-E1 mouse osteoblasts was found in prostatic cancer, but not in normal and benign hypertrophic prostates.     

Doppler US of the urinary system and renal vessels in normal and pathologic conditions

The interest of Doppler ultrasound (US) in urinary tract investigation has dramatically increased during the past 10 years. It can provide useful diagnostic informations in pedicular and intrarenal vascular disorders, some medical nephropathies, in the assessment of renal tumors and urinary tract disorders including urolithiasis, acute obstruction and ureteral reflux. Recent technical improvements including the development of US contrast agents (microbubbles) have contributed to increase the diagnostic accuracy of the technique.     

Expression of cathepsin L in human testis under diverse infertility conditions

The cathepsin family of proteolytic enzymes play an important role in the remodeling seminiferous epithelia in rodent testis. In an effort to uncover the cathepsin L expression in diverse pathological conditions in human testis, the immunohistochemical localization of cathepsin L was conducted in human testis under diverse male infertility condition including spermatogenic hypoplasia and testis cancer. In seminiferous tubule of normal, non-obstructive azoospermic, decreased spermatogenesis, and maturation arrest conditions, cathepsin L was found in both germ cells and Sertoli cells. In contrast, there was no visible expression of cathepsin L in seminiferous tubule tissues from Sertoli cell-only syndrome, spermatogenic hypoplasia, and testicular cancer. Our result suggests that the cross-talk between germ cells and Sertoli cells is crucial for the control of cathepsin L expression in human testis. The absence of expression of cathepsin L in germ cell cancer emphasizes that cathepsin L expression in Sertoli cells is regulated by functional germ cells in human testis.     

Angiogenic activity of normal and pathologic human thyroid tissue.

Thyroid tissue was collected from 60 patients during operations for various thyroid conditions. The tissue's angiogenic capacity was assessed in a chick chorioallantoic membrane preparation. Angiogenic activity was observed in 22 (85%) of 26 solitary follicular neoplasms, in none of ten papillary carcinomas and in one of seven glands with Graves' disease (all pretreated with propranolol). Of 17 glands with euthyroid multinodular colloid goitre, three (18%) showed angiogenic activity. No angiogenic activity was detected in normal thyroid tissue from 26 patients. Angiogenic activity of diseased human thyroid does not seem to be a marker of thyroid malignancy.     

Lipofuscin granules in normal,benign and malignant human prostatic tissue

Summary Confirmation and extension of the identification and variation of the frequency of lipofuscin granules in sections of specimens of normal, benign and malignant human prostatic tissue by fluorescent microscopy was obtained. However, the suggestion of the possible relationship between the presence of these granules and alterations in the metabolic processes within the prostate occuring in consequence of senescence and/or disease-specific factors is perhaps somewhat questionable as cellular and structural variations ranging from the benign to the most anaplastic were frequently observed in the same microscopic section.The experimental phases of the present study were supported in part by a grant from the John A. Hartford Foundation, Inc. during the previous appointment of RJA as Director, Division of Immunology, Millard Fillmore Hospital, Buffalo, New York     

组织蛋白酶D在膀胱移行细胞癌中的免疫组化研究

目的：探讨组织蛋白酶Ｄ（ＣＤ）的表达与膀胱移行细胞癌（ＢＴＣＣ）的生物学行为之间的关系。方法：应用２免疫组织化学ＡＢＣ法对３３例ＢＴＣＣ及１２例正常膀胱组织中ＣＤ怕进行检测,结果：正常膀胱组织移行细胞均呈弱阳性表达,ＢＴＣＣ肿瘤细胞中,强阳性表达率为４８．４８％,显著高于正常对照组,且在不同病理分级与临床分期、单发与多发、初发与复发之间均有显著性差异。结论：ＣＤ表达与ＢＴＣＣ生物学特性密切相关;Ｃ     

Distribution of the constitutive NO-synthase isoforms (bNOS and ecNOS) in the normal and hyperplastic human prostate

Summary Nitric oxide (NO) is suggested as an important mediator for the regulation of biological processes. In the present study we tried to determine histochemically and immunohistochemically the localization and distribution of the constitutive NO-synthase isoforms (bNOS and eNOS) of 14 normal non-obstructive and 12 hyperplastic obstructive human prostates. Differentiated nitrinergic innervation was shown for the prostate glands, firbromuscular stroma and blood vessels by NADPH-diaphorase staining and immunohistochemically with specific NOS antibodies. In the specimens with benign prostatic hyperplasia nitrinergic innervation seems to be distinctly reduced. The vascular distribution of NOS provides evidence for segmental differentiation of NO-mediated vascular regulation. The NADPH-diaphorase reaction was not confirmed immunohistochemically by the specific NOS antibody in the glandular epithelium. The distribution of NO synthase shows the importance of nitric oxide in the regulation of smooth muscle tone, blood flow and secretory function in the normal and hyperplastic human prostate.      

Sex steroid receptors in normal and hyperplastic human prostate

The concentrations of sex steroid receptors (per unit DNA) were measured in normal periurethral and peripheral prostatic tissue samples from seven men (mean age 64 years; range 54-71 years) undergoing cystectomy for bladder cancer, and in hyperplastic nodules from 15 men with BPH (mean age 69 years; range 60-89). Occupied androgen (AR) and estrogen (ER) receptors were measured with an improved exchange procedure, where receptor-binding sites were stabilized by a combinatorial procedure involving careful washout of extracellular secretory products (including proteases) prior to homogenization, inclusion of 0.5 mM phenylmethyl sulfonylfluoride (PMSF) and 20 mM molybdate in the exchange medium, and long-term incubation at 0-4 degrees C. Bound radioligands were separated by a hydroxylapatite (HAP) batch adsorption procedure. Maximal specific exchange binding of 3H-R 1881 or 3H-estradiol in total homogenates of human prostate samples was achieved after incubation periods of about 72 h at 0-4 degrees C. In contrast, progestin receptors (PR) were readily available for binding 3H-R 5020; thus overnight binding at 0-4 degrees C was routinely used to measure PR. Binding specificities and equilibrium binding constants (calculated from 8-point Scatchard plots, correcting for nonsaturable binding) were found to be characteristic for AR, PR, and ER, respectively. The receptor results obtained in this study demonstrate that no significant differences existed in total AR per unit DNA between hyperplastic and either central or peripheral prostatic tissue samples; PR was present in both zones of normal prostatic tissue as often as in BPH samples, with PR concentrations significantly lower in hyperplastic samples; and ER was irregularly detected in both normal and hyperplastic tissue in low concentration relative to AR and PR; the frequency of ER detection was much lower in BPH than in normal prostate tissue. Studies of steroid receptor content relative to enzyme markers specific for epithelial and stromal cells in BPH samples showed a positive correlation between acid phosphatase activity (a specific marker for epithelial cells) and both AR and PR. No correlation was observed between AR or PR with either prolyl hydroxylase or myosin ATPase (specific markers for stromal cells). These observations suggest that PR, as well as AR, is primarily associated with the epithelial elements of prostate. Because of the relative infrequency of ER, similar correlation of ER with enzyme markers was not possible.     

Tissue culture of normal human post-pubertal prostate

Total prostatectomies were performed in 10 young male cadaver renal donors and explant cultures were prepared in Falcon flasks. Growth of a monolayer of predominantly epithelial cells occurred rapidly (latent time 3-5 days) and the flasks became confluent within 15-17 days. The monolayers grew well even when a needle was used to circumscribe and remove the explants. Passaging of monolayer cells by seeding at a density of 5 x 10(5) resulted in the vigorous growth of epithelial cells. However, the cultures were eventually overgrown by fibroblasts. Similar explant cultures of benign prostatic hyperplasia or prostatic carcinoma demonstrated a longer latent time, rarely attained confluence, died after explant removal, and could not be passaged.