Macrophage activation by polysaccharide biological response modifier isolated from Aloe vera L. var. chinensis (Haw.) Berg.

A mannose-rich polysaccharide biological response modifier (BRM), derived from Aloe vera L. var. chinensis (Haw.) Berg., was demonstrated to be a potent murine B- and T-cell stimulator in our previous study. We here report the stimulatory activity of PAC-I on murine peritoneal macrophage. The polysaccharide when injected into mice enhanced the migration of macrophages to the peritoneal cavity. Peritoneal macrophage when treated by PAC-I in vitro had increased expression of MHC-II and FcgammaR, and enhanced endocytosis, phagocytosis, nitric oxide production, TNF-alpha secretion and tumor cell cytotoxicity. The administration of PAC-I into allogeneic ICR mice stimulated systemic TNF-alpha production in a dose-dependent manner and prolonged the survival of tumor-bearing mice. PAC-I is thus a potent stimulator of murine macrophage and the in vitro observed tumoricidal properties of activated macrophage might account for the in vivo antitumor properties of PAC-I. Our research findings may have therapeutic implications in tumor immunotherapy.

Chemical and biological characterization of a polysaccharide biological response modifier from Aloe vera L. var. chinensis (Haw.) Berg.

Three purified polysaccharide fractions designated as PAC-I, PAC-II, and PAC-III were prepared from Aloe vera L. var. chinensis (Haw.) Berg. by membrane fractionation and gel filtration HPLC. The polysaccharide fractions had molecular weights of 10,000 kDa, 1300 kDa, and 470 kDa, respectively. The major sugar residue in the polysaccharide fractions is mannose, which was found to be 91.5% in PAC-I, 87.9% in PAC-II, and 53.7% in PAC-III. The protein contents in the polysaccharide fractions was undetectable. NMR study of PAC-I and PAC-II demonstrated the polysaccharides shared the same structure. The main skeletons of PAC-I and PAC-II are beta-(1-->4)-D linked mannose with acetylation at C-6 of manopyranosyl. The polysaccharide fractions stimulated peritoneal macrophages, splenic T and B cell proliferation, and activated these cells to secrete TNF-alpha, IL-1 beta, INF-gamma, IL-2, and IL-6. The polysaccharides were nontoxic and exhibited potent indirect antitumor response in murine model. PAC-I, which had the highest mannose content and molecular weight, was found to be the most potent biological response modifier of the three fractions. Our results suggested that the potency of aloe polysaccharide fraction increases as mannose content and molecular weight of the polysaccharide fraction increase.

Intravenous pyogenic granuloma: immunohistochemical consideration--a case report.

Intravenous pyogenic granuloma is a rare form of pyogenic granuloma in which the whole lesion appears as a single polypoid mass projecting into the lumen of a vein. Histologically, this benign lesion is similar to pyogenic granuloma of other locations and is characterized by lobular proliferation of capillaries embedded in a fibromyxoid stroma. The following report illustrated the classic findings associated with an intravenous pyogenic granuloma in a young woman. A brief review of this rare entity follows the case report. Although the history and physical findings were approximately the same in each patient, they do not seem characteristic enough to allow for a definite preoperative diagnosis. The clinical differential diagnosis of intravenous pyogenic granuloma is varied and requires careful pathologic attention if excised. Complete local excision with a small portion of the vein is the treatment of choice.

Detection of human papillomavirus in esophageal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV) DNA has been identified in esophageal carcinomas. However, the incidence of HPV varies significantly in different geographic locations. In the current study, neoplasms from two separate geographic regions were analyzed for the presence of HPV DNA: METHODS: One hundred and ten esophageal squamous cell carcinomas, 83 from Beijing, China and 27 from Cincinnati, Ohio, were examined for the presence of HPV DNA: In situ hybridization and polymerase chain reaction (PCR) using both consensus primers for the HPV L1 gene and type specific primers for the E6 gene of HPV types 6, 16, and 18 were performed. RESULTS: In situ hybridization failed to demonstrate any HPV type (6, 11, 16, 18, 31, 33, or 35) in any tumor specimen. Likewise, PCR using consensus primers for the HPV L1 gene was negative in all samples. Three of the Chinese specimens (4.29%) were positive for HPV using E6 type specific primers. One tumor contained HPV type 6 DNA, whereas the other 2 contained HPV type 16 DNA. One Cincinnati tumor (4.35%) was positive for HPV 16 by type specific primer. None of the specimens contained HPV 18 DNA. CONCLUSIONS: The incidence of HPV DNA in esophageal carcinoma specimens from Beijing, China and Cincinnati, Ohio is similar. The incidence of HPV in tumors from Beijing is significantly lower than that reported for those from other regions of China where the incidence of esophageal cancer is higher. Thus, although HPV may play a role in esophageal carcinogenesis, this role may be more pronounced in those regions of the world with a high incidence of the disease, and may be less important in areas with moderate or low risks for esophageal cancer.

Differential sensitivities of E6 type-specific and L1 consensus primers in the detection of human papillomavirus in anal carcinoma.

Anogenital malignancy has been increasing in incidence in recent decades. There is strong evidence in the literature suggesting that human papillomavirus (HPV) plays a role in the genesis of anogenital neoplasia. In addition, identification of oncogenic HPV types in anogenital carcinomas may have prognostic significance. The method used to detect HPV infection, however, affects the frequency with which viral DNA is identified. We examined tissues from 56 patients with anal squamous cell carcinoma for the presence of HPV DNA by in situ hybridization and polymerase chain reaction using both consensus and type-specific primers to determine if HPV detection varies when different methods are used. In situ hybridization identified the presence of HPV DNA in 41.1% of patients. Polymerase chain reaction using type-specific probes for the HPV E6 gene demonstrated HPV DNA in 46% of anal carcinomas, whereas polymerase chain reaction with consensus primers detected HPV DNA in only 16.3% of cases. All cases containing HPV type 6 were identified with L1 primers, whereas only three of 23 cases containing HPV type 16 were identified. The differences in the rate of HPV detection by the two polymerase chain reactions methods are most likely related to L1 gene loss in cells containing integrated HPV type 16.

The relationship of human papillomavirus to proliferation and ploidy in carcinoma of the anus.

BACKGROUND: Human papillomavirus (HPV) infections have been implicated in anogenital neoplasia in both sexes. In this study, the authors postulated that HPV infections induce squamous epithelium to become hyperproliferative and aneuploid. METHODS: To test this hypothesis, formalin fixed, paraffin embedded tissues were analyzed for the presence of HPV by in situ hybridization. S-phase fraction and DNA content were evaluated by flow cytometry. Proliferative indices also were analyzed using an antibody to proliferating cell nuclear antigen (PCNA). RESULTS: Human papillomavirus DNA was present in 48.1% of the carcinomas. All but one HPV-positive tumor contained HPV 16/18 DNA. The remaining tumor contained only HPV 6/11. No correlation was found between HPV status, patient age, or tumor differentiation. Thirty-three percent of tumors were aneuploid. Only two patients had aneuploid tumors that were HPV-negative; these patients received preoperative radiotherapy. The average S-phase fraction was significantly higher (P < 0.01) in HPV-positive versus HPV-negative lesions. The PCNA index for HPV positive tumors was also significantly higher than that observed in negative tumors (p < 0.003). CONCLUSION: The presence of HPV in tumor cells is significantly associated with an increased proliferative rate and aneuploid status of tumors compared with HPV-negative tumors. These findings are consistent with the fact that viral proteins binding to tumor suppressor gene proteins can deregulate the cell cycle and lead to genomic instability.

The molecular biology of esophageal and gastric cancer and their precursors: oncogenes, tumor suppressor genes, and growth factors.

The evolution of sequential histological changes from normal cells through invasive cancer affords the cancer biologist the opportunity to identify separate molecular steps involved in cancer progression. As one studies the development of human carcinoma, it becomes apparent that multiple genetic alterations affecting both cellular proto-oncogenes and tumor suppressor genes are involved during the development and progression of both esophageal and gastric cancers. The different histological forms of both esophageal and gastric carcinomas as well as their differing etiologies result in the possibility that a spectrum of genetic changes is involved in different tumor types. p53 abnormalities occur frequently in tumors arising in both organs, and in both sites p53 abnormalities can be observed in precancerous lesions as well as in overt cancer. Subsequent abnormalities affecting other genes (eg, epithelial growth factor receptors [EGFRs]) potentially enhance the growth potential of tumors. This review focuses on abnormalities of oncogenes, tumor suppressor genes, and growth factors commonly found in cancers of the esophagus and stomach.

Methylenedioxymethamphetamine's capacity to establish place preferences and modify intake of an alcoholic beverage.

Doses of 0.2, 2.0, 6.3 and 20.0 mg/kg 3,4-methylenedioxymethamphetamine (MDMA), a putative neurotoxin at serotonergic neurons and a recreational drug, were assessed using Sprague-Dawley rats in the conditioned place preference (CPP) test. Also, the drug's effects on intake of a sweetened ethanol solution (ES) was assessed. The CP testing involved multiple administrations of MDMA with frequent periodic testing (weekly for 4 weeks) of MDMA's effects. Doses of 2.0 and 6.3 mg/kg produced positive CPPs with every test. MDMA also affected rats' gain in body weight across the 4 weeks of dosing. The 2.0 mg/kg reliably incremented gain in body weight, while the 20.0 mg/kg dose reliably attenuated it. In the drinking experiment, water-deprived rats (22 h/day) were given daily opportunities to drink either tap water or a sweetened ES. When stable intakes were achieved, MDMA's effects were assessed across repeated daily administrations (12 days) and subsequently (16 days). MDMA, dose-relatedly, decreased intake of both ES and water with the highest dose leading to marked loss in body weight. Intakes of fluids were not modified markedly subsequent to dosing. In summary, MDMA is an agent that produces a positive CPP (providing further evidence for MDMA's abuse liability), produces changes in weight gain and nonselectively reduces fluid intake among fluid-deprived rats.

PCP, THC, ethanol, and morphine and consumption of palatable solutions.

Water-deprived rats were given daily opportunities (2.0-hr sessions) to take water or a sweet solution (20% or 24% sugar-water). After stable intakes of each fluid were achieved, the effects of phencyclidine hydrochloride (PCP), delta-9-tetrahydrocannabinol (THC), ethanol (E), and morphine (M) on intakes were tested. PCP, THC, and M all enhanced intake of the sweet solution, while E produced varying effects across doses tested. With other rats, nearly the same procedure was used except that the test solution presented with water was 0.9% sodium chloride. Doses of PCP enhanced intake of the salty solution. These data, combined with the data from similar studies of the effects of opioids and benzodiazepines, indicate that a wide variety of agents that are self-administered also modify intake of ingesta.