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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
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Disease relevance of Vulva


High impact information on Vulva

  • The let-23 receptor/mpk-1 MAP kinase signaling pathway induces the vulva in C. elegans [6].
  • LOV-1 is the closest C. elegans homologue of PKD1. lov-1 is expressed in adult males in sensory neurons of the rays, hook and head, which mediate response, vulva location, and potentially chemotaxis to hermaphrodites, respectively [7].
  • The lin-3 gene is necessary for induction of the Caenorhabditis elegans vulva by the anchor cell [8].
  • DEP-1 amplifies in the developing vulva and the excretory system the small differences in the amount of EGF signal received by equivalent precursor cells to achieve binary cell fate decisions [9].
  • Here we show the major role of SUMO during the development of the Caenorhabditis elegans reproductive system. smo-1 deletion mutants develop into sterile adults with abnormal somatic gonad, germ line, and vulva [10].

Chemical compound and disease context of Vulva


Biological context of Vulva

  • In cog-2 mutants, the anchor cell does not fuse to the uterine seam cell and, instead, remains at the apex of the vulva, blocking the connection between the vulval and uterine lumens, resulting in an egg-laying defective phenotype [16].
  • Thus, in P. pacificus lin-39 specifies the vulva equivalence group by inhibiting programmed cell death [17].
  • In this study, we have investigated the role of ceh-20, the C. elegans ortholog of the HOX co-factor Extradenticle (Exd/Pbx), and unc-62, the C. elegans ortholog of Homothorax (Hth/Meis/Prep), in two processes that are regulated by Hox gene lin-39: cell migration and vulva formation [18].
  • By examining the fusion state and division patterns of the cells in the developing vulva of nT1 mutants, we demonstrate that egl-18/elt-6 prevent fusion and promote cell proliferation at multiple steps of vulval development [19].
  • In Caenorhabditis elegans, MTA1-like genes regulate cell polarity, migration, embryonic patterning, and vulva development [20].

Anatomical context of Vulva

  • The nematode even-skipped homolog vab-7 regulates gonad and vulva position in Pristionchus pacificus [21].
  • In Caenorhabditis elegans, it localizes Let-23, a receptor tyrosine kinase, to the basolateral side of vulval epithelium, a step crucial for proper vulva development [22].
  • Specifically, lin-11 is expressed in the ventral uterine intermediate precursor (pi) cells and their progeny (the utse and uv1 cells), which connect the uterus to the vulva [23].
  • Upper- and lower-extremity lymphoscintigraphy was performed on 50 patients with proven carcinoma of the breast, gastrointestinal system, genitourinary tract, lung, and vulva; 42 patients had 131I-antibodies to carcinoembryonic antigen (CEA) and 8 patients had 131I-normal goat immunoglobulin G [24].
  • We demonstrate that lin-42 acts broadly, timing developmental events in the gonad, vulva, and sex myoblasts, in addition to its well-established role in timing terminal differentiation of the hypodermis [25].

Associations of Vulva with chemical compounds

  • We propose that the regulation of UDP-glucuronic acid production in a specific subset of vulval cells helps determine the shape of the vulva [26].
  • New monoclonal antibodies recognizing epidermal differentiation-associated keratins in formalin-fixed, paraffin-embedded tissue. Keratin 10 expression in carcinoma of the vulva [27].
  • The changes in vulva were more dramatic in May than in November and resembled those observed in ewes treated with estradiol [28].
  • Following complete ablation of the lesions by one or more treatment modalities, 45 patients applied a single dose of 5% 5-fluorouracil cream biweekly to the vagina and/or vulva for at least six months [29].
  • Six patients with Paget's disease of the vulva, four after local excision of the gross lesion, one after multiple biopsies, and one after a radical vulvectomy, were successfully treated using the CO2 laser [30].

Gene context of Vulva


Analytical, diagnostic and therapeutic context of Vulva

  • Standard therapy for squamous cell carcinoma (SCC) of the vulva consists of radical surgery and inguinal node dissection [35].
  • Superior localisation and imaging of radiolabelled monoclonal antibody E48 F(ab')2 fragment in xenografts of human squamous cell carcinoma of the head and neck and of the vulva as compared to monoclonal antibody E48 IgG [36].
  • Between January 1960 and December 1982, 142 patients with carcinoma in situ of the vulva were treated at Cedars-Sinai Medical Center and UCLA Medical Center. Primary treatment consisted of wide excision in 45 patients; vulvectomy in 23 patients; topical chemotherapy in 9 patients; and CO2 laser therapy in 42 patients [12].
  • Tissues from 32 women with multicentric squamous cell neoplasia of the anogenital region (72 anatomically distinct lesions at the cervix, vagina, vulva, perineum, or anus) were tested for the presence of human papillomavirus with the polymerase chain reaction or in situ hybridization [37].
  • METHODS: Thirty-five cases of SCC of the vulva were evaluated for CD44 splice variants -3v, -4v, -5v, and -7v expression by immunocytochemistry [38].


  1. Preferential retention of codon 72 arginine p53 in squamous cell carcinomas of the vulva occurs in cancers positive and negative for human papillomavirus. Brooks, L.A., Tidy, J.A., Gusterson, B., Hiller, L., O'Nions, J., Gasco, M., Marin, M.C., Farrell, P.J., Kaelin, W.G., Crook, T. Cancer Res. (2000) [Pubmed]
  2. Suppression of various human tumor cell lines by a dominant negative H-ras mutant. Ogiso, Y., Sakai, N., Watari, H., Yokoyama, T., Kuzumaki, N. Gene Ther. (1994) [Pubmed]
  3. Frequent expression of the tumor antigen CAK1 in squamous-cell carcinomas. Chang, K., Pastan, I., Willingham, M.C. Int. J. Cancer (1992) [Pubmed]
  4. TP53 mutations in vulval lichen sclerosus adjacent to squamous cell carcinoma of the vulva. Rolfe, K.J., MacLean, A.B., Crow, J.C., Benjamin, E., Reid, W.M., Perrett, C.W. Br. J. Cancer (2003) [Pubmed]
  5. CD44v3 and v6 variant isoform expression correlates with poor prognosis in early-stage vulvar cancer. Tempfer, C., Sliutz, G., Haeusler, G., Speiser, P., Reinthaller, A., Breitenecker, G., Vavra, N., Kainz, C. Br. J. Cancer (1998) [Pubmed]
  6. MAP kinase signaling specificity mediated by the LIN-1 Ets/LIN-31 WH transcription factor complex during C. elegans vulval induction. Tan, P.B., Lackner, M.R., Kim, S.K. Cell (1998) [Pubmed]
  7. A polycystic kidney-disease gene homologue required for male mating behaviour in C. elegans. Barr, M.M., Sternberg, P.W. Nature (1999) [Pubmed]
  8. The gene lin-3 encodes an inductive signal for vulval development in C. elegans. Hill, R.J., Sternberg, P.W. Nature (1992) [Pubmed]
  9. The C. elegans homolog of the mammalian tumor suppressor Dep-1/Scc1 inhibits EGFR signaling to regulate binary cell fate decisions. Berset, T.A., Hoier, E.F., Hajnal, A. Genes Dev. (2005) [Pubmed]
  10. The small ubiquitin-like modifier (SUMO) is required for gonadal and uterine-vulval morphogenesis in Caenorhabditis elegans. Broday, L., Kolotuev, I., Didier, C., Bhoumik, A., Gupta, B.P., Sternberg, P.W., Podbilewicz, B., Ronai, Z. Genes Dev. (2004) [Pubmed]
  11. Effective multimodality treatment for advanced epidermoid carcinoma of the female genital tract. Kalra, J., Cortes, E., Chen, S., Krumholz, B., Rovinsky, J.J., Molho, L., Seltzer, V., Papantoniou, P., Lee, J.Y. J. Clin. Oncol. (1985) [Pubmed]
  12. Treatment of vulvar carcinoma in situ with the CO2 laser. Leuchter, R.S., Townsend, D.E., Hacker, N.F., Pretorius, R.G., Lagasse, L.D., Wade, M.E. Gynecol. Oncol. (1984) [Pubmed]
  13. Aggressive angiomyxoma of the vulva: Dramatic response to gonadotropin-releasing hormone agonist therapy. McCluggage, W.G., Jamieson, T., Dobbs, S.P., Grey, A. Gynecol. Oncol. (2006) [Pubmed]
  14. Arterial infusion of dacarbazine and cisplatin for recurrent regionally confined melanoma. Frost, D.B., Patt, Y.Z., Mavligit, G., Chuang, V.P., Wallace, S. Archives of surgery (Chicago, Ill. : 1960) (1985) [Pubmed]
  15. Bleomycin, methotrexate, and CCNU in locally advanced or recurrent, inoperable, squamous-cell carcinoma of the vulva: an EORTC Gynaecological Cancer Cooperative Group Study. European Organization for Research and Treatment of Cancer. Wagenaar, H.C., Colombo, N., Vergote, I., Hoctin-Boes, G., Zanetta, G., Pecorelli, S., Lacave, A.J., van Hoesel, Q., Cervantes, A., Bolis, G., Namer, M., Lhommé, C., Guastalla, J.P., Nooij, M.A., Poveda, A., Scotto di Palumbo, V., Vermorken, J.B. Gynecol. Oncol. (2001) [Pubmed]
  16. COG-2, a sox domain protein necessary for establishing a functional vulval-uterine connection in Caenorhabditis elegans. Hanna-Rose, W., Han, M. Development (1999) [Pubmed]
  17. The Pristionchus HOX gene Ppa-lin-39 inhibits programmed cell death to specify the vulva equivalence group and is not required during vulval induction. Sommer, R.J., Eizinger, A., Lee, K.Z., Jungblut, B., Bubeck, A., Schlak, I. Development (1998) [Pubmed]
  18. The roles of two C. elegans HOX co-factor orthologs in cell migration and vulva development. Yang, L., Sym, M., Kenyon, C. Development (2005) [Pubmed]
  19. The nT1 translocation separates vulval regulatory elements from the egl-18 and elt-6 GATA factor genes. Koh, K., Bernstein, Y., Sundaram, M.V. Dev. Biol. (2004) [Pubmed]
  20. Emerging roles of MTA family members in human cancers. Kumar, R., Wang, R.A., Bagheri-Yarmand, R. Semin. Oncol. (2003) [Pubmed]
  21. The nematode even-skipped homolog vab-7 regulates gonad and vulva position in Pristionchus pacificus. Jungblut, B., Sommer, R.J. Development (2001) [Pubmed]
  22. Molecular analysis of the X11-mLin-2/CASK complex in brain. Borg, J.P., Lõpez-Figueroa, M.O., de Taddèo-Borg, M., Kroon, D.E., Turner, R.S., Watson, S.J., Margolis, B. J. Neurosci. (1999) [Pubmed]
  23. The lin-11 LIM domain transcription factor is necessary for morphogenesis of C. elegans uterine cells. Newman, A.P., Acton, G.Z., Hartwieg, E., Horvitz, H.R., Sternberg, P.W. Development (1999) [Pubmed]
  24. Lymphoscintigraphy with radionuclide-labeled antibodies to carcinoembryonic antigen. DeLand, F.H., Kim, E.E., Goldenberg, D.M. Cancer Res. (1980) [Pubmed]
  25. Novel heterochronic functions of the Caenorhabditis elegans period-related protein LIN-42. Tennessen, J.M., Gardner, H.F., Volk, M.L., Rougvie, A.E. Dev. Biol. (2006) [Pubmed]
  26. The Caenorhabditis elegans vulval morphogenesis gene sqv-4 encodes a UDP-glucose dehydrogenase that is temporally and spatially regulated. Hwang, H.Y., Horvitz, H.R. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  27. New monoclonal antibodies recognizing epidermal differentiation-associated keratins in formalin-fixed, paraffin-embedded tissue. Keratin 10 expression in carcinoma of the vulva. Ivanyi, D., Ansink, A., Groeneveld, E., Hageman, P.C., Mooi, W.J., Heintz, A.P. J. Pathol. (1989) [Pubmed]
  28. Clinical changes in ovariectomized ewes exposed to phytoestrogens and 17 beta-estradiol implants. Nwannenna, A.I., Lundh, T.J., Madej, A., Fredriksson, G., Björnhag, G. Proc. Soc. Exp. Biol. Med. (1995) [Pubmed]
  29. Prophylactic topical 5-fluorouracil following treatment of human papillomavirus-associated lesions of the vulva and vagina. Krebs, H.B. Obstetrics and gynecology. (1986) [Pubmed]
  30. Paget's disease of the vulva treated by combined surgery and laser. Ewing, T.L. Gynecol. Oncol. (1991) [Pubmed]
  31. The let-23 gene necessary for Caenorhabditis elegans vulval induction encodes a tyrosine kinase of the EGF receptor subfamily. Aroian, R.V., Koga, M., Mendel, J.E., Ohshima, Y., Sternberg, P.W. Nature (1990) [Pubmed]
  32. Cell fates and fusion in the C. elegans vulval primordium are regulated by the EGL-18 and ELT-6 GATA factors -- apparent direct targets of the LIN-39 Hox protein. Koh, K., Peyrot, S.M., Wood, C.G., Wagmaister, J.A., Maduro, M.F., Eisenmann, D.M., Rothman, J.H. Development (2002) [Pubmed]
  33. The C. elegans vulval induction gene lin-2 encodes a member of the MAGUK family of cell junction proteins. Hoskins, R., Hajnal, A.F., Harp, S.A., Kim, S.K. Development (1996) [Pubmed]
  34. Papillomavirus, p53 alteration, and primary carcinoma of the vulva. Pilotti, S., D'Amato, L., Della Torre, G., Donghi, R., Longoni, A., Giarola, M., Sampietro, G., De Palo, G., Pierotti, M.A., Rilke, F. Diagn. Mol. Pathol. (1995) [Pubmed]
  35. Radiation response of vulvar squamous cell carcinoma (UM-SCV-1A, UM-SCV-1B, UM-SCV-2, and A-431) cells in vitro. Pekkola-Heino, K., Kulmala, J., Grenman, S., Carey, T.E., Grenman, R. Cancer Res. (1989) [Pubmed]
  36. Superior localisation and imaging of radiolabelled monoclonal antibody E48 F(ab')2 fragment in xenografts of human squamous cell carcinoma of the head and neck and of the vulva as compared to monoclonal antibody E48 IgG. Gerretsen, M., Quak, J.J., Suh, J.S., van Walsum, M., Meijer, C.J., Snow, G.B., van Dongen, G.A. Br. J. Cancer (1991) [Pubmed]
  37. Human papillomavirus infection in women with multicentric squamous cell neoplasia. Beckmann, A.M., Acker, R., Christiansen, A.E., Sherman, K.J. Am. J. Obstet. Gynecol. (1991) [Pubmed]
  38. Prognostic value of CD44 expression in invasive squamous cell carcinoma of the vulva. Rodríguez-Rodríguez, L., Sancho-Torres, I., Miller Watelet, L., Gibbon, D.G., Comerci, J.T., Mesonero, C. Gynecol. Oncol. (1999) [Pubmed]
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