Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the localization of squamous cell cancer associated antigens (SCCAA) in dysplasia, cancer in situ (CIS) and microinvasive SCC of the uterine cervix, since detection of SCCAA in these subjects is highly effective for early diagnosis. Anti-squamous cell cancer associated antibody (Anti SCCAAb IgG) was prepared by immunizing rabbits with specific components at around PI 6.1 that were originally purified from SCC of maxillary sinus. In this study, the following results were obtained by the immunoperoxidase method. (1) Eleven out of 15(73%) cases of dysplasia, 20 out of 26(77%) cases of CIS, 21 out of 24(88%) cases of Stage I, 13 out of 14(93%) cases of Stage II and 9 out of 10(90%) cases of Stage III-IV in the clinical stages of SCC showed positive staining, while controls of unrelated SCC were almost negative. (2) The SCCAA positive ratio was 2 out of 2 cases of small cell nonkeratinized type, 86% in large cell nonkeratinized type and 94% in Keratinized type of SCC. (3) The SCCAA was demonstrated on all the layers of stratified squamous epithelium in a lesion of CIS and some layers migrated to adjacent nonneoplastic lesion with lateral invasion in middle layer. These results suggest that the demonstration of SCCAA may be useful in diagnosing the malignant transformation of squamous epithelium in the early stage of SCC.
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PMID:[Immunohistochemical studies on a new antigens associated with squamous cell cancer in oncogenesis of uterine cervical cancer]. 199 17

Cell surface carbohydrates are excellent markers of cellular differentiation and maturation processes due to their great structural and antigenic diversity as well as their known biosynthetic precursor/product relationships. Using a panel of monoclonal antibodies with well-defined carbohydrate specificities we have studied the expression of biosynthetically related antigens in normal and psoriatic skin. Two "families" of carbohydrate structures were investigated. One series of structures based on N-acetyllactosamine chains (type 2 chain: N-acetyllactosamine and fucosylated derivates hereof of H, Lex, Ley and sialyl-Lex) and another based on the simple mucin type core structures (type 3 chain: Tn, T and sialylated derivates hereof as well as the fucosylated derivative, H). Previously we have found these carbohydrate structures define distinct cell layers in stratified squamous epithelia of mucosa of the cheek, esophagus and uterine cervix. In normal and uninvolved epidermis, N-acetyllactosamine and T carbohydrates were found in the spinous cell layer, whereas the fucosylated derivates, H structures, were found in the granular cell layers above. The fucosylated and sialylated derivate of N-acetyllactosamine, sialylated Lex, had the same distribution as N-acetyllactosamine and T structures. This sequential expression of carbohydrates is similar to our previous findings in mucosa. However, in contrast to mucosa, normal skin basal cells did not label. The glycosylation pattern in psoriatic epithelium was changed in two ways. 1) Some carbohydrates (types 2 and 3 chain H and T) were expressed at an earlier stage of cell maturation. 2) The biosynthetic precursors to T structures, Tn and sialyl-Tn, which are not expressed in normal skin, and are often considered cancer-associated antigens, appeared in psoriatic skin. The Tn-antigen was expressed on basal and lower spinous cells, whereas the sialyl-Tn was only found on basal cells above the dermal papillae. The findings in the present work support previous studies of changes in cell surface glycosylation in psoriatic epidermis and demonstrate the appearance of tumor-associated antigens in highly proliferative, but benign, stratified epithelium.
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PMID:Cell surface glycosylation patterns in psoriasis. 218 Apr 41

In female rats, vaginocervical stimulation induces neuroendocrine responses necessary for pregnancy as well as analgesia to a variety of noxious stimuli. In this study, Fos immunocytochemistry was used to detect vaginocervical stimulation-induced changes in the activity of spinal neurons at levels T11-S3, segments known to receive afferent input from nerves which innervate the reproductive tract. Adult ovariectomized estrogen and progesterone-treated rats were killed 1 h after receiving mating stimulation from males, which included five or 15 intromissions, mounts-without-intromission by use of either vaginal masks or genitally-anaesthetized males, or immediately after being removed from their home cages. At all spinal levels, Fos labelling was lowest in the home cage group (50 +/- 22 cells), intermediate in the groups receiving intromissions (84 +/- 8 and 118 +/- 22 cells) and highest in groups receiving mounts-without-intromission stimulation (187 +/- 21 and 218 +/- 35 cells). Significant increases above control levels following intromissive stimulation were observed at levels L6, S1 and S2. Surprisingly, both groups receiving mounts-without-intromission showed significantly higher numbers of Fos-positive cells than did the fully mated groups at all levels. Analysis of selected spinal segments by Rexed's laminae revealed that intromissive stimulation increased Fos labelling above control levels in laminae II-V and X at L6, and laminae I, II, V and X at S1; vaginocervical stimulation did not increase labelling at L1. The greater Fos responses seen in mounts-without-intromission animals than in control or intromitted animals were apparent at L1, L6 and S1 within the same laminae (II-V and X). These results suggest that stimulation of the uterine cervix initiates activity within L6-S2 neurons which receive pelvic nerve afferents and that such stimulation suppresses activity at all levels within populations of neurons normally activated by cutaneous somatic inputs received from male mounts. As antinociceptive agents are known to suppress c-fos expression, vaginocervical stimulation received during natural mating may be capable of initiating spinal and/or brain mechanisms of analgesia.
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PMID:Vaginocervical stimulation suppresses the expression of c-fos induced by mating in thoracic, lumbar and sacral segments of the female rat. 884 89

Cancer predisposition in some families is known to be the result of germ-line mutations. The most noteworthy hereditary gynecologic cancer syndromes include hereditary breast-ovarian cancer (HBOC) syndrome, wherein BRCA1 and BRCA2 germ-line mutations have been identified, and hereditary nonpolyposis colorectal cancer (HNPCC) of the Lynch syndrome II variant, wherein hMSH2, hMLH1, hPMS2, hMSH3, and hMSH6 germ-line mutations have been identified. DNA testing for specific cancer-associated germ-line mutations is now available for HBOC and HNPCC syndrome family members who are in the direct line of inheritance. Genetic counseling is mandatory prior to DNA testing and at the time of disclosure of findings. A patient found to be negative for the family's particular cancer-associated germ-line mutation can revert to general population screening recommendations. When a deleterious mutation is identified, the physician is able to predict a patient's lifetime susceptibility to breast and ovarian carcinomas in the HBOC syndrome or the cancers which characterize the Lynch syndrome II variant of HNPCC, particularly carcinomas of the colon, endometrium, and ovary. Management strategies can be offered which are designed to take advantage of the natural history of that distinct hereditary cancer syndrome. We discuss the unfolding developments concerning familial and heritable susceptibilities, molecular genetics, and possible carcinogenic co-factors of the three most common gynecologic cancers: carcinomas of the uterine cervix, endometrium, and ovary. We offer rationales for management based on current epidemiologic and clinical data and emerging technologies.
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PMID:Hereditary Factors in Gynecologic Cancer. 1038 22

As human papillomavirus (HPV) becomes accepted as the central cause of cervical cancer, longitudinal studies are shifting focus away from causality to a more detailed investigation of the natural history of HPV infections. These studies commonly require repeated samples for HPV testing over several years, usually collected during a pelvic exam, which is inconvenient to the participants and costly to the study. To alleviate the inconvenience and cost of repeated clinic visits, it has been proposed that women collect cervicovaginal cells themselves, hopefully increasing participation in the natural history studies. We evaluated the technical feasibility of self-collection of cervicovaginal cells using a Dacron swab for HPV DNA detection. We compared the self-collected swab sample and two clinician-administered swab samples (one from the endocervix and another from the ectocervix) from a total of 268 women participating in a case-control study of adenocarcinoma and squamous cell carcinomas of the uterine cervix (111 cases and 157 controls). HPV DNA was detected and genotyped using an L1 consensus PCR assay. The overall agreement between the clinician- and self-collected swabs was excellent [88.1%; kappa = 0.73 (95% confidence interval (CI), 0.61-0.85)]. The correlation was highest between the two clinician-administered swabs [kappa = 0.81 (95% CI, 0.69-0.93)] but was still excellent when comparing either clinician-administered swab to the self-administered sample [kappa = 0.75 (95% CI, 0.63-0.87) and 0.67 (95% CI, 0.55-0.79) for ectocervix and endocervix, respectively]. The type-specific agreement between samples was higher for high-risk, or cancer-associated, HPV genotypes than for low risk, noncancer-associated HPV genotypes when comparing the self-administered swab sample to the clinician-administered swab sample (kappa = 0.78 for high-risk versus 0.66 for low-risk HPV infections, t = -1.45, P = 0.15). The decrease in agreement for low risk types was largely attributable to an increased detection of these types in the self-administered sample (McNemar's chi2 = 6.25, P = 0.01 for clinician- versus self-administered swab comparisons). The agreement did not vary significantly by age, menopausal status, case status, or clinic center. We have demonstrated that a self-collected Dacron swab sample of cervicovaginal cells is a technically feasible alternative to clinician-administered cervical cell collection in natural history studies of HPV and cervical cancer.
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PMID:Evaluation of self-collected cervicovaginal cell samples for human papillomavirus testing by polymerase chain reaction. 1121 78

Human papillomavirus (HPV) DNA has been detected in the great majority of cancers of the uterine cervix and anus, whereas the association of HPV DNA with cancer at other anogenital sites has produced less consistent results. This study was designed to compare HPV exposure among anogenital cancer cases and matched controls. Cases (1782) of anogenital cancer diagnosed in the Seattle area from 1978 to 1998 were identified and interviewed. Their responses were compared with those of 2383 age- and sex-matched controls. Blood was drawn at interview from both cases and controls and tested for antibodies to HPV-16 and HPV-18. Tissue blocks were tested for HPV DNA for 649 cases. Serum antibodies to HPV-16 were associated with in situ and invasive cancer at all sites among men and women with the exception of in situ penile cancer. Anti-HPV-18 antibodies were associated with cancers at all sites among women. The increased risk of cancer associated with HPV-16 seropositivity ranged from odds ratio = 1.8 (95% confidence interval, 1.4-2.5) for adenocarcinoma of the cervix to odds ratio = 5.9 (95% confidence interval, 3.4-10.3) for anal cancer in men. Associations between seroprevalence and cancers were stronger when analyses were restricted to HPV-16- or HPV-18 DNA-positive cases. HPV DNA was detected in >80% of cancers from all sites tested. HPV-16 DNA was the type most frequently detected at all sites (range, 40.9-82.2%). HPV-18 DNA was detected in 44.7% of adenocarcinomas of the cervix but detected much less often (2.6-18.1%) at other sites. These findings support an important role for HPV infection in anogenital cancer at all sites. Differences in the proportion of seropositives among HPV-16 DNA-positive cases by site suggest either that the immune response varies by site or that cancer development may lead to changes in antibody responses in a site-specific fashion.
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PMID:Human papillomavirus 16 and 18 L1 serology compared across anogenital cancer sites. 1128 Jul 49

The thesis is based on 13 publications in English and a review of the literature. The underlying work was done with the overall aim to describe incidence patterns for anal squamous carcinoma (anal SC) and to contribute new insight into the causes of this neoplasm. The work, supported by the Danish Cancer Society, was carried out in the period 1991-2000 while I was employed at 1) the Danish Cancer Registry, 2) Statens Serum Institute, Department of Epidemiology Research, and 3) the National Cancer Institute, Viral Epidemiology Branch, Maryland. Study designs employed include a ) population-based incidence studies in Denmark and the United States, b) register-based case-control studies and cohort studies for the scrutiny of multiple cancer patterns among patients with anal SC and for the study of anal SC risk among individuals with certain non-malignant diseases of the anal region as well as among persons with the acquired immuno-deficiency syndrome (AIDS), c) a nationwide interview-based case-control study of risk factors for anal SC and in Denmark and Sweden, and d) a combined molecular biological and histological analysis examining the association of human papillomavirus (HPV) status with histopathological and anatomical characteristics in anal SC tissues. The epidemiology of anal SC has changed remarkably during the second half of the 20th century. In Denmark, age-adjusted incidence rates per 100,000 person-years increased during the period 1943-1997 from around 0.2 among both men an women to 0.5 among men and 1.0 among women. Where systematically studied, incidence rates of anal SC have also been found to increase in a few other countries (Sweden and the United States). Register-based multiple cancer studies have shown an excess of previous and subsequent genital cancers of squamous histology among women with anal SC. This is likely to reflect common susceptibility toward infection with cancer-associated HPV types shared by all anogenital organs covered by squamous epithelium. A study based on data from the United States supports the possible role of anogenital SC-associated HPV types in the development of some tonsillar cancers. Observations in other register-based investigations and in the Danish-Swedish case-control study challenge the long held belief that benign anal lesions (e.g. hemorrhoids) and anal inflammation (e.g. in association with Crohn's disease) are linked to an increased risk of anal SC. The work documents strong links between a variety of sexual behavior measures and the risk of anal SC. The previously observed excess of anal SC among homosexual men is confirmed. Unlike in previous studies, an increased risk of anal SC associated with promiscuous heterosexual activity is also documented among both men and women. Measures of sexual extroversion, rather than sexual preference, are linked to the risk of anal SC presumably by means of higher rates of anal HPV infection in people with such behaviors. A new hypothesis is proposed to explain how smoking, the only consistently observed non-sexual risk factor in previous studies, might be associated with anal SC risk. A study of the short-term cancer profile among 309.365 AIDS patients in the United States provided no evidence to support immunosuppression as a major risk factor for anal SC in the first two years after the AIDS diagnosis. With the introduction around 1996 of highly active anti-retroviral therapy regimens, however, the future may hold a para-doxical increase in the incidence of anal SC along with the increased life expectancy in this population. Examination of tumor tissues from patients in Denmark and Sweden by the polymerase chain reaction techique showed a high proportion of anal SCs to be positive for types of HPV that are associated with high risk of cervical cancer (90%, 100%, and 58% among women, homosexual men, and heterosexual men, respectively). Tumor tissues from control subjects with adenocarcinoma of the rectum were consistently HPV-negative. A combined molecular biological and histological analysis showed that anal SCs with likely origin in the anal canal are 7.5 times more likely to be HPV-positive than anal SCs with likely origin in the perianal skin. Additionally, cancer of the anal canal are more likely than those of the perianal skin to be characterized histologically by small or medium-sized tumor cells, basaloid features, and little or no keratinization. Epidemiological studies from the past two decades have contributed imprtantly to our current understanding of anal SC and its causes. Most cases of this neoplasm can now be considered as a consequence of sexually or otherwise acquired infection in the anal mucosa with types of HPV already known to be involved in cancers of the uterine cervix. Expectedly, the upward trend in the incidence of anal SC seen over the past half century will continue in many years to come. However, there is currently widespread, yet cautious, optimism regarding the prospects for a prophylactic HPV vaccine. It this optimism is justified, the future may bring drastic reductions in the incidence of HPV-associated morbidities, including SC.
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PMID:On the etiology of anal squamous carcinoma. 1223 81

In the female rat, the integrity of the ventral noradrenergic bundle (VNAB) is necessary to carry stimuli from the uterine cervix and vagina to brain areas involved in mating-induced pseudopregnancy. Because adrenal hormones are known to alter noradrenergic function, we examined whether adrenalectomy altered mating-induced Fos expression in the A1 and A2 noradrenergic cell groups that project through the VNAB. Ovariectomized females were adrenalectomized (ADX) or sham-operated (Sham) and, 2 weeks after surgery, were given oestrogen and progesterone and mated. They received 15 intromissions, five intromissions or 15 mounts-without-intromission (mounts-only) from a male. Two hours after mating, rats were perfused and brains were collected; controls were perfused after being taken directly from their home cage. After immunocytochemical staining, Fos-immunoreactive (Fos-IR) and dopamine-beta-hydroxylase-immunoreactive (DBH-IR) cells and the percentage of DBH cells that were labelled with Fos (% DBH/Fos) were counted. In the A1 area, Fos-IR and percentage DBH/Fos were not affected by adrenalectomy. Although an overall effect of mating treatment was found for both measures, no specific mating treatment increased labelled cells above home cage levels. In the caudal, middle and rostral A2, 15 intromissions induced a significant increase in Fos-IR in Sham females above all other groups and a higher percentage of DBH/Fos in the middle and rostral A2 areas. ADX females showed no rise in either Fos-IR or percentage DBH/Fos after 15 intromissions. However, in the middle and rostral A2, ADX females showed significantly increased Fos-IR and percentage DBH/Fos after mounts-only treatment above Sham mounts-only females and all other ADX groups. These results demonstrate that adrenal hormones suppress activation of A2 cells to mounts-only stimuli but contribute to A2 activation in response to intromissions from males. The latter effect may result from stress associated with receipt of vaginocervical stimulation during mating.
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PMID:Fos expression after mating in noradrenergic cells of the A1 and A2 areas of the medulla is altered by adrenalectomy. 1534 13

miR-126 is an endothelial-specific microRNA essential for maintaining vessel integrity during development. Its role of tumor angiogenesis in cancer stroma is unclear. This study investigated the temporal and spatial expression and the role of miR-126 in the course of cervical carcinogenesis. miR-126 was found to be mainly expressed in the stromal endothelium of the uterine cervix. This downregulation was recapitulated in a cell coculture model, wherein cross talk of cervical cancer cells and fibroblasts induced a downregulation of miR-126 in human umbilical vein endothelial cells, with consequent increase of tube formation. Coinjection of cancer-associated fibroblasts of human cervix enhanced tumorigenesis of cervical cancer cells, with an increase of microvessel density and dye retention in the tumor vasculature. In association with angiogenesis, host-originated miR-126 in these xenograft tumors was progressively downregulated, whereas supplement of the miR-126 precursor in the coinjection suppressed angiogenesis and tumor growth. A proangiogenic gene adrenomedullin (ADM), which was found to be upregulated in the stroma of cervical cancer and which localized mainly in the blood and lymphatic vessels, was identified as a target of inhibition by miR-126 at the carcinoma in situ-to-invasion stage. The study suggests a cancer stroma cross talk induced repression of miR-126 and upregulation of ADM, and probably other proangiogenic factors, to facilitate angiogenesis and invasion growth of cervical cancer.
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PMID:Repression of miR-126 and upregulation of adrenomedullin in the stromal endothelium by cancer-stromal cross talks confers angiogenesis of cervical cancer. 2401 27

It is largely recognized that fibroblast activation protein (FAP) is expressed in cancer-associated fibroblasts (CAFs) of many human carcinomas. Furthermore, FAP was recently also reported to be expressed in carcinoma cells of the breast, stomach, pancreatic ductal adenocarcinoma, colorectum, and uterine cervix. The carcinoma cell expression pattern of FAP has been described in several types of cancers, but the role of FAP in oral squamous cell carcinoma (OSCC) is unknown. The role of endogenous FAP in epithelium-derived tumors and molecular mechanisms has also not been reported. In this study, FAP was found to be expressed in carcinoma cells of OSCC and was upregulated in OSCC tissue samples compared with benign tissue samples using immunohistochemistry. In addition, its expression level was closely correlated with overall survival of patients with OSCC. Silencing FAP inhibited the growth and metastasis of OSCC cells in vitro and in vivo. Mechanistically, knockdown of FAP inactivated PTEN/PI3K/AKT and Ras-ERK and its downstream signaling regulating proliferation, migration, and invasion in OSCC cells, as the inhibitory effects of FAP on the proliferation and metastasis could be rescued by PTEN silencing. Our study suggests that FAP acts as an oncogene and may be a potential therapeutic target for patients with OSCC.
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PMID:Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma. 2472 80


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