Wortmannin-mediated inhibition of phosphatidylinositol 3-kinase activity triggers apoptosis in normal and neoplastic B lymphocytes which are in cell cycle

The B cell functional response following ligation of surface(s) lgM is dependent upon the differentiation stage of the populationstudied: cross-linking slgM promotes proliferation of restingtonsillar follicular mantle (FM) B lymphocytes but induces apoptosisin the susceptible Epstein- Barr virus genome-negative Burkittlymphoma (BL) cell line Ramos (Ramos-BL). This study investigateswhether phosphatidylinositol-3-kinase (Pl3-kinase), which hasbeen reported to be intimately involved in the regulation ofcellular growth, plays a role in the regulation of these sig-promoted B cell responses, and uses the selective and irreversibleinhibitor of Pl3-kinase activity, wortmannin (Wm). In Ramos-BLB cells, at 8 h post-treatment, Wm triggers a transient increasein apoptosis of 16 ± 6.9% with a concomitant cellularloss of 16 ± 6.1% from the G₁ phase of cell cycle; [³H]thymidineincorporation also decreases by 33 ± 5.0%, from 37,274c.p.m. ± 10% to 25,127 c.p.m. ± 4.0%. Moreover,at 72 h culture, Wm inhibits anti-lgM-induced FM B lymphocytelevels of [³H]thymidine incorporation typically by 47% and triggers80% apoptosis from the G₀G₁ phase of cell cycle. Ramos-BL Bcells exhibit high basal levels of Pl3-kinase activity, as determinedby immunoprecipitation with antibody to the p85 regulatory subunitof Pl3-kinase and ³²P incorporation into phosphatidylinositol,which is not significantly affected by anti-lgM stimulation;by contrast, anti-lgM stimulates significant Pl3-kinase activityover negligible basal levels in FM B lymphocytes. Pre-treatmentwith Wm inhibits Pl3-kinase activity in both cell types. Takentogether these data indicate that in Ramos-BL B cells slgM-triggeredgrowth arrest and apoptosis is Pl3- kinase independent, whereasPl3-kinase activity is critical for slgM-triggered mitogenesisof FM B lymphocytes. Thus Pl3-kinase plays a pivotal role inthe regulation of both normal and neoplastic B lymphocyte progressionthrough the cell cycle, such that if this Pl3-kinase-dependentpathway is inhibited these cells default to apoptosis.     

Intravesical instillation therapy with bacillus Calmette-Guérin for superficial bladder cancer: Study of the mechanism of bacillus Calmette-Guérin immunotherapy

AIM: In order to clarify the initial step of the mechanism by which bacillus Calmette-Guérin (BCG) exhibits antitumor activity via the immune response induced in the bladder submucosa after intravesical BCG therapy for human bladder cancer, various cytokines secreted in the urine after BCG instillation were measured. METHODS: After transurethral resection of bladder cancer, a 6-week course of BCG instillation was performed. At the first and sixth weeks' dosings, spontaneously excreted urine was collected before and 4, 8, and 24 h after BCG instillation. The urinary cytokines were determined by Sandwich enzyme-linked immunosorbent assay using monoclonal antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1beta, IL-8, interferon (IFN)-gamma, and IL-12. RESULTS: After the BCG therapy, various cytokines, such as GM-CSF, TNF-alpha, G-CSF, IL-1beta, IL-8, IFN-gamma, and IL-12 were secreted, comprising the immune response cascade. The mean urinary excretions of GM-CSF and TNF-alpha 4 h after the sixth week's instillation were significantly higher than the pre-instillation levels. There were no significant increases in the urinary IFN-gamma or IL-12 levels between 4 and 24 h after the sixth week's instillation. The TNF-alpha level 4 h after the sixth week's instillation had a strong tendency towards the absence of recurrence, with a mean follow-up of 54.1 months. The Kaplan-Meier curve showed the 2, 5, and 10-year recurrence-free survival rates were 72.4%, 65.8%, and 56.4%, respectively. CONCLUSIONS: We suggested that the urinary levels of TNF-alpha might be essential in antitumor activity after BCG therapy and might play an important role in the prevention of bladder tumor recurrence.     

Cytokeratin 7 and 20 as immunohistochemical markers in identification of primary tumors in craniospinal metastases: Do they have a significant role?

Cytokeratin (CK)7 and CK20, the low molecular weight cytokeratins, have been found to have a benefit in the differential diagnosis of some epithelial neoplasms. In the present study, the actual role of these markers in the search of primary tumors in 32 patients with craniospinal metastasis of an unknown primary site at presentation, is evaluated. A series of 36 patients with a known primary tumor were presented for comparison. In the first group, two CK7 and CK20 expression profiles were observed; 87% of metastatic tumors were CK7+/CK20‐ and 13% CK7‐/CK20‐. The lung was the major source (82%) of CK7+/CK20‐ metastatic tumors, whereas it represented only 38% of primary tumor in the second group of a known primary site (P = 0.006). Given the fact that metastatic tumors to the craniospinal axis of an unknown primary site are frequently CK7+/CK20‐, and they have commonly metastasized from the lung, it is doubtful that immunohistochemistry is really helpful. However, CT scan and MRI of the chest still play an important role. Many patients in the present study had to undertake these imaging studies, regardless of the CK7/CK20 result. The immunostains may be useful in cases with other expression profiles, but such examples constituted only a minority in the present study.     

Fine-needle cytology of an eccrine spiradenoma of the breast: diagnosis made by a holistic approach.

Eccrine spiradenoma is a rather rare adnexal tumor of the skin. When the clinical presentation is that of a breast neoplasm, diagnosis can be difficult. As cytology was a new procedure for this tumor, the approach of choice appeared to be a holistic one. The cytologic picture showed bland groups of uniformly sized cuboid cells with scant cytoplasm, round to ovoid nuclei, and inconspicuous nucleoli, while in the groups rosettelike structures could be discerned. Only by integrating the data of clinical history, inspection, palpation, reaction on breast puncture, and immunologic findings could the diagnosis be made.     

Solid variant of odontogenic keratocyst

A case of an unusual lesion from the maxilla is presented. Macroscopically, the lesion was solid and histologically consisted of 'multiple separate keratocysts' of varying size that infiltrated into the surrounding bone and soft tissues. Panoramic image and CT scans showed a multilocular honeycomb ill-defined radiolucency with infiltration into the maxillary sinus and floor of orbit. This lesion should be differentiated from similar odontogenic lesions, such as keratoameloblastoma and papilliferous keratoameloblastoma. As there was no evidence of follicles, islands of ameloblastoma, or papilliferous structures in the entire specimen, the lesion could not be diagnosed as either a keratoameloblastoma or a papilliferous keratoameloblastoma. The invasive and destructive growth behavior, the histopathological features, and the histochemical pattern of the collagen stroma imply that this solid lesion is a neoplasia. It is suggested that the proper term for this lesion is solid variant of odontogenic keratocyst.     

Malignant Rhabdoid Tumor of the Breast: A Case Report

A 66-year-old woman time of 10 days. One month after radicalmastectomy, there was local recurrence, followed by multiplepulmonary metastases, and the patient died of respiratory failure5 months after surgery. The gray-white-colored tumor measured13x12x;10 cm, and its border was well defined. The tumor wascomposed of diffusely growing round or polygonal cells withvesicular nuclei, prominent nucleoli, and ample cytoplasm containingeosinophilic inclusions. Lymph node involvement was widespread.Both vimentin and keratin were clearly demonstrated by immunohistochemicalstaining. Ultrastructural studies revealed that the MRT cellscontained cytoplasmic whorls of intermediate filaments.     

Expression of ɛBP, a β-galactoside-binding soluble lectin, in normal and neoplastic epidermis

Abstract The study of animal lectins and glycoconjugates has become an important area of research in biomedical sciences, as these molecules are believed to play important roles in a variety of biological processes. This report describes a study of the expression of an animal lectin, IgE-binding protein (?BP), also known as Mac-2 and CBP35, in human skin. We have analyzed cultured human keratinocytes as well as normal human skin and a number of epidermal neoplasms, by immunoblotting. immuno-fluorescence and immunohistochemistry. We showed that ?BP is expressed in human keratinocytes, hair follicles, sebaceous and sweat glands. We found that cBP expression retains in various epidermal neoplasms, including basal cell carcinoma, squamous cell carcinoma and keratoacan-thoma, although the level of expression appears to be reduced as compared to normal epidermis. The immunohistochemical analysis also suggests that the level of ?BP expression appears to be dependent on the degree of cellular differentiation of keratinocytes.     

Hypercalcemia and pancreatic endocrine neoplasia with elevated PTH-rP: Report of two new cases and subject review

Humoral hypercalcemia of malignancy is widely associated with tumor production of parathyroid hormone related protein (PTH-rP). This peptide functions in endocrine, autocrine and paracrine mechanisms in a manner similar to PTH; increasing renal uptake of calcium, decreasing retention of phosphorous, and stimulating adenylate cyclase and phospholipase C. Although PTH-rP production has been well documented in neoplasms of the exocrine pancreas, we present here two cases of endocrine pancreatic neoplasms elaborating PTH-rP. We then review the literature of previous cases and delve into the pathophysiology of this peptide.     

Diagnostic imaging of spinal cord lesions

Magnetic resonance imaging (MRI) has greatly facilitated morphologic evaluation of spinal cord lesions. Eleven cases representative of inflammatory, demyelinating, neoplastic and vascular diseases, are presented which illustrate and summarize important abnormal features in spinal cord imaging, particularly MR findings. Recently, specialised techniques such as MR angiography, fat-inhibiting methods, dynamic MRI and functional imaging have been developed. These methods have facilitated not only lesion diagnosis but also qualitative assessment, and are being used to analyze pathophysiology. Comprehensive diagnoses based on such modalities may be important in determining indications for surgery or defining the extent of surgery or the intensity of other treatments.     

前列腺体积与前列腺特异抗原及抗原密度关系的多元回归研究

对１００例前列腺增生患者的前列腺体积，年龄，血清前列腺特异抗原，抗原密度进行多元回归与相关分析。结果；年龄和前列腺体积与血清ＰＳＡ浓度显著相关，其中，体积与ＰＳＡ之间的年龄与体积之间具有相关性、而年龄与ＰＳＡ之间无相关性，体积每增加１０ｃｍ＾３，ＰＳＡ增高０．９μｇ／Ｌ。