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Sample records for basal cell naevus

  1. Segmental basal cell naevus syndrome caused by an activating mutation in smoothened.

    PubMed

    Khamaysi, Z; Bochner, R; Indelman, M; Magal, L; Avitan-Hersh, E; Sarig, O; Sprecher, E; Bergman, R

    2016-07-01

    Aberrant sonic hedgehog signalling, mostly due to PTCH1 mutations, has been shown to play a central role in the pathogenesis of basal cell carcinoma (BCC), as well as in basal cell naevus syndrome (BCNS). Mutations in smoothened (SMO) encoding a receptor for sonic hedgehog have been reported in sporadic BCCs but not in BCNS. We report a case with multiple BCCs, pits and comedones in a segmental distribution over the upper part of the body, along with other findings compatible with BCNS. Histopathologically, there were different types of BCC. A heterozygous mutation (c.1234C>T, p.L412F) in SMO was detected in three BCCs but not in peripheral blood lymphocytes or the uninvolved skin. These were compatible with the type 1 mosaic form of BCNS. The p.L412F mutation was found experimentally to result in increased SMO transactivating activity, and the patient responded to vismodegib therapy. Activating mutations in SMO may cause BCNS. The identification of a gain-of-function mutation in SMO causing a type 1 mosaic form of BCNS further expands our understanding of the pathogenesis of BCC, with implications for the treatment of these tumours, whether sporadic or inherited. PMID:26822128

  2. Basal Cell Carcinoma (BCC)

    MedlinePlus

    ... carcinomas: Infiltrating basal cell carcinomas can be more aggressive and locally destructive than other types of basal ... to treat them early and with slightly more aggressive techniques. Excision – The basal cell carcinoma is cut ...

  3. Basal Cell Carcinoma

    PubMed Central

    Lanoue, Julien

    2016-01-01

    Basal cell carcinoma is the most commonly occurring cancer in the world and overall incidence is still on the rise. While typically a slow-growing tumor for which metastases is rare, basal cell carcinoma can be locally destructive and disfiguring. Given the vast prevalence of this disease, there is a significant overall burden on patient well-being and quality of life. The current mainstay of basal cell carcinoma treatment involves surgical modalities, such as electrodessication and curettage, excision, cryosurgery, and Mohs micrographic surgery. Such methods are typically reserved for localized basal cell carcinoma and offer high five-year cure rates, but come with the risk of functional impairment, disfigurement, and scarring. Here, the authors review the evidence and indications for nonsurgical treatment modalities in cases where surgery is impractical, contraindicated, or simply not desired by the patient. PMID:27386043

  4. Basal cell skin cancer

    MedlinePlus

    ... occur in younger people who have had extensive sun exposure. You are more likely to get basal cell ... severe sunburns early in life Long-term daily sun exposure (such as the sun exposure received by people ...

  5. Basal cell cancer (image)

    MedlinePlus

    ... is needed to prove the diagnosis of basal cell carcinoma. Treatment varies depending on the size, depth, and location of the cancer. Early treatment by a dermatologist may result in a cure rate of more than 95%, but regular examination ...

  6. Polythelia within Becker's naevus.

    PubMed

    Urbani, C E; Betti, R

    1998-01-01

    We report a case of accessory mammary tissue of type 2a (or polythelia) entirely localized within a Becker's naevus of mixed type in a 32-year-old Caucasian woman. Polythelia was congenital in origin while Becker's naevus appeared during puberty. Renal ultrasonographic studies, laboratory examinations and other instrumental investigations were either normal or negative. Although the association of accessory mammary tissue with Becker's naevus has previously been reported--also in the form of mammorenal and acromammorenal syndromes--this is the first case characterized by an anatomic overlap between the two anomalies. It may be the expression of a common disturbance acting early in embryogenesis in the specific developmental fields involved. PMID:9568418

  7. Nevoid basal cell carcinoma syndrome

    MedlinePlus

    ... of this disorder is a type of skin cancer called basal cell carcinoma , that develops around the time of puberty. Other ... if: You or any family members have nevoid basal cell carcinoma syndrome, especially if you are planning to have ...

  8. Bilateral Ota naevus.

    PubMed

    Ruiz-Villaverde, R; Blasco Melguizo, J; Buendía Eisman, A; Serrano Ortega, S

    2003-07-01

    We present the case of a 22-year-old woman, who had presented since the age of 15 a pale-blue spot spread on the right-hand side of her forehead and in her bulbar conjunctiva (first and second branches of the trigeminus nerve), consistent with Ota naevus. A few years later another with similar characteristics appeared on the other side of her forehead, cheek and sclera. No deafness, neurological defect nor visual loss were detected. We comment on the rarity of this case because the patient is Caucasian and also we explain the main complications derived of this disease and consider the therapeutic options. PMID:12834455

  9. A distinctive melanocytic lesion associated with melanoma-prone dysplastic naevus syndrome: the hybrid naevus.

    PubMed

    Schubert, C; Parwaresch, R; Rudolph, P

    2001-02-01

    Clinically and histologically, the concept of dysplastic nevi remains controversial. To elaborate more precise criteria for the nevi of patients with dysplastic naevus syndrome (DNS), we examined 58 nevi from seven DNS patients who developed one or several malignant melanomas. Clinical presentation and histomorphology were evaluated, and immunohistochemistry was performed using proliferation marker Ki-S5 and antibody DO-7 to the p53 protein. Sixty nevi from individuals without history of melanoma served as controls. Of the DNS nevi, 21 (36.2%) exhibited no morphological particularities. The remaining 37 nevi presented distinctive histological features consisting of a slight epidermal acanthosis, spitzoid vertically oriented nests of dyscohesive nevus cells, and single-standing atypical melanocytes in the basal cell layer of the epidermis. Immunohistochemical analysis revealed an average proliferation index of 2.5%, which significantly surpassed the mean growth fraction of conventional dysplastic nevi (<1%). No increase in p53 expression was observed. Characteristically, active proliferation was found in junctional single-standing melanocytes with or without nuclear atypia rather than in nest-shaped compounds. In conclusion, certain moles of patients with DNS possess distinctive features. The newly characterized criteria may provide a basis for the diagnosis of DNS and might help to identify patients at increased risk for malignant melanoma by examination of a single biopsy. PMID:11253119

  10. [Basal and spinous cell epitheliomas].

    PubMed

    Shaw, M; Sanguinetti, O; de Kaminsky, A R; Kaminsky, C A

    1975-01-01

    A study on 502 epithelial cutaneous cancers was carried out by the authors. The study included 377 basal cell carcinomas (57,5% in males and 42,4% in females) and 125 squamous cell carcinomas (78,4% in males and 21,6% in females). The basal cell carcinomas in both sexs had an earlier onset than the squamous cell carcinomas. PMID:1241706

  11. Multiple pigmented basal cell carcinomas.

    PubMed

    Shoji, T; Lee, J; Hong, S H; Oh, C H; Kim, W K; Bhawan, J

    1998-04-01

    Basal cell carcinoma is the most common of all skin cancers and the most prevalent one among Caucasians. Rarely, these tumors are seen in other races. We report a 77-year-old Korean woman who presented with multiple darkly pigmented enlarging nodules on her scalp, face, trunk, and extremities. The patient had first noted a 6-mm pigmented lesion on her left eyebrow 10 years previously. Since then, other lesions had appeared in many locations on her body. She had been otherwise healthy and without a history of exposure to arsenic or radiation. There was no family history of skin cancer, xeroderma pigmentosum, or basal cell nevus syndrome. On physical examination, multiple darkly pigmented dome-shaped papules and nodules were present on her scalp, face, right forearm, lower abdomen, and inguinal areas. They ranged in size from 0.5 mm to 2 cm. The larger ones showed central ulceration. Multiple biopsy specimens from different sites showed pigmented basal cell carcinomas. Clinically, there was no evidence of nevus sebaceus, xeroderma pigmentosum, basal cell nevus syndrome, or immunodeficiency. Clinical workup including chest radiography, abdominal ultrasound, bone scan, and brain computerized axial tomography scan did not demonstrate primary or secondary tumors. The results of serologic and hematologic tests were also within normal limits. This is an unusual case report of multiple pigmented basal cell carcinomas in an Asian woman without any predisposing risk factors. PMID:9557792

  12. Basal cell carcinoma – diagnosis

    PubMed Central

    Bowszyc-Dmochowska, Monika; Strzelecka-Węklar, Daria; Dańczak-Pazdrowska, Aleksandra; Adamski, Zygmunt

    2013-01-01

    Basal cell carcinoma is the most common skin cancer in the Caucasian population. The cancer arises in sun exposed areas of the skin. The incidence of morbidity is high and it is still growing. The metastatic rate is low, but the enlarging tumor may cause severe tissue disfigurement and a poor cosmetic outcome. The diagnosis is usually clinical but there are many subtypes of this carcinoma and correct diagnosis is the clue to appropriate treatment of the lesion. The main problem in basal cell carcinoma management is the high recurrence rate. PMID:24592119

  13. "Basal Cell Blanche": A Diagnostic Maneuver to Increase Early Detection of Basal Cell Carcinomas.

    PubMed

    Quach, Olivia Leigh; Barry, Megan; Roberts Cruse, Allison; Wilson, Barbara B

    2016-01-01

    Basal cell carcinomas represent one of the most common skin cancers and often present initially in the primary care setting. Subtle basal cell carcinomas may be difficult to detect, and early detection of these carcinomas remains important in limiting patient morbidity. In this article, we present a simple diagnostic maneuver, "basal cell blanche," to increase early detection of basal cell carcinomas. PMID:27170799

  14. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

    PubMed

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy. PMID:26971503

  15. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    PubMed Central

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome. PMID:25506011

  16. Schwann cell basal lamina and nerve regeneration.

    PubMed

    Ide, C; Tohyama, K; Yokota, R; Nitatori, T; Onodera, S

    1983-12-12

    Nerve segments approximately 7 mm long were excised from the predegenerated sciatic nerves of mice, and treated 5 times by repetitive freezing and thawing to kill the Schwann cells. Such treated nerve segments were grafted into the original places so as to be in contact with the proximal stumps. The animals were sacrificed 1, 2, 3, 5, 7 and 10 days after the grafting. The grafts were examined by electron microscopy in the middle part of the graft, i.e. 3-4 mm distal to the proximal end and/or near the proximal and distal ends of the graft. In other instances, the predegenerated nerve segments were minced with a razor blade after repetitive freezing and thawing. Such minced nerves were placed in contact with the proximal stumps of the same nerves. The animals were sacrificed 10 days after the grafting. Within 1-2 days after grafting, the dead Schwann cells had disintegrated into fragments. They were then gradually phagocytosed by macrophages. The basal laminae of Schwann cells, which were not attacked by macrophages, remained as empty tubes (basal lamina scaffolds). In the grafts we examined, no Schwann cells survived the freezing and thawing process. The regenerating axons always grew out through such basal lamina scaffolds, being in contact with the inner surface of the basal lamina (i.e. the side originally facing the Schwann cell plasma membrane). No axons were found outside of the scaffolds. One to two days after grafting, the regenerating axons were not associated with Schwann cells, but after 5-7 days they were accompanied by Schwann cells which were presumed to be migrating along axons from the proximal stumps. Ten days after grafting, proliferating Schwann cells observed in the middle part of the grafts had begun to sort out axons. In the grafts of minced nerves, the fragmented basal laminae of the Schwann cells re-arranged themselves into thicker strands or small aggregations of basal laminae. The regenerating axons, without exception, attached to one side

  17. Epithelial-Mesenchymal Transition Protein Expression in Basal Cell Adenomas and Basal Cell Adenocarcinomas.

    PubMed

    Tesdahl, Brennan A; Wilson, Thomas C; Hoffman, Henry T; Robinson, Robert A

    2016-06-01

    Basal cell adenomas and basal cell adenocarcinomas show marked histomorphologic similarity and are separated microscopically primarily by the invasive characteristics of the adenocarcinomas. We wished to explore potential differences in the expression of epithelial-mesenchymal transition associated proteins in these two tumor types. A tissue microarray was constructed utilizing 29 basal cell adenomas and 16 basal cell adenocarcinomas. Immunohistochemical expression of E-cadherin, beta-catenin, Twist 1 and vimentin were investigated. Both tumors expressed all proteins in a relatively similar manner. Nuclear beta-catenin was essentially limited to the abluminal cell populations in both tumor types. E-cadherin was limited largely to luminal locations but was more prevalent in the adenocarcinomas as compared to the adenomas. Primarily abluminal expression for vimentin was seen, sometimes present in an apical dot-like pattern. Distinct populations of cellular expression of these four markers of epithelial mesenchymal transition were present but were similar in locations in both tumors with no patterns discerned to separate basal cell adenoma from basal cell adenocarcinoma. Given these findings, the mechanisms by which basal cell adenocarcinoma is able to invade while its counterpart, basal cell adenoma can not, may be more complex than in other tumor types. PMID:26442856

  18. Limbal Basal Cell Density Decreases in Limbal Stem Cell Deficiency

    PubMed Central

    Chan, Eric H; Chen, Luxia; Rao, Jian Yu; Yu, Fei; Deng, Sophie X.

    2016-01-01

    Purpose To investigate changes in limbal basal epithelial cell density in eyes with limbal stem cell deficiency (LSCD) using in vivo confocal laser scanning microscopy Design retrospective observational comparative study Methods A total of 43 eyes of 30 patients diagnosed with LSCD were included in the study. Ten eyes from normal subjects were included as control. Confocal imaging of the central cornea, and the superior, nasal, inferior and temporal limbus were collected using the Heidelberg Retina Tomograph III Rostock Corneal Module. Basal cell density in all locations was measured by two independent observers. Results The mean basal cell density of the normal group was 9264 ±598 cells/mm2 in the cornea and 7120 ±362 cells/mm2 in the limbus. In the LSCD group, the mean basal cell density in the cornea decreased 31.0% (6389 ±1820 cells/mm2, p<0.001) and in the limbus decreased 23.6% (5440 ±1123 cells/mm2, p<0.001) compared to that in the control. There was a trend of basal cell density decline in more advanced stage of LSCD. The basal cell density declined in the unaffected regions at a similar degree as that in the affected region in sectoral LSCD (p>0.05). The basal cell diameter increased by 24.6% in the cornea (14.7 μm) and by 15.7% in the limbus (15.5 μm) compared to the control. Conclusions Basal cell density in both central cornea and limbus decreases in LSCD. LSCs are affected globally and basal cell density could be used as a parameter to measure LSC function at the early stages of the disease process. PMID:26149968

  19. Basal cell nevus syndrome - close-up of palm (image)

    MedlinePlus

    ... skeletal abnormalities. Skin manifestations include pits in the palms and soles, and numerous basal cell carcinomas. This ... close-up of the pits found in the palm of an individual with basal cell nevus syndrome.

  20. Spontaneous regression of a conjunctival naevus.

    PubMed

    Haldar, Shreya; Leyland, Martin

    2016-01-01

    Conjunctival naevi are one of the most common lesions affecting the conjunctiva. While benign in the vast majority of cases, the risk of malignant transformation necessitates regular follow-up. They are well known to increase in size; however, we present the first photo-documented case of spontaneous regression of conjunctival naevus. In most cases, surgical excision is performed due to the clinician's concerns over malignancy. However, a substantial proportion of patients request excision. Highlighting the potential for regression of the lesion is important to ensure patients make an informed decision when contemplating such surgery. PMID:27581234

  1. Basal Cell Carcinoma. Part 1: Basal Cell Carcinoma Has Come of Age.

    PubMed

    Deng, Min; Marsch, Amanda F; Petronic-Rosic, Vesna

    2015-01-01

    Almost 2 centuries after its recognition, basal cell carcinoma (BCC) remains the most common cancer worldwide, with a 30% overall lifetime risk in the United States and an incidence that continues to increase annually. The increasing incidence of BCC is multifactorial and likely correlates to multiple risk factors, including exposure to both ionizing and UV radiation. Despite its relatively indolent growth, what was once referred to as a rodent ulcer or basal cell epithelioma is now identified as a full-fledged malignancy. The authors describe the societal burden of this disease and characterize its malignant potential, emphasizing associated clinical and histopathologic prognostic features. PMID:26380507

  2. Cell cycle of globose basal cells in rat olfactory epithelium.

    PubMed

    Huard, J M; Schwob, J E

    1995-05-01

    The olfactory epithelium of adult mammals has the unique property of generating olfactory sensory neurons throughout life. Cells of the basal compartment, which include horizontal and globose basal cells, are responsible for the ongoing process of neurogenesis in this system. We report here that the globose basal cells in olfactory epithelium of rats, as in mice, are the predominant type of proliferating cell, and account for 97.6% of the actively dividing cells in the basal compartment of the normal epithelium. Globose basal cells have not been fully characterized in terms of their proliferative properties, and the dynamic aspects of neurogenesis are not well understood. As a consequence, it is uncertain whether cell kinetic properties are under any regulation that could affect the rate of neurogenesis. To address this gap in our knowledge, we have determined the duration of both the synthesis phase (S-phase) and the full cell cycle of globose basal cells in adult rats. The duration of the S-phase was found to be 9 hr in experiments utilizing sequential injections of either IdU followed by BrdU or 3H-thy followed by BrdU. The duration of the cell cycle was determined by varying the time interval between the injections of 3H-thy and BrdU and tracking the set of cells that exit S shortly after the first injection. With this paradigm, the interval required for these cells to traverse G2, M, G1, and a second S-phase, is equivalent to the duration of one mitotic cycle and equals 17 hr. These observations serve as the foundation to assess whether the cell cycle duration is subject to regulation in response to experimental injury, and whether such regulation is partly responsible for changes in the rate of neurogenesis in such settings. PMID:7647371

  3. Radiation-induced basal cell carcinoma

    PubMed Central

    Zargari, Omid

    2015-01-01

    Background: The treatment of tinea capitis using radiotherapy was introduced at the beginning of the twentieth century. A variety of cancers including basal cell carcinoma (BCC) are seen years after this treatment. Objective: We sought to determine the clinical characteristics of BCCs among irradiated patients. Methods: The clinical records of all patients with BCC in a clinic in north of Iran were reviewed. Results: Of the 58 cases of BCC, 29 had positive history for radiotherapy in their childhood. Multiple BCCs were seen in 79.3% and 10.3% of patients with history and without history of radiotherapy, respectively. Conclusions: X-ray radiation is still a major etiologic factor in developing BCC in northern Iran. Patients with positive history for radiotherapy have higher rate of recurrence. PMID:26114066

  4. Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

    PubMed Central

    Lo Muzio, Lorenzo

    2008-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs), odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies). Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm) are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull) are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling). Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome). Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser ablation, photodynamic

  5. Distinctive Patterns of CTNNB1 (β-Catenin) Alterations in Salivary Gland Basal Cell Adenoma and Basal Cell Adenocarcinoma.

    PubMed

    Jo, Vickie Y; Sholl, Lynette M; Krane, Jeffrey F

    2016-08-01

    Salivary gland basaloid neoplasms are diagnostically challenging. Limited publications report that some basal cell adenomas harbor CTNNB1 mutations, and nuclear β-catenin expression is prevalent. We evaluated β-catenin expression in basal cell adenomas and adenocarcinomas in comparison with salivary tumors in the differential diagnosis and performed targeted genetic analysis on a subset of cases. β-catenin immunohistochemistry was performed on formalin-fixed, paraffin-embedded whole sections from 73 tumors. Nuclear staining was scored semiquantitatively by extent and intensity. DNA was extracted from 6 formalin-fixed, paraffin-embedded samples (5 basal cell adenomas, 1 basal cell adenocarcinoma) for next-generation sequencing. Nuclear β-catenin staining was present in 18/22 (82%) basal cell adenomas; most were diffuse and strong and predominant in the basal component. Two of 3 basal cell adenocarcinomas were positive (1 moderate focal; 1 moderate multifocal). All adenoid cystic carcinomas (0/20) and pleomorphic adenomas (0/20) were negative; 2/8 epithelial-myoepithelial carcinomas showed focal nuclear staining. Most β-catenin-negative tumors showed diffuse membranous staining in the absence of nuclear staining. Four of 5 basal cell adenomas had exon 3 CTNNB1 mutations, all c.104T>C (p.I35T). Basal cell adenocarcinoma showed a more complex genomic profile, with activating mutations in PIK3CA, biallelic inactivation of NFKBIA, focal CYLD deletion, and without CTNNB1 mutation despite focal β-catenin expression. Nuclear β-catenin expression has moderate sensitivity (82%) for basal cell adenoma but high specificity (96%) in comparison with its morphologic mimics. CTNNB1 mutation was confirmed in most basal cell adenomas tested, and findings in basal cell adenocarcinoma suggest possible tumorigenic mechanisms, including alterations in PI3K and NF-κB pathways and transcriptional regulation. PMID:27259009

  6. New basal cell carcinoma susceptibility loci

    PubMed Central

    Stacey, Simon N.; Helgason, Hannes; Gudjonsson, Sigurjon A.; Thorleifsson, Gudmar; Zink, Florian; Sigurdsson, Asgeir; Kehr, Birte; Gudmundsson, Julius; Sulem, Patrick; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R.; Thorisdottir, Kristin; Ragnarsson, Rafn; Fuentelsaz, Victoria; Corredera, Cristina; Gilaberte, Yolanda; Grasa, Matilde; Planelles, Dolores; Sanmartin, Onofre; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Nexø, Bjørn A.; Tjønneland, Anne; Overvad, Kim; Jonasson, Jon G.; Tryggvadottir, Laufey; Johannsdottir, Hrefna; Kristinsdottir, Anna M.; Stefansson, Hreinn; Masson, Gisli; Magnusson, Olafur T.; Halldorsson, Bjarni V.; Kong, Augustine; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Vogel, Ulla; Kumar, Rajiv; Nagore, Eduardo; Mayordomo, José I.; Gudbjartsson, Daniel F.; Olafsson, Jon H.; Stefansson, Kari

    2015-01-01

    In an ongoing screen for DNA sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conduct a genome-wide association study (GWAS) of 24,988,228 SNPs and small indels detected through whole-genome sequencing of 2,636 Icelanders and imputed into 4,572 BCC patients and 266,358 controls. Here we show the discovery of four new BCC susceptibility loci: 2p24 MYCN (rs57244888[C], OR=0.76, P=4.7 × 10−12), 2q33 CASP8-ALS2CR12 (rs13014235[C], OR=1.15, P=1.5 × 10−9), 8q21 ZFHX4 (rs28727938[G], OR=0.70, P=3.5 × 10−12) and 10p14 GATA3 (rs73635312[A], OR=0.74, P=2.4 × 10−16). Fine mapping reveals that two variants correlated with rs73635312[A] occur in conserved binding sites for the GATA3 transcription factor. In addition, expression microarrays and RNA-seq show that rs13014235[C] and a related SNP rs700635[C] are associated with expression of CASP8 splice variants in which sequences from intron 8 are retained. PMID:25855136

  7. The effective treatment of basal cell carcinoma.

    PubMed

    Skelton, Lucy Anne

    Basal cell carcinoma (BCC) accounts for 75% of all skin cancers and its incidence is rising by between 3-8% each year (Szeimies and Karrer, 2006). As a result, the development of new therapeutic strategies and treatment methods for the removal of BCC is crucial in combating what is a growing problem. Surgical techniques, such as Mohs micrographic surgery, cryotherapy/cryosurgery, curettage and carbon dioxide laser therapy, as well as non-surgical techniques, such as radiotherapy, are recognized as potential options. The aim of this article is to critically review some of the current literature in order to substantiate the efficacy of destructive and non-surgical techniques as reliable alternatives to surgery for the management/removal of BCCs. The success rate, cosmetic outcome, pain and discomfort, recurrence rates, and the cost associated with each method are explored and discussed. Results of the review indicate that no one treatment is completely superior. According to the research, simple excision and Mohs micrographic surgery provide the lowest recurrence rates. However, in relation to success rates, patients tolerance of the treatment and cosmetic outcomes, and depending on the type of BCC involved, other treatment methods do offer reliable alternatives. PMID:19329898

  8. Giant basal cell carcinoma of the forehead: a case report.

    PubMed

    Rudić, Milan; Kranjcec, Zoran; Lisica-Sikić, Natasa; Kovacić, Marijan

    2012-03-01

    Giant basal cell carcinoma (GBCC) is defined as a tumor 5cm or greater in diameter. They present less than 1% of all basal cell carcinomas. We present a case of an 85-year-old male patient with a giant ulcerating tumor of the left forehead (measuring 7x6 cm). Under local anesthesia tumor was surgically excised. No involvement of the underlying periostal or bone structure was noted. Pathohystological exam revealed the giant basal cell carcinoma, with free surgical margins. Giant basal cell carcinomas are rare tumors and are usually result of a long duration and patient neglect. In comparison to the ordinary basal cell carcinoma these tumors have a higher metastatic potential. Surgical resection with negative surgical margin is the best possible treatment option. PMID:22816239

  9. How Are Squamous and Basal Cell Skin Cancers Diagnosed?

    MedlinePlus

    ... often enough to cure basal and squamous cell skin cancers without further treatment. There are different types of skin biopsies. The ... and Prevention Early Detection, Diagnosis, and Staging Treating Skin Cancer - ... Your Doctor After Treatment What`s New in Skin Cancer - Basal and Squamous ...

  10. [Extensive basal cell cancer of the scalp - case reports].

    PubMed

    Olędzki, Szymon; Modrzejewski, Andrzej; Department Of Surgery And Emergency Nursing Pomeranian Medical University In Szczecin Poland, Ryszard

    2016-07-01

    Basal-cell canceris a slow growing, rarely metastasizes, locally malignant skin cancer. Patients with this neoplasm usually have excellent prognosis. Potentially, in some cases, a good prognosis cause a delay in therapy. Delay or withdrawal from treatment might lead to higher local extension of tumour with the destruction of the surrounding tissue. In this article we are presenting two patients with extensive basal cell cancer. The first patient underwent plastic surgery for extensive basal-cell carcinoma located in the parietal and temporal area. The second patient was observed due to recurrence of extensive basal cell carcinoma in the parietal region. Local advancement of the primary tumor could be a reason for the lack of radicality of surgery. Such advancement is rarely seen nowadays. The cases demonstrate the need for awareness about the possible severe course of the disease. PMID:27590651

  11. [Extensive basal cell cancer of the scalp - case reports].

    PubMed

    Olędzki, Szymon; Modrzejewski, Andrzej; Department Of Surgery And Emergency Nursing Pomeranian Medical University In Szczecin Poland, Ryszard

    2016-08-01

    Basal-cell canceris a slow growing, rarely metastasizes, locally malignant skin cancer. Patients with this neoplasm usually have excellent prognosis. Potentially, in some cases, a good prognosis cause a delay in therapy. Delay or withdrawal from treatment might lead to higher local extension of tumour with the destruction of the surrounding tissue. In this article we are presenting two patients with extensive basal cell cancer. The first patient underwent plastic surgery for extensive basal-cell carcinoma located in the parietal and temporal area. The second patient was observed due to recurrence of extensive basal cell carcinoma in the parietal region. Local advancement of the primary tumor could be a reason for the lack of radicality of surgery. Such advancement is rarely seen nowadays. The cases demonstrate the need for awareness about the possible severe course of the disease. PMID:27591446

  12. PERIANAL BASAL CELL CARCINOMA—AN UNUSUAL SITE OF OCCURRENCE

    PubMed Central

    Nagendra Naidu, D V; Rajakumar, V

    2010-01-01

    Basal cell carcinoma is the most common nonmelanoma skin cancer. Its occurrence in the perianal region is very rare. Awareness of its benign behavior in this region, in contrast to the earlier reports, is vital in its management. Local excision seems to provide adequate control. We are herewith reporting an extremely rare case of a 69-year-old male with basal cell carcinoma treated adequately with local excision. PMID:20606890

  13. The relation between dermoscopy and histopathology of basal cell carcinoma*

    PubMed Central

    Emiroglu, Nazan; Cengiz, Fatma Pelin; Kemeriz, Funda

    2015-01-01

    BACKGROUND: Basal cell carcinoma is the most frequent cancer in fair-skinned populations and dermoscopy is an important, non-invasive technique that aids in the diagnosis of Basal cell carcinoma. OBJECTIVES: The aim of this study was to evaluate the relationship between histopathological subtypes and dermoscopic features of Basal cell carcinoma. METHODS: This study included 98 patients with clinically and histopathologically confirmed Basal cell carcinomas. The dermoscopic features of the lesions from each patient were analyzed before the histopathological findings were evaluated. RESULTS: Dermoscopic structures were observed in all 98 patients and irregular vascularity was identified in 78 patients (79.6%). The most common vascular pattern was the presence of arborizing vessels (42 patients, 42.9%) followed by arborizing microvessels (21 patients, 21.4%) and short fine telangiectasias (SFTs; 15 patients, 15.3%). White streaks (38 patients, 38.8%), translucency (31 patients, 31.6%), a milky-pink to red background (42 patients, 42.9%), and erosion/ulceration (29 patients, 29.6%) were also observed. Pigmented islands were seen as blue-gray globules (7 patients, 7.1%) and blue-gray ovoid nests (42 patients, 42.9%). The pigment distribution pattern was maple leaf-like areas in 9 patients (9.2 %) and spoke wheel-like areas in 6 patients (6.1%). CONCLUSIONS: Basal cell carcinomas show a wide spectrum of dermoscopic features. Arborizing vessels were the most common dermoscopic findings in Basal cell carcinomas, while superficial Basal cell carcinomas displayed mainly milky-pink to red areas, and arborizing microvessels. The most common dermoscopic features of pigmented types were islands of pigment (blue-gray globules, blue-gray ovoid nests). In conclusion, dermoscopy can be used as a valuable tool for the diagnosis of Basal cell carcinomas and prediction of their histopathological subtypes. PMID:26131865

  14. Heterogeneity of basal keratinocytes: nonrandom distribution of thymidine-labeled basal cells in confluent cultures is not a technical artifact

    SciTech Connect

    Milstone, L.M.; LaVigne, J.F.

    1985-06-01

    Basal surface autoradiography of (/sup 3/H)dThd-labeled, confluent, keratinocyte cultures reveals that proliferating cells have a nonrandom, patterned distribution. Unlabeled cells, likewise, appear nonrandomly in clusters. The authors show here that failure to detect DNA synthesis in some basal cells in culture is not an artifact caused either by physical separation of the labeled nuclei from the radiographic emulsion or by a diffusion barrier that would prevent (/sup 3/H)dThd from reaching basal cells.

  15. Nuclear morphometry and chromatin textural characteristics of basal cell carcinoma*

    PubMed Central

    Mendaçolli, Paola Jung; Brianezi, Gabrielli; Schmitt, Juliano Vilaverde; Marques, Mariângela Esther Alencar; Miot, Hélio Amante

    2015-01-01

    Histological subtypes of basal cell carcinoma have biological, evolutionary and distinct prognostic behavior. The analysis of characteristics of the nucleus can provide data on their cellular physiology and behavior. The authors of this study evaluated nuclear morphological parameters and textural patterns of chromatin from different subtypes of basal cell carcinoma: nodular (n=37), superficial (n=28) and sclerodermiform (n=28). The parameters were compared between neoplasms' subtypes and with unaffected adjacent basal epithelium. Nuclear area and diameter of sclerodermiform neoplasms were superior to the other subtypes. Chromatin's color intensity and fractal dimension were less intense in superficial subtypes. Nuclear roundness and chromatin's entropy presented lower values in tumors than in normal epithelium. There was significant correlation between morphological and textural variables of normal skin and tumors. Morphometric elements and textural chromatin's homogeneity of basal cell carcinomas may be related to evolutionary, biological and behavior particularities related to each histotype. PMID:26734870

  16. New therapeutic options for actinic keratosis and basal cell carcinoma.

    PubMed

    Sligh, James E

    2014-06-01

    Actinic keratosis (AK) is a common premalignant skin lesion that is frequently treated by cryosurgery. Basal cell carcinoma is the most common malignancy of man, and early-stage lesions are usually cured via surgery. Advanced basal cell carcinoma may require more extensive surgery resulting in deformity, and many advanced lesions cannot be treated surgically. Several recent developments have improved therapeutic options for both conditions. Cryosurgery is still a mainstay of treatment for AK, but the introduction of effective topical agents, imiquimod cream and ingenol mebutate, has provided alternatives to cryosurgery. For advanced basal cell carcinoma, the small-molecule inhibitor vismodegib has proven to be an effective therapy for lesions that are not amenable to surgery and has demonstrated ability to achieve dramatic improvement in advanced, potentially disfiguring cancer. PMID:25268601

  17. Basal cell carcinomas in elderly patients treated by cryotherapy.

    PubMed

    Chiriac, Anca; Mihaila, Doina; Foia, Liliana; Solovan, Caius

    2013-01-01

    Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain) can be applied and resolve such cases. PMID:23569366

  18. Basal cell carcinomas in elderly patients treated by cryotherapy

    PubMed Central

    Chiriac, Anca; Mihaila, Doina; Foia, Liliana; Solovan, Caius

    2013-01-01

    Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain) can be applied and resolve such cases. PMID:23569366

  19. The use of lasers in Becker's naevus: An evidence-based review.

    PubMed

    Momen, Sophie; Mallipeddi, Raj; Al-Niaimi, Firas

    2016-08-01

    Becker's naevus is a hamartoma that often appears during puberty. Clinically this presents with a pigmented and often hairy patch most often on the shoulders. Treatment has always been challenging and lasers are often used with mixed results. This article reviews the evidence of all the laser treatments used in Becker's naevus and analyses the findings from the published studies and trials. PMID:26735085

  20. Basal cell carcinomas in a young woman with Steinert's disease.

    PubMed

    Miraglia, E; Cantisani, C; Giustini, S; Ambrifi, M; Soda, G; Calvieri, S

    2014-08-01

    Steinert's disease or Myotonic dystrophy type I (DM1) is an autosomal dominant disease characterized by myotonia, muscular dystrophy, cataracts, hypogonadism, frontal balding, and electrocardiographic alterations.Several tumors have been associated with DM1 such as pilomatricoma, thymomas and insulinomas. Herein, we describe the unusual onset of multiple basal cell carcinomas in a young woman with DM1. PMID:25148278

  1. Basal Cell Carcinoma Developing from Trichoepithelioma: Review of Three Cases

    PubMed Central

    Satyanarayana, M. Ananta; Aryasomayajula, Sirish; Krishna, B.A. Rama

    2016-01-01

    Trichoepitheliomas (TE) are benign tumours but occasionally can undergo transformation to malignant neoplasms more commonly as Basal Cell Carcinoma (BCC). The correct diagnosis between these tumours is very important because basal cell carcinoma is locally aggressive neoplasm and requires total surgical excision with wide healthy margins while trichoepithelioma needs simple excision. We describe three patients who developed basal cell carcinoma with facial trichoepitheliomas. The only clinical feature that distinguished the carcinomas from the trichoepitheliomas was their larger size, in all three patients, one patient with recurrent, hyper pigmented swelling with surface ulceration and in another patient there are multiple trichoepitheliomas, and other family members are also affected. The history, clinical features and histopathological findings were suggestive of the evolution of basal cell carcinoma directly from trichoepithelioma in our first two cases, but in the third case TE and BCC were separate lesions on face and we are uncertain about whether the BCC developed independently or by transformation from a trichoepithelioma. Based on our clinicopathological observations in the three patients and reports in the recent literature, BCC with follicular differentiation and trichoepithelioma are considered to be highly related. PMID:27134936

  2. Basal cell adenoma of maxillary sinus mimicking ameloblastoma.

    PubMed

    Bhagde, Priya Anil; Barpande, Suresh Ramchandra; Bhavthankar, Jyoti Dilip; Humbe, Jayanti G

    2016-01-01

    Basal cell adenoma (BCA) is a rare basaloid tumor, with only 20% of cases occurring in minor salivary glands. Histologically, BCA is characterized by the presence of basaloid cells and may frequently be mistaken with canalicular adenoma, basal cell adenocarcinoma, adenoid cystic carcinoma and basaloid squamous cell carcinoma. Immunohistochemistry may aid in arriving at a final diagnosis as in the present case. Reported here is a case of locally aggressive BCA. Histologically, the lesion mimicked ameloblastoma and other entities which posed a diagnostic challenge. There are no reports of BCA presenting as an aggressive lesion available in English literature so far; moreover, merely a single case of BCA of maxillary sinus has been previously reported to the best of our cognition. This case report highlights the rarity of this tumor with regards to its site of origin, clinical behavior and histopathological mimics. PMID:27194878

  3. Basal cell adenoma of maxillary sinus mimicking ameloblastoma

    PubMed Central

    Bhagde, Priya Anil; Barpande, Suresh Ramchandra; Bhavthankar, Jyoti Dilip; Humbe, Jayanti G

    2016-01-01

    Basal cell adenoma (BCA) is a rare basaloid tumor, with only 20% of cases occurring in minor salivary glands. Histologically, BCA is characterized by the presence of basaloid cells and may frequently be mistaken with canalicular adenoma, basal cell adenocarcinoma, adenoid cystic carcinoma and basaloid squamous cell carcinoma. Immunohistochemistry may aid in arriving at a final diagnosis as in the present case. Reported here is a case of locally aggressive BCA. Histologically, the lesion mimicked ameloblastoma and other entities which posed a diagnostic challenge. There are no reports of BCA presenting as an aggressive lesion available in English literature so far; moreover, merely a single case of BCA of maxillary sinus has been previously reported to the best of our cognition. This case report highlights the rarity of this tumor with regards to its site of origin, clinical behavior and histopathological mimics. PMID:27194878

  4. What's New in Research and Treatment of Basal and Squamous Cell Skin Cancers?

    MedlinePlus

    ... for basal and squamous cell skin cancers What’s new in basal and squamous cell skin cancer research? ... cancer cells. Researchers are working to apply this new information to strategies for preventing and treating skin ...

  5. Multiple keratocystic odontogenic tumors in nevoid basal cell carcinoma syndrome

    PubMed Central

    Pereira, Treville; Tamgadge, Avinash; Sapdhare, Swati; Pujar, Ashwini

    2015-01-01

    Keratocystic odontogenic tumor (KCOT) is of particular interest because its recurrence rate is high and its behavior is aggressive. Nevoid basal cell carcinoma syndrome (NBCCS), which is also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and with a predisposition to neoplasms. These multiple KCOTs have warranted an aggressive treatment at the earliest because of the damage and possible complications. Recurrence of these lesions is a characteristic feature that has to be considered while explaining the prognosis to the patient. Here, we report a case of a 14-year-old boy with clinical features of basal cell nevus syndrome and multiple KCOTs. In addition to the other common features, congenitally missing third molars in all the four quadrants is a feature which has not been previously reported in association with NBCCS in Indian patients. PMID:26981489

  6. Investigational agents in metastatic basal cell carcinoma: focus on vismodegib

    PubMed Central

    Batty, Nicolas; Kossoff, Ellen; Dy, Grace K

    2012-01-01

    Vismodegib (GDC-0449, 2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzamide, Erivedge™) is a novel first-in-human, first-in class, orally bio-available Hedgehog pathway signaling inhibitor of the G-protein coupled receptor-like protein smoothened (SMO) which was approved in the United States on January 2012. This signaling pathway is involved in the carcinogenesis of several types of tumor, as exemplified by basal cell carcinoma. This review focuses on the role of the Hedgehog pathway in the pathogenesis of basal cell carcinoma, the pharmacology and the clinical activity of vismodegib, as well as a brief summary of investigational agents in development targeting this pathway.

  7. Autofluorescence imaging of basal cell carcinoma by smartphone RGB camera

    NASA Astrophysics Data System (ADS)

    Lihachev, Alexey; Derjabo, Alexander; Ferulova, Inesa; Lange, Marta; Lihacova, Ilze; Spigulis, Janis

    2015-12-01

    The feasibility of smartphones for in vivo skin autofluorescence imaging has been investigated. Filtered autofluorescence images from the same tissue area were periodically captured by a smartphone RGB camera with subsequent detection of fluorescence intensity decreasing at each image pixel for further imaging the planar distribution of those values. The proposed methodology was tested clinically with 13 basal cell carcinoma and 1 atypical nevus. Several clinical cases and potential future applications of the smartphone-based technique are discussed.

  8. Prostatic inflammation enhances basal-to-luminal differentiation and accelerates initiation of prostate cancer with a basal cell origin

    PubMed Central

    Kwon, Oh-Joon; Zhang, Li; Ittmann, Michael M.; Xin, Li

    2014-01-01

    Chronic inflammation has been shown to promote the initiation and progression of diverse malignancies by inducing genetic and epigenetic alterations. In this study, we investigate an alternative mechanism through which inflammation promotes the initiation of prostate cancer. Adult murine prostate epithelia are composed predominantly of basal and luminal cells. Previous studies revealed that the two lineages are largely self-sustained when residing in their native microenvironment. To interrogate whether tissue inflammation alters the differentiation program of basal cells, we conducted lineage tracing of basal cells using a K14-CreER;mTmG model in concert with a murine model of prostatitis induced by infection from the uropathogenic bacteria CP9. We show that acute prostatitis causes tissue damage and creates a tissue microenvironment that induces the differentiation of basal cells into luminal cells, an alteration that rarely occurs under normal physiological conditions. Previously we showed that a mouse model with prostate basal cell-specific deletion of Phosphatase and tensin homolog (K14-CreER;Ptenfl/fl) develops prostate cancer with a long latency, because disease initiation in this model requires and is limited by the differentiation of transformation-resistant basal cells into transformation-competent luminal cells. Here, we show that CP9-induced prostatitis significantly accelerates the initiation of prostatic intraepithelial neoplasia in this model. Our results demonstrate that inflammation results in a tissue microenvironment that alters the normal prostate epithelial cell differentiation program and that through this cellular process inflammation accelerates the initiation of prostate cancer with a basal cell origin. PMID:24367088

  9. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review.

    PubMed

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda P

    2016-06-01

    Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis. PMID:27398205

  10. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

    PubMed Central

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

    2016-01-01

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

  11. Basal Cell Carcinoma of the Penis: A Case Report and Review of the Literature

    PubMed Central

    Roewe, R. J.; Uhlman, Matthew A.; Bockholt, Nathan A.

    2014-01-01

    Basal cell carcinoma of the penis is an extremely rare entity, accounting for less than 0.03% of all basal cell carcinomas. Fortunately, wide local excision of such lesions is generally curative. Fewer than 25 cases have been reported in the literature describing penile basal cell carcinoma. Here we report a case of penile basal cell carcinoma cured with wide local excision. PMID:25298901

  12. Two Cases of Nevoid Basal Cell CarcinomaSyndrome in One Family

    PubMed Central

    Ryu, Dong Jin; Kwon, Yeon Sook; Roh, Mi Ryung

    2008-01-01

    The nevoid basal cell carcinoma syndrome, or Gorlin-Goltz syndrome, is an autosomal dominant multiple system disorder with high penetrance and variable expressions, although it can also arise spontaneously. The diagnostic criteria for nevoid basal cell carcinoma syndrome include multiple basal cell carcinomas, palmoplantar pits, multiple odontogenic keratocysts, skeletal anomalies, positive family history, ectopic calcification and neurological anomalies. We report a brother and sister who were both diagnosed with nevoid basal cell carcinoma syndrome. PMID:27303197

  13. Basal cell carcinoma develops in contact with the epidermal basal cell layer - a three-dimensional morphological study.

    PubMed

    Pirici, Ionica; Ciurea, Marius Eugen; Mîndrilă, Ion; Avrămoiu, Ioan; Pirici, Alexandru; Nicola, Monica Georgiana; Rogoveanu, Otilia Constantina

    2016-01-01

    Basal cell carcinoma is the most common malignant tumor of the skin, and it develops most frequently on the areas of the body that make its treatment and care extremely difficult, especially in cases of neglecting or aggressive growth and invasion. Both typical mild cases as well as locally aggressive tumor types do not tend to metastasize, and it has been postulated that they should share some common biological and morphological features that might explain this behavior. In this study, we have utilized a high-resolution three-dimensional reconstruction technique on pathological samples from 15 cases of common aggressive (fibrosing and adenoid types) and mild (superficial type) basal cell carcinomas, and showed that all these types shared contact points and bridges with the underlying basal cell layer of the epidermis or with the outmost layer of the hair follicle. The connections found had in fact the highest number for fibrosing type (100%), compared to the superficial (85.71%) and adenoid (55%) types. The morphology of the connection bridges was also different, adjacent moderate to abundant inflammatory infiltrate seeming to lead to a loss of basaloid features in these areas. For the adenoid type, tumor islands seemed to be connected also to each other more strongly, forming a common "tumor lace", and while it has been showed that superficial and fibrosing types have higher recurrence risks, all together these data might iterate a connection between the number of bridging points and the biological and clinical manifestation of this skin tumor. PMID:27151694

  14. Photodynamic therapy in the treatment of basal cell carcinoma

    PubMed Central

    Matei, C; Tampa, M; Poteca, T; Panea-Paunica, G; Georgescu, SR; Ion, RM; Popescu, SM; Giurcaneanu, C

    2013-01-01

    Photodynamic therapy (PDT) is a medical procedure based on the activation of the molecules of various exogenous or endogenous chemical substances called photosensitizers by a light source emitting radiation of an adequate wavelength, usually situated in the visible spectrum; photosensitizers are chemical compounds bearing the capacity to selectively concentrate in the neoplastic cells. The energy captured by the molecules of these substances pervaded in the tumor cells is subsequently discharged in the surrounding tissue, triggering certain photodynamic reactions that result in the destruction of the tumor. The procedure is applicable in numerous medical fields. Skin basal cell carcinoma (BCC), the most frequent type of cancer of the human species, is a cutaneous tumor that responds very well to this innovative treatment method. By reviewing numerous recent studies in the field, this article aims to present the role and the indications of photodynamic therapy in the management of basal cell carcinoma, as well as the most important results achieved so far by this therapy in the field of dermato-oncology. PMID:23599819

  15. Neglected basal cell carcinoma in a schizophrenic patient.

    PubMed

    Shah, Hassan A; Lee, Hui Bae Harold; Nunery, William R

    2008-01-01

    Obtaining informed consent from patients with mental disorders can be a complicated and involved process, potentially resulting in decisions contrary to the advice of physicians. We present a schizophrenic patient with an invasive basal cell carcinoma involving the periocular structures and the right orbit. Exenteration was recommended with en bloc resection of the tumor. The ethical and legal committees decided against surgical intervention. Rather, the patient was admitted for medical treatment of his mental illness. A multidisciplinary approach with consultation of a psychiatrist, social worker, and ethical and legal committees is often necessary in the care of patients with mental illness. PMID:19033856

  16. A Case of Axillary Adenoid Basal Cell Carcinoma

    PubMed Central

    Kim, Soo Ho; Ko, Woo Tae; Lee, Jong Im

    2008-01-01

    Basal cell carcinoma (BCC) is the most common skin cancer with a steadily increasing incidence. Ultraviolet radiation is considered the single most important risk factor for BCC, because the tumor occurs most frequently in sun-exposed areas of the body, with approximately four of five BCCs occurring on the face. BCC occurs infrequently in non-sun-exposed skin. The axilla is one of the most sun-protected areas of the body, and BCC arising at this site is very rare. We herein report a case of adenoid BCC which arose from the axilla in a 33-year-old woman. PMID:27303153

  17. Dermoscopic features of small size pigmented basal cell carcinomas.

    PubMed

    Takahashi, Asuka; Hara, Hiroyuki; Aikawa, Miwa; Ochiai, Toyoko

    2016-05-01

    Dermoscopic images of histologically proven pigmented basal cell carcinomas (BCC) were retrospectively assessed to compare the dermoscopic features of BCC of 3 mm or less in diameter (n = 6) with BCC of 4-6 mm in diameter (n = 11). All lesions lacked the presence of a pigment network. BCC with a diameter of 3 mm or less had fewer positive dermoscopic features compared with the 4-6 mm in diameter BCC. Multiple blue-gray globules and large blue-gray ovoid nests were frequently present. Dermoscopy is a useful tool for early diagnosis of pigmented BCC, even when they are small. PMID:26458728

  18. Injury induces direct lineage segregation of functionally distinct airway basal stem/progenitor cell subpopulations.

    PubMed

    Pardo-Saganta, Ana; Law, Brandon M; Tata, Purushothama Rao; Villoria, Jorge; Saez, Borja; Mou, Hongmei; Zhao, Rui; Rajagopal, Jayaraj

    2015-02-01

    Following injury, stem cells restore normal tissue architecture by producing the proper number and proportions of differentiated cells. Current models of airway epithelial regeneration propose that distinct cytokeratin 8-expressing progenitor cells, arising from p63(+) basal stem cells, subsequently differentiate into secretory and ciliated cell lineages. We now show that immediately following injury, discrete subpopulations of p63(+) airway basal stem/progenitor cells themselves express Notch pathway components associated with either secretory or ciliated cell fate commitment. One basal cell population displays intracellular Notch2 activation and directly generates secretory cells; the other expresses c-myb and directly yields ciliated cells. Furthermore, disrupting Notch ligand activity within the basal cell population at large disrupts the normal pattern of lineage segregation. These non-cell-autonomous effects demonstrate that effective airway epithelial regeneration requires intercellular communication within the broader basal stem/progenitor cell population. These findings have broad implications for understanding epithelial regeneration and stem cell heterogeneity. PMID:25658372

  19. Basal body structure and cell cycle-dependent biogenesis in Trypanosoma brucei.

    PubMed

    Vaughan, Sue; Gull, Keith

    2015-01-01

    Basal bodies are microtubule-based organelles that assemble cilia and flagella, which are critical for motility and sensory functions in all major eukaryotic lineages. The core structure of the basal body is highly conserved, but there is variability in biogenesis and additional functions that are organism and cell type specific. Work carried out in the protozoan parasite Trypanosoma brucei has arguably produced one of the most detailed dissections of basal body structure and biogenesis within the context of the flagellar pocket and associated organelles. In this review, we provide a detailed overview of the basic basal body structure in T. brucei along with the accessory structures and show how basal body movements during the basal body duplication cycle orchestrate cell and organelle morphogenesis. With this in-depth three-dimensional knowledge, identification of many basal body genes coupled with excellent genetic tools makes it an attractive model organism to study basal body biogenesis and maintenance. PMID:26862392

  20. A Pooled Analysis of Melanocytic Naevus Phenotype and the Risk of Cutaneous Melanoma at Different Latitudes

    PubMed Central

    Chang, Yu-mei; Newton-Bishop, Julia A; Bishop, D Timothy; Armstrong, Bruce K; Bataille, Veronique; Bergman, Wilma; Berwick, Marianne; Bracci, Paige M; Elwood, J Mark; Ernstoff, Marc S; Green, Adèle C; Gruis, Nelleke A; Holly, Elizabeth A; Ingvar, Christian; Kanetsky, Peter A; Karagas, Margaret R; Le Marchand, Loïc; Mackie, Rona M; Olsson, Håkan; Østerlind, Anne; Rebbeck, Timothy R; Reich, Kristian; Sasieni, Peter; Siskind, Victor; Swerdlow, Anthony J; Titus-Ernstoff, Linda; Zens, Michael S; Ziegler, Andreas; Barrett, Jennifer H

    2008-01-01

    An abnormal naevus phenotype is associated with an increased risk of melanoma. We report a pooled analysis conducted using individual naevus data from 15 case-control studies (5,421 melanoma cases and 6,966 controls). The aims were to quantify better the risk, and to determine whether relative risk varied by latitude. Bayesian unconditional logistic random coefficients models were employed to study the risk associated with naevus characteristics. Participants with whole body naevus counts in the highest of four population-based categories had a greatly increased risk of melanoma compared with those in the lowest category (pooled odds ratio (pOR) 6.9 (95% confidence interval (CI): 4.4, 11.2) for those aged <50 years and pOR 5.1 (95% CI: 3.6, 7.5) for those aged ≥50). The pOR for presence compared with absence of any clinically atypical naevi was 4.0 (95% CI: 2.8, 5.8). The pORs for 1–2 and ≥3 large naevi on the body compared with none were 2.9 (95% CI: 1.9, 4.3) and 7.1 (95% CI: 4.7, 11.6), respectively. The relative heterogeneities among studies were small for most measures of naevus phenotype, except for the analysis of naevus counts on the arms, which may have been due to methodological differences among studies. The pooled analysis also suggested that an abnormal naevus phenotype is associated most with melanomas on intermittently sun-exposed sites. The presence of increased numbers of naevi, large naevi and clinically atypical naevi on the body are robust risk factors for melanoma showing little variation in relative risk among studies performed at different latitudes. PMID:18792098

  1. Microscopic fluorescence spectral analysis of basal cell carcinomas

    NASA Astrophysics Data System (ADS)

    He, Qingli; Lui, Harvey; Zloty, David; Cowan, Bryce; Warshawski, Larry; McLean, David I.; Zeng, Haishan

    2007-05-01

    Background and Objectives. Laser-induced autofluorescence (LIAF) is a promising tool for cancer diagnosis. This method is based on the differences in autofluorescence spectra between normal and cancerous tissues, but the underlined mechanisms are not well understood. The objective of this research is to study the microscopic origins and intrinsic fluorescence properties of basal cell carcinoma (BCC) for better understanding of the mechanism of in vivo fluorescence detection and margin delineation of BCCs on skin patients. A home-made micro- spectrophotometer (MSP) system was used to image the fluorophore distribution and to measure the fluorescence spectra of various microscopic structures and regions on frozen tissue sections. Materials and Methods. BCC tissue samples were obtained from 14 patients undergoing surgical resections. After surgical removal, each tissue sample was immediately embedded in OCT medium and snap-frozen in liquid nitrogen. The frozen tissue block was then cut into 16-μm thickness sections using a cryostat microtome and placed on microscopic glass slides. The sections for fluorescence study were kept unstained and unfixed, and then analyzed by the MSP system. The adjacent tissue sections were H&E stained for histopathological examination and also served to help identify various microstructures on the adjacent unstained sections. The MSP system has all the functions of a conventional microscope, plus the ability of performing spectral analysis on selected micro-areas of a microscopic sample. For tissue fluorescence analysis, 442nm He-Cd laser light is used to illuminate and excite the unstained tissue sections. A 473-nm long pass filter was inserted behind the microscope objective to block the transmitted laser light while passing longer wavelength fluorescence signal. The fluorescence image of the sample can be viewed through the eyepieces and also recorded by a CCD camera. An optical fiber is mounted onto the image plane of the photograph

  2. Dermatocosmetologic aspects of treatment of basal-cell skin cancer

    NASA Astrophysics Data System (ADS)

    Geinitz, A. V.; Stranadko, Ye. F.; Yusupova, Zh. M.; Tkachenko, S. B.

    2005-08-01

    The obtained clinical findings demonstrate excellent results after surgical MSC treatment with the application of modem laser surgical technologies. All the operated patients were under oncologist"s control during 1.5-2.5 years. In 6 cases we observed topical recurrences which needed a repeated intervention. Thus, our experience of applying LPh for surgical treatment of basal-cell carcinomas of the head and neck dem- onstrate that in the analysed cases it is more reasonable to use two models of laser devices different in their physical parameters. These devices are used at different surgical stages so as to provide a precise effect in laser tumour va- porization within the borders of the healthy tissue, to make better vascular coagulation and laser smoothing of wound surface. Immediate, direct and long-term results of modern surgical lasers" application for treating skin BSC almost in all cases give good and excellent cosmetic effect after such intenventions.

  3. Novel Hedgehog pathway targets against basal cell carcinoma

    SciTech Connect

    Tang, Jean Y. So, P.-L.; Epstein, Ervin H.

    2007-11-01

    The Hedgehog signaling pathway plays a key role in directing growth and patterning during embryonic development and is required in vertebrates for the normal development of many structures, including the neural tube, axial skeleton, skin, and hair. Aberrant activation of the Hedgehog (Hh) pathway in adult tissue is associated with the development of basal cell carcinoma (BCC), medulloblastoma, and a subset of pancreatic, gastrointestinal, and other cancers. This review will provide an overview of what is known about the mechanisms by which activation of Hedgehog signaling leads to the development of BCCs and will review two recent papers suggesting that agents that modulate sterol levels might influence the Hh pathway. Thus, sterols may be a new therapeutic target for the treatment of BCCs, and readily available agents such as statins (HMG-CoA reductase inhibitors) or vitamin D might be helpful in reducing BCC incidence.

  4. Gorlin's syndrome, or nevoid basal cell carcinoma syndrome.

    PubMed Central

    Fitzpatrick, P. J.; Thompson, G. A.

    1982-01-01

    Gorlin's syndrome is a condition inherited in an autosomal dominant fashion. It involves many organs, but principally affects the skin, skeleton, and endocrine and nervous systems. The most common features are multiple nervi and basal cell carcinomas of the skin, benign jaw cysts, dyskeratotic pits in the palms and soles, rib and vertebral abnormalities, brachymetacarpalism, and calcification of the falx cerebri. In 14 patients, 4 of whom belonged to one family, the age at the time of diagnosis ranged from 11 to 63 years. Ten patients are alive, but five are severely disfigured by carcinomas. Two patients died of complications resulting from uncontrolled tumours, and two died of other cancers. New skin tumours constantly develop; small ones can be excised, but large ones require extensive surgery with or without radiotherapy. Images FIG. 1 FIG. 2 FIG. 3 FIG. 4 FIG. 5 FIG. 6 FIG. 7 FIG. 9 FIG. 10 FIG. 11 PMID:7116263

  5. Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face.

    PubMed

    Feller, L; Khammissa, R A G; Kramer, B; Altini, M; Lemmer, J

    2016-01-01

    Ultraviolet light (UV) is an important risk factor for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin. These cancers most commonly affect persons with fair skin and blue eyes who sunburn rather than suntan. However, each of these cancers appears to be associated with a different pattern of UV exposure and to be mediated by different intracellular molecular pathways.Some melanocortin 1 receptor (MC1R) gene variants play a direct role in the pathogenesis of cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma apart from their role in determining a cancer-prone pigmentory phenotype (fair skin, red hair, blue eyes) through their interactions with other genes regulating immuno-inflammatory responses, DNA repair or apoptosis.In this short review we focus on the aetiological role of UV in cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma and cutaneous melanoma of the skin, and on some associated biopathological events. PMID:26850723

  6. Enrichment of Mammary Basal and Luminal Cells for Cell-of-Origin Metastasis Studies.

    PubMed

    Kabeer, Farhia; Podsypanina, Katrina; Darrasse-Jèze, Guillaume

    2016-01-01

    The mammary gland is an important model system in metastasis research. Mammary epithelial stem cells are of particular interest because of their capacity for regeneration and their role in cancer initiation. This protocol describes how to enrich for mammary basal and luminal epithelial cells using fluorescence-activated cell sorting (FACS). PMID:26832681

  7. Plasticity of basal cells during postnatal development in the rat epididymis

    PubMed Central

    Shum, Winnie W C; Hill, Eric; Brown, Dennis; Breton, Sylvie

    2014-01-01

    Our previous study has shown that basal cells sense luminal factors by forming a narrow body projection that can cross epithelial tight junctions. As a first step toward characterizing the structural plasticity of basal cells, in this study, we followed their appearance and morphology in the rat epididymis and vas deferens (VD) during postnatal development and examined their modulation by androgens in adulthood. Immunofluorescence labeling for cytokeratin 5 showed that basal cells are absent at birth. They progressively appear in a retrograde manner from the VD and cauda epididymis to the initial segments during the postnatal weeks PNW1–3. At the onset of differentiation, basal cells are in contact with the lumen and their nucleus is located at the same level as that of adjacent epithelial cells. Basal cells then position their nucleus to the base of the epithelium, and while some are still in contact with the lumen, others have a ‘dome-shaped’ appearance. At PNW5–6, basal cells form a loose network at the base of the epithelium, and luminal-reaching basal cells are rarely detected. The arrival of spermatozoa during PNW7–8 did not trigger the development of projections in basal cells. However, cells with a narrow luminal-reaching projection began to reappear between PNW8 and PNW12 in the corpus and the cauda. Treatment with flutamide from PNW10 to PNW12 significantly reduced the number of luminal-reaching basal cell projections. In summary, basal cells exhibit significant structural plasticity during differentiation. Fewer apical-reaching projections were detected after flutamide treatment in adulthood, indicating the role of androgens in the luminal-sensing function of basal cells. PMID:23960170

  8. New common variants affecting susceptibility to basal cell carcinoma.

    PubMed

    Stacey, Simon N; Sulem, Patrick; Masson, Gisli; Gudjonsson, Sigurjon A; Thorleifsson, Gudmar; Jakobsdottir, Margret; Sigurdsson, Asgeir; Gudbjartsson, Daniel F; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R; Thorisdottir, Kristin; Ragnarsson, Rafn; Scherer, Dominique; Hemminki, Kari; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Botella-Estrada, Rafael; Soriano, Virtudes; Juberias, Pablo; Saez, Berta; Gilaberte, Yolanda; Fuentelsaz, Victoria; Corredera, Cristina; Grasa, Matilde; Höiom, Veronica; Lindblom, Annika; Bonenkamp, Johannes J; van Rossum, Michelle M; Aben, Katja K H; de Vries, Esther; Santinami, Mario; Di Mauro, Maria G; Maurichi, Andrea; Wendt, Judith; Hochleitner, Pia; Pehamberger, Hubert; Gudmundsson, Julius; Magnusdottir, Droplaug N; Gretarsdottir, Solveig; Holm, Hilma; Steinthorsdottir, Valgerdur; Frigge, Michael L; Blondal, Thorarinn; Saemundsdottir, Jona; Bjarnason, Hjördis; Kristjansson, Kristleifur; Bjornsdottir, Gyda; Okamoto, Ichiro; Rivoltini, Licia; Rodolfo, Monica; Kiemeney, Lambertus A; Hansson, Johan; Nagore, Eduardo; Mayordomo, José I; Kumar, Rajiv; Karagas, Margaret R; Nelson, Heather H; Gulcher, Jeffrey R; Rafnar, Thorunn; Thorsteinsdottir, Unnur; Olafsson, Jon H; Kong, Augustine; Stefansson, Kari

    2009-08-01

    In a follow-up to our previously reported genome-wide association study of cutaneous basal cell carcinoma (BCC), we describe here several new susceptibility variants. SNP rs11170164, encoding a G138E substitution in the keratin 5 (KRT5) gene, affects risk of BCC (OR = 1.35, P = 2.1 x 10(-9)). A variant at 9p21 near CDKN2A and CDKN2B also confers susceptibility to BCC (rs2151280[C]; OR = 1.19, P = 6.9 x 10(-9)), as does rs157935[T] at 7q32 near the imprinted gene KLF14 (OR = 1.23, P = 5.7 x 10(-10)). The effect of rs157935[T] is dependent on the parental origin of the risk allele. None of these variants were found to be associated with melanoma or fair-pigmentation traits. A melanoma- and pigmentation-associated variant in the SLC45A2 gene, L374F, is associated with risk of both BCC and squamous cell carcinoma. Finally, we report conclusive evidence that rs401681[C] in the TERT-CLPTM1L locus confers susceptibility to BCC but protects against melanoma. PMID:19578363

  9. Sonic hedgehog signaling in Basal cell nevus syndrome.

    PubMed

    Athar, Mohammad; Li, Changzhao; Kim, Arianna L; Spiegelman, Vladimir S; Bickers, David R

    2014-09-15

    The hedgehog (Hh) signaling pathway is considered to be a major signal transduction pathway during embryonic development, but it usually shuts down after birth. Aberrant Sonic hedgehog (Shh) activation during adulthood leads to neoplastic growth. Basal cell carcinoma (BCC) of the skin is driven by this pathway. Here, we summarize information related to the pathogenesis of this neoplasm, discuss pathways that crosstalk with Shh signaling, and the importance of the primary cilium in this neoplastic process. The identification of the basic/translational components of Shh signaling has led to the discovery of potential mechanism-driven druggable targets and subsequent clinical trials have confirmed their remarkable efficacy in treating BCCs, particularly in patients with nevoid BCC syndrome (NBCCS), an autosomal dominant disorder in which patients inherit a germline mutation in the tumor-suppressor gene Patched (Ptch). Patients with NBCCS develop dozens to hundreds of BCCs due to derepression of the downstream G-protein-coupled receptor Smoothened (SMO). Ptch mutations permit transposition of SMO to the primary cilium followed by enhanced expression of transcription factors Glis that drive cell proliferation and tumor growth. Clinical trials with the SMO inhibitor, vismodegib, showed remarkable efficacy in patients with NBCCS, which finally led to its FDA approval in 2012. PMID:25172843

  10. Time-resolved multiphoton imaging of basal cell carcinoma

    NASA Astrophysics Data System (ADS)

    Cicchi, R.; Sestini, S.; De Giorgi, V.; Stambouli, D.; Carli, P.; Massi, D.; Pavone, F. S.

    2007-02-01

    We investigated human cutaneous basal cell carcinoma ex-vivo samples by combined time resolved two photon intrinsic fluorescence and second harmonic generation microscopy. Morphological and spectroscopic differences were found between malignant skin and corresponding healthy skin tissues. In comparison with normal healthy skin, cancer tissue showed a different morphology and a mean fluorescence lifetime distribution slightly shifted towards higher values. Topical application of delta-aminolevulinic acid to the lesion four hours before excision resulted in an enhancement of the fluorescence signal arising from malignant tissue, due to the accumulation of protoporphyrines inside tumor cells. Contrast enhancement was prevalent at tumor borders by both two photon fluorescence microscopy and fluorescence lifetime imaging. Fluorescence-based images showed a good correlation with conventional histopathological analysis, thereby supporting the diagnostic accuracy of this novel method. Combined morphological and lifetime analysis in the study of ex-vivo skin samples discriminated benign from malignant tissues, thus offering a reliable, non-invasive tool for the in-vivo analysis of inflammatory and neoplastic skin lesions.

  11. Clinical outcome of surgical treatment for periorbital basal cell carcinoma.

    PubMed

    Kakudo, Natsuko; Ogawa, Yutaka; Suzuki, Kenji; Kushida, Satoshi; Kusumoto, Kenji

    2009-11-01

    Basal cell carcinoma (BCC) has a predilection for the periorbital region, which is a special, prominent, cosmetic, functional area to protect the eyeball. For squamous cell carcinoma and melanoma, extensive resection with reconstruction is performed. In contrast, for BCC, resection is often confined to a small to medium-sized area, necessitating higher-quality reconstructive surgery. We analyze the surgical outcomes of treatment for periorbital BCC, and evaluate reconstruction method after resection. Forty-nine patients with periorbital BCC had surgery in our hospital over 20 years. Age, gender of the patients, and size, localization, and histology of the tumor, and surgical procedures, and their early and late complications were analyzed retrospectively. BCC was most frequently occurred in the lower lid (55%), followed by inner canthus (19%), upper lid (17%), and outer canthus (9%). The histologic classifications were solid (80%), morphea (7%), mix (7%), superficial (2%), keratotic (2%), and adenoid (2%). Recurrence of the tumor was observed in 2 advanced cases in patients treated with resection of the tumor including surrounding tissue 5 mm from the margin. A rotation advancement cheek flap procedure was most frequently applied. Horizontal shift of the skin was most effective to prevent postoperative lagophthalmos. BCC occurred most frequently in the lower lid within the periorbital area. Rotation advancement of cheek flap with horizontal shift of the skin is most effective procedure in both appearance and function of the eyelid. PMID:19801921

  12. Are the basal cells of the mammalian epididymis still an enigma?

    PubMed

    Arrighi, S

    2014-10-01

    Basal cells are present in the columnar pseudostratified epithelium covering the epididymis of all mammalian species, which regulates the microenvironment where the functionally incompetent germ cells produced by the testis are matured and stored. Striking novelties have come from investigations on epididymal basal cells in the past 30-40 years. In addition to an earlier hypothesised scavenger role for basal cells, linked to their proven extratubular origin and the expression of macrophage antigens, basal cells have been shown to be involved in cell-cell cross-talk, as well as functioning as luminal sensors to regulate the activity of principal and clear cells. Involvement of basal cells in the regulation of electrolyte and water transport by principal cells was hypothesised. This control is suggested to be mediated by the local formation of prostaglandins. Members of the aquaporin (AQP) and/or aquaglyceroporin family (AQP3, AQP7 and AQP8) are also specifically expressed in the rat epididymal basal cells. Transport of glycerol and glycerylphosphorylcholine from the epithelium of the epididymis to the lumen in relation to sperm maturation may be mediated by AQP. Most probably basal cells collaborate to the building up of the blood-epididymis barrier through cell adhesion molecules, implying an involvement in immune control exerted towards sperm cells, which are foreigners in the environment in which they were produced. PMID:24138802

  13. TERT Promoter Mutations Are Frequent in Cutaneous Basal Cell Carcinoma and Squamous Cell Carcinoma

    PubMed Central

    Griewank, Klaus G.; Murali, Rajmohan; Schilling, Bastian; Schimming, Tobias; Möller, Inga; Moll, Iris; Schwamborn, Marion; Sucker, Antje; Zimmer, Lisa; Schadendorf, Dirk; Hillen, Uwe

    2013-01-01

    Activating mutations in the TERT promoter were recently identified in up to 71% of cutaneous melanoma. Subsequent studies found TERT promoter mutations in a wide array of other major human cancers. TERT promoter mutations lead to increased expression of telomerase, which maintains telomere length and genomic stability, thereby allowing cancer cells to continuously divide, avoiding senescence or apoptosis. TERT promoter mutations in cutaneous melanoma often show UV-signatures. Non-melanoma skin cancer, including basal cell carcinoma and squamous cell carcinoma, are very frequent malignancies in individuals of European descent. We investigated the presence of TERT promoter mutations in 32 basal cell carcinomas and 34 cutaneous squamous cell carcinomas using conventional Sanger sequencing. TERT promoter mutations were identified in 18 (56%) basal cell carcinomas and in 17 (50%) cutaneous squamous cell carcinomas. The recurrent mutations identified in our cohort were identical to those previously described in cutaneous melanoma, and showed a UV-signature (C>T or CC>TT) in line with a causative role for UV exposure in these common cutaneous malignancies. Our study shows that TERT promoter mutations with UV-signatures are frequent in non-melanoma skin cancer, being present in around 50% of basal and squamous cell carcinomas and suggests that increased expression of telomerase plays an important role in the pathogenesis of these tumors. PMID:24260374

  14. Cell cycle-dependent regulation of RNA polymerase II basal transcription activity.

    PubMed Central

    Yonaha, M; Chibazakura, T; Kitajima, S; Yasukochi, Y

    1995-01-01

    Regulation of transcription by RNA polymerase II (pol II) in eukaryotic cells requires both basal and regulatory transcription factors. In this report we have investigated in vitro pol II basal transcription activity during the cell cycle by using nuclear extracts from synchronized HeLa cells. It is shown that pol II basal transcription activity is low in the S and G2 phases and high in early G1 phase and TFIID is the rate limiting component of pol II basal transcription activity during the cell cycle. Further analyses reveal that TFIID exists as a less active form in the S and G2 phases and nuclear extracts from S and G2 phase cells contain a heat-sensitive repressor(s) of TATA box binding protein (TBP). These results suggest that pol II basal transcription activity is regulated by a qualitative change in the TFIID complex, which could involve repression of TBP, during the cell cycle. Images PMID:7479063

  15. Chemopreventive opportunities to control basal cell carcinoma: Current perspectives.

    PubMed

    Tilley, Cynthia; Deep, Gagan; Agarwal, Rajesh

    2015-09-01

    Basal cell carcinoma (BCC) is a major health problem with approximately 2.8 million new cases diagnosed each year in the United States. BCC incidences have continued to rise due to lack of effective chemopreventive options. One of the key molecular characteristics of BCC is the sustained activation of hedgehog signaling through inactivating mutations in the tumor suppressor gene patch (Ptch) or activating mutations in Smoothened. In the past, several studies have addressed targeting the activated hedgehog pathway for the treatment and prevention of BCC, although with toxic effects. Other studies have attempted BCC chemoprevention through targeting the promotional phase of the disease especially the inflammatory component. The compounds that have been utilized in pre-clinical and/or clinical studies include green and black tea, difluoromethylornithine, thymidine dinucleotide, retinoids, non-steroidal anti-inflammatory drugs, vitamin D3, and silibinin. In this review, we have discussed genetic and epigenetic modifications that occur during BCC development as well as the current state of BCC pre-clinical and clinical chemoprevention studies. PMID:26053157

  16. Diagnosis and Management of Hereditary Basal Cell Skin Cancer.

    PubMed

    Shanley, Susan; McCormack, Christopher

    2016-01-01

    Basal cell carcinoma (BCC) is the most common cancer in Caucasians worldwide and its incidence is rising. It is generally considered a sporadic tumour, most likely to affect fair-skinned individuals exposed to ultraviolet (UV) radiation. This chapter focusses on the approach to recognising the relatively few individuals in whom a high-risk hereditary susceptibility may be present. Gorlin syndrome is the main consideration and the gene most commonly mutated is PTCH1, a key regulator of the Hedgehog developmental pathway. Recently, loss of function of another gene in the same pathway, SUFU, has been found to explain a subset of families. Understanding the pathogenesis of familial BCCs has advanced the understanding of the biology of sporadic tumours and led to targeted therapy trials. The management of familial BCCs remains a challenge due to significant unmet needs for non-surgical treatments and a high burden of disease for the individual. Together with the prospect of advances in gene discovery and translation, these challenges highlight the need for ongoing review of at-risk and affected individuals by a multidisciplinary team. PMID:27075355

  17. Clinicopathological analysis of recurrent basal cell carcinoma of the eyelid

    PubMed Central

    Zieliński, Tomasz; Antoszewski, Bogusław; Sporny, Stanisław

    2016-01-01

    Introduction Basal cell carcinoma (BCC) is the most common malignant neoplasm of the eyelids and surrounding structures, usually developing in the area of the lower lid and medial canthus. Invasive forms of BCC are connected with a high risk of recurrence, often due to incomplete excision of these lesions. Aim Clinical and pathological analysis of recurrent BCCs of the eyelids and surrounding structures. Material and methods We present clinical and pathological analysis including immunohistochemical reaction to Ki-67 antigen of 19 patients (11 women, 8 men) operated for recurrent BCCs of the eyelids in 2000–2012. Results In most cases, recurrences were present on the lower lid and in the medial canthus. In 15 patients the histopathological type did not change and in 4 cases it transformed into more invasive forms. The values of Ki-67 index for primary BCCs ranged between 1% and 20%, and for relapsing lesions between 11% and 48%. Conclusions Proper clinical and pathological evaluation to determine the risk of relapse in BCCs of the eyelids and surrounding structures should include the analysis of prognostic factors, in particular location and size, histopathological type and radicalness of surgical treatment of primary BCCs. Clinical and pathological analysis of patients with recurrent BCC of the eyelids and surrounding structures should be combined with the evaluation of proliferation index Ki-67, which is essential for prognosis and choice of the appropriate therapeutic method. PMID:26985178

  18. Neglected Basal Cell Carcinomas in the 21st Century

    PubMed Central

    Varga, Erika; Korom, Irma; Raskó, Zoltán; Kis, Erika; Varga, János; Oláh, Judit; Kemény, Lajos

    2011-01-01

    Although tumors on the surface of the skin are considered to be easily recognizable, neglected advanced skin neoplasms are encountered even in the 21st century. There can be numerous causes of the delay in the diagnosis: fear of the diagnosis and the treatment, becoming accustomed to a slowly growing tumor, old age, a low social milieu, and an inadequate hygienic culture are among the factors leading some people not to seek medical advice. The treatment of such advanced neoplasms is usually challenging. The therapy of neglected cases demands an individual multidisciplinary approach and teamwork. Basal cell carcinoma (BCC), the most common cutaneous tumor, usually develops in the elderly, grows slowly, and has an extremely low metastatic potential; these factors are suggesting that BCCs might well be the “ideal candidates” for neglected tumors. Five neglected advanced cases of BCC were diagnosed in our dermatological institute between 2000 and 2009. The clinical characteristics and treatment modalities of these neoplasms are discussed, together with the possible causes of the neglect. PMID:21151693

  19. Morphological Spectrum of Basal Cell Carcinoma in Southern Karnataka

    PubMed Central

    Lobo, Flora Dorothy; Naik, Ramdas; Khadilkar, Urmila Niranjan; Kini, Hema; Kini, Ullal Anand

    2016-01-01

    Introduction Basal Cell Carcinoma (BCC) is the most common skin cancer worldwide, which appears over sun-exposed skin as slow-growing, locally invasive lesion that rarely metastasizes. Many phenotypic presentations are possible. BCCs are more common in males and tend to occur in older people. Majority is found on the head and neck. Many histopathological subtypes have been defined including nodular, micronodular, cystic, superficial, pigmented, adenoid, infiltrating, sclerosing, keratotic, infundibulocystic, metatypical, basosquamous and fibroepitheliomatous. Mixed patterns are common. Aim The aim was to study morphological spectrum of BCC in a tertiary care hospital in southern Karnataka. Materials and Methods This was a retrospective analysis of 100 cases of BCCs reported in the Department of Pathology over a 9-year period from 2006 to 2014. Results The mean age of presentation was 62 years. There was slight female preponderance (56%). The most common location was face (65%) and the most common presentation was ulceration (45%). Of the 100 BCCs, 50% were nodular, 13% infiltrating, 6% basosquamous, 4% superficial, 3% keratotic, 3% multinodular and 1% mixed. Conclusion BCC, besides being the commonest cutaneous cancer, is also known for its numerous histological patterns which are shown to have prognostic implications. This study reveals the frequency of the various histological patterns of BCC in southern Karnataka, where it has been rarely studied before. PMID:27504291

  20. Ionizing Radiation Exposure and Basal Cell Carcinoma Pathogenesis.

    PubMed

    Li, Changzhao; Athar, Mohammad

    2016-03-01

    This commentary summarizes studies showing risk of basal cell carcinoma (BCC) development in relationship to environmental, occupational and therapeutic exposure to ionizing radiation (IR). BCC, the most common type of human cancer, is driven by the aberrant activation of hedgehog (Hh) signaling. Ptch, a tumor suppressor gene of Hh signaling pathway, and Smoothened play a key role in the development of radiation-induced BCCs in animal models. Epidemiological studies provide evidence that humans exposed to radiation as observed among the long-term, large scale cohorts of atomic bomb survivors, bone marrow transplant recipients, patients with tinea capitis and radiologic workers enhances risk of BCCs. Overall, this risk is higher in Caucasians than other races. People who were exposed early in life develop more BCCs. The enhanced IR correlation with BCC and not other common cutaneous malignancies is intriguing. The mechanism underlying these observations remains undefined. Understanding interactions between radiation-induced signaling pathways and those which drive BCC development may be important in unraveling the mechanism associated with this enhanced risk. Recent studies showed that Vismodegib, a Smoothened inhibitor, is effective in treating radiation-induced BCCs in humans, suggesting that common strategies are required for the intervention of BCCs development irrespective of their etiology. PMID:26930381

  1. Sonidegib phosphate: new approval for basal cell carcinoma.

    PubMed

    Tibes, R

    2016-05-01

    Basal cell carcinoma (BCC), although mostly locally confined, is the most common cancer. Most BCCs harbor inactivating mutations in the membrane receptor/gene Ptch, thereby activating the Hedgehog signaling pathway (Hh) via the essential signaling molecule Smoothened (SMO). Novel small-molecule inhibitors or antagonists of SMO have shown excellent response rates in patients with locally advanced, unresectable and metastatic BCC in roughly 35-60% of patients, with disease control rates and clinical benefit being even higher. Sonidegib is the second-in-class SMO inhibitor approved for locally advanced, unresectable and metastatic BCC. Sonidegib is given once daily continuously, with specific side effects as listed in the label indication. Resistance develops over time and knowledge gleaned from other SMO inhibitors indicates that SMO mutations preventing drug binding as well as mechanisms activating the Hh pathway downstream of SMO are responsible, ultimately reactivating Hh pathway signaling. The next challenge will be to define novel salvage and SMO combination strategies for BCC and other tumors. PMID:27376162

  2. Treatment of Basal Cell Carcinoma with Curettage Followed by Imiquimod 3.75% Cream

    PubMed Central

    Patel, Rita V.; Birge, Miriam B.

    2011-01-01

    Basal cell carcinoma is the most common form of nonmelanoma skin cancer in the United States. Treatment modalities include both surgical, medical, or combination therapy. In the following case, the authors report the successful treatment of a basal cell carcinoma on the nose with curettage followed by topical imiquimod 3.75% cream. PMID:21607193

  3. Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse Epithelial Basal Cells.

    PubMed

    Mou, Hongmei; Vinarsky, Vladimir; Tata, Purushothama Rao; Brazauskas, Karissa; Choi, Soon H; Crooke, Adrianne K; Zhang, Bing; Solomon, George M; Turner, Brett; Bihler, Hermann; Harrington, Jan; Lapey, Allen; Channick, Colleen; Keyes, Colleen; Freund, Adam; Artandi, Steven; Mense, Martin; Rowe, Steven; Engelhardt, John F; Hsu, Ya-Chieh; Rajagopal, Jayaraj

    2016-08-01

    Functional modeling of many adult epithelia is limited by the difficulty in maintaining relevant stem cell populations in culture. Here, we show that dual inhibition of SMAD signaling pathways enables robust expansion of primary epithelial basal cell populations. We find that TGFβ/BMP/SMAD pathway signaling is strongly activated in luminal and suprabasal cells of several epithelia, but suppressed in p63+ basal cells. In airway epithelium, SMAD signaling promotes differentiation, and its inhibition leads to stem cell hyperplasia. Using dual SMAD signaling inhibition in a feeder-free culture system, we have been able to expand airway basal stem cells from multiple species. Expanded cells can produce functional airway epithelium physiologically responsive to clinically relevant drugs, such as CFTR modulators. This approach is effective for the clonal expansion of single human cells and for basal cell populations from epithelial tissues from all three germ layers and therefore may be broadly applicable for modeling of epithelia. PMID:27320041

  4. Clonal Dynamics Reveal Two Distinct Populations of Basal Cells in Slow-Turnover Airway Epithelium.

    PubMed

    Watson, Julie K; Rulands, Steffen; Wilkinson, Adam C; Wuidart, Aline; Ousset, Marielle; Van Keymeulen, Alexandra; Göttgens, Berthold; Blanpain, Cédric; Simons, Benjamin D; Rawlins, Emma L

    2015-07-01

    Epithelial lineages have been studied at cellular resolution in multiple organs that turn over rapidly. However, many epithelia, including those of the lung, liver, pancreas, and prostate, turn over slowly and may be regulated differently. We investigated the mouse tracheal epithelial lineage at homeostasis by using long-term clonal analysis and mathematical modeling. This pseudostratified epithelium contains basal cells and secretory and multiciliated luminal cells. Our analysis revealed that basal cells are heterogeneous, comprising approximately equal numbers of multipotent stem cells and committed precursors, which persist in the basal layer for 11 days before differentiating to luminal fate. We confirmed the molecular and functional differences within the basal population by using single-cell qRT-PCR and further lineage labeling. Additionally, we show that self-renewal of short-lived secretory cells is a feature of homeostasis. We have thus revealed early luminal commitment of cells that are morphologically indistinguishable from stem cells. PMID:26119728

  5. Laser ablation of basal cell carcinomas guided by confocal microscopy

    NASA Astrophysics Data System (ADS)

    Sierra, Heidy; Cordova, Miguel; Nehal, Kishwer; Rossi, Anthony; Chen, Chih-Shan Jason; Rajadhyaksha, Milind

    2016-02-01

    Laser ablation offers precise and fast removal of superficial and early nodular types of basal cell carcinomas (BCCs). Nevertheless, the lack of histological confirmation has been a limitation. Reflectance confocal microscopy (RCM) imaging combined with a contrast agent can offer cellular-level histology-like feedback to detect the presence (or absence) of residual BCC directly on the patient. We conducted an ex vivo bench-top study to provide a set of effective ablation parameters (fluence, number of passes) to remove superficial BCCs while also controlling thermal coagulation post-ablation to allow uptake of contrast agent. The results for an Er:YAG laser (2.9 um and pulse duration 250us) show that with 6 passes of 25 J/cm2, thermal coagulation can be effectively controlled, to allow both the uptake of acetic acid (contrast agent) and detection of residual (or absence) BCCs. Confirmation was provided with histological examination. An initial in vivo study on 35 patients shows that the uptake of contrast agent aluminum chloride) and imaging quality is similar to that observed in the ex vivo study. The detection of the presence of residual tumor or complete clearance was confirmed in 10 wounds with (additional) histology and in 25 lesions with follow-up imaging. Our results indicate that resolution is sufficient but further development and use of appropriate contrast agent are necessary to improve sensitivity and specificity. Advances in RCM technology for imaging of lateral and deep margins directly on the patient may provide less invasive, faster and less expensive image-guided approaches for treatment of BCCs.

  6. Long-noncoding RNAs in basal cell carcinoma.

    PubMed

    Sand, Michael; Bechara, Falk G; Sand, Daniel; Gambichler, Thilo; Hahn, Stephan A; Bromba, Michael; Stockfleth, Eggert; Hessam, Schapoor

    2016-08-01

    Long noncoding RNAs (lncRNAs) are fundamental regulators of pre- and post-transcriptional gene regulation. Over 35,000 different lncRNAs have been described with some of them being involved in cancer formation. The present study was initiated to describe differentially expressed lncRNAs in basal cell carcinoma (BCC). Patients with BCC (n = 6) were included in this study. Punch biopsies were harvested from the tumor center and nonlesional epidermal skin (NLES, control, n = 6). Microarray-based lncRNA and mRNA expression profiles were identified through screening for 30,586 lncRNAs and 26,109 protein-coding transcripts (mRNAs). The microarray data were validated by RT-PCR in a second set of BCC versus control samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of mRNAs were performed to assess biologically relevant pathways. A total of 1851 lncRNAs were identified as being significantly up-regulated, whereas 2165 lncRNAs were identified as being significantly down-regulated compared to nonlesional skin (p < 0.05). Oncogenic and/or epidermis-specific lncRNAs, such as CASC15 or ANRIL, were among the differentially expressed sequences. GO analysis showed that the highest enriched GO targeted by up-regulated transcripts was "extracellular matrix." KEGG pathway analysis showed the highest enrichment scores in "Focal adhesion." BCC showed a significantly altered lncRNA and mRNA expression profile. Dysregulation of previously described lncRNAs may play a role in the molecular pathogenesis of BCC and should be subject of further analysis. PMID:26861560

  7. Facial dermis grafts after removal of basal cell carcinomas.

    PubMed

    Han, Seung-Kyu; Yoon, Won-Young; Jeong, Seong-Ho; Kim, Woo-Kyung

    2012-11-01

    Selecting a proper reconstruction method is the key to success in skin cancer management, especially for lesions involving the face. Using a skin graft is usually straightforward when covering a skin defect; however, major concerns in skin grafting include a poor color match in the recipient-site and donor-site morbidity. To overcome these limitations, the authors have developed a dermis graft, which utilizes a de-epithelialized split-thickness skin graft method. The purpose of this retrospective study was to report reliability of dermis grafts after removal of basal cell carcinomas (BCCs) on the face by presenting our clinical experience with them. This study included 38 patients who were treated for facial defects created by resection of BCCs. The locations of the defects were as follows: nose (n = 17), orbital area (n = 14), cheek (n = 4), temple area (n = 2), and forehead (n = 1). The defects ranged in size from 3.3 to 6.5 cm. Functional and cosmetic outcomes, postoperative complications, and patient satisfaction were assessed. The patients were followed up for 12 to 36 months. The entire dermis graft re-epithelialized after grafting within 17 to 27 days. Most of the patients had satisfactory results in both functional and cosmetic matters with high-quality skin characteristics. There were no significant complications and no recurrences were observed during the follow-up period. Patient satisfaction with the dermis graft was also excellent. The dermis graft may be used reliably for covering defects after removal of BCCs on the face. PMID:23172436

  8. PD-L1 Expression Is Increased in a Subset of Basal Type Breast Cancer Cells

    PubMed Central

    Soliman, Hatem; Khalil, Farah; Antonia, Scott

    2014-01-01

    Background Tumor cells express programmed death ligand 1 (PD-L1) and is a key immune evasion mechanism. PD-L1 expression in multiple breast cancer cell lines was evaluated to identify intrinsic differences that affect their potential for immune evasion. Methods PD-L1 expression was analyzed in six breast cancer cell lines: AU565&MCF7 (luminal), BT20&HCC1143 (basal A), MDA231&HCC38 (basal B). Surface and intracellular PD-L1 expression +/− interferon γ for 48 hours was measured by flow cytometry. PD-L1 gene expression data for all breast cancer cell lines in the Comprehensive Cell Line Encyclopedia (CCLE) was analyzed. Correlation between PD-L1 levels and clinicopathologic parameters was analyzed within Oncomine datasets. A tissue microarray containing 61 invasive breast cancer primary tumor cores was stained for PD-L1 expression and analyzed. Results Basal breast cancer cells constitutively express the highest levels of PD-L1. All cell lines increased PD-L1 expression with interferon γ, but basal B cells (MDA-231 and HCC38) demonstrated the largest increases. There were no differences in protein localization between cell lines. In the CCLE data, basal cell lines demonstrated higher mean PD-L1 expression compared to luminal cell lines. High PD-L1 expressing basal cell lines over-express genes involved in invasion, proliferation, and chemoresistance compared to low PD-L1 basal cell lines. High PD-L1 basal cell lines had lower expression of IRF2BP2 and higher STAT1 levels compared to low PD-L1 expressing cell lines. Within Oncomine datasets PDL1 mRNA levels were higher in basal type tumors. The TMA analysis demonstrated that lymph node positive cases had higher levels of PD-L1 protein expression compared to lymph node negative cases. Conclusions Basal type breast cancer (especially basal B) express greater levels of PD-L1 constitutively and with IFN γ. High PD-L1 basal cells over-express genes involved in invasion, motility, and chemoresistance. Targeting PD-L1

  9. Le naevus bleu cellulaire atypique du poignet: à propos d'un cas et revue de la literature

    PubMed Central

    Boussakri, Hassan; Roux, Jean Luc; Durand, Luc; Elibrahimi, Abdelhalim; Elmrini, Abdelmajid

    2014-01-01

    Le naevus bleu cellulaire atypique est une entité pathologique rare et sa localisation au niveau du poignet est exceptionnelle. Il est Considéré comme une Variante à des caractéristiques intermédiaires entre le naevus bleu cellulaire typique et le naevus bleu malin, dont l’évolution est incertaine. Le but de notre travail est d'attirer l'attention sur cette variété lésionnelle rare et de discuter les diagnostiques différentiels, ainsi que décrire les aspects histologique et les options thérapeutiques possibles. PMID:25426206

  10. Successful imiquimod treatment of multiple basal cell carcinomas after radiation therapy for Hodgkin's disease.

    PubMed

    Beyeler, Mirjam; Urosevic, Mirjana; Pestalozzi, Bernhard; Dummer, Reinhard

    2005-01-01

    We present a case of a 55-year-old male patient who developed five basal cell carcinomas 23 years after radiation therapy of Hodgkin's disease. In 1980 he received radiation therapy twice. Due to relapses, he was treated with aggressive polychemotherapy and underwent autologous stem cell transplantation, which then led to complete remission. Until now he is in complete remission. However, multiple superficial basal cell carcinomas have developed on irradiation fields that have been successfully treated by imiquimod. PMID:15701596

  11. Sequential development of apical-basal and planar polarities in aggregating epitheliomuscular cells of Hydra.

    PubMed

    Seybold, Anna; Salvenmoser, Willi; Hobmayer, Bert

    2016-04-01

    Apical-basal and planar cell polarities are hallmarks of metazoan epithelia required to separate internal and external environments and to regulate trans- and intracellular transport, cytoskeletal organization, and morphogenesis. Mechanisms of cell polarization have been intensively studied in bilaterian model organisms, particularly in early embryos and cultured cells, while cell polarity in pre-bilaterian tissues is poorly understood. Here, we have studied apical-basal and planar polarization in regenerating (aggregating) clusters of epitheliomuscular cells of Hydra, a simple representative of the ancestral, pre-bilaterian phylum Cnidaria. Immediately after dissociation, single epitheliomuscular cells do not exhibit cellular polarity, but they polarize de novo during aggregation. Reestablishment of the Hydra-specific epithelial bilayer is a result of short-range cell sorting. In the early phase of aggregation, apical-basal polarization starts with an enlargement of the epithelial apical-basal diameter and by the development of belt-like apical septate junctions. Specification of the basal pole of epithelial cells occurs shortly later and is linked to synthesis of mesoglea, development of hemidesmosome-like junctions, and formation of desmosome-like junctions connecting the basal myonemes of neighbouring cells. Planar polarization starts, while apical-basal polarization is already ongoing. It is executed gradually starting with cell-autonomous formation, parallelization, and condensation of myonemes at the basal end of each epithelial cell and continuing with a final planar alignment of epitheliomuscular cells at the tissue level. Our findings reveal that epithelial polarization in Hydra aggregates occurs in defined steps well accessible by histological and ultrastructural techniques and they will provide a basis for future molecular studies. PMID:26921448

  12. [Basal cell carcinoma of prostate: a report of three cases].

    PubMed

    Liu, Z; Ma, L L; Zhang, S D; Lu, M; Tian, Y; He, Q; Jin, J

    2016-02-18

    To explore the clinical pathological characteristics and improve the recognition in the diagnosis and treatment of basal cell carcinoma (BCC) of prostate. Three cases of BCC of prostate were reported and the relevant literature was reviewed to investigate the diagnosis and treatment of this disease. We analyzed three cases of prostatic BCC. Their ages were within a range of 57 to 83 years. One of them complained of hematuria and two complained of dysuria. All of them presented with prostatic hyperplasia. Two of them presented with high prostate specific antigen (PSA) and one with normal PSA. Case 1 had prostate cancer invasion of bladder, rectal fascia, with lymph node metastasis, bone metastasis and lung metastases. The patient received bladder resection+bilateral ureteral cutaneous ureterostomy+lymph node dissection on November 2, 2014 . Postoperative pathological diagnosis showed BCC. Reexamination of pelvic enhanced MRI in January 8, 2015 suggested pelvic recurrence. Abdominal enhanced CT showed multiple liver metastases and pancreatic metastasis on July 11, 2015. Prostate cancer specific death occurred in October 2015. Case 2 was diagnosed as BCC in prostate biopsy on March 27, 2015. Positron emission tomography and computed tomography (PET-CT) showed pulmonary metastasis and bone metastasis. Then the patient received chemotherapy, endocrine therapy and local radiation therapy. Reexamination of PET-CT on January 11, 2016 showed that the lung metastase tumors and bone metastase tumors were larger than before. Up to January 10, 2016, the patient was still alive. Postoperative pathological changes of transurethral resection of prostate (TURP) in case 3 showed BCC might be considered. The PET-CT suggested residual prostate cancer, which might be associated with bilateral pelvic lymph node metastasis. In April 20, 2016, the review of PET-CT showed pelvic huge irregular hybrid density shadow, about 14.5 cm×10.0 cm×12.9 cm in size, and tumor recurrence was

  13. Basal cell adenoma of the parotid gland. Case report and review of the literature.

    PubMed

    González-García, Raúl; Nam-Cha, Syong H; Muñoz-Guerra, Mario F; Gamallo-Amat, C

    2006-03-01

    Basal cell adenoma of the salivary glands is an uncommon type of monomorphous adenoma. Its most frequent location is the parotid gland. It usually appears as a firm and mobile slow-growing mass. Histologically, isomorphic cells in nests and interlaced trabecules with a prominent basal membrane are observed. It is also characterized by the presence of a slack and hyaline stroma and the absence of myxoid or condroid stroma. In contrast to pleomorphic adenoma, it tends to be multiple and its recurrence rate after surgical excision is high. Due to prognostic implications, differential diagnosis with basal cell adenocarcinoma, adenoid cystic carcinoma and basaloid squamous cell carcinoma is mandatory. We describe a case of basal cell adenoma of the parotid gland. We also review the literature and discuss the diagnosis and management of this rare entity. PMID:16505803

  14. Imaging of basal cell carcinoma tissue using en-face OCT

    NASA Astrophysics Data System (ADS)

    Penmetsa, Bhanu Rakesh; Khandwala, Mona; Bradu, Adrian; Hughes, Michael; Jones, Carole A.; Schofield, John; Podoleanu, Adrian Gh.

    2008-09-01

    We have investigated the applicability of en-face OCT in imaging freshly excised biopsies of Basal Cell Carcinoma. Encouraging results have been obtained in identifying tumor features and abnormal skin architecture.

  15. Basal Cell Carcinoma: A Comprehensive Review of Existing and Emerging Nonsurgical Therapies.

    PubMed

    Lanoue, Julien; Goldenberg, Gary

    2016-05-01

    Basal cell carcinoma is the most commonly occurring cancer in the world and overall incidence is still on the rise. While typically a slow-growing tumor for which metastases is rare, basal cell carcinoma can be locally destructive and disfiguring. Given the vast prevalence of this disease, there is a significant overall burden on patient well-being and quality of life. The current mainstay of basal cell carcinoma treatment involves surgical modalities, such as electrodessication and curettage, excision, cryosurgery, and Mohs micrographic surgery. Such methods are typically reserved for localized basal cell carcinoma and offer high five-year cure rates, but come with the risk of functional impairment, disfigurement, and scarring. Here, the authors review the evidence and indications for nonsurgical treatment modalities in cases where surgery is impractical, contraindicated, or simply not desired by the patient. PMID:27386043

  16. Nevoid basal cell carcinoma syndrome. Profile of genetic and environmental factors in oncogenesis

    SciTech Connect

    Howell, J.B.

    1984-07-01

    Nevoid basal cell carcinomas (NBCCs) are a prototype of a genetic form of basal cell carcinoma. These basal cell cancers, rather than being caused by genetic factors alone, are most likely the product of genetic and environmental factors. The NBCC syndrome provides a model for studying tumors induced by ionizing radiation and for viewing carcinogenesis as a multistage process explainable by a minimum of two steps. The interaction of genetic and environmental factors in producing tumors to which an individual is predisposed can be studied in patients with the NBCC syndrome and childhood medulloblastoma that was treated by radiation therapy. Individuals with the NBCC syndrome represent a special subgroup with a hereditary predisposition to basal cell carcinoma in whom ionizing radiation may supply the subsequent mutation necessary for tumor development. The genetically altered epidermis underlying the palm and sole pits found in patients with the syndrome represents basal cell carcinoma in situ from which basal cell carcinomas develop, albeit infrequently. The restrained biologic behavior of most of these tumors contrasts with the usual destructive behavior of the NBCCs of the head and neck in the same patient.

  17. KRT14 marks a subpopulation of bladder basal cells with pivotal role in regeneration and tumorigenesis

    PubMed Central

    Papafotiou, George; Paraskevopoulou, Varvara; Vasilaki, Eleni; Kanaki, Zoi; Paschalidis, Nikolaos; Klinakis, Apostolos

    2016-01-01

    The urothelium is a specialized epithelium that lines the urinary tract. It consists of three different cell types, namely, basal, intermediate and superficial cells arranged in relatively distinct cell layers. Normally, quiescent, it regenerates fast upon injury, but the regeneration process is not fully understood. Although several reports have indicated the existence of progenitors, their identity and exact topology, as well as their role in key processes such as tissue regeneration and carcinogenesis have not been clarified. Here we show that a minor subpopulation of basal cells, characterized by the expression of keratin 14, possesses self-renewal capacity and also gives rise to all cell types of the urothelium during natural and injury-induced regeneration. Moreover, these cells represent cells of origin of urothelial cancer. Our findings support the hypothesis of basally located progenitors with profound roles in urothelial homoeostasis. PMID:27320313

  18. Rho-associated protein kinase inhibition enhances airway epithelial Basal-cell proliferation and lentivirus transduction.

    PubMed

    Horani, Amjad; Nath, Aditya; Wasserman, Mollie G; Huang, Tao; Brody, Steven L

    2013-09-01

    The identification of factors that regulate airway epithelial cell proliferation and differentiation are essential for understanding the pathophysiology of airway diseases. Rho-associated protein kinases (ROCKs) are downstream effector proteins of RhoA GTPase that direct the functions of cell cytoskeletal proteins. ROCK inhibition with Y27632 has been shown to enhance the survival and cloning of human embryonic stem cells and pluripotent cells in other tissues. We hypothesized that Y27632 treatment exerts a similar effect on airway epithelial basal cells, which function as airway epithelial progenitor cells. Treatment with Y27632 enhanced basal-cell proliferation in cultured human tracheobronchial and mouse tracheal epithelial cells. ROCK inhibition accelerated the maturation of basal cells, characterized by a diminution of the cell size associated with cell compaction and the expression of E-cadherin at cell-cell junctions. Transient treatment of cultured basal cells with Y27632 did not affect subsequent ciliated or mucous cell differentiation under air-liquid interface conditions, and allowed for the initial use of lower numbers of human or mouse primary airway epithelial cells than otherwise possible. Moreover, the use of Y27632 during lentivirus-mediated transduction significantly improved posttransduction efficiency and the selection of a transduced cell population, as determined by reporter gene expression. These findings suggest an important role for ROCKs in the regulation of proliferation and maturation of epithelial basal cells, and demonstrate that the inhibition of ROCK pathways using Y27632 provides an adjunctive tool for the in vitro genetic manipulation of airway epithelial cells by lentivirus vectors. PMID:23713995

  19. A Case of Basal Cell Carcinoma with Outer Hair Follicle Sheath Differentiation.

    PubMed

    Onishi, Masazumi; Takahashi, Kazuhiro; Maeda, Fumihiko; Akasaka, Toshihide

    2015-01-01

    A 70-year-old Japanese man presented at our hospital with an asymptomatic, blackish, irregularly shaped plaque with a gray nodule in the periphery on his left lower leg. The lesion had been present for 10 years and had recently enlarged, associated with bleeding. Histopathologically, the tumor consisted of three distinct parts: The first part showed massive aggregation of basophilic basaloid cells with peripheral palisading and abundant melanin granules, and was diagnosed as solid-type basal cell carcinoma. The second part showed aggregation of clear cells with squamous eddies, and was diagnosed as proliferating trichilemmal tumor. The third part showed reticular aggregation of basaloid cells with infundibular cysts in the papillary dermis, and was diagnosed as infundibulocystic basal cell carcinoma. We diagnosed this tumor as basal cell carcinoma with various forms of hair follicle differentiation, including differentiation into the outer root sheath. PMID:26955331

  20. A Case of Basal Cell Carcinoma with Outer Hair Follicle Sheath Differentiation

    PubMed Central

    Onishi, Masazumi; Takahashi, Kazuhiro; Maeda, Fumihiko; Akasaka, Toshihide

    2015-01-01

    A 70-year-old Japanese man presented at our hospital with an asymptomatic, blackish, irregularly shaped plaque with a gray nodule in the periphery on his left lower leg. The lesion had been present for 10 years and had recently enlarged, associated with bleeding. Histopathologically, the tumor consisted of three distinct parts: The first part showed massive aggregation of basophilic basaloid cells with peripheral palisading and abundant melanin granules, and was diagnosed as solid-type basal cell carcinoma. The second part showed aggregation of clear cells with squamous eddies, and was diagnosed as proliferating trichilemmal tumor. The third part showed reticular aggregation of basaloid cells with infundibular cysts in the papillary dermis, and was diagnosed as infundibulocystic basal cell carcinoma. We diagnosed this tumor as basal cell carcinoma with various forms of hair follicle differentiation, including differentiation into the outer root sheath. PMID:26955331

  1. Discovery of Genes Expressed In Basal Endosperm Transfer Cells in Maize Using 454 Transcriptome Sequencing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Basal endosperm transfer cells (BETCs) constitute one of the four cell types in an endosperm with a major role in solute acquisition and transport functions from the mother plant. The BETCs with their wall-in-growth (WIG) feature that greatly increase plasma membrane area of each cell are critical f...

  2. Basal cell carcinoma in a blue-fronted amazon parrot (Amazona aestiva).

    PubMed

    Tell, L A; Woods, L; Mathews, K G

    1997-01-01

    Tumors of the integumentary system are relatively common in companion birds. Dermal tumors in pet birds can be epithelial, mesenchymal, or vascular in origin. Basal cell carcinomas appear to be extremely rare in birds. An adult female blue-fronted Amazon parrot was examined because it exhibited bilateral cervical masses that extended from the base of the skull to the ingluvial region. The tumors were removed by surgical excision. Microscopic examination of the masses revealed neoplastic epithelial cells that extended to all borders of the sections; scattered vessels with neoplastic cells within their lumens were also found. The histopathologic diagnosis was basal cell carcinoma. Six weeks postoperatively, the masses recurred and the bird was euthanatized. This report suggests that basal cell carcinomas should be considered as a differential for avian dermal tumors. This neoplastic condition can be aggressive and has the potential to metastasize. PMID:9356728

  3. Primary Cilia on Horizontal Basal Cells Regulate Regeneration of the Olfactory Epithelium

    PubMed Central

    Joiner, Ariell M.; Green, Warren W.; McIntyre, Jeremy C.; Allen, Benjamin L.; Schwob, James E.

    2015-01-01

    The olfactory epithelium (OE) is one of the few tissues to undergo constitutive neurogenesis throughout the mammalian lifespan. It is composed of multiple cell types including olfactory sensory neurons (OSNs) that are readily replaced by two populations of basal stem cells, frequently dividing globose basal cells and quiescent horizontal basal cells (HBCs). However, the precise mechanisms by which these cells mediate OE regeneration are unclear. Here, we show for the first time that the HBC subpopulation of basal stem cells uniquely possesses primary cilia that are aligned in an apical orientation in direct apposition to sustentacular cell end feet. The positioning of these cilia suggests that they function in the detection of growth signals and/or differentiation cues. To test this idea, we generated an inducible, cell type-specific Ift88 knock-out mouse line (K5rtTA;tetOCre;Ift88fl/fl) to disrupt cilia formation and maintenance specifically in HBCs. Surprisingly, the loss of HBC cilia did not affect the maintenance of the adult OE but dramatically impaired the regeneration of OSNs following lesion. Furthermore, the loss of cilia during development resulted in a region-specific decrease in neurogenesis, implicating HBCs in the establishment of the OE. Together, these results suggest a novel role for primary cilia in HBC activation, proliferation, and differentiation. SIGNIFICANCE STATEMENT We show for the first time the presence of primary cilia on a quiescent population of basal stem cells, the horizontal basal cells (HBCs), in the olfactory epithelium (OE). Importantly, our data demonstrate that cilia on HBCs are necessary for regeneration of the OE following injury. Moreover, the disruption of HBC cilia alters neurogenesis during the development of the OE, providing evidence that HBCs participate in the establishment of this tissue. These data suggest that the mechanisms of penetrance for ciliopathies in the OE extend beyond that of defects in olfactory sensory

  4. Chibby promotes ciliary vesicle formation and basal body docking during airway cell differentiation.

    PubMed

    Burke, Michael C; Li, Feng-Qian; Cyge, Benjamin; Arashiro, Takeshi; Brechbuhl, Heather M; Chen, Xingwang; Siller, Saul S; Weiss, Matthew A; O'Connell, Christopher B; Love, Damon; Westlake, Christopher J; Reynolds, Susan D; Kuriyama, Ryoko; Takemaru, Ken-Ichi

    2014-10-13

    Airway multiciliated epithelial cells play crucial roles in the mucosal defense system, but their differentiation process remains poorly understood. Mice lacking the basal body component Chibby (Cby) exhibit impaired mucociliary transport caused by defective ciliogenesis, resulting in chronic airway infection. In this paper, using primary cultures of mouse tracheal epithelial cells, we show that Cby facilitates basal body docking to the apical cell membrane through proper formation of ciliary vesicles at the distal appendage during the early stages of ciliogenesis. Cby is recruited to the distal appendages of centrioles via physical interaction with the distal appendage protein CEP164. Cby then associates with the membrane trafficking machinery component Rabin8, a guanine nucleotide exchange factor for the small guanosine triphosphatase Rab8, to promote recruitment of Rab8 and efficient assembly of ciliary vesicles. Thus, our study identifies Cby as a key regulator of ciliary vesicle formation and basal body docking during the differentiation of airway ciliated cells. PMID:25313408

  5. Repression of Igf1 expression by Ezh2 prevents basal cell differentiation in the developing lung.

    PubMed

    Galvis, Laura A; Holik, Aliaksei Z; Short, Kieran M; Pasquet, Julie; Lun, Aaron T L; Blewitt, Marnie E; Smyth, Ian M; Ritchie, Matthew E; Asselin-Labat, Marie-Liesse

    2015-04-15

    Epigenetic mechanisms involved in the establishment of lung epithelial cell lineage identities during development are largely unknown. Here, we explored the role of the histone methyltransferase Ezh2 during lung lineage determination. Loss of Ezh2 in the lung epithelium leads to defective lung formation and perinatal mortality. We show that Ezh2 is crucial for airway lineage specification and alveolarization. Using optical projection tomography imaging, we found that branching morphogenesis is affected in Ezh2 conditional knockout mice and the remaining bronchioles are abnormal, lacking terminally differentiated secretory club cells. Remarkably, RNA-seq analysis revealed the upregulation of basal genes in Ezh2-deficient epithelium. Three-dimensional imaging for keratin 5 further showed the unexpected presence of a layer of basal cells from the proximal airways to the distal bronchioles in E16.5 embryos. ChIP-seq analysis indicated the presence of Ezh2-mediated repressive marks on the genomic loci of some but not all basal genes, suggesting an indirect mechanism of action of Ezh2. We found that loss of Ezh2 de-represses insulin-like growth factor 1 (Igf1) expression and that modulation of IGF1 signaling ex vivo in wild-type lungs could induce basal cell differentiation. Altogether, our work reveals an unexpected role for Ezh2 in controlling basal cell fate determination in the embryonic lung endoderm, mediated in part by repression of Igf1 expression. PMID:25790853

  6. Clinical, Histopathological and Therapeutical Analysis of Inferior Eyelid Basal Cell Carcinomas

    PubMed Central

    Totir, M; Alexandrescu, C; Pirvulescu, R; Gradinaru, S; Costache, M

    2014-01-01

    Rationale: Eyelids are very susceptible area for non-melanoma skin cancers; among that, basal cell carcinoma has the highest incidence (almost 90% of malignant eyelid tumors) and 50-60% of eyelid basal cell carcinomas appear on inferior eyelid. Objective: To analyze clinical features of inferior eyelid basal cell carcinoma and to determine the efficacy of surgical treatment with frozen sectioncontrolled margins and methods of primary reconstruction of defects. Methods: A review of medical records of cases with primary inferior eyelid basal cell carcinoma treated by surgical excision with urgent histopathology controlled margins by FS technique, doubled by paraffin examination from October 2011 to October 2014. After histopathology confirmation of tumor free margins, proper inferior eyelid reconstruction was performed. Results: The review resulted in 36 patients with 36 lesions analyzed by clinical, histopatological and therapeuticalaspectswith a mean follow-up of 20 months. All lesions were primary BCC affecting inferior eyelid. There were no recurrence in the follow-up period. Inferior eyelid reconstruction techniques were direct closure for small defects and complex techniques for defects more than one third of eyelid length. Discussion: Appropriate eyelid examination is mandatory in any routine ophthalmic check-up. Clinical signs suggestive of BCC should be familiar to ophthalmologist in order to have an early diagnosis and treatment for these tumors. Surgical treatment with FS controlled excision followed by eyelid reconstruction is an efficient treatment for inferior eyelid BCC. Abbreviations: basal cell carcinoma (BCC); frozen section (FS);Mohs micrographic surgery (MMS). PMID:27057245

  7. Acitretin systemic and retinoic acid 0.1% cream supression of basal cell carcinoma

    PubMed Central

    Zhang, Xi-Bao; Zhang, San-Quan; Li, Chang-Xing; Huang, Zhen-Ming; Luo, Yu-Wu

    2010-01-01

    Retinoids have been used for years as monotherapy and/or in combination for treatment and suppression of cutaneous malignancies in patients with basal cell nevus syndrome, xeroderma pigmentosum, or cutaneous T-cell lymphoma (CTCL) basal cell carcinoma (BCC). We report 4 cases with BCC confirmed by histopathology who were treated by short-term systemic acitretin combined with retinoic acid 0.1% cream. The 4 cases with BCC showed good response to the treatment without severe adverse effects during treatment and follow-up. The finding suggests that acitretin may be an appropriate treatment option for elderly patients who require less invasive treatment for BCC. PMID:25386240

  8. The dysplastic naevus syndrome in patients with cutaneous malignant melanoma in Western Australia.

    PubMed

    English, D R; Menz, J; Heenan, P J; Elder, D E; Watt, J D; Armstrong, B K

    1986-09-01

    One hundred and three patients with cutaneous malignant melanoma responded to an invitation to attend a dermatology outpatient clinic. All patients with a family history of melanoma, a history of multiple melanomas, or histological evidence of a dysplastic naevus that was associated with their melanoma were invited. A random sample of other patients with cutaneous malignant melanoma was also invited to attend. First-degree relatives of patients with the dysplastic naevus syndrome (DNS) were invited for a similar examination. DNS was found in 27% of the patients with a family history of melanoma, multiple melanomas, or histological evidence of a dysplastic naevus in association with their melanoma, and in 6% of the remaining patients who were selected at random. DNS was estimated to be present in 12.8% of 17- to 55-year-old patients with cutaneous malignant melanoma in the Perth region, while familial DNS was present in 4.5%. Patients with melanomas with DNS were more likely to be young men and to have numerous naevi, particularly on the lateral surfaces of the arms, shoulders and trunk, than were patients with melanomas without the syndrome. PMID:3747894

  9. Clonal Dynamics Reveal Two Distinct Populations of Basal Cells in Slow-Turnover Airway Epithelium

    PubMed Central

    Watson, Julie K.; Rulands, Steffen; Wilkinson, Adam C.; Wuidart, Aline; Ousset, Marielle; Van Keymeulen, Alexandra; Göttgens, Berthold; Blanpain, Cédric; Simons, Benjamin D.; Rawlins, Emma L.

    2015-01-01

    Summary Epithelial lineages have been studied at cellular resolution in multiple organs that turn over rapidly. However, many epithelia, including those of the lung, liver, pancreas, and prostate, turn over slowly and may be regulated differently. We investigated the mouse tracheal epithelial lineage at homeostasis by using long-term clonal analysis and mathematical modeling. This pseudostratified epithelium contains basal cells and secretory and multiciliated luminal cells. Our analysis revealed that basal cells are heterogeneous, comprising approximately equal numbers of multipotent stem cells and committed precursors, which persist in the basal layer for 11 days before differentiating to luminal fate. We confirmed the molecular and functional differences within the basal population by using single-cell qRT-PCR and further lineage labeling. Additionally, we show that self-renewal of short-lived secretory cells is a feature of homeostasis. We have thus revealed early luminal commitment of cells that are morphologically indistinguishable from stem cells. PMID:26119728

  10. Prostate cancer stem cells: do they have a basal or luminal phenotype?

    PubMed

    Maitland, Norman J; Frame, Fiona M; Polson, Euan S; Lewis, John L; Collins, Anne T

    2011-02-01

    The prostate is a luminal secretory tissue whose function is regulated by male sex hormones. Castration produces involution of the prostate to a reversible basal state, and as the majority of prostate cancers also have a luminal phenotype, drug-induced castration is a front line therapy. It has therefore been assumed that the tumor arises from transformation of a luminal progenitor cell. Here, we demonstrate that a minority basal "cancer stem cell" (CSC) population persists in primary human prostate cancers, as in normal prostate, serving as a reservoir for tumor recurrence after castration therapy. While the CSCs exhibit a degree of phenotypic fluidity from different patients, the tumor-initiating cells in immunocompromised mice express basal markers (such as p63), but do not express androgen receptor (AR) or markers of luminal differentiation (PSA, PAP) when freshly fractionated from human tissues or following culture in vitro. Estrogen receptors α and β and AR are transcriptionally active in the transit amplifying (TA) cell (the progeny of SC). However, AR protein is consistently undetectable in TA cells. The prostate-specific TMPRSS2 gene, while upregulated by AR activity in luminal cells, is also transcribed in basal populations, confirming that AR acts as an expression modulator. Selected cells with basal phenotypes are tumor initiating, but the resultant tumors are phenotypically intermediate, with focal expression of AR, AMACR, and p63. In vitro differentiation experiments, employing lentivirally transduced SCs with a luminal (PSA-probasin) promoter regulating a fluorescent indicator gene, confirm that the basal SCs are the source of luminal progeny. PMID:21761340

  11. Human and murine prostate basal/stem cells are not direct targets of prolactin.

    PubMed

    Sackmann-Sala, Lucila; Angelergues, Antoine; Boutillon, Florence; d'Acremont, Bruno; Maidenberg, Marc; Oudard, Stéphane; Goffin, Vincent

    2015-09-01

    Local overexpression of prolactin (PRL) in the prostate of Pb-PRL transgenic mice induces benign prostate tumors exhibiting marked amplification of the epithelial basal/stem cell compartment. However, PRL-activated intracellular signaling seems to be restricted to luminal cells, suggesting that basal/stem cells may not be direct targets of PRL. Given their described role as prostate cancer-initiating cells, it is important to understand the mechanisms that regulate basal/stem cells. In this study, we evaluated whether PRL can act directly on these cells, by growing them as prostaspheres. For this, primary 3D prostasphere cultures were prepared from unfractionated cells isolated from freshly harvested human and mouse benign prostate tissues and subjected to PRL stimulation in vitro. None of the various concentrations of PRL tested showed any effects on the sizes or numbers of the prostaspheres generated. In addition, neither activation of canonical PRL-induced signaling pathways (Stat5, Stat3 or Erk1/2) nor increased expression of the proliferation marker Ki-67 were detected by immunostaining in PRL-stimulated prostaspheres. Consistent with the absence of response, PRL receptor mRNA levels were generally undetectable in mouse sphere cells. We conclude that human and mouse prostate basal/stem cells are not direct targets of PRL action. The observed amplification of basal/stem cells in Pb-PRL prostates might be due to paracrine mechanisms originating from PRL action on other cell compartments. Our current efforts are aimed at unraveling these mechanisms. PMID:25888939

  12. Basal cell carcinoma and the carcinogenic role of aberrant Hedgehog signaling.

    PubMed

    Saran, Anna

    2010-06-01

    Basal cell carcinoma (BCC) is the most frequent cancer in the white population and its incidence appears to be increasing worldwide. While the majority of BCCs arise sporadically, many cases are attributable to basal cell nevus syndrome, or Gorlin syndrome, an autosomal dominantly inherited disorder characterized by the occurrence of multiple BCCs and by extracutaneous tumors. Genetic studies on patients with basal cell nevus syndrome indicate deregulation of the Hedgehog (Hh) pathway in epidermal keratinocytes as the primary event in the pathogenesis of BCC. This article summarizes the recent progress in understanding Hh-dependent BCC tumorigenesis, as well as evidence for deregulation of other molecular pathways, primarily the Wnt developmental pathway. Understanding the molecular genetics of BCC development has provided new opportunities for molecular therapy of this cancer by targeting Hh and other signaling pathways. PMID:20528237

  13. Basal cell nevus syndrome: clinical and molecular review and case report.

    PubMed

    Pino, Livia Cristina de Melo; Balassiano, Laila Klotz de Almeida; Sessim, Marlene; de Almeida, Ana Paula Moura; Empinotti, Vinicius Dequech; Semenovitch, Ivan; Treu, Curt; Lupi, Omar

    2016-04-01

    Basal cell nevus syndrome (BCNS), also referred to as nevoid basal cell carcinoma syndrome or Gorlin-Goltz syndrome, was first described by Gorlin and Goltz in 1960 as an autosomal dominant disorder characterized by the early appearance of multiple basal cell carcinomas (BCCs), keratocysts of the jaw, ectopic calcifications, palmar and plantar pits, and anomalies of the ocular, skeletal, and reproductive systems. The genesis of this cancer's etiology in relation to BCNS was unclear until a few years ago when molecular analysis studies suggested a relationship between BCC and the loss-of-function mutations of the patched gene (PTCH) found on chromosome arm 9q. PTCH inhibits signaling by the membrane protein Smoothened (Smo), and this inhibition is relieved by binding sonic hedgehog (SHH) to PTCH. We describe a patient with multiple BCCs associated with x-ray anomalies of BCNS and review the basis of the SHH signaling pathway and clinical aspects of BCNS. PMID:26356331

  14. Prostate Sphere-forming Stem Cells Are Derived from the P63-expressing Basal Compartment.

    PubMed

    Huang, Yanqing; Hamana, Tomoaki; Liu, Junchen; Wang, Cong; An, Lei; You, Pan; Chang, Julia Y F; Xu, Jianming; McKeehan, Wallace L; Wang, Fen

    2015-07-17

    Prostate stem cells (P-SCs) are capable of giving rise to all three lineages of prostate epithelial cells, including basal, luminal, and neuroendocrine cells. Multiple methods have been used to identify P-SCs in adult prostates. These include in vivo renal capsule implantation of a single epithelial cell with urogenital mesenchymal cells, in vitro prostasphere and organoid cultures, and lineage tracing with castration-resistant Nkx3.1 expression (CARN), in conjunction with expression of cell type-specific markers. Both organoid culture and CARN tracing show the existence of P-SCs in the luminal compartment. Although prostasphere cells predominantly express basal cell-specific cytokeratin and P63, the lineage of prostasphere-forming cells in the P-SC hierarchy remains to be determined. Using lineage tracing with P63(CreERT2), we show here that the sphere-forming P-SCs are P63-expressing cells and reside in the basal compartment. Therefore we designate them as basal P-SCs (P-bSCs). P-bSCs are capable of differentiating into AR(+) and CK18(+) organoid cells, but organoid cells cannot form spheres. We also report that prostaspheres contain quiescent stem cells. Therefore, the results show that P-bSCs represent stem cells that are early in the hierarchy of overall prostate tissue stem cells. Understanding the contribution of the two types of P-SCs to prostate development and prostate cancer stem cells and how to manipulate them may open new avenues for control of prostate cancer progression and relapse. PMID:26032419

  15. Airway basal stem cells: a perspective on their roles in epithelial homeostasis and remodeling.

    PubMed

    Rock, Jason R; Randell, Scott H; Hogan, Brigid L M

    2010-01-01

    The small airways of the human lung undergo pathological changes in pulmonary disorders, such as chronic obstructive pulmonary disease (COPD), asthma, bronchiolitis obliterans and cystic fibrosis. These clinical problems impose huge personal and societal healthcare burdens. The changes, termed 'pathological airway remodeling', affect the epithelium, the underlying mesenchyme and the reciprocal trophic interactions that occur between these tissues. Most of the normal human airway is lined by a pseudostratified epithelium of ciliated cells, secretory cells and 6-30% basal cells, the proportion of which varies along the proximal-distal axis. Epithelial abnormalities range from hypoplasia (failure to differentiate) to basal- and goblet-cell hyperplasia, squamous- and goblet-cell metaplasia, dysplasia and malignant transformation. Mesenchymal alterations include thickening of the basal lamina, smooth muscle hyperplasia, fibrosis and inflammatory cell accumulation. Paradoxically, given the prevalence and importance of airway remodeling in lung disease, its etiology is poorly understood. This is due, in part, to a lack of basic knowledge of the mechanisms that regulate the differentiation, maintenance and repair of the airway epithelium. Specifically, little is known about the proliferation and differentiation of basal cells, a multipotent stem cell population of the pseudostratified airway epithelium. This Perspective summarizes what we know, and what we need to know, about airway basal cells to evaluate their contributions to normal and abnormal airway remodeling. We contend that exploiting well-described model systems using both human airway epithelial cells and the pseudostratified epithelium of the genetically tractable mouse trachea will enable crucial discoveries regarding the pathogenesis of airway disease. PMID:20699479

  16. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness.

    PubMed

    Silapunt, Sirunya; Chen, Leon; Migden, Michael R

    2016-09-01

    Treatment of locally advanced basal cell carcinomas (laBCCs) with large, aggressive, destructive, and disfiguring tumors, or metastatic disease is challenging. Dysregulation of the Hedgehog (Hh) signaling pathway has been identified in the vast majority of basal cell carcinomas (BCCs). There are two United States Food and Drug Administration (US FDA)-approved Hh pathway inhibitors (HPIs) that exhibit antitumor activity in advanced BCC with an acceptable safety profile. Common adverse effects include muscle spasms, dysgeusia, alopecia, fatigue, nausea and weight loss. PMID:27583029

  17. Coexistence of Solid (Nodular) and Differentiated (Adenoid) Basal Cell Carcinoma at the Same Anatomical Site

    PubMed Central

    Rao, Angoori Gnaneshwar

    2015-01-01

    Coexistence of two different histopathological types of basal cell carcinomas (BCCs) in the same anatomical site is rare and interesting. Herein, we report a case of coexistence of nodular and adenoid BCC in a 78-year-old peasant who presented with a plaque and a globular swelling on left paranasal region of few years duration. Histopathology of skin biopsy with immunohistochemistry study using antibodies to S100, epithelial membrane antigen (EMA) and cytokeratin 7 (CK 7) from the margin of the ulcer and globular swelling confirmed the diagnosis that revealed features of nodular and adenoid basal cell carcinoma, respectively. Investigative work up did not reveal evidence of metastasis. PMID:26538745

  18. Hedgehog pathway inhibition in advanced basal cell carcinoma: latest evidence and clinical usefulness

    PubMed Central

    Silapunt, Sirunya; Chen, Leon; Migden, Michael R.

    2016-01-01

    Treatment of locally advanced basal cell carcinomas (laBCCs) with large, aggressive, destructive, and disfiguring tumors, or metastatic disease is challenging. Dysregulation of the Hedgehog (Hh) signaling pathway has been identified in the vast majority of basal cell carcinomas (BCCs). There are two United States Food and Drug Administration (US FDA)-approved Hh pathway inhibitors (HPIs) that exhibit antitumor activity in advanced BCC with an acceptable safety profile. Common adverse effects include muscle spasms, dysgeusia, alopecia, fatigue, nausea and weight loss. PMID:27583029

  19. Effect of Photofrin on skin reflection of basal cell nevus syndrome patients

    NASA Astrophysics Data System (ADS)

    Grossweiner, Leonard I.; Jones, Linda R.; Koehler, Irmgard K.; Bilgin, Mehmet D.

    1996-04-01

    Skin reflection spectra were measured before and 24 hours after administration of Photofrin (Reg. TM) to basal cell nevus syndrome (BCNS) patients. The drug reduced the reflectivity of uninvolved BCNS skin and increased the reflectivity of basal cell cancers. Photofrin (Reg. TM) absorption in normal rat skin and uninvolved BCNS skin was resolved by the diffusion approximation. Optical constants calculated with a two-layer skin model indicate that the drug increased light scattering in tumor tissues. The possible use of reflection spectra for PDT light dosimetry is discussed.

  20. Treatment of Basal Cell Carcinoma in the Elderly: What Nondermatologists Need to Know.

    PubMed

    Wiznia, Lauren E; Federman, Daniel G

    2016-07-01

    As the population ages and incidence of basal cell carcinoma continues to increase, we will be faced more frequently with difficult treatment decisions for basal cell carcinoma in the elderly. Different treatment options, including surgical excision, electrodessication and curettage, cryosurgery, imiquimod, photodynamic therapy, 5-fluorouracil, radiation therapy, vismodegib, combination therapy, and observation, may be considered on the basis of tumor characteristics. Given the wide range of therapeutic options, treatments can be tailored to achieve patients' goals of care within their anticipated life expectancy. PMID:27046242

  1. Origin of Ameloblastoma From Basal Cells of the Oral Epithelium- Establishing the Relation Using Neuroectodermal Markers

    PubMed Central

    Suneela, S; Narayan, T V; Shreedhar, Balasundari; Mohanty, Leeky; Shenoy, Sadhana; Swaminathan, Uma

    2014-01-01

    Background and Objectives: Basal cell layer of the oral epithelium has been rightfully regarded as a potential source of odontogenic tumours and cysts, but, without substantial evidence. Also, whether the basal cell layer retains within it, some properties of ectomesenchyme, which was imbibed during the early embryogenesis and hence its neuroectodermal relation, is not known. Here, an attempt is made to establish the hidden neuroectodermal potential of the oral epithelium, especially the basal layer, by observing the expression of known neuroectodermal markers, NSE (Neuron Specific Enolase), Synaptophysin and CD99. The expression of the same markers has also been studied in Ameloblastoma, connecting it with oral epithelium, in turn establishing basal cell layer as a potential source of Ameloblastoma. Materials and Methods: Sections of formalin fixed, paraffin embedded tissue samples of 20 cases of Ameloblastoma and 10 cases of Normal Retromolar mucosa, were stained immunohistochemically with NSE, Synaptophysin, CD99 and also with CK-19 and evaluated for positive expression. Results: Positive reaction was obtained in all the cases of Ameloblastoma and NRM (Normal Retromolar mucosa) with NSE, all the cases of Ameloblastoma and eight cases of NRM with Synaptophysin and in six cases of Ameloblastoma and NRM with CD99. The staining was diffuse and more marked in case of NSE than Synaptophysin and CD99. CK19 staining done to assure that the tissue antigenicity was maintained was positive in all the samples. Interpretation and Conclusion: A strong relationship between the neuroectoderm, Ameloblastoma and the basal layer of the oral epithelium is established by the study. It favours the hypothesis that the basal cell layer of oral mucosa may be the sought out culprit in most cases of the Ameloblastomas, especially those occurring in the non-tooth bearing area. This would call for the need to incorporate additional therapy in the form of mucosal striping along with the

  2. Neddylation controls basal MKK7 kinase activity in breast cancer cells.

    PubMed

    Zhu, T; Wang, J; Pei, Y; Wang, Q; Wu, Y; Qiu, G; Zhang, D; Lv, M; Li, W; Zhang, J

    2016-05-19

    The c-Jun NH2-terminal protein kinase (JNK) pathway has been implicated in mammary tumor development. However, the molecular mechanisms regulating JNK activity in breast cancer cells remain unclear. Here, we report that the inhibition of ubiquitination-like post-translational modification neddylation through different strategies results in enhanced basal JNK phosphorylation in human breast cancer cells. The upregulation of basal JNK phosphorylation upon neddylation inhibition is independent of the deneddylation of Cullins, the well-characterized neddylation substrates. Since augmented basal JNK phosphorylation via ectopic MKK7 expression impedes proliferation and the epithelial-to-mesenchymal transition (EMT) phenotype, the neddylation system might contribute to mammary tumor development partially through limiting basal JNK phosphorylation. Further exploration reveals that MKK7, a JNK-specific MAP2K, undergoes neddylation in human breast cancer cells. MKK7 co-precipitates with a fragment of Ran-binding protein 2 (RanBP2), a large multimodular and pleiotropic protein that has been recognized as a SUMO E3 ligase. Knockdown of RanBP2 attenuates MKK7 neddylation and augments basal JNK phosphorylation without affecting the neddylation of Cullins, whereas ectopic expression of a RanBP2 fragment possessing SUMO E3 activity (RanBP2ΔFG) manifests the opposite effects. In vitro neddylation assays confirm that RanBP2ΔFG works as the neddylation E3 ligase for MKK7. The basal kinase activity of endogenous MKK7 increases upon RanBP2 knockdown but decreases upon the ectopic expression of RanBP2ΔFG. Furthermore, purified MKK7 shows reduced basal kinase activity after in vitro neddylation by RanBP2ΔFG. Consistently, RanBP2 knockdown leads to reduced proliferation and impaired EMT phenotype in human breast cancer cells and the effects of RanBP2 knockdown are reversed by simultaneous MKK7 knockdown. Taken together, our data suggest that MKK7 undergoes neddylation in human breast

  3. Tyrosine kinase-mediated axial motility of basal cells revealed by intravital imaging

    PubMed Central

    Roy, Jeremy; Kim, Bongki; Hill, Eric; Visconti, Pablo; Krapf, Dario; Vinegoni, Claudio; Weissleder, Ralph; Brown, Dennis; Breton, Sylvie

    2016-01-01

    Epithelial cells are generally considered to be static relative to their neighbours. Basal cells in pseudostratified epithelia display a single long cytoplasmic process that can cross the tight junction barrier to reach the lumen. Using in vivo microscopy to visualize the epididymis, a model system for the study of pseudostratified epithelia, we report here the surprising discovery that these basal cell projections—which we call axiopodia—periodically extend and retract over time. We found that axiopodia extensions and retractions follow an oscillatory pattern. This movement, which we refer to as periodic axial motility (PAM), is controlled by c-Src and MEK1/2–ERK1/2. Therapeutic inhibition of tyrosine kinase activity induces a retraction of these projections. Such unexpected cell motility may reflect a novel mechanism by which specialized epithelial cells sample the luminal environment. PMID:26868824

  4. Tyrosine kinase-mediated axial motility of basal cells revealed by intravital imaging.

    PubMed

    Roy, Jeremy; Kim, Bongki; Hill, Eric; Visconti, Pablo; Krapf, Dario; Vinegoni, Claudio; Weissleder, Ralph; Brown, Dennis; Breton, Sylvie

    2016-01-01

    Epithelial cells are generally considered to be static relative to their neighbours. Basal cells in pseudostratified epithelia display a single long cytoplasmic process that can cross the tight junction barrier to reach the lumen. Using in vivo microscopy to visualize the epididymis, a model system for the study of pseudostratified epithelia, we report here the surprising discovery that these basal cell projections--which we call axiopodia--periodically extend and retract over time. We found that axiopodia extensions and retractions follow an oscillatory pattern. This movement, which we refer to as periodic axial motility (PAM), is controlled by c-Src and MEK1/2-ERK1/2. Therapeutic inhibition of tyrosine kinase activity induces a retraction of these projections. Such unexpected cell motility may reflect a novel mechanism by which specialized epithelial cells sample the luminal environment. PMID:26868824

  5. Basal cell nevus syndrome. Presentation of six cases and literature review.

    PubMed

    Díaz-Fernández, José María; Infante-Cossío, Pedro; Belmonte-Caro, Rodolfo; Ruiz-Laza, Luis; García-Perla-García, Alberto; Gutiérrez-Pérez, José Luis

    2005-01-01

    Basal cell nevus syndrome, also known as Gorlin-Goltz syndrome, is an autosomal dominant inherited disorder which is characterised by the presence of multiple maxillary keratocysts and facial basal cell carcinomas, along with other less frequent clinical characteristics such us musculo-skeletal disturbances (costal and vertebrae malformations), characteristic facies, neurological (calcification of the cerebral falx, schizophrenia, learning difficulties), skin (cysts, lipomas, fibromas), sight, hormonal, etc. On occasions it can be associated with aggressive basal cell carcinomas and malignant neoplasias, for which early diagnosis and treatment is essential, as well as family detection and genetic counselling. Currently there are new lines of investigation based on biomolecular studies, which aim at identifying the molecules responsible for these cysts and thus allowing an early diagnosis of these patients. In its clinical management and follow up, the odonto-stomatologist, the maxillofacial surgeon and several other medical specialists are involved. In this paper a review of the literature, and six cases of patients affected by multi-systemic and varied clinical expression of basal cell nevus syndrome, are presented. PMID:15800468

  6. Fibroepithelioma of Pinkus in continuity with nodular basal cell carcinoma: A rare presentation.

    PubMed

    Dongre, Atul M; Khopkar, Uday S; Kalyanpad, Yogesh N; Gole, Prachi V

    2016-01-01

    Fibroepithelioma of Pinkus and nodular basal cell carcinoma (BCC) are different morphological variants of BCC. It is very rare to see both the variants together in a single lesion. Here we report a case of a 56-year-old female who presented with a nodule on the trunk, which on biopsy showed features of both nodular BCC and fibroepithelioma of Pinkus. PMID:27559504

  7. Fibroepithelioma of Pinkus in continuity with nodular basal cell carcinoma: A rare presentation

    PubMed Central

    Dongre, Atul M.; Khopkar, Uday S.; Kalyanpad, Yogesh N.; Gole, Prachi V.

    2016-01-01

    Fibroepithelioma of Pinkus and nodular basal cell carcinoma (BCC) are different morphological variants of BCC. It is very rare to see both the variants together in a single lesion. Here we report a case of a 56-year-old female who presented with a nodule on the trunk, which on biopsy showed features of both nodular BCC and fibroepithelioma of Pinkus. PMID:27559504

  8. Basal Cell Adenoma of Palate, a Rare Occurrence with Review of Literature.

    PubMed

    Yadav, Achla Bharti; Narwal, Anjali; Devi, Anju; Kumar, Sanjay; Yadav, Sumit Kumar

    2015-09-01

    Basal cell adenoma is an uncommon benign epithelial neoplasm of salivary gland which derives its name from the basaloid appearance of tumor cells and accounting for 1-2 % of all salivary gland epithelial tumors. This tumor usually arises in the major salivary glands, with the parotid being the most frequent site of occurrence, followed by the upper lip; while it is very rare in the minor salivary glands. Microscopically, it is composed of isomorphic cells similar to basal cells with nuclear palisading. We report a case of BCA presenting as an asymptomatic swelling over the right side of palate of 55-year-old female patient. A follow-up of 1 year revealed no recurrence. This report emphasizes the rare site of occurrence of this tumor and briefly reviews the literature. PMID:26535412

  9. Basal Cell Adenoma of Palate, a Rare Occurrence with Review of Literature

    PubMed Central

    Yadav, Achla Bharti; Narwal, Anjali; Devi, Anju; Kumar, Sanjay; Yadav, Sumit Kumar

    2015-01-01

    Basal cell adenoma is an uncommon benign epithelial neoplasm of salivary gland which derives its name from the basaloid appearance of tumor cells and accounting for 1-2 % of all salivary gland epithelial tumors. This tumor usually arises in the major salivary glands, with the parotid being the most frequent site of occurrence, followed by the upper lip; while it is very rare in the minor salivary glands. Microscopically, it is composed of isomorphic cells similar to basal cells with nuclear palisading. We report a case of BCA presenting as an asymptomatic swelling over the right side of palate of 55-year-old female patient. A follow-up of 1 year revealed no recurrence. This report emphasizes the rare site of occurrence of this tumor and briefly reviews the literature. PMID:26535412

  10. Stereotaxic probabilistic maps of the magnocellular cell groups in human basal forebrain

    PubMed Central

    Zaborszky, L.; Hoemke, L.; Mohlberg, H.; Schleicher, A.; Amunts, K.; Zilles, K.

    2008-01-01

    The basal forebrain contains several interdigitating anatomical structures, including the diagonal band of Broca, the basal nucleus of Meynert, the ventral striatum, and also cell groups underneath the globus pallidus that bridge the centromedial amygdala to the bed nucleus of the stria terminalis. Among the cell populations, the magnocellular, cholinergic corticopetal projection neurons have received particular attention due to their loss in Alzheimer’s disease. In MRI images, the precise delineation of these structures is difficult due to limited spatial resolution and contrast. Here, using microscopic delineations in ten human postmortem brains, we present stereotaxic probabilistic maps of the basal forebrain areas containing the magnocellular cell groups. Cytoarchitectonic mapping was performed in silver stained histological serial sections. The positions and the extent of the magnocellular cell groups within the septum (Ch1-2), the horizontal limb of the diagonal band (Ch3), and in the sublenticular part of the basal forebrain (Ch4) were traced in high-resolution digitized histological sections, 3D reconstructed, and warped to the reference space of the MNI single subject brain. The superposition of the cytoarchitectonic maps in the MNI brain shows the intersubject variability of the various Ch compartments and their stereotaxic position relative to other brain structures. Both the right and left Ch4 regions showed significantly smaller volumes when age was considered as a covariate. Probabilistic maps of compartments of the basal forebrain magnocellular system are now available as an open source reference for correlation with fMRI, PET, and structural MRI data of the living human brain. PMID:18585468

  11. Nrf2 sensitizes prostate cancer cells to radiation via decreasing basal ROS levels.

    PubMed

    Liu, Min; Yao, Xu-Dong; Li, Wei; Geng, Jiang; Yan, Yang; Che, Jian-Ping; Xu, Yun-Fei; Zheng, Jun-Hua

    2015-01-01

    Androgen deprivation therapy (ADT) was reported to lower basal ROS level in prostate cancer (PCa) and to sensitize PCa to radiation. We aimed to seek for the underlying molecular mechanism and to develop novel additive treatments to ADT in this regard. We simulated human androgen milieu in vitro and tested the ROS level in PCa cells undergoing ADT. We also tested the Nrf2 level in PCa cells with or without ADT. Genetic and pharmaceutical upregulation of Nrf2 was applied in vitro and in vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without castration to investigate whether Nrf2 overexpression supplemented the effect of ADT in PCa. We first discovered that androgen deprivation increased basal ROS level in PCa cells with AR expression. We then found that genetic Nrf2 upregulation lowered basal ROS similar to ADT. Also, SFN sensitized PCa cell to radiation via upregulation of Nrf2. We then found that Nrf2 level in control TRAMP groups was lower than castration or SFN groups. The SFN treated TRAMP mice showed similar level of Nrf2 to castration. Genetic and pharmaceutical upregulation of Nrf2 lowered the ROS in PCa cells and sensitized PCa cells to radiation similar to ADT, implicating possible administration of SFN in place of ADT for PCa patients requiring radiotherapy. PMID:25728635

  12. WEE1 inhibition sensitizes basal breast cancer cells to TRAIL-induced apoptosis

    PubMed Central

    Garimella, Sireesha V; Rocca, Andrea; Lipkowitz, Stanley

    2011-01-01

    Tumor Necrosis Factor (TNF)-Related Apoptosis Inducing Ligand (TRAIL) is a member of the TNF super family and has been shown to induce apoptosis in many cancer cell lines but not in normal cells. Breast cancers can be divided into different subgroups based on the expression of estrogen and progesterone receptors, HER-2 amplification, or the lack of these three markers (known as triple-negative or basal-type breast cancer). Our group and others have shown previously that triple-negative breast cancer cell lines are sensitive to TRAIL while others are relatively resistant. In an earlier study, we reported that inhibition of WEE1, a cell cycle checkpoint regulator, causes increased cell death in breast cancer cell lines. In this study, we tested the effects of WEE1 inhibition on TRAIL-mediated apoptosis in breast cancer cell lines. Pre-treatment with WEE1 inhibitor or knockdown of WEE1 increased the toxicity of TRAIL in the basal/triple-negative breast cancer cell lines compared to WEE1 inhibitor or TRAIL treatment alone. The enhanced cell death is attributed to increased surface expression of death receptors, increased caspase activation which could be blocked by the pan-caspase inhibitor, Z-VAD-FMK, thereby rescuing cells from caspase-mediated apoptosis. The cell death was initiated primarily by caspase-8 since knockdown of caspase-8 and not of any other initiator caspases (i.e, caspase-2, -9, or -10) rescued cells from WEE1 inhibitor sensitized TRAIL-induced cell death. Taken together, the data suggest that the combination of WEE1 inhibitor and TRAIL could provide a novel combination for the treatment of basal/triple-negative breast cancer. PMID:22112940

  13. Characterization of basal pseudopod-like processes in ileal and colonic PYY cells

    PubMed Central

    Bohórquez, Diego V.; Chandra, Rashmi; Samsa, Leigh Ann; Vigna, Steven R.

    2014-01-01

    The peptide tyrosine tyrosine (PYY) is produced and secreted from L cells of the gastrointestinal mucosa. To study the anatomy and function of PYY-secreting L cells, we developed a transgenic PYY-green fluorescent protein mouse model. PYY-containing cells exhibited green fluorescence under UV light and were immunoreactive to antibodies against PYY and GLP-1 (glucagon-like peptide-1, an incretin hormone also secreted by L cells). PYY-GFP cells from 15 μm thick sections were imaged using confocal laser scanning microscopy and three-dimensionally (3D) reconstructed. Results revealed unique details of the anatomical differences between ileal and colonic PYY-GFP cells. In ileal villi, the apical portion of PYY cells makes minimal contact with the lumen of the gut. Long pseudopod-like basal processes extend from these cells and form an interface between the mucosal epithelium and the lamina propria. Some basal processes are up to 50 μm in length. Multiple processes can be seen protruding from one cell and these often have a terminus resembling a synapse that appears to interact with neighboring cells. In colonic crypts, PYY-GFP cells adopt a spindle-like shape and weave in between epithelial cells, while maintaining contact with the lumen and lamina propria. In both tissues, cytoplasmic granules containing the hormones PYY and GLP-1 are confined to the base of the cell, often filling the basal process. The anatomical arrangement of these structures suggests a dual function as a dock for receptors to survey absorbed nutrients and as a launching platform for hormone secretion in a paracrine fashion. PMID:21061049

  14. Focal hyperhidrosis secondary to eccrine naevus successfully treated with botulinum toxin type A.

    PubMed

    Lera, M; España, A; Idoate, M Á

    2015-08-01

    Eccrine naevus (EN) is a rare skin hamartoma included in the organoid group of epidermal naevi, histologically defined as focal hyperplasia and/or hypertrophy of eccrine glands. Clinically, EN usually presents as hyperhidrotic patches with no visible skin changes, frequently located on the forearms. The decision to treat EN or not usually depends on the grade of hyperhidrosis, but there is no therapeutic consensus because of the rarity of this condition. We present a case diagnosed as EN in an adult patient with severe localized hyperhidrosis, which was successfully treated with botulinum toxin. PMID:25816711

  15. PTCH mutations and deletions in patients with typical nevoid basal cell carcinoma syndrome and in patients with a suspected genetic predisposition to basal cell carcinoma: a French study

    PubMed Central

    Soufir, N; Gerard, B; Portela, M; Brice, A; Liboutet, M; Saiag, P; Descamps, V; Kerob, D; Wolkenstein, P; Gorin, I; Lebbe, C; Dupin, N; Crickx, B; Basset-Seguin, N; Grandchamp, B

    2006-01-01

    The patched (PTCH) mutation rate in nevoid basal cell carcinoma syndrome (NBCCS) reported in various studies ranges from 40 to 80%. However, few studies have investigated the role of PTCH in clinical conditions suggesting an inherited predisposition to basal cell carcinoma (BCC), although it has been suggested that PTCH polymorphisms could predispose to multiple BCC (MBCC). In this study, we therefore performed an exhaustive analysis of PTCH (mutations detection and deletion analysis) in 17 patients with the full complement of criteria for NBCCS (14 sporadic and three familial cases), and in 48 patients suspected of having a genetic predisposition to BCC (MBCC and/or age at diagnosis ⩽40 years and/or familial BCC). Eleven new germline alterations of the PTCH gene were characterised in 12 out of 17 patients harbouring the full complement of criteria for the syndrome (70%). These were frameshift mutations in five patients, nonsense mutations in five patients, a small inframe deletion in one patient, and a large germline deletion in another patient. Only one missense mutation (G774R) was found, and this was in a patient affected with MBCC, but without any other NBCCS criterion. We therefore suggest that patients harbouring the full complement of NBCCS criteria should as a priority be screened for PTCH mutations by sequencing, followed by a deletion analysis if no mutation is detected. In other clinical situations that suggest genetic predisposition to BCC, germline mutations of PTCH are not common. PMID:16909134

  16. Basal cell adenoma of the parotid gland: Cytological diagnosis of an uncommon tumor.

    PubMed

    Bhat, Amoolya; Rao, Madhuri; Geethamani, V; Shetty, Archana C

    2015-01-01

    Basal cell adenoma (BCA) is a rare benign epithelial tumor of the salivary gland, displaying monomorphic basaloid cells without a myxochondroid component, representing 1-3% of all salivary gland neoplasms seen predominantly in women over 50 years of age. It is uncommon in young adults. Cytodiagnosis of basaloid tumors chiefly basal cell adenoma of the salivary gland, is extremely challenging. The cytological differential diagnoses range from benign to malignant, neoplastic to non- neoplastic lesions. Histopathological examination is a must for definitive diagnosis, as these entities differ in prognosis and therapeutic aspects. We present a 22-years-old male with this uncommon diagnosis with a discussion on the role of cytological diagnosis. Fine needle aspiration cytology is a simple, minimally invasive method for the preoperative diagnosis of various types of neoplastic and non-neoplastic lesions. The knowledge of its pitfalls and limitations contributes to a more effective approach to treatment. PMID:26097318

  17. Basal Release of ATP: An Autocrine-Paracrine Mechanism for Cell Regulation

    PubMed Central

    Corriden, Ross; Insel, Paul A.

    2011-01-01

    Cells release adenosine triphosphate (ATP), which activates plasma membrane–localized P2X and P2Y receptors and thereby modulates cellular function in an autocrine or paracrine manner. Release of ATP and the subsequent activation of P2 receptors help establish the basal level of activation (sometimes termed “the set point”) for signal transduction pathways and regulate a wide array of responses that include tissue blood flow, ion transport, cell volume regulation, neuronal signaling, and host-pathogen interactions. Basal release and autocrine or paracrine responses to ATP are multifunctional and evolutionarily conserved, and they provide an economical means for the modulation of cell, tissue, and organismal biology. PMID:20068232

  18. Perineural Infiltration of Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma Without Clinical Features

    SciTech Connect

    Lin, Charles; Tripcony, Lee; Keller, Jacqui; Poulsen, Michael; Martin, Jarad; Jackson, James; Dickie, Graeme

    2012-01-01

    Purpose: To review the factors that influence outcome and patterns of relapse in patients with cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) with perineural infiltration (PNI) without clinical or radiologic features, treated with surgery and radiotherapy. Methods and Materials: Between 1991 and 2004, 222 patients with SCC or BCC with PNI on pathologic examination but without clinical or radiologic PNI features were identified. Charts were reviewed retrospectively and relevant data collected. All patients were treated with curative intent; all had radiotherapy, and most had surgery. The primary endpoint was 5-year relapse-free survival from the time of diagnosis. Results: Patients with SCC did significantly worse than those with BCC (5-year relapse-free survival, 78% vs. 91%; p < 0.01). Squamous cell carcinoma with PNI at recurrence did significantly worse than de novo in terms of 5-year local failure (40% vs. 19%; p < 0.01) and regional relapse (29% vs. 5%; p < 0.01). Depth of invasion was also a significant factor. Of the PNI-specific factors for SCC, focal PNI did significantly better than more-extensive PNI, but involved nerve diameter or presence of PNI at the periphery of the tumor were not significant factors. Conclusions: Radiotherapy in conjunction with surgery offers an acceptable outcome for cutaneous SCC and BCC with PNI. This study suggests that focal PNI is not an adverse feature.

  19. Basal p21 controls population heterogeneity in cycling and quiescent cell cycle states

    PubMed Central

    Overton, K. Wesley; Spencer, Sabrina L.; Noderer, William L.; Meyer, Tobias; Wang, Clifford L.

    2014-01-01

    Phenotypic heterogeneity within a population of genetically identical cells is emerging as a common theme in multiple biological systems, including human cell biology and cancer. Using live-cell imaging, flow cytometry, and kinetic modeling, we showed that two states—quiescence and cell cycling—can coexist within an isogenic population of human cells and resulted from low basal expression levels of p21, a Cyclin-dependent kinase (CDK) inhibitor (CKI). We attribute the p21-dependent heterogeneity in cell cycle activity to double-negative feedback regulation involving CDK2, p21, and E3 ubiquitin ligases. In support of this mechanism, analysis of cells at a point before cell cycle entry (i.e., before the G1/S transition) revealed a p21–CDK2 axis that determines quiescent and cycling cell states. Our findings suggest a mechanistic role for p21 in generating heterogeneity in both normal tissues and tumors. PMID:25267623

  20. Production of 3-D Airway Organoids From Primary Human Airway Basal Cells and Their Use in High-Throughput Screening.

    PubMed

    Hild, Marc; Jaffe, Aron B

    2016-01-01

    The ability of human airway basal cells to serve as progenitor cells in the conducting airway makes them an attractive target in a number of respiratory diseases associated with epithelial remodeling. This unit describes a protocol for the culture of 'bronchospheres', three-dimensional (3-D) organoids that are derived from primary human airway basal cells. Mature bronchospheres are composed of functional multi-ciliated cells, mucin-producing goblet cells, and airway basal cells. In contrast to existing methods used for the culture of well-differentiated human airway epithelial cells, bronchospheres do not require growth on a permeable support and can be cultured in 384-well assay plates. The system provides a mechanism for investigating the regulation of basal cell fate during airway epithelial morphogenesis, as well as a basis for studying the function of the human airway epithelium in high-throughput assays. © 2016 by John Wiley & Sons, Inc. PMID:27171795

  1. An unusual case report of basal cell adenoma: A Diagnostic Enchanter

    PubMed Central

    Rehani, Shweta; Mehendiratta, Monica; Kumra, Madhumani; Gupta, Ramakant; Jain, Kanu

    2014-01-01

    Oral lesions show a wide range of biologic behaviours. There are various lesions which may mimic others and present in such an unusual manner thus making them very difficult to diagnose clinico-pathologically. An accurate diagnosis is not only important for correct treatment planning but also for determination of prognosis. Thus, it is very important for a surgical pathologist to be aware of the various atypical presentations of the lesions. The present unusual case report of basal cell adenoma occurring on upper lip with frank areas of calcifications and abundant inspissated mucoid secretions is an example of one such case. BCA is an uncommon benign epithelial salivary gland neoplasm. It is one of the nine subcategories of salivary gland epithelial tumours according to WHO 2005 classification of salivary gland tumors. It is composed of basaloid cells organized with a prominent basal cell layer and distinct basement membrane-like structure and no myxochondroid stromal component as seen in pleomorphic adenomas. To our best knowledge, no case in English literature has been reported BCA with exuberant inspissated mucoid secretions and frank areas of calcifications to such a large extent and this is the first case to report the same. Key words: Basal cell adenoma, calcifications, diagnosis, inspissated mucoid secretions, surgical pathologist. PMID:25674334

  2. Tyrosine phosphorylation modulates store-operated calcium entry in cultured rat epididymal basal cells.

    PubMed

    Zuo, Wu-Lin; Du, Jian-Yang; Huang, Jie-Hong; Li, Sheng; Zhang, Geng; Chen, Si-Liang; Ruan, Ye-Chun; Cheng, Christopher H K; Zhou, Wen-Liang

    2011-04-01

    Store-operated calcium entry (SOCE) is essential for many cellular processes. In this study, we investigated modulation of SOCE by tyrosine phosphorylation in rat epididymal basal cells. The intracellular Ca(2+) ([Ca(2+)]i) measurement showed that SOCE occurred in rat epididymal basal cells by pretreating the cells with thapsigargin (Tg), the inhibitor of sarco-endoplasmic reticulum Ca(2+)-ATPase. To identify the role of Ca(2+) channels in this response, we examined the effects of transient receptor potential canonical channel blockers 2-aminoethoxydiphenyl borate (2-APB), 1-[β-[3-(4-methoxyphenyl)pro-poxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride(SKF96365), Gd(3+), and non-selective cation channel blocker Ni(2+) respectively on SOCE and found that these blockers could inhibit the Ca(2+) influx to different extent. Furthermore, we studied the regulation of SOCE by tyrosine kinase pathway. The inhibitor of tyrosine kinase genistein remarkably suppressed the SOCE response, whereas sodium orthovanadate, the inhibitor of tyrosine phosphatase, greatly enhanced it. The results suggest that tyrosine kinase pathway plays a significant role in the initiation of SOCE and positively modulates SOCE in epididymal basal cells. PMID:20857412

  3. GRHL2 coordinates regeneration of a polarized mucociliary epithelium from basal stem cells

    PubMed Central

    Gao, Xia; Bali, Aman S.; Randell, Scott H.

    2015-01-01

    Pseudostratified airway epithelium of the lung is composed of polarized ciliated and secretory cells maintained by basal stem/progenitor cells. An important question is how lineage choice and differentiation are coordinated with apical–basal polarity and epithelial morphogenesis. Our previous studies indicated a key integrative role for the transcription factor Grainyhead-like 2 (Grhl2). In this study, we present further evidence for this model using conditional gene deletion during the regeneration of airway epithelium and clonal organoid culture. We also use CRISPR/Cas9 genome editing in primary human basal cells differentiating into organoids and mucociliary epithelium in vitro. Loss of Grhl2 inhibits organoid morphogenesis and the differentiation of ciliated cells and reduces the expression of both notch and ciliogenesis genes (Mcidas, Rfx2, and Myb) with distinct Grhl2 regulatory sites. The genome editing of other putative target genes reveals roles for zinc finger transcription factor Znf750 and small membrane adhesion glycoprotein in promoting ciliogenesis and barrier function as part of a network of genes coordinately regulated by Grhl2. PMID:26527742

  4. Review of photodynamic therapy in actinic keratosis and basal cell carcinoma

    PubMed Central

    Ericson, Marica B; Wennberg, Ann-Marie; Larkö, Olle

    2008-01-01

    The number of non-melanoma skin cancers is increasing worldwide, and so also the demand for effective treatment modalities. Topical photodynamic therapy (PDT) using aminolaevulinic acid or its methyl ester has recently become good treatment options for actinic keratosis and basal cell carcinoma; especielly when treating large areas and areas with field cancerization. The cure rates are usually good, and the cosmetic outcomes excellent. The only major side effect reported is the pain experienced by the patients during treatment. This review covers the fundamental aspects of topical PDT and its application for treatment of actinic keratosis and basal cell carcinoma. Both potentials and limitations will be reviewed, as well as some recent development within the field. PMID:18728698

  5. Nevoid Basal Cell Carcinoma Syndrome: A Case Report and Review of Korean Cases

    PubMed Central

    Jung, Eun-Joo; Shin, Hyokeun; Baek, Jin-A; Leem, Dae-Ho; Ko, Seung-O

    2014-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is a rare autosomal genetic disease caused by a PTCH mutation. The disease is characterized by multiple basal cell carcinomas of the skin, multiple keratocystic odontogenic tumors (KCOTs) in the jaw, palmar and/or plantar pits, bifid ribs, ectopic calcification of the falx cerebri, and skeletal abnormalities. Early diagnosis is difficult in many cases because there may be a number of systemic symptoms. The purpose of this study is to report the case of a 12-year-old girl who was hospitalized with multiple KCOTs that occurred in the upper and lower jaws. Through characteristic clinical symptoms and radiologic findings, she was finally diagnosed as having NBCCS. This study also aims to organize the symptoms often observed in Korea using previously published case reports to provide useful information for the early diagnosis of NBCCS. PMID:27489849

  6. Complications of the naevoid basal cell carcinoma syndrome: results of a population based study.

    PubMed

    Evans, D G; Ladusans, E J; Rimmer, S; Burnell, L D; Thakker, N; Farndon, P A

    1993-06-01

    There are many potential complications which have been reported in association with the naevoid basal cell carcinoma syndrome. We have been able to show the relative frequencies of these problems in a population based study of 84 cases in the north west of England. The major complications of basal cell carcinomas and jaw cysts occur in over 90% of patients by 40 years of age, but may both occur before 10 years of age. Less well described complications are ovarian calcification or fibroma (24%), medulloblastoma (5%), cardiac fibroma (3%), cleft palate (5%), and ophthalmic abnormalities such as squint or cataract (26%). This study more clearly defines the possible complications of the syndrome and gives clearer guidelines for counselling and screening affected and at risk persons. PMID:8326488

  7. Review of Ocular Manifestations of Nevoid Basal Cell Carcinoma Syndrome: What an Ophthalmologist Needs to Know

    PubMed Central

    Chen, Judy J.; Sartori, Juliana; Aakalu, Vinay K.; Setabutr, Pete

    2015-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is a rare, autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs), odontogenic keratocysts, palmar and/or plantar pits, and ectopic calcifications of the falx cerebri. Myriad ophthalmologic findings are associated with NBCCS, including periocular BCCs, hypertelorism, strabismus, myelinated nerve fibers, and disorders of the retina and retinal pigment epithelium. We performed a literature search in PubMed for articles on the ophthalmologic manifestations of Gorlin syndrome, published between 1984 and 2014. Of 33 papers, 31 were included. Although Gorlin syndrome is due to mutations in a single gene, it displays variable phenotypic expressivity. Therefore, familiarity with this disorder across clinical specialties is necessary to avoid misdiagnosis. The ophthalmologist should be included in the multidisciplinary team for the management of Gorlin syndrome in order to prevent visual loss and improve the quality of life of these patients. PMID:26692711

  8. Superficial Basal Cell Carcinoma on the Face is a Diagnostic Challenge

    PubMed Central

    Singha, Joydeep; Patel, Naval

    2016-01-01

    Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer. The incidence of BCC is rising. The nodular, superficial spreading, and infiltrating variants are the three most commonly encountered types of BCC in descending order of prevalence. Superficial spreading basal cell carcinoma (SSBCC) accounts for 15-26% of all cases of BCC. It usually occurs on the trunk and upper extremities, but may be seen on the face. Surgical excision is the most commonly used treatment for BCC. Topical chemotherapy agents such as imiquimod or 5-fluorouracil (5-FU) may be various alternatives or adjuvants in the treatment of SSBCC. characteristically shows areas of uninvolved skin between tumor nests.[7] PMID:27057051

  9. Dynamic focus optical coherence tomography: feasibility for improved basal cell carcinoma investigation

    NASA Astrophysics Data System (ADS)

    Nasiri-Avanaki, M. R.; Aber, Ahmed; Hojjatoleslami, S. A.; Sira, Mano; Schofield, John B.; Jones, Carole; Podoleanu, A. Gh.

    2012-03-01

    Basal cell carcinoma (BCC) is the most common form of skin cancer. To improve the diagnostic accuracy, additional non-invasive methods of making a preliminary diagnosis have been sought. We have implemented an En-Face optical coherence tomography (OCT) for this study in which the dynamic focus was integrated into it. With the dynamic focus scheme, the coherence gate moves synchronously with the peak of confocal gate determined by the confocal interface optics. The transversal resolution is then conserved throughout the depth range and an enhanced signal is returned from all depths. The Basal Cell Carcinoma specimens were obtained from the eyelid a patient. The specimens under went analysis by DF-OCT imaging. We searched for remarkable features that were visualized by OCT and compared these findings with features presented in the histology slices.

  10. Giant Basal Cell Carcinoma: A 12-Year Follow-up Case Report.

    PubMed

    Jiménez-Hernández, Fabiola; Caballero-Centeno, Ana M; Barrera-Pérez, María; Ramos-Garibay, José A

    2016-01-01

    Giant basal cell carcinomas (GBCCs) are a strange and aggressive variety of basal cell carcinomas (BCCs); they are characterized by deep tissue invasion, rapid growth, high risk of metastasis, and a poor prognosis. GBCCs represent 0.4%-1% of all BCCs. The pathogenesis of GBCC is sometimes linked to a spontaneous mutation in the PTCH gene, mapped to the q22.33 locus of chromosome 9. The key factor in the development of GBCC, in at least 30% of the cases, is the delay in seeking medical attention (7.5 ± 3.1 years). This is associated to a poor socioeconomic level, deficient hygiene, mental illness, advanced age, and the fact that BCCs are painless lesions. The authors present a Mexican female with a 2-year ulcer diagnosed as a GBCC in the year 2000, its initial therapeutic approach, and her follow-up during the next 12 years. PMID:26332533

  11. Superficial Basal Cell Carcinoma on the Face is a Diagnostic Challenge.

    PubMed

    Singha, Joydeep; Patel, Naval

    2016-01-01

    Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer. The incidence of BCC is rising. The nodular, superficial spreading, and infiltrating variants are the three most commonly encountered types of BCC in descending order of prevalence. Superficial spreading basal cell carcinoma (SSBCC) accounts for 15-26% of all cases of BCC. It usually occurs on the trunk and upper extremities, but may be seen on the face. Surgical excision is the most commonly used treatment for BCC. Topical chemotherapy agents such as imiquimod or 5-fluorouracil (5-FU) may be various alternatives or adjuvants in the treatment of SSBCC. characteristically shows areas of uninvolved skin between tumor nests.[7]. PMID:27057051

  12. Airway basal cells of healthy smokers express an embryonic stem cell signature relevant to lung cancer.

    PubMed

    Shaykhiev, Renat; Wang, Rui; Zwick, Rachel K; Hackett, Neil R; Leung, Roland; Moore, Malcolm A S; Sima, Camelia S; Chao, Ion Wa; Downey, Robert J; Strulovici-Barel, Yael; Salit, Jacqueline; Crystal, Ronald G

    2013-09-01

    Activation of the human embryonic stem cell (hESC) signature genes has been observed in various epithelial cancers. In this study, we found that the hESC signature is selectively induced in the airway basal stem/progenitor cell population of healthy smokers (BC-S), with a pattern similar to that activated in all major types of human lung cancer. We further identified a subset of 6 BC-S hESC genes, whose coherent overexpression in lung adenocarcinoma (AdCa) was associated with reduced lung function, poorer differentiation grade, more advanced tumor stage, remarkably shorter survival, and higher frequency of TP53 mutations. BC-S shared with hESC and a considerable subset of lung carcinomas a common TP53 inactivation molecular pattern which strongly correlated with the BC-S hESC gene expression. These data provide transcriptome-based evidence that smoking-induced reprogramming of airway BC toward the hESC-like phenotype might represent a common early molecular event in the development of aggressive lung carcinomas in humans. PMID:23857717

  13. Basal Cell Carcinoma: Pathogenesis, Epidemiology, Clinical Features, Diagnosis, Histopathology, and Management

    PubMed Central

    Marzuka, Alexander G.; Book, Samuel E.

    2015-01-01

    Basal cell carcinoma (BCC) is the most common malignancy. Exposure to sunlight is the most important risk factor. Most, if not all, cases of BCC demonstrate overactive Hedgehog signaling. A variety of treatment modalities exist and are selected based on recurrence risk, importance of tissue preservation, patient preference, and extent of disease. The pathogenesis, epidemiology, clinical features, diagnosis, histopathology, and management of BCC will be discussed in this review. PMID:26029015

  14. Nevoid Basal Cell Carcinoma Syndrome - Clinical and Radiological Findings of Three Cases

    PubMed Central

    Ali, Ibrahim K; Karjodkar, Freny R; Sansare, Kaustubh; Salve, Prashant; Goyal, Shikha

    2016-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder, characterized by skeletal anomalies and multiple keratocystic odontogenic tumors of the jaws. The skeletal anomalies of this syndrome are mandibular prognathism, bossing of frontal and parietal bones, high-arched palate, and bifid rib. We report three cases with NBCCS, emphasizing the clinical and radiographic findings, the importance of the early diagnosis of NBCCS, and a preventive multidisciplinary approach in the management of NBCCS.

  15. Self-treatment of a basal cell carcinoma with "black and yellow salve".

    PubMed

    Osswald, Sandra S; Elston, Dirk M; Farley, Mary F; Alberti, John G; Cordero, Steven C; Kalasinsky, Victor F

    2005-09-01

    Patients may seek "alternative" or "non-traditional" therapies for dermatologic problems, frequently in search of a miraculous cure. However, many of these medicaments contain unknown compounds with questionable benefit and a potential for significant harm. We describe a patient who developed a large ulceration on her nose after applying "black and yellow salves" obtained from Mexico in an attempt to self-treat a basal cell carcinoma. PMID:16112364

  16. 980nm laser for difficult-to-treat basal cell carcinoma

    NASA Astrophysics Data System (ADS)

    Derjabo, A. D.; Cema, I.; Lihacova, I.; Derjabo, L.

    2013-06-01

    Begin basal cell carcinoma (BCC) is most common skin cancer over the world. There are around 20 modalities for BCC treatment. Laser surgery is uncommon option. We demonstrate our long term follow up results. Aim: To evaluate long term efficacy of a 980nm diode laser for the difficult-to-treat basal cell carcinoma. Materials and Methods: 167 patients with 173 basal cell carcinoma on the nose were treated with a 980 nm diode laser from May 1999 till May 2005 at Latvian Oncology center. All tumors were morphologically confirmed. 156 patients were followed for more than 5 years. Results: The lowest recurrence rate was observed in cases of superficial BCC, diameter<6mm bet the highest recurrence rate was in cases of infiltrative BCC and nodular recurrent BCC. Conclusions: 980 nm diode laser is useful tool in dermatology with high long term efficacy, good acceptance by the patients and good cosmetics results.

  17. Type 2 Fibroblast Growth Factor Receptor Signaling Preserves Stemness and Prevents Differentiation of Prostate Stem Cells from the Basal Compartment.

    PubMed

    Huang, Yanqing; Hamana, Tomoaki; Liu, Junchen; Wang, Cong; An, Lei; You, Pan; Chang, Julia Y F; Xu, Jianming; Jin, Chengliu; Zhang, Zhongying; McKeehan, Wallace L; Wang, Fen

    2015-07-17

    Prostate stem cells (P-SCs) are capable of giving rise to all three lineages of prostate epithelial cells, which include basal, luminal, and neuroendocrine cells. Two types of P-SCs have been identified in both human and mouse adult prostates based on prostasphere or organoid cultures, cell lineage tracing, renal capsule implantation, and expression of luminal- and basal-specific proteins. The sphere-forming P-SCs are from the basal cell compartment that express P63, and are therefore designated as basal P-SCs (P-bSCs). Luminal P-SCs (P-lSCs) express luminal cytokeratins and Nkx3.1. Herein, we report that the type 2 FGF receptor (FGFR2) signaling axis is crucial for preserving stemness and preventing differentiation of P-bSCs. FGFR2 signaling mediated by FGFR substrate 2α (FRS2α) is indispensable for formation and maintenance of prostaspheres derived from P63(+) P-bSCs. Ablation of Fgfr2 in P63(+) cells in vitro causes the disintegration of prostaspheres. Ablation of Fgfr2 in vivo reduces the number of P63-expressing basal cells and enriches luminal cells. This suggests a basal stem cell-to-luminal cell differentiation. In addition, ablation of Fgfr2 in P63(+) cells causes defective postnatal development of the prostate. Therefore, the data indicate that FGFR2 signaling is critical for preserving stemness and preventing differentiation of P-bSCs. PMID:26032417

  18. G protein–dependent basal and evoked endothelial cell vWF secretion

    PubMed Central

    Rusu, Luiza; Andreeva, Alexandra; Visintine, David J.; Kim, Kyungho; Vogel, Stephen M.; Stojanovic-Terpo, Aleksandra; Chernaya, Olga; Liu, Guoquan; Bakhshi, Farnaz R.; Haberichter, Sandra L.; Iwanari, Hiroko; Kusano-Arai, Osamu; Suzuki, Nobuchika; Hamakubo, Takao; Kozasa, Tohru; Cho, Jaehyung; Du, Xiaoping

    2014-01-01

    von Willebrand factor (vWF) secretion by endothelial cells (ECs) is essential for hemostasis and thrombosis; however, the molecular mechanisms are poorly understood. Interestingly, we observed increased bleeding in EC-Gα13−/−;Gα12−/− mice that could be normalized by infusion of human vWF. Blood from Gα12−/− mice exhibited significantly reduced vWF levels but normal vWF multimers and impaired laser-induced thrombus formation, indicating that Gα12 plays a prominent role in EC vWF secretion required for hemostasis and thrombosis. In isolated buffer-perfused mouse lungs, basal vWF levels were significantly reduced in Gα12−/−, whereas thrombin-induced vWF secretion was defective in both EC-Gαq−/−;Gα11−/− and Gα12−/− mice. Using siRNA in cultured human umbilical vein ECs and human pulmonary artery ECs, depletion of Gα12 and soluble N-ethylmaleimide-sensitive-fusion factor attachment protein α (α-SNAP), but not Gα13, inhibited both basal and thrombin-induced vWF secretion, whereas overexpression of activated Gα12 promoted vWF secretion. In Gαq, p115 RhoGEF, and RhoA-depleted human umbilical vein ECs, thrombin-induced vWF secretion was reduced by 40%, whereas basal secretion was unchanged. Finally, in vitro binding assays revealed that Gα12 N-terminal residues 10-15 mediated the binding of Gα12 to α-SNAP, and an engineered α-SNAP binding-domain minigene peptide blocked basal and evoked vWF secretion. Discovery of obligatory and complementary roles of Gα12 and Gαq/11 in basal vs evoked EC vWF secretion may provide promising new therapeutic strategies for treatment of thrombotic disease. PMID:24081657

  19. CAMSAP3 orients the apical-to-basal polarity of microtubule arrays in epithelial cells.

    PubMed

    Toya, Mika; Kobayashi, Saeko; Kawasaki, Miwa; Shioi, Go; Kaneko, Mari; Ishiuchi, Takashi; Misaki, Kazuyo; Meng, Wenxiang; Takeichi, Masatoshi

    2016-01-12

    Polarized epithelial cells exhibit a characteristic array of microtubules that are oriented along the apicobasal axis of the cells. The minus-ends of these microtubules face apically, and the plus-ends face toward the basal side. The mechanisms underlying this epithelial-specific microtubule assembly remain unresolved, however. Here, using mouse intestinal cells and human Caco-2 cells, we show that the microtubule minus-end binding protein CAMSAP3 (calmodulin-regulated-spectrin-associated protein 3) plays a pivotal role in orienting the apical-to-basal polarity of microtubules in epithelial cells. In these cells, CAMSAP3 accumulated at the apical cortices, and tethered the longitudinal microtubules to these sites. Camsap3 mutation or depletion resulted in a random orientation of these microtubules; concomitantly, the stereotypic positioning of the nucleus and Golgi apparatus was perturbed. In contrast, the integrity of the plasma membrane was hardly affected, although its structural stability was decreased. Further analysis revealed that the CC1 domain of CAMSAP3 is crucial for its apical localization, and that forced mislocalization of CAMSAP3 disturbs the epithelial architecture. These findings demonstrate that apically localized CAMSAP3 determines the proper orientation of microtubules, and in turn that of organelles, in mature mammalian epithelial cells. PMID:26715742

  20. Microelectrode bioimpedance analysis distinguishes basal and claudin-low subtypes of triple negative breast cancer cells.

    PubMed

    Srinivasaraghavan, Vaishnavi; Strobl, Jeannine; Agah, Masoud

    2015-08-01

    Triple negative breast cancer (TNBC) is highly aggressive and has a poor prognosis when compared to other molecular subtypes. In particular, the claudin-low subtype of TNBC exhibits tumor-initiating/cancer stem cell like properties. Here, we seek to find new biomarkers to discriminate different forms of TNBC by characterizing their bioimpedance. A customized bioimpedance sensor with four identical branched microelectrodes with branch widths adjusted to accommodate spreading of individual cells was fabricated on silicon and pyrex/glass substrates. Cell analyses were performed on the silicon devices which showed somewhat improved inter-electrode and intra-device reliability. We performed detailed analysis of the bioimpedance spectra of four TNBC cell lines, comparing the peak magnitude, peak frequency and peak phase angle between claudin-low TNBC subtype represented by MDA-MB-231 and Hs578T with that of two basal cells types, the TNBC MDA-MB-468, and an immortalized non-malignant basal breast cell line, MCF-10A. The claudin-low TNBC cell lines showed significantly higher peak frequencies and peak phase angles than the properties might be useful in distinguishing the clinically significant claudin-low subtype of TNBC. PMID:26216474

  1. The basal chorionic trophoblast cell layer: An emerging coordinator of placenta development.

    PubMed

    Walentin, Katharina; Hinze, Christian; Schmidt-Ott, Kai M

    2016-03-01

    During gestation, fetomaternal exchange occurs in the villous tree (labyrinth) of the placenta. Development of this structure depends on tightly coordinated cellular processes of branching morphogenesis and differentiation of specialized trophoblast cells. The basal chorionic trophoblast (BCT) cell layer that localizes next to the chorioallantoic interface is of critical importance for labyrinth morphogenesis in rodents. Gcm1-positive cell clusters within this layer initiate branching morphogenesis thereby guiding allantoic fetal blood vessels towards maternal blood sinuses. Later these cells differentiate and contribute to the syncytiotrophoblast of the fetomaternal barrier. Additional cells within the BCT layer sustain continued morphogenesis, possibly through a repopulating progenitor population. Several mouse mutants highlight the importance of a structurally intact BCT epithelium, and a growing number of studies addresses its patterning and epithelial architecture. Here, we review and discuss emerging concepts in labyrinth development focussing on the biology of the BCT cell layer. PMID:26778584

  2. Basal-like breast cancer cells induce phenotypic and genomic changes in macrophages.

    PubMed

    Stewart, Delisha A; Yang, Yinmeng; Makowski, Liza; Troester, Melissa A

    2012-06-01

    Basal-like breast cancer (BBC) is an aggressive subtype of breast cancer that has no biologically targeted therapy. The interactions of BBCs with stromal cells are important determinants of tumor biology, with inflammatory cells playing well-recognized roles in cancer progression. Despite the fact that macrophage-BBC communication is bidirectional, important questions remain about how BBCs affect adjacent immune cells. This study investigated monocyte-to-macrophage differentiation and polarization and gene expression in response to coculture with basal-like versus luminal breast cancer cells. Changes induced by coculture were compared with changes observed under classical differentiation and polarization conditions. Monocytes (THP-1 cells) exposed to BBC cells in coculture had altered gene expression with upregulation of both M1 and M2 macrophage markers. Two sets of M1 and M2 markers were selected from the PCR profiles and used for dual immunofluorescent staining of BBC versus luminal cocultured THP-1s, and cancer-adjacent, benign tissue sections from patients diagnosed with BBCs or luminal breast cancer, confirming the differential expression patterns. Relative to luminal breast cancers, BBCs also increased differentiation of monocytes to macrophages and stimulated macrophage migration. Consistent with these changes in cellular phenotype, a distinct pattern of cytokine secretion was evident in macrophage-BBC cocultures, including upregulation of NAP-2, osteoprotegerin, MIG, MCP-1, MCP-3, and interleukin (IL)-1β. Application of IL-1 receptor antagonist (IL-1RA) to cocultures attenuated BBC-induced macrophage migration. These data contribute to an understanding of the BBC-mediated activation of the stromal immune response, implicating specific cytokines that are differentially expressed in basal-like microenvironments and suggesting plausible targets for modulating immune responses to BBCs. PMID:22532586

  3. Human skeletal myotubes display a cell-autonomous circadian clock implicated in basal myokine secretion

    PubMed Central

    Perrin, Laurent; Loizides-Mangold, Ursula; Skarupelova, Svetlana; Pulimeno, Pamela; Chanon, Stephanie; Robert, Maud; Bouzakri, Karim; Modoux, Christine; Roux-Lombard, Pascale; Vidal, Hubert; Lefai, Etienne; Dibner, Charna

    2015-01-01

    Objective Circadian clocks are functional in all light-sensitive organisms, allowing an adaptation to the external world in anticipation of daily environmental changes. In view of the potential role of the skeletal muscle clock in the regulation of glucose metabolism, we aimed to characterize circadian rhythms in primary human skeletal myotubes and investigate their roles in myokine secretion. Methods We established a system for long-term bioluminescence recording in differentiated human myotubes, employing lentivector gene delivery of the Bmal1-luciferase and Per2-luciferase core clock reporters. Furthermore, we disrupted the circadian clock in skeletal muscle cells by transfecting siRNA targeting CLOCK. Next, we assessed the basal secretion of a large panel of myokines in a circadian manner in the presence or absence of a functional clock. Results Bioluminescence reporter assays revealed that human skeletal myotubes, synchronized in vitro, exhibit a self-sustained circadian rhythm, which was further confirmed by endogenous core clock transcript expression. Moreover, we demonstrate that the basal secretion of IL-6, IL-8 and MCP-1 by synchronized skeletal myotubes has a circadian profile. Importantly, the secretion of IL-6 and several additional myokines was strongly downregulated upon siClock-mediated clock disruption. Conclusions Our study provides for the first time evidence that primary human skeletal myotubes possess a high-amplitude cell-autonomous circadian clock, which could be attenuated. Furthermore, this oscillator plays an important role in the regulation of basal myokine secretion by skeletal myotubes. PMID:26629407

  4. Basal Cell Adenoma with Perplexity in Diagnosis – A Case Report

    PubMed Central

    Rehani, Shweta; Mathias, Yulia; Wadhwa, Manish

    2016-01-01

    Every salivary gland tumour irrespective of its benign or malignant nature or occurrence, exhibits certain unique and overlapping histopathologic features. Basal Cell Adenoma (BCA) is a rare salivary gland tumour and hence it becomes our responsibility to report every case with unique histopathologic features so that it can add to our present knowledge of this lesion. Often, the pathologists experience difficulty while diagnosing lesions like BCA which contain basaloid cells due to its similarity with other lesions of similar histological appearance. Hence, this paper discusses a case of BCA with rare histopathologic features along with the possible differential diagnosis. PMID:27135016

  5. A colonization of basal cell carcinoma by malignant melanoma in situ resembling a malignant basomelanocytic tumor.

    PubMed

    Goeser, Megan; DiMaio, Dominick J

    2014-11-01

    We report a case of colonization of basal cell carcinoma (BCC) by malignant melanoma in situ (MIS) simulating a malignant basomelanocytic tumor. A biopsy of a pigmented lesion present on an 83-year-old man's scalp displayed intimate admixing of basaloid and melanocytic cells. This seemingly inseparable combination of BCC and neoplastic melanocytes has been referred to as a malignant basomelanocytic tumor. However, our case also displays an adjacent component of MIS, thus favoring colonization of BCC by MIS as the etiology. To our knowledge, this is the third case report of colonization of BCC by MIS resembling a malignant basomelanocytic tumor. PMID:24752214

  6. Citrus consumption and risk of basal cell carcinoma and squamous cell carcinoma of the skin.

    PubMed

    Wu, Shaowei; Cho, Eunyoung; Feskanich, Diane; Li, Wen-Qing; Sun, Qi; Han, Jiali; Qureshi, Abrar A

    2015-10-01

    Animal experiments have demonstrated the photocarcinogenic properties of furocoumarins, a group of naturally occurring chemicals that are rich in citrus products. We conducted a prospective study for citrus consumption and risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin based on data from 41530 men in the Health Professionals Follow-up Study (1986-2010) and 63759 women in the Nurses' Health Study (1984-2010) who were free of cancers at baseline. Over 24-26 years of follow-up, we documented 20840 incident BCCs and 3544 incident SCCs. Compared to those who consumed citrus products less than twice per week, the pooled multivariable-adjusted hazard ratios were 1.03 [95% confidence interval (95% CI): 0.99-1.08] for BCC and 1.14 (95% CI: 1.00-1.30) for SCC for those who consumed two to four times per week, 1.06 (95% CI: 1.01-1.11) for BCC and 1.15 (95% CI: 1.02-1.28) for SCC for five to six times per week, 1.11 (95% CI: 1.06-1.16) for BCC and 1.22 (95% CI: 1.08-1.37) for SCC for once to 1.4 times per day and 1.16 (95% CI: 1.09-1.23) for BCC and 1.21 (95% Cl: 1.06-1.38) for SCC for 1.5 times per day or more (P trend = 0.001 for BCC and 0.04 for SCC). In contrast, consumption of non-citrus fruit and juice appeared to be inversely associated with risk of BCC and SCC. Our findings support positive associations between citrus consumption and risk of cutaneous BCC and SCC in two cohorts of men and women, and call for further investigations to better understand the potential photocarcinogenesis associated with dietary intakes. PMID:26224304

  7. PKC activation sensitizes basal-like breast cancer cell lines to Smac mimetics

    PubMed Central

    Cornmark, L; Holmgren, C; Masoumi, K; Larsson, C

    2016-01-01

    There is a need for novel strategies to initiate cancer cell death. One approach is the use of Smac mimetics, which antagonize inhibitor of apoptosis proteins (IAPs). Recent studies have shown that combinations of Smac mimetics such as LBW242 or LCL161 in combination with chemotherapeutic agents increase cancer cell death. Here we show that the protein kinase C (PKC) activator TPA together with the Smac mimetic LBW242 induces cell death in two basal breast cancer cell lines (MDA-MB-468 and BT-549) that are resistant to Smac mimetic as single agent. Ten other LBW242-insensitive cancer cell lines were not influenced by the TPA+LBW242 combination. The TPA+LBW242 effect was suppressed by the PKC inhibitor GF109203X, indicating dependence on PKC enzymatic activity. The PKC effect was mediated via increased synthesis and release of TNFα, which can induce death in the presence of Smac mimetics. The cell death, coinciding with caspase-3 cleavage, was suppressed by caspase inhibition and preceded by the association of RIP1 with caspase-8, as seen in complex II formation. Smac mimetics, but not TPA, induced the non-canonical NF-κB pathway in both MDA-MB-231 and MDA-MB-468 cells. Blocking the canonical NF-κB pathway suppressed TPA induction of TNFα in MDA-MB-468 cells whereas isolated downregulation of either the canonical or non-canonical pathways did not abolish the Smac mimetic induction of the NF-κB driven genes TNFα and BIRC3 in MDA-MB-231 cells although the absolute levels were suppressed. A combined downregulation of the canonical and non-canonical pathways further suppressed TNFα levels and inhibited Smac mimetic-mediated cell death. Our data suggest that in certain basal breast cancer cell lines co-treatment of TPA with a Smac mimetic induces cell death highlighting the potential of using these pathways as molecular targets for basal-like breast cancers. PMID:27551497

  8. Arecoline decreases interleukin-6 production and induces apoptosis and cell cycle arrest in human basal cell carcinoma cells

    SciTech Connect

    Huang, Li-Wen; Hsieh, Bau-Shan; Cheng, Hsiao-Ling; Hu, Yu-Chen; Chang, Wen-Tsan; Chang, Kee-Lung

    2012-01-15

    Arecoline, the most abundant areca alkaloid, has been reported to decrease interleukin-6 (IL-6) levels in epithelial cancer cells. Since IL-6 overexpression contributes to the tumorigenic potency of basal cell carcinoma (BCC), this study was designed to investigate whether arecoline altered IL-6 expression and its downstream regulation of apoptosis and the cell cycle in cultured BCC-1/KMC cells. BCC-1/KMC cells and a human keratinocyte cell line, HaCaT, were treated with arecoline at concentrations ranging from 10 to 100 μg/ml, then IL-6 production and expression of apoptosis- and cell cycle progress-related factors were examined. After 24 h exposure, arecoline inhibited BCC-1/KMC cell growth and decreased IL-6 production in terms of mRNA expression and protein secretion, but had no effect on HaCaT cells. Analysis of DNA fragmentation and chromatin condensation showed that arecoline induced apoptosis of BCC-1/KMC cells in a dose-dependent manner, activated caspase-3, and decreased expression of the anti-apoptotic protein Bcl-2. In addition, arecoline induced progressive and sustained accumulation of BCC-1/KMC cells in G2/M phase as a result of reducing checkpoint Cdc2 activity by decreasing Cdc25C phosphatase levels and increasing p53 levels. Furthermore, subcutaneous injection of arecoline led to decreased BCC-1/KMC tumor growth in BALB/c mice by inducing apoptosis. This study demonstrates that arecoline has potential for preventing BCC tumorigenesis by reducing levels of the tumor cell survival factor IL-6, increasing levels of the tumor suppressor factor p53, and eliciting cell cycle arrest, followed by apoptosis. Highlights: ► Arecoline has potential to prevent against basal cell carcinoma tumorigenesis. ► It has more effectiveness on BCC as compared with a human keratinocyte cell line. ► Mechanisms involved including reducing tumor cells’ survival factor IL-6, ► Decreasing Cdc25C phosphatase, enhancing tumor suppressor factor p53, ► Eliciting G2/M

  9. By promoting cell differentiation, miR-100 sensitizes basal-like breast cancer stem cells to hormonal therapy

    PubMed Central

    Cargnelutti, Marilisa; Iovino, Flora; Callari, Maurizio; Cimino, Daniela; Todaro, Matilde; Mangiapane, Laura Rosa; Giammona, Alessandro; Cordova, Adriana; Montemurro, Filippo; Taverna, Daniela; Daidone, Maria Grazia

    2015-01-01

    Basal-like breast cancer is an aggressive tumor subtype with a poor response to conventional therapies. Tumor formation and relapse are sustained by a cell subset of Breast Cancer Stem Cells (BrCSCs). Here we show that miR-100 inhibits maintenance and expansion of BrCSCs in basal-like cancer through Polo-like kinase1 (Plk1) down-regulation. Moreover, miR-100 favors BrCSC differentiation, converting a basal like phenotype into luminal. It induces the expression of a functional estrogen receptor (ER) and renders basal-like BrCSCs responsive to hormonal therapy. The key role played by miR-100 in breast cancer free-survival is confirmed by the analysis of a cohort of patients’ tumors, which shows that low expression of miR-100 is a negative prognostic factor and is associated with gene signatures of high grade undifferentiated tumors. Our findings indicate a new possible therapeutic strategy, which could make aggressive breast cancers responsive to standard treatments. PMID:25537513

  10. Preparation of primary myogenic precursor cell/myoblast cultures from basal vertebrate lineages.

    PubMed

    Froehlich, Jacob Michael; Seiliez, Iban; Gabillard, Jean-Charles; Biga, Peggy R

    2014-01-01

    Due to the inherent difficulty and time involved with studying the myogenic program in vivo, primary culture systems derived from the resident adult stem cells of skeletal muscle, the myogenic precursor cells (MPCs), have proven indispensible to our understanding of mammalian skeletal muscle development and growth. Particularly among the basal taxa of Vertebrata, however, data are limited describing the molecular mechanisms controlling the self-renewal, proliferation, and differentiation of MPCs. Of particular interest are potential mechanisms that underlie the ability of basal vertebrates to undergo considerable postlarval skeletal myofiber hyperplasia (i.e. teleost fish) and full regeneration following appendage loss (i.e. urodele amphibians). Additionally, the use of cultured myoblasts could aid in the understanding of regeneration and the recapitulation of the myogenic program and the differences between them. To this end, we describe in detail a robust and efficient protocol (and variations therein) for isolating and maintaining MPCs and their progeny, myoblasts and immature myotubes, in cell culture as a platform for understanding the evolution of the myogenic program, beginning with the more basal vertebrates. Capitalizing on the model organism status of the zebrafish (Danio rerio), we report on the application of this protocol to small fishes of the cyprinid clade Danioninae. In tandem, this protocol can be utilized to realize a broader comparative approach by isolating MPCs from the Mexican axolotl (Ambystoma mexicanum) and even laboratory rodents. This protocol is now widely used in studying myogenesis in several fish species, including rainbow trout, salmon, and sea bream(1-4). PMID:24835774

  11. Glucose Enhances Basal or Melanocortin-Induced cAMP-Response Element Activity in Hypothalamic Cells.

    PubMed

    Breit, Andreas; Wicht, Kristina; Boekhoff, Ingrid; Glas, Evi; Lauffer, Lisa; Mückter, Harald; Gudermann, Thomas

    2016-07-01

    Melanocyte-stimulating hormone (MSH)-induced activation of the cAMP-response element (CRE) via the CRE-binding protein in hypothalamic cells promotes expression of TRH and thereby restricts food intake and increases energy expenditure. Glucose also induces central anorexigenic effects by acting on hypothalamic neurons, but the underlying mechanisms are not completely understood. It has been proposed that glucose activates the CRE-binding protein-regulated transcriptional coactivator 2 (CRTC-2) in hypothalamic neurons by inhibition of AMP-activated protein kinases (AMPKs), but whether glucose directly affects hypothalamic CRE activity has not yet been shown. Hence, we dissected effects of glucose on basal and MSH-induced CRE activation in terms of kinetics, affinity, and desensitization in murine, hypothalamic mHypoA-2/10-CRE cells that stably express a CRE-dependent reporter gene construct. Physiologically relevant increases in extracellular glucose enhanced basal or MSH-induced CRE-dependent gene transcription, whereas prolonged elevated glucose concentrations reduced the sensitivity of mHypoA-2/10-CRE cells towards glucose. Glucose also induced CRCT-2 translocation into the nucleus and the AMPK activator metformin decreased basal and glucose-induced CRE activity, suggesting a role for AMPK/CRTC-2 in glucose-induced CRE activation. Accordingly, small interfering RNA-induced down-regulation of CRTC-2 expression decreased glucose-induced CRE-dependent reporter activation. Of note, glucose also induced expression of TRH, suggesting that glucose might affect the hypothalamic-pituitary-thyroid axis via the regulation of hypothalamic CRE activity. These findings significantly advance our knowledge about the impact of glucose on hypothalamic signaling and suggest that TRH release might account for the central anorexigenic effects of glucose and could represent a new molecular link between hyperglycaemia and thyroid dysfunction. PMID:27144291

  12. Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome

    SciTech Connect

    Kimonis, V.E.; Yang, M.L.; Bale, S.J.

    1997-03-31

    Nevoid basal cell carcinoma syndrome (NBCC; Gorlin syndrome), an autosomal dominant disorder linked to 9q22.3-q31, and caused by mutations in PTC, the human homologue of the Drosophila patched gene, comprises multiple basal cell carcinomas, keratocysts of the jaw, palmar/plantar pits, spine and rib anomalies and calcification of the falx cerebri. We reviewed the findings on 105 affected individuals examined at the NIH since 1985. The data included 48 males and 57 females ranging in age from 4 months to 87 years. Eighty percent of whites (71/90) and 38% (5/13) of African-Americans had at least one basal cell carcinoma (BCC), with the first tumor occurring at a mean age of 23 (median 20) years and 21 (median 20) years, respectively. Excluding individuals exposed to radiation therapy, the number of BCCs ranged from 1 to >1,000 (median 8) and 1 to 3 (median 2), respectively, in the 2 groups. Jaw cysts occurred in 78/105 (74%) with the first tumor occurring in 80% by the age of 20 years. The number of total jaw cysts ranged from 1 to 28 (median 3). Palmar pits and plantar pits were seen in 87%. Ovarian fibromas were diagnosed by ultrasound in 9/52 (17%) at a mean age of 30 years. Medulloblastoma occurred in 4 patients at a mean age of 2.3 years. Three patients had cleft lip or palate. Physical findings include {open_quotes}coarse face{close_quotes} in 54%, relative macrocephaly in 50%, hypertelorism in 42%, frontal bossing in 27%, pectus deformity in 13%, and Sprengel deformity in 11%. This study delineates the frequency of the clinical and radiological anomalies in NBCC in a large population of US patients and discusses guidelines for diagnosis and management. 48 refs., 3 figs., 5 tabs.

  13. Facial Basal Cell Carcinoma Treated with Topical 5% Imiquimod Cream with Dermoscopic Evaluation.

    PubMed

    Singal, Archana; Daulatabad, Deepashree; Pandhi, Deepika; Arora, V K

    2016-01-01

    Basal cell carcinoma (BCC) is the most common skin cancer worldwide. Surgical excision is considered to be the primary therapeutic modality wherever possible. For inoperable cases, 5% imiquimod seems to be a good alternative. We present two cases of nodular pigmented BCCs on the face in elderly women successfully treated with 5% imiquimod cream application resulting in complete clinical clearance of lesion as well as on histology and dermatoscopy. There was no recurrence of the lesion on 2 years follow-up for the first and 1.5 years for the second patient. PMID:27398014

  14. Facial Basal Cell Carcinoma Treated with Topical 5% Imiquimod Cream with Dermoscopic Evaluation

    PubMed Central

    Singal, Archana; Daulatabad, Deepashree; Pandhi, Deepika; Arora, VK

    2016-01-01

    Basal cell carcinoma (BCC) is the most common skin cancer worldwide. Surgical excision is considered to be the primary therapeutic modality wherever possible. For inoperable cases, 5% imiquimod seems to be a good alternative. We present two cases of nodular pigmented BCCs on the face in elderly women successfully treated with 5% imiquimod cream application resulting in complete clinical clearance of lesion as well as on histology and dermatoscopy. There was no recurrence of the lesion on 2 years follow-up for the first and 1.5 years for the second patient. PMID:27398014

  15. Analysis and diagnosis of basal cell carcinoma (BCC) via infrared imaging

    NASA Astrophysics Data System (ADS)

    Flores-Sahagun, J. H.; Vargas, J. V. C.; Mulinari-Brenner, F. A.

    2011-09-01

    In this work, a structured methodology is proposed and tested through infrared imaging temperature measurements of a healthy control group to establish expected normality ranges and of basal cell carcinoma patients (a type of skin cancer) previously diagnosed through biopsies of the affected regions. A method of conjugated gradients is proposed to compare measured dimensionless temperature difference values (Δ θ) between two symmetric regions of the patient's body, that takes into account the skin, the surrounding ambient and the individual core temperatures and doing so, the limitation of the results interpretation for different individuals become simple and nonsubjective. The range of normal temperatures in different regions of the body for seven healthy individuals was determined, and admitting that the human skin exhibits a unimodal normal distribution, the normal range for each region was considered to be the mean dimensionless temperature difference plus/minus twice the standard deviation of the measurements (Δθ±2σ) in order to represent 95% of the population. Eleven patients with previously diagnosed basal cell carcinoma through biopsies were examined with the method, which was capable of detecting skin abnormalities in all cases. Therefore, the conjugated gradients method was considered effective in the identification of the basal cell carcinoma through infrared imaging even with the use of a low optical resolution camera (160 × 120 pixels) and a thermal resolution of 0.1 °C. The method could also be used to scan a larger area around the lesion in order to detect the presence of other lesions still not perceptible in the clinical exam. However, it is necessary that a temperature differences mesh-like mapping of the healthy human body skin is produced, so that the comparison of the patient Δ θ could be made with the exact region of such mapping in order to possibly make a more effective diagnosis. Finally, the infrared image analyzed through the

  16. Profile of vismodegib and its potential in the treatment of advanced basal cell carcinoma.

    PubMed

    Macha, Muzafar A; Batra, Surinder K; Ganti, Apar Kishor

    2013-01-01

    Basal cell carcinoma (BCC) is the most common human malignancy. Recent advances in our understanding of the critical biologic pathways implicated in the development and progression of BCC have led to the development of the first molecular targeted therapy for this disease. The hedgehog pathway is mutated in virtually all patients with BCC and recent trials with vismodegib, an inhibitor of this pathway, have shown significant responses. This review will discuss the importance of the hedgehog pathway in the pathogenesis of BCC and describe in detail the pharmacology of vismodegib in relation to its activity in advanced BCC. PMID:23940421

  17. PERIUNGUAL BASAL CELL CARCINOMA: A CASE REPORT WITH REVIEW OF LITERATURE

    PubMed Central

    Bandyopadhyay, Debabrata; Sen, Sumit

    2011-01-01

    Basal cell carcinomas (BCCs) are considered to be uncommon around the nail plate. An indolent lesion of this region should arouse suspicion of potential malignancy and a skin biopsy should be undertaken without delay. Early diagnosis can enable the physician to render simpler nondestructive modalities of treatment. In this article, we describe such a case of longstanding BCC of this region mimicking a traumatic ulcer. The nature of the ailment was finally discovered on biopsy and the carcinoma was initially treated with topical Imiquimod. PMID:21716555

  18. HDAC6 activity is not required for basal autophagic flux in metastatic prostate cancer cells.

    PubMed

    Watson, Gregory W; Wickramasekara, Samanthi; Fang, Yufeng; Maier, Claudia S; Williams, David E; Dashwood, Roderick H; Perez, Viviana I; Ho, Emily

    2016-06-01

    Histone deacetylase 6 is a multifunctional lysine deacetylase that is recently emerging as a central facilitator of response to stress and may play an important role in cancer cell proliferation. The histone deacetylase 6-inhibitor tubacin has been shown to slow the growth of metastatic prostate cancer cells and sensitize cancer cells to chemotherapeutic agents. However, the proteins histone deacetylase 6 interacts with, and thus its role in cancer cells, remains poorly characterized. Histone deacetylase 6 deacetylase activity has recently been shown to be required for efficient basal autophagic flux. Autophagy is often dysregulated in cancer cells and may confer stress resistance and allow for cell maintenance and a high proliferation rate. Tubacin may therefore slow cancer cell proliferation by decreasing autophagic flux. We characterized the histone deacetylase 6-interacting proteins in LNCaP metastatic prostate cancer cells and found that histone deacetylase 6 interacts with proteins involved in several cellular processes, including autophagy. Based on our interaction screen, we assessed the impact of the histone deacetylase 6-inhibitor tubacin on autophagic flux in two metastatic prostate cancer cell lines and found that tubacin does not influence autophagic flux. Histone deacetylase 6 therefore influences cell proliferation through an autophagy-independent mechanism. PMID:26643866

  19. White sponge naevus with minimal clinical and histological changes: report of three cases.

    PubMed

    Lucchese, Alberta; Favia, Gianfranco

    2006-05-01

    White sponge naevus (WSN) is a rare autosomal dominant disorder that predominantly affects non-cornified stratified squamous epithelia: oral mucosa, oesophagus, anogenital area. It has been shown to be related to keratin defects, because of mutations in the genes encoding mucosal-specific keratins K4 and K13. We illustrate three cases diagnosed as WSN, following the clinical and histological criteria, with unusual appearance. They presented with minimal clinical and histological changes that could be misleading in the diagnosis. The patients showed diffuse irregular plaques with a range of presentations from white to rose coloured mucosae involving the entire oral cavity. In one case the lesion was also present in the vaginal area. The histological findings included epithelial thickening, parakeratosis and extensive vacuolization of the suprabasal keratinocytes, confirming WSN diagnosis. Clinical presentation and histopathology of WSN are discussed in relation to the differential diagnosis of other oral leukokeratoses. PMID:16630298

  20. MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells

    PubMed Central

    Wang, Yubao; Lee, Young-Mi; Baitsch, Lukas; Huang, Alan; Xiang, Yi; Tong, Haoxuan; Lako, Ana; Von, Thanh; Choi, Christine; Lim, Elgene; Min, Junxia; Li, Li; Stegmeier, Frank; Schlegel, Robert; Eck, Michael J; Gray, Nathanael S; Mitchison, Timothy J; Zhao, Jean J

    2014-01-01

    Despite marked advances in breast cancer therapy, basal-like breast cancer (BBC), an aggressive subtype of breast cancer usually lacking estrogen and progesterone receptors, remains difficult to treat. In this study, we report the identification of MELK as a novel oncogenic kinase from an in vivo tumorigenesis screen using a kinome-wide open reading frames (ORFs) library. Analysis of clinical data reveals a high level of MELK overexpression in BBC, a feature that is largely dependent on FoxM1, a master mitotic transcription factor that is also found to be highly overexpressed in BBC. Ablation of MELK selectively impairs proliferation of basal-like, but not luminal breast cancer cells both in vitro and in vivo. Mechanistically, depletion of MELK in BBC cells induces caspase-dependent cell death, preceded by defective mitosis. Finally, we find that Melk is not required for mouse development and physiology. Together, these data indicate that MELK is a normally non-essential kinase, but is critical for BBC and thus represents a promising selective therapeutic target for the most aggressive subtype of breast cancer. DOI: http://dx.doi.org/10.7554/eLife.01763.001 PMID:24844244

  1. p120 Catenin Suppresses Basal Epithelial Cell Extrusion in Invasive Pancreatic Neoplasia.

    PubMed

    Hendley, Audrey M; Wang, Yue J; Polireddy, Kishore; Alsina, Janivette; Ahmed, Ishrat; Lafaro, Kelly J; Zhang, Hao; Roy, Nilotpal; Savidge, Samuel G; Cao, Yanna; Hebrok, Matthias; Maitra, Anirban; Reynolds, Albert B; Goggins, Michael; Younes, Mamoun; Iacobuzio-Donahue, Christine A; Leach, Steven D; Bailey, Jennifer M

    2016-06-01

    Aberrant regulation of cellular extrusion can promote invasion and metastasis. Here, we identify molecular requirements for early cellular invasion using a premalignant mouse model of pancreatic cancer with conditional knockout of p120 catenin (Ctnnd1). Mice with biallelic loss of p120 catenin progressively develop high-grade pancreatic intraepithelial neoplasia (PanIN) lesions and neoplasia accompanied by prominent acute and chronic inflammatory processes, which is mediated, in part, through NF-κB signaling. Loss of p120 catenin in the context of oncogenic Kras also promotes remarkable apical and basal epithelial cell extrusion. Abundant single epithelial cells exit PanIN epithelium basally, retain epithelial morphology, survive, and display features of malignancy. Similar extrusion defects are observed following p120 catenin knockdown in vitro, and these effects are completely abrogated by the activation of S1P/S1pr2 signaling. In the context of oncogenic Kras, p120 catenin loss significantly reduces expression of genes mediating S1P/S1pr2 signaling in vivo and in vitro, and this effect is mediated at least, in part, through activation of NF-κB. These results provide insight into mechanisms controlling early events in the metastatic process and suggest that p120 catenin and S1P/S1pr2 signaling enhance cancer progression by regulating epithelial cell invasion. Cancer Res; 76(11); 3351-63. ©2016 AACR. PMID:27032419

  2. MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells.

    PubMed

    Wang, Yubao; Lee, Young-Mi; Baitsch, Lukas; Huang, Alan; Xiang, Yi; Tong, Haoxuan; Lako, Ana; Von, Thanh; Choi, Christine; Lim, Elgene; Min, Junxia; Li, Li; Stegmeier, Frank; Schlegel, Robert; Eck, Michael J; Gray, Nathanael S; Mitchison, Timothy J; Zhao, Jean J

    2014-01-01

    Despite marked advances in breast cancer therapy, basal-like breast cancer (BBC), an aggressive subtype of breast cancer usually lacking estrogen and progesterone receptors, remains difficult to treat. In this study, we report the identification of MELK as a novel oncogenic kinase from an in vivo tumorigenesis screen using a kinome-wide open reading frames (ORFs) library. Analysis of clinical data reveals a high level of MELK overexpression in BBC, a feature that is largely dependent on FoxM1, a master mitotic transcription factor that is also found to be highly overexpressed in BBC. Ablation of MELK selectively impairs proliferation of basal-like, but not luminal breast cancer cells both in vitro and in vivo. Mechanistically, depletion of MELK in BBC cells induces caspase-dependent cell death, preceded by defective mitosis. Finally, we find that Melk is not required for mouse development and physiology. Together, these data indicate that MELK is a normally non-essential kinase, but is critical for BBC and thus represents a promising selective therapeutic target for the most aggressive subtype of breast cancer.DOI: http://dx.doi.org/10.7554/eLife.01763.001. PMID:24844244

  3. Basal-cell keratins in cervical reserve cells and a comparison to their expression in cervical intraepithelial neoplasia.

    PubMed Central

    Smedts, F.; Ramaekers, F.; Troyanovsky, S.; Pruszczynski, M.; Robben, H.; Lane, B.; Leigh, I.; Plantema, F.; Vooijs, P.

    1992-01-01

    Expression of keratins 5, 14 and 17 in endocervical subcolumnar reserve cells was detected by means of immunohistochemical studies using polypeptide specific monoclonal antibodies. These particular keratins that were found among others in basal cells could also be detected to a variable extent in metaplastic and dysplastic cervical lesions. In some cases of immature squamous metaplasia all three keratin subtypes were expressed throughout the full thickness of the epithelium. In contrast, in mature squamous metaplasia a compartmentalization of these keratins was observed. Mature squamous metaplastic epithelium showed a keratin distribution pattern comparable to ectocervical squamous epithelium, with the exception of keratin 17, which was only sporadically found in the basal layer of ectocervical epithelium and was always present in the basal cells of mature squamous metaplastic epithelium. During progression of cervical intraepithelial neoplasia a clear increase in the expression of keratin 17 was observed. However, also keratins 5 and 14 were expressed. Our results demonstrate that a considerable number of premalignant lesions of the uterine cervix express the same keratins as found in the progenitor reserve cells. Lesions that lack expression of keratin 17 may form a distinct group, which are regressive in nature and do not progress into cervical cancer. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:1372156

  4. The WNT-controlled transcriptional regulator LBH is required for mammary stem cell expansion and maintenance of the basal lineage.

    PubMed

    Lindley, Linsey E; Curtis, Kevin M; Sanchez-Mejias, Avencia; Rieger, Megan E; Robbins, David J; Briegel, Karoline J

    2015-03-01

    The identification of multipotent mammary stem cells (MaSCs) has provided an explanation for the unique regenerative capacity of the mammary gland throughout adult life. However, it remains unclear what genes maintain MaSCs and control their specification into the two epithelial lineages: luminal and basal. LBH is a novel transcription co-factor in the WNT pathway with hitherto unknown physiological function. LBH is expressed during mammary gland development and aberrantly overexpressed in aggressive 'basal' subtype breast cancers. Here, we have explored the in vivo role of LBH in mammopoiesis. We show that in postnatal mammary epithelia, LBH is predominantly expressed in the Lin(-)CD29(high)CD24(+) basal MaSC population. Upon conditional inactivation of LBH, mice exhibit pronounced delays in mammary tissue expansion during puberty and pregnancy, accompanied by increased luminal differentiation at the expense of basal lineage specification. These defects could be traced to a severe reduction in the frequency and self-renewal/differentiation potential of basal MaSCs. Mechanistically, LBH induces expression of key epithelial stem cell transcription factor ΔNp63 to promote a basal MaSC state and repress luminal differentiation genes, mainly that encoding estrogen receptor α (Esr1/ERα). Collectively, these studies identify LBH as an essential regulator of basal MaSC expansion/maintenance, raising important implications for its potential role in breast cancer pathogenesis. PMID:25655704

  5. Epigenetic silencing of ARRDC3 expression in basal-like breast cancer cells

    NASA Astrophysics Data System (ADS)

    Soung, Young Hwa; Pruitt, Kevin; Chung, Jun

    2014-01-01

    Arrestin domain-containing 3 (ARRDC3) is a tumor suppressor whose expression is either lost or suppressed in basal-like breast cancer (BLBC). However, the mechanism by which BLBC suppresses ARRDC3 expression is not established. Here, we show that expression of ARRDC3 in BLBC cells is suppressed at the transcriptional level. Suppression of ARRDC3 expression in BLBC cells involves epigenetic silencing as inhibitors of class III histone deacetylases (HDACs) significantly restores ARRDC3 levels in BLBC cells. SIRT2, among class III HDACs, plays a major role in epigenetic silencing of ARRDC3 in MDA-MB-231 cells. Acetylation levels of the ARRDC3 promoter in BLBC cells is significantly lower than that of other sub-types of BC cells. Chromatin immunopreciptitation analysis established SIRT2 binding at ARRDC3 promoter in BLBC cells. Our studies indicate that SIRT2 dependent epigenetic silencing of ARRDC3 is one of the important events that may contribute to the aggressive nature of BLBC cells.

  6. [Basal cell nevus syndrome. Presentation of 2 cases. 1 associated with medulloblastoma].

    PubMed

    Balsa, R E; Ingratta, S M; Galeano, F A; Raffaeli, C A; Drut, R; Vestfrid, M

    1985-01-01

    A case of nevoid basal-cell carcinoma syndrome in a four years old girl with preceding familiar history is reported. In her epithelioma father numerous basocellular, milia cysts, mandibular cysts, dentition disorders, brain falx calcifica ted and hiperkeratosis of the sole of the feet were described. Clinically, the girl presented initial migraine and vomits together with macrocephalus, bossing forehead, hypertelorism, physical disorders, retarded maturation, "keel" thorax, genu recurvatum, hallux valgus, hammerfinger, pigmented nevus and hyperkeratosis of the sole of the feet. Radiologically diastasis of the skull suture with jagged image, endocranial hypertension, signs of macrocephalus of the facial bones, calcification of the brain falx, bridge of the sella turcica, bifid ribs and fusion of the ribs was observed. The axial computed tomography showed calcification of the vermix cerebelosus and severe hydrocephalus suggesting the presence of an occupant mass. After total surgical removal of the mass, the histological examination revealed a medulloblastoma. The skin biopsy of a cutaneous nevic element showed a basal-cell epithelioma. With the exception of an ovarian fibroma and fusion of the vertebras non appreciable because of the age. With the exception of the ovarian fibroma and the fusion of the vertebras, the patient showed the same characteristics as those described in the classification of Gorlin. The importance of this paper communication lie on the preceding familiar history, infrequency, compromise of different systems, malignant tendency of the cutaneous lesions and frequent association with non cutaneous neoplasias. PMID:3887060

  7. The Importance of Cytokeratin 19 Expression in the Differentiation of Basal Cell Carcinoma and Trichoepithelioma

    PubMed Central

    Sehitoglu, Ibrahim; Yurdakul, Cüneyt; Saygin, Ismail; Üstüner, Pelin; Dilek, Nursel

    2015-01-01

    Introduction: Basal cell carcinoma (BCC) is the most common skin neoplasm reported in human. On the other hand, trichoepithelioma (TE) is a rare, benign tumour of skin adnexa. The differentiation of BCC and TE may be difficult since their morphological findings are similar. In a few studies, it has been determined that undifferentiated basaloid cells are highly positively stained with cytokeratin 19. Aim: The aim of this study was the comparison of cytokeratin 19 expression in cases of BCC and TE. Materials and Methods: Sections of skin tissues of 17 TE, 25 BCC and 12 non-neoplastic cases were used for cytokeratin 19 (CK19) immunohistochemical staining. Results: Staining with CK19 of the BCC cases gave 15(60%) diffuse, 7 (28%) focal and 3 (12%) negative staining. On the other hand, among TE cases, 2 (12%) gave diffuse, 5 (29%) focal and 10 (59%) negative staining with CK19. In the non-neoplastic skin tissue samples, while positive staining with cytokeratin 19 in the outer root sheath of hair follicles and sweat glands were observed, there was no staining in basal layers. Conclusion: CK19 expression may be helpful in the differential diagnosis of BCC and TE especially in small skin biopsy samples in which morphologic differentiation is difficult. PMID:25737992

  8. A Case of Orbital Myiasis in Recurrent Eyelid Basal Cell Carcinoma Invasive into the Orbit.

    PubMed

    Pandey, Triptesh Raj; Shrestha, Gulshan Bahadur; Sitaula, Ranju Kharel; Shah, Dev Narayan

    2016-01-01

    Introduction. Orbital myiasis is the infestation of the orbital tissues by fly larvae or maggots. Compromise of periorbital tissues by malignant disease, surgery, ischemia, or infection may predispose the patient to orbital myiasis. Case Report. A 73-year-old male patient with neglected recurrent basal cell carcinoma of the eyelid invasive into the orbit presented with complaints of intense itching and crawling sensation with maggots wriggling and falling from the wound of left orbit. The patient improved following manual removal of the maggots along with oral Ivermectin treatment. Recurrence of the basal cell carcinoma was confirmed by punch biopsy from the wound and extended exenteration of the orbit followed by reconstructive surgery was done. Conclusion. Orbital myiasis is a rare and preventable ocular morbidity that can complicate the malignancies resulting in widespread tissue destruction. The broad spectrum antiparasitic agent, Ivermectin, can be used as noninvasive means to treat orbital myiasis. In massive orbital myiasis and those associated with malignancies, exenteration of the orbit must be seriously considered. PMID:27595028

  9. Reconstructive rhinoplasty in cases with basal cell carcinoma of the nose.

    PubMed

    Anghel, I; Anghel, A G

    2012-01-01

    Basal cell Carcinoma (BCC) is the most common type of skin cancer, 85% of BCC are located in the head and neck area, of which 30% on the nose. The author present a retrospective study, own experience in surgical treatment in 31 cases with basal cell carcinoma of the nose operated in the period 2005-2011. The age of patients was between 50 to 90 years old. The anatomical site of the nose the most frecvently involved was ala 58%, and followed of the nasal tip 18%, lateral nose wall 12%, dorsum 9% and 3% basalioma terebrans. In all of the cases in this study it was performed the repair of the skin tumour defects of the nose, using varied local skin flaps, septal graft and auricle cartilage free grafts a ndcomposite (skin + cartilage) of conchal and helical rim. Treatment methods were depend on the tumor localization and extension. The best treatment option in BCC of the nose was radical surgical excision whith safety margin of the tumour, followed of reconstructive rhinoplasty. PMID:22844837

  10. Basal Cell Skin Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

    PubMed

    Bichakjian, Christopher K; Olencki, Thomas; Aasi, Sumaira Z; Alam, Murad; Andersen, James S; Berg, Daniel; Bowen, Glen M; Cheney, Richard T; Daniels, Gregory A; Glass, L Frank; Grekin, Roy C; Grossman, Kenneth; Higgins, Susan A; Ho, Alan L; Lewis, Karl D; Lydiatt, Daniel D; Nehal, Kishwer S; Nghiem, Paul; Olsen, Elise A; Schmults, Chrysalyne D; Sekulic, Aleksandar; Shaha, Ashok R; Thorstad, Wade L; Tuli, Malika; Urist, Marshall M; Wang, Timothy S; Wong, Sandra L; Zic, John A; Hoffmann, Karin G; Engh, Anita

    2016-05-01

    Basal cell carcinoma (BCC) of the skin is the most common cancer, with a higher incidence than all other malignancies combined. Although it is rare to metastasize, patients with multiple or frequently recurring BCC can suffer substantial comorbidity and be difficult to manage. Assessment of risk is a key element of management needed to inform treatment selection. The overall management of BCC primarily consists of surgical approaches, with radiation therapy as an alternate or adjuvant option. Many superficial therapies for BCC have been explored and continue to be developed, including topicals, cryosurgery, and photodynamic therapy. Two hedgehog pathway inhibitors were recently approved by the FDA for systemic treatment of advanced and metastatic BCC, and others are in development. The NCCN Guidelines for Basal Cell Skin Cancer, published in full herein, include recommendations for selecting among the various surgical approaches based on patient-, lesion-, and disease-specific factors, as well as guidance on when to use radiation therapy, superficial therapies, and hedgehog pathway inhibitors. PMID:27160235

  11. Basal cell carcinoma of the eyelids and solar ultraviolet radiation exposure

    PubMed Central

    Lindgren, G.; Diffey, B.; Larko, O.

    1998-01-01

    AIMS—To compare the distribution of eyelid basal cell carcinoma (BCC) with the relative ultraviolet radiation (UVR) exposure to different sites on the eyelids.
METHODS—The location of BCC on the eyelids was allocated to one of seven regions. The UVR exposure was recorded with a polymer film attached to the eyelids at seven sites in a manikin and in human subjects.
RESULTS—Localisation of the 329 tumours was mainly on the lower eyelids (225 tumours), and the medial canthal regions (87 tumours). There was no association between UVR doses at the seven sites of the eyelids and the location of BCCs. The UVR exposure was similar on the upper and lower eyelids, while the number of tumours on the lower eyelids outnumbered the upper lids by a factor of 13 (17 upper, 225 lower)
CONCLUSION—UVR exposure only partially explains the aetiology of periorbital BCC.

 Keywords: polysulphone film; basal cell carcinoma; ultraviolet radiation; eyelid PMID:9930273

  12. Novel Patched 1 mutations in patients with nevoid basal cell carcinoma syndrome – case report

    PubMed Central

    Škodrić-Trifunović, Vesna; Stjepanović, Mihailo; Savić, Živorad; Ilić, Miroslav; Kavečan, Ivana; Jovanović Privrodski, Jadranka; Spasovski, Vesna; Stojiljković, Maja; Pavlović, Sonja

    2015-01-01

    Nevoid basal cell carcinoma syndrome (Gorlin syndrome) is a rare autosomal dominant disorder characterized by numerous basal cell carcinomas, keratocystic odontogenic tumors of the jaws, and diverse developmental defects. This disorder is associated with mutations in tumor suppressor gene Patched 1 (PTCH1). We present two patients with Gorlin syndrome, one sporadic and one familial. Clinical examination, radiological, and CT imaging, and mutation screening of PTCH1 gene were performed. Family members, as well as eleven healthy controls were included in the study. Both patients fulfilled the specific criteria for diagnosis of Gorlin syndrome. Molecular analysis of the first patient showed a novel frameshift mutation in exon 6 of PTCH1gene (c.903delT). Additionally, a somatic frameshift mutation in exon 21 (c.3524delT) along with germline mutation in exon 6 was detected in tumor-derived tissue sample of this patient. Analysis of the second patient, as well as two affected family members, revealed a novel nonsense germline mutation in exon 8 (c.1148 C>A). PMID:25727044

  13. Loss of Blm enhances basal cell carcinoma and rhabdomyosarcoma tumorigenesis in Ptch1+/- mice.

    PubMed

    Davari, Parastoo; Hebert, Jennifer L; Albertson, Donna G; Huey, Bing; Roy, Ritu; Mancianti, Maria L; Horvai, Andrew E; McDaniel, Lisa D; Schultz, Roger A; Epstein, Ervin H

    2010-06-01

    Basal cell carcinomas (BCCs) have relative genomic stability and relatively benign clinical behavior but whether these two are related causally is unknown. To investigate the effects of introducing genomic instability into murine BCCs, we have compared ionizing radiation-induced tumorigenesis in Ptch1(+/-) mice versus that in Ptch1(+/-) mice carrying mutant Blm alleles. We found that BCCs in Ptch1(+/-) Blm(tm3Brd/tm3Brd) mice had a trend toward greater genomic instability as measured by array comprehensive genomic hybridization and that these mice developed significantly more microscopic BCCs than did Ptch1(+/-) Blm(+/tm3Brd) or Ptch1(+/-) Blm(+/+) mice. The mutant Blm alleles also markedly enhanced the formation of rhabdomyosarcomas (RMSs), another cancer to which Ptch1(+/)(-) mice and PTCH1(+/)(-) (basal cell nevus syndrome) patients are susceptible. Highly recurrent but different copy number changes were associated with the two tumor types and included losses of chromosomes 4 and 10 in all BCCs and gain of chromosome 10 in 80% of RMSs. Loss of chromosome 11 and 13, including the Trp53 and Ptch1 loci, respectively, occurred frequently in BCCs, suggesting tissue-specific selection for genes or pathways that collaborate with Ptch deficiency in tumorigenesis. Despite the quantitative differences, there was no dramatic qualititative difference in the BCC or RMS tumors associated with the mutant Blm genotype. PMID:19995795

  14. A Case of Orbital Myiasis in Recurrent Eyelid Basal Cell Carcinoma Invasive into the Orbit

    PubMed Central

    Shrestha, Gulshan Bahadur; (Sitaula), Ranju Kharel; Shah, Dev Narayan

    2016-01-01

    Introduction. Orbital myiasis is the infestation of the orbital tissues by fly larvae or maggots. Compromise of periorbital tissues by malignant disease, surgery, ischemia, or infection may predispose the patient to orbital myiasis. Case Report. A 73-year-old male patient with neglected recurrent basal cell carcinoma of the eyelid invasive into the orbit presented with complaints of intense itching and crawling sensation with maggots wriggling and falling from the wound of left orbit. The patient improved following manual removal of the maggots along with oral Ivermectin treatment. Recurrence of the basal cell carcinoma was confirmed by punch biopsy from the wound and extended exenteration of the orbit followed by reconstructive surgery was done. Conclusion. Orbital myiasis is a rare and preventable ocular morbidity that can complicate the malignancies resulting in widespread tissue destruction. The broad spectrum antiparasitic agent, Ivermectin, can be used as noninvasive means to treat orbital myiasis. In massive orbital myiasis and those associated with malignancies, exenteration of the orbit must be seriously considered. PMID:27595028

  15. Detection of Basal Cell Carcinoma Using Color and Histogram Measures of Semitranslucent Areas

    PubMed Central

    Stoecker, William V.; Gupta, Kapil; Shrestha, Bijaya; Wronkiewiecz, Mark; Chowdhury, Raeed; Stanley, R. Joe; Xu, Jin; Moss, Randy H.; Celebi, M. Emre; Rabinovitz, Harold S.; Oliviero, Margaret; Malters, Joseph M.; Kolm, Isabel

    2009-01-01

    Background Semitranslucency, defined as a smooth, jelly-like area with varied, near-skin-tone color, can indicate a diagnosis of basal cell carcinoma (BCC) with high specificity. This study sought to analyze potential areas of semitranslucency with histogram-derived texture and color measures to discriminate BCC from non-semitranslucent areas in non-BCC skin lesions. Methods For 210 dermoscopy images, the areas of semitranslucency in 42 BCCs and comparable areas of smoothness and color in 168 non-BCCs were selected manually. Six color measures and six texture measures were applied to the semitranslucent areas of the BCC and the comparable areas in the non-BCC images. Results Receiver operating characteristic (ROC) curve analysis showed that the texture measures alone provided greater separation of BCC from non-BCC than the color measures alone. Statistical analysis showed that the four most important measures of semitranslucency are three histogram measures: contrast, smoothness, and entropy, and one color measure: blue chromaticity. Smoothness is the single most important measure. The combined 12 measures achieved a diagnostic accuracy of 95.05% based on area under the ROC curve. Conclusion Texture and color analysis measures, especially smoothness, may afford automatic detection of basal cell carcinoma images with semitranslucency. PMID:19624424

  16. Evolutionary Changes in the Developmental Origin of Hatching Gland Cells in Basal Ray-Finned Fishes.

    PubMed

    Nagasawa, Tatsuki; Kawaguchi, Mari; Yano, Tohru; Sano, Kaori; Okabe, Masataka; Yasumasu, Shigeki

    2016-06-01

    Hatching gland cells (HGCs) originate from different germ layers between frogs and teleosts, although the hatching enzyme genes are orthologous. Teleostei HGCs differentiate in the mesoendodermal cells at the anterior end of the involved hypoblast layer (known as the polster) in late gastrula embryos. Conversely, frog HGCs differentiate in the epidermal cells at the neural plate border in early neurula embryos. To infer the transition in the developmental origin of HGCs, we studied two basal ray-finned fishes, bichir (Polypterus) and sturgeon. We observed expression patterns of their hatching enzyme (HE) and that of three transcription factors that are critical for HGC differentiation: KLF17 is common to both teleosts and frogs; whereas FoxA3 and Pax3 are specific to teleosts and frogs, respectively. We then inferred the transition in the developmental origin of HGCs. In sturgeon, the KLF17, FoxA3, and HE genes were expressed during the tailbud stage in the cell mass at the anterior region of the body axis, a region corresponding to the polster in teleost embryos. In contrast, the bichir was suggested to possess both teleost- and amphibian-type HGCs, i.e. the KLF17 and FoxA3 genes were expressed in the anterior cell mass corresponding to the polster, and the KLF17, Pax3 and HE genes were expressed in dorsal epidermal layer of the head. The change in developmental origin is thought to have occurred during the evolution of basal ray-finned fish, because bichir has two HGCs, while sturgeon only has the teleost-type. PMID:27268981

  17. Asymmetric segregation of template DNA strands in basal-like human breast cancer cell lines

    PubMed Central

    2013-01-01

    Background and methods Stem or progenitor cells from healthy tissues have the capacity to co-segregate their template DNA strands during mitosis. Here, we set out to test whether breast cancer cell lines also possess the ability to asymmetrically segregate their template DNA strands via non-random chromosome co-segregation, and whether this ability correlates with certain properties attributed to breast cancer stem cells (CSCs). We quantified the frequency of asymmetric segregation of template DNA strands in 12 human breast cancer cell lines, and correlated the frequency to molecular subtype, CD44+/CD24-/lo phenotype, and invasion/migration ability. We tested if co-culture with human mesenchymal stem cells, which are known to increase self-renewal, can alter the frequency of asymmetric segregation of template DNA in breast cancer. Results We found a positive correlation between asymmetric segregation of template DNA and the breast cancer basal-like and claudin-low subtypes. There was an inverse correlation between asymmetric segregation of template DNA and Her2 expression. Breast cancer samples with evidence of asymmetric segregation of template DNA had significantly increased invasion and borderline significantly increased migration abilities. Samples with high CD44+/CD24-/lo surface expression were more likely to harbor a consistent population of cells that asymmetrically segregated its template DNA; however, symmetric self-renewal was enriched in the CD44+/CD24-/lo population. Co-culturing breast cancer cells with human mesenchymal stem cells expanded the breast CSC pool and decreased the frequency of asymmetric segregation of template DNA. Conclusions Breast cancer cells within the basal-like subtype can asymmetrically segregate their template DNA strands through non-random chromosome segregation. The frequency of asymmetric segregation of template DNA can be modulated by external factors that influence expansion or self-renewal of CSC populations. Future

  18. Computer simulation of wound closure in epithelial tissues: Cell-basal-lamina adhesion

    NASA Astrophysics Data System (ADS)

    Nagai, Tatsuzo; Honda, Hisao

    2009-12-01

    The mechanism of wound closure in epithelial tissues, i.e., cell monolayer sheets, is investigated through computer simulations. A wound means an area in which some cells have been removed from the normal tissue. The vertex dynamics cell model [T. Nagai and H. Honda, Philos. Mag. B 81, 699 (2001)], which describes morphogenesis of epithelial tissues using the concepts of statistical physics, is modified and applied to the closure of small wounds without mitosis. It is shown that cell-basal-lamina adhesion governs the wound closure competing with cell-cell adhesion and cell elasticity. The simulation results reproduce the actual wound closure process qualitatively and partly quantitatively. The closing proceeds with the translation of the edges of wound polygons toward the wound center and the intermittent reduction in the number of polygon edges. Over time, the process leads to an exponential decrease in the wound area. A shape factor is introduced to describe the wound shape quantitatively and is used to examine the time variation thereof. A method for determining model parameters by comparison with the experiments is given.

  19. Comparison between mALA- and ALA-PDT in the treatment of basal cell carcinomas

    NASA Astrophysics Data System (ADS)

    Schleier, Peter; Zenk, Witold; Hyckel, Peter; Berndt, Alexander

    2006-02-01

    Introduction: The external application of aminoleavulinic acid (ALA), which is a substrate of physiologic cell metabolism, represents a possible treatment option in superficial basal cell carcinomas (BCC). The development of new ALA-esters (mALA) with potential for higher penetration depths promises higher therapeutic success. This research aimed to prove the following hypothesis: The cytotoxic effect of the mALA- photodynamic therapy (mALA-PDT), when compared to the ALA-PDT, leads to a higher clinical success rate. Material and Methods: 24 patients with multiple facial tumors, after having received several local surgical excisions with known histology, were treated with either ALA- or mALA-PDT, during the past two years. In total, 89 basal cell carcinoma, 45 actinic keratoses, 6 keratoacanthoma, and 2 squamous cell carcinomas were treated. ALA-PDT: A thermo gel with 40 % mALA or ALA was applied from a cooled syringe. Three to five hours after gel application the skin was cleaned from any gel residues. Irradiation was done with a diode laser and was performed in two sessions, each 10 min long. After intervals of 2, 4 and 12 weeks, the patients were recalled to assess therapeutic efficacy. This was followed by photographic documentation. Results: More than 80% of the tumors treated primarily were resolved successfully. A recurrence rate of approximately 15% was observed. Three per cent of the tumors showed no reaction to therapy. There were no statistically significant differences between the two therapeutic groups. Discussion: The advantage of the use of ALA lies foremost in the fast metabolic use of the body's own photosensitizer PpIX. There are no known side effects of this therapy. Moreover, external application is superior to systemic application with regard to patient management. The method can be combined with other therapies. Although the mALA should have a better penetration in tumor tissue, the therapeutic outcome is similar to the use of ALA.

  20. Flattop regulates basal body docking and positioning in mono- and multiciliated cells

    PubMed Central

    Gegg, Moritz; Böttcher, Anika; Burtscher, Ingo; Hasenoeder, Stefan; Van Campenhout, Claude; Aichler, Michaela; Walch, Axel; Grant, Seth G N; Lickert, Heiko

    2014-01-01

    Planar cell polarity (PCP) regulates basal body (BB) docking and positioning during cilia formation, but the underlying mechanisms remain elusive. In this study, we investigate the uncharacterized gene Flattop (Fltp) that is transcriptionally activated during PCP acquisition in ciliated tissues. Fltp knock-out mice show BB docking and ciliogenesis defects in multiciliated lung cells. Furthermore, Fltp is necessary for kinocilium positioning in monociliated inner ear hair cells. In these cells, the core PCP molecule Dishevelled 2, the BB/spindle positioning protein Dlg3, and Fltp localize directly adjacent to the apical plasma membrane, physically interact and surround the BB at the interface of the microtubule and actin cytoskeleton. Dlg3 and Fltp knock-outs suggest that both cooperatively translate PCP cues for BB positioning in the inner ear. Taken together, the identification of novel BB/spindle positioning components as potential mediators of PCP signaling might have broader implications for other cell types, ciliary disease, and asymmetric cell division. DOI: http://dx.doi.org/10.7554/eLife.03842.001 PMID:25296022

  1. Optimization of the basal medium for improving production and secretion of taxanes from suspension cell culture of Taxus baccata L

    PubMed Central

    2012-01-01

    Background and purpose of the study Taxol is one of the most effective anticancer drugs that isolated from Taxus sp. due to the slow growth of Taxus trees and low concentration of Taxol in the tissues, the biotechnological approaches especially plant cell culture have been considered to produce Taxol in commercial scale. Methods We investigated the effects of basal medium type used in culture media on production of Taxol and other taxane compounds from cell suspension culture of T. baccata L. Briefly, five commonly basal media including Gamborg, Murashige and Skoog, Woody Plant, Schenk and Hildebrandt, and Driver and Kuniyuki medium were used for preparing separate suspension culture media. The intra- and extra-cellular yields of taxanes were analyzed by using HPLC after 21 days period of culturing. Results The yields of taxanes were significantly different for the cultures prepared by different basal media. Moreover, the effects of basal medium on the yield of products differed for varius taxane compounds. Maximum yields of Baccatin III (10.03 mgl-1) and 10-deacetyl baccatin III (4.2 mgl-1) were achieved from the DKW basal media, but the yield of Taxol was maximum (16.58 mgl-1) in the WPM basal media. Furthermore, the secretion of taxanes from the cells into medium was also considerably affected by the type of basal medium. The maximum extra-cellular yield of Taxol (7.81 mgl-1), Baccatin III (5.0 mgl-1), and 10-deacetyl baccatin III (1.45 mgl-1) were also obtained by using DKW basal medium that were significantly higher than those obtained from other culture media. PMID:23352123

  2. Basal Cancer Cell Survival Involves JNK2 Suppression of a Novel JNK1/c-Jun/Bcl-3 Apoptotic Network

    PubMed Central

    Ahmed, Shafiq Uddin; Milner, Jo

    2009-01-01

    Background The regulation of apoptosis under basal (non-stress) conditions is crucial for normal mammalian development and also for normal cellular turnover in different tissues throughout life. Deficient regulation of basal apoptosis, or its perturbation, can result in impaired development and/or disease states including cancer. In contrast to stress-induced apoptosis the regulation of apoptosis under basal conditions is poorly understood. To address this issue we have compared basal- and stress-induced apoptosis in human epithelial cells of normal and cancerous origins. For this purpose we focussed our study on the opposing pro-apoptotic JNK/anti-apoptotic NFκB pathways. Methodology/Principal Findings Combinatorial RNAi plus gene knockout were employed to access and map basal regulatory pathways of apoptosis. Follow-on, in-depth analyses included exogenous expression of phosphorylation mutants and chromatin immunoprecipitation. We demonstrate that basal apoptosis is constitutively suppressed by JNK2 in a range of human cancer cell lines. This effect was not observed in non-cancer cells. Silencing JNK2 by RNAi resulted in JNK1-dependent apoptosis of cancer cells via up-regulation of the AP-1 factor c-Jun. Unexpectedly we discovered that JNK1 and c-Jun promote basal apoptosis in the absence of “activating phosphorylations” typically induced by stress. Hypo-phosphorylated c-Jun accumulated to high levels following JNK2 silencing, auto-regulated its own expression and suppressed expression of Bcl-3, an unusual IκB protein and regulator of NFκB. Basal apoptosis was mediated by components of the TNFα response pathway but was mechanistically distinct from TNFα-induced apoptosis. Conclusions/Significance Our results demonstrate that mechanistically distinct pathways operate to regulate apoptosis in mammalian cells under basal (physiological) versus stress-induced conditions. We also describe a novel apoptotic network which governs the basal survival of cancer

  3. Multiciliated cell basal bodies align in stereotypical patterns coordinated by the apical cytoskeleton.

    PubMed

    Herawati, Elisa; Taniguchi, Daisuke; Kanoh, Hatsuho; Tateishi, Kazuhiro; Ishihara, Shuji; Tsukita, Sachiko

    2016-08-29

    Multiciliated cells (MCCs) promote fluid flow through coordinated ciliary beating, which requires properly organized basal bodies (BBs). Airway MCCs have large numbers of BBs, which are uniformly oriented and, as we show here, align linearly. The mechanism for BB alignment is unexplored. To study this mechanism, we developed a long-term and high-resolution live-imaging system and used it to observe green fluorescent protein-centrin2-labeled BBs in cultured mouse tracheal MCCs. During MCC differentiation, the BB array adopted four stereotypical patterns, from a clustering "floret" pattern to the linear "alignment." This alignment process was correlated with BB orientations, revealed by double immunostaining for BBs and their asymmetrically associated basal feet (BF). The BB alignment was disrupted by disturbing apical microtubules with nocodazole and by a BF-depleting Odf2 mutation. We constructed a theoretical model, which indicated that the apical cytoskeleton, acting like a viscoelastic fluid, provides a self-organizing mechanism in tracheal MCCs to align BBs linearly for mucociliary transport. PMID:27573463

  4. Differential regulation of the Hippo pathway by adherens junctions and apical-basal cell polarity modules.

    PubMed

    Yang, Chih-Chao; Graves, Hillary K; Moya, Ivan M; Tao, Chunyao; Hamaratoglu, Fisun; Gladden, Andrew B; Halder, Georg

    2015-02-10

    Adherens junctions (AJs) and cell polarity complexes are key players in the establishment and maintenance of apical-basal cell polarity. Loss of AJs or basolateral polarity components promotes tumor formation and metastasis. Recent studies in vertebrate models show that loss of AJs or loss of the basolateral component Scribble (Scrib) cause deregulation of the Hippo tumor suppressor pathway and hyperactivation of its downstream effectors Yes-associated protein (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ). However, whether AJs and Scrib act through the same or independent mechanisms to regulate Hippo pathway activity is not known. Here, we dissect how disruption of AJs or loss of basolateral components affect the activity of the Drosophila YAP homolog Yorkie (Yki) during imaginal disc development. Surprisingly, disruption of AJs and loss of basolateral proteins produced very different effects on Yki activity. Yki activity was cell-autonomously decreased but non-cell-autonomously elevated in tissues where the AJ components E-cadherin (E-cad) or α-catenin (α-cat) were knocked down. In contrast, scrib knockdown caused a predominantly cell-autonomous activation of Yki. Moreover, disruption of AJs or basolateral proteins had different effects on cell polarity and tissue size. Simultaneous knockdown of α-cat and scrib induced both cell-autonomous and non-cell-autonomous Yki activity. In mammalian cells, knockdown of E-cad or α-cat caused nuclear accumulation and activation of YAP without overt effects on Scrib localization and vice versa. Therefore, our results indicate the existence of multiple, genetically separable inputs from AJs and cell polarity complexes into Yki/YAP regulation. PMID:25624491

  5. Mitochondrial permeabilization without caspase activation mediates the increase of basal apoptosis in cells lacking Nrf2.

    PubMed

    Ariza, Julia; González-Reyes, José A; Jódar, Laura; Díaz-Ruiz, Alberto; de Cabo, Rafael; Villalba, José Manuel

    2016-06-01

    Nuclear factor E2-related factor-2 (Nrf2) is a cap'n'collar/basic leucine zipper (b-ZIP) transcription factor which acts as sensor of oxidative and electrophilic stress. Low levels of Nrf2 predispose cells to chemical carcinogenesis but a dark side of Nrf2 function also exists because its unrestrained activation may allow the survival of potentially dangerous damaged cells. Since Nrf2 inhibition may be of therapeutic interest in cancer, and a decrease of Nrf2 activity may be related with degenerative changes associated with aging, it is important to investigate how the lack of Nrf2 function activates molecular mechanisms mediating cell death. Murine Embryonic Fibroblasts (MEFs) bearing a Nrf2 deletion (Nrf2KO) displayed diminished cellular growth rate and shortened lifespan compared with wild-type MEFs. Basal rates of DNA fragmentation and histone H2A.X phosphorylation were higher in Nrf2KO MEFs, although steady-state levels of reactive oxygen species were not significantly increased. Enhanced rates of apoptotic DNA fragmentation were confirmed in liver and lung tissues from Nrf2KO mice. Apoptosis in Nrf2KO MEFs was associated with a decrease of Bcl-2 but not Bax levels, and with the release of the mitochondrial pro-apoptotic factors cytochrome c and AIF. Procaspase-9 and Apaf-1 were also increased in Nrf2KO MEFs but caspase-3 was not activated. Inhibition of XIAP increased death in Nrf2KO but not in wild-type MEFs. Mitochondrial ultrastructure was also altered in Nrf2KO MEFs. Our results support that Nrf2 deletion produces mitochondrial dysfunction associated with mitochondrial permeabilization, increasing basal apoptosis through a caspase-independent and AIF-dependent pathway. PMID:27016073

  6. EGF shifts human airway basal cell fate toward a smoking-associated airway epithelial phenotype.

    PubMed

    Shaykhiev, Renat; Zuo, Wu-Lin; Chao, Ionwa; Fukui, Tomoya; Witover, Bradley; Brekman, Angelika; Crystal, Ronald G

    2013-07-16

    The airway epithelium of smokers acquires pathological phenotypes, including basal cell (BC) and/or goblet cell hyperplasia, squamous metaplasia, structural and functional abnormalities of ciliated cells, decreased number of secretoglobin (SCGB1A1)-expressing secretory cells, and a disordered junctional barrier. In this study, we hypothesized that smoking alters airway epithelial structure through modification of BC function via an EGF receptor (EGFR)-mediated mechanism. Analysis of the airway epithelium revealed that EGFR is enriched in airway BCs, whereas its ligand EGF is induced by smoking in ciliated cells. Exposure of BCs to EGF shifted the BC differentiation program toward the squamous and epithelial-mesenchymal transition-like phenotypes with down-regulation of genes related to ciliogenesis, secretory differentiation, and markedly reduced junctional barrier integrity, mimicking the abnormalities present in the airways of smokers in vivo. These data suggest that activation of EGFR in airway BCs by smoking-induced EGF represents a unique mechanism whereby smoking can alter airway epithelial differentiation and barrier function. PMID:23818594

  7. Nodulocystic Basal Cell Carcinoma Arising Directly from a Seborrheic Keratosis: A Rare Case Report

    PubMed Central

    Shibao, Kana; Okiyama, Naoko; Tanaka, Ryota; Maruyama, Hitoshi; Fujisawa, Yasuhiro; Fujimoto, Manabu

    2016-01-01

    Seborrheic keratoses (SKs) are common epidermal tumors composed of benign keratinocytes. Malignant skin tumors including basal cell carcinoma (BCC) rarely arise within SKs. We report a rare case of an 82-year-old man with nodulocystic BCC that appeared at the center of a scaly hyperpigmented SK that had been presented for more than 10 years. It was histologically confirmed that CK19-positive BCC arose directly from the wall of the pseudohorn cyst, a part of the SK. Nodular and/or cystic BCC also rarely arise within SKs while the most common histologic type of BCC within SKs is the superficial type. Careful observation of SKs is important even though it is rarely a background condition for malignant transformation. PMID:27512194

  8. Germline sequence variants in TGM3 and RGS22 confer risk of basal cell carcinoma

    PubMed Central

    Stacey, Simon N.; Sulem, Patrick; Gudbjartsson, Daniel F.; Jonasdottir, Aslaug; Thorleifsson, Gudmar; Gudjonsson, Sigurjon A.; Masson, Gisli; Gudmundsson, Julius; Sigurgeirsson, Bardur; Benediktsdottir, Kristrun R.; Thorisdottir, Kristin; Ragnarsson, Rafn; Fuentelsaz, Victoria; Corredera, Cristina; Grasa, Matilde; Planelles, Dolores; Sanmartin, Onofre; Rudnai, Peter; Gurzau, Eugene; Koppova, Kvetoslava; Hemminki, Kari; Nexø, Bjørn A; Tjønneland, Anne; Overvad, Kim; Johannsdottir, Hrefna; Helgadottir, Hafdis T.; Thorsteinsdottir, Unnur; Kong, Augustine; Vogel, Ulla; Kumar, Rajiv; Nagore, Eduardo; Mayordomo, José I.; Rafnar, Thorunn; Olafsson, Jon H.; Stefansson, Kari

    2014-01-01

    To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide association study of 38.5 million single nucleotide polymorphisms (SNPs) and small indels identified through whole-genome sequencing of 2230 Icelanders. We imputed genotypes for 4208 BCC patients and 109 408 controls using Illumina SNP chip typing data, carried out association tests and replicated the findings in independent population samples. We found new BCC susceptibility loci at TGM3 (rs214782[G], P = 5.5 × 10−17, OR = 1.29) and RGS22 (rs7006527[C], P = 8.7 × 10−13, OR = 0.77). TGM3 encodes transglutaminase type 3, which plays a key role in production of the cornified envelope during epidermal differentiation. PMID:24403052

  9. Multiple facial basal cell carcinomas in xeroderma pigmentosum treated with topical imiquimod 5% cream.

    PubMed

    Yang, Jian-Qiang; Chen, Xian-Yu; Engle, Michelle Yixiao; Wang, Jian-You

    2015-01-01

    Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by solar sensitivity, photophobia, early onset of freckling, and solar-induced cutaneous neoplastic changes. Management of patients with XP is a therapeutic challenge as they usually develop multiple cutaneous malignancies, making surgical therapy difficult, and continue to form skin malignancies at a high rate. We describe a 30-year-old Chinese man with XP who had been previously treated with excision and dermatoplasty. Upon recurrence of multiple superficial, ulcerative, and pigmented lesions, imiquimod 5% cream was recommended for 4 months. His multiple facial lesions demonstrated an excellent response to topical imiquimod 5% cream with minor side effects. This favorable response indicates that topical application of imiquimod 5% cream is an effective means of treating multiple basal cell carcinomas in XP. PMID:25754701

  10. Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma

    PubMed Central

    Chahal, Harvind S.; Wu, Wenting; Ransohoff, Katherine J.; Yang, Lingyao; Hedlin, Haley; Desai, Manisha; Lin, Yuan; Dai, Hong-Ji; Qureshi, Abrar A.; Li, Wen-Qing; Kraft, Peter; Hinds, David A.; Tang, Jean Y.; Han, Jiali; Sarin, Kavita Y.

    2016-01-01

    Basal cell carcinoma (BCC) is the most common cancer worldwide with an annual incidence of 2.8 million cases in the United States alone. Previous studies have demonstrated an association between 21 distinct genetic loci and BCC risk. Here, we report the results of a two-stage genome-wide association study of BCC, totalling 17,187 cases and 287,054 controls. We confirm 17 previously reported loci and identify 14 new susceptibility loci reaching genome-wide significance (P<5 × 10−8, logistic regression). These newly associated SNPs lie within predicted keratinocyte regulatory elements and in expression quantitative trait loci; furthermore, we identify candidate genes and non-coding RNAs involved in telomere maintenance, immune regulation and tumour progression, providing deeper insight into the pathogenesis of BCC. PMID:27539887

  11. Hybrid image representation learning model with invariant features for basal cell carcinoma detection

    NASA Astrophysics Data System (ADS)

    Arevalo, John; Cruz-Roa, Angel; González, Fabio A.

    2013-11-01

    This paper presents a novel method for basal-cell carcinoma detection, which combines state-of-the-art methods for unsupervised feature learning (UFL) and bag of features (BOF) representation. BOF, which is a form of representation learning, has shown a good performance in automatic histopathology image classi cation. In BOF, patches are usually represented using descriptors such as SIFT and DCT. We propose to use UFL to learn the patch representation itself. This is accomplished by applying a topographic UFL method (T-RICA), which automatically learns visual invariance properties of color, scale and rotation from an image collection. These learned features also reveals these visual properties associated to cancerous and healthy tissues and improves carcinoma detection results by 7% with respect to traditional autoencoders, and 6% with respect to standard DCT representations obtaining in average 92% in terms of F-score and 93% of balanced accuracy.

  12. The first experience in estimation of basal cell carcinoma cryoresistence using noninvasive spectrophotometry

    NASA Astrophysics Data System (ADS)

    Andrukhina, V. V.; Litvinova, K. S.; Nikitin, A. A.; Spiridonova, N. Z.; Rogatkin, D. A.

    2010-02-01

    The urgency of BCC study affecting maxillofacial area and neck is not only caused by high prevalence of this disease, but also insufficient efficiency of existing treatment methods which lead to full or partial recovery only in 60-80% of cases. We analyzed the results of 198 BCC cases cryosurgical treatment. 33 (16,6%) patients showed continued tumor growth. It has been hypothesized that the behavior and character of microcirculation changes during patient's testing have to correlate with damaging rate of tumors that will allow to develop indications for surgical treatment with local destruction - cryosurgery or cryolaser treatment. We have tested the new group of 33 patients with primary and recurrence types of basal cell carcinoma (BCC) by means of Laser Doppler Flowmetry, Tissues Reflectance Oximetry, Laser Fluorescence Diagnostics before operation. It was shown that the microcirculatory data indicates the presence of cryoresistance.

  13. The first experience in estimation of basal cell carcinoma cryoresistence using noninvasive spectrophotometry

    NASA Astrophysics Data System (ADS)

    Andrukhina, V. V.; Litvinova, K. S.; Nikitin, A. A.; Spiridonova, N. Z.; Rogatkin, D. A.

    2009-10-01

    The urgency of BCC study affecting maxillofacial area and neck is not only caused by high prevalence of this disease, but also insufficient efficiency of existing treatment methods which lead to full or partial recovery only in 60-80% of cases. We analyzed the results of 198 BCC cases cryosurgical treatment. 33 (16,6%) patients showed continued tumor growth. It has been hypothesized that the behavior and character of microcirculation changes during patient's testing have to correlate with damaging rate of tumors that will allow to develop indications for surgical treatment with local destruction - cryosurgery or cryolaser treatment. We have tested the new group of 33 patients with primary and recurrence types of basal cell carcinoma (BCC) by means of Laser Doppler Flowmetry, Tissues Reflectance Oximetry, Laser Fluorescence Diagnostics before operation. It was shown that the microcirculatory data indicates the presence of cryoresistance.

  14. Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma.

    PubMed

    Chahal, Harvind S; Wu, Wenting; Ransohoff, Katherine J; Yang, Lingyao; Hedlin, Haley; Desai, Manisha; Lin, Yuan; Dai, Hong-Ji; Qureshi, Abrar A; Li, Wen-Qing; Kraft, Peter; Hinds, David A; Tang, Jean Y; Han, Jiali; Sarin, Kavita Y

    2016-01-01

    Basal cell carcinoma (BCC) is the most common cancer worldwide with an annual incidence of 2.8 million cases in the United States alone. Previous studies have demonstrated an association between 21 distinct genetic loci and BCC risk. Here, we report the results of a two-stage genome-wide association study of BCC, totalling 17,187 cases and 287,054 controls. We confirm 17 previously reported loci and identify 14 new susceptibility loci reaching genome-wide significance (P<5 × 10(-8), logistic regression). These newly associated SNPs lie within predicted keratinocyte regulatory elements and in expression quantitative trait loci; furthermore, we identify candidate genes and non-coding RNAs involved in telomere maintenance, immune regulation and tumour progression, providing deeper insight into the pathogenesis of BCC. PMID:27539887

  15. Cutaneous basal cell carcinoma arising within a keloid scar: a case report.

    PubMed

    Goder, Maya; Kornhaber, Rachel; Bordoni, Daniele; Winkler, Eyal; Haik, Josef; Tessone, Ariel

    2016-01-01

    Basal cell carcinomas (BCCs) are one of the most frequent cutaneous malignancies. The majority of BCCs are reported to occur on the auricular helix and periauricular region due to ultraviolet light exposure. Despite the frequency of BCCs, those that develop within scar tissue are rare, and the phenomenon of keloid BCCs has rarely been reported in the literature. Keloid collagen within BCCs is associated with morphoeiform characteristics, ulceration, or necrosis. Extensive keloid collagen is often seen in BCCs of the ear region, a site prone to keloid scarring. This article presents a rare case of a secondary tumor (BCC) which arose on top of a primary tumor (keloid scar) on the right auricle region in a healthy 23-year-old female after an ear piercing 2 years prior. To our knowledge, the tumor described in this case, in contrast to keloidal BCCs, has never been reported in the literature. PMID:27536142

  16. Cutaneous basal cell carcinoma arising within a keloid scar: a case report

    PubMed Central

    Goder, Maya; Kornhaber, Rachel; Bordoni, Daniele; Winkler, Eyal; Haik, Josef; Tessone, Ariel

    2016-01-01

    Basal cell carcinomas (BCCs) are one of the most frequent cutaneous malignancies. The majority of BCCs are reported to occur on the auricular helix and periauricular region due to ultraviolet light exposure. Despite the frequency of BCCs, those that develop within scar tissue are rare, and the phenomenon of keloid BCCs has rarely been reported in the literature. Keloid collagen within BCCs is associated with morphoeiform characteristics, ulceration, or necrosis. Extensive keloid collagen is often seen in BCCs of the ear region, a site prone to keloid scarring. This article presents a rare case of a secondary tumor (BCC) which arose on top of a primary tumor (keloid scar) on the right auricle region in a healthy 23-year-old female after an ear piercing 2 years prior. To our knowledge, the tumor described in this case, in contrast to keloidal BCCs, has never been reported in the literature. PMID:27536142

  17. Advanced Basal cell carcinoma in a patient with schizoaffective disorder: constraints and management.

    PubMed

    Taylor, Elise J; Golas, Liliya; Martel, Joseph R; Martel, James B

    2013-01-01

    The approach used by the authors for managing a patient with a schizoaffective disorder and advanced basal cell carcinoma involving the eyelids, orbit, and face is presented. Complexities included the advanced nature of the disease, neglect of the patient's condition due to schizoaffective disorder, the difficulty of obtaining informed consent, the required aggressive surgical intervention, reconstruction, and the necessary management during the postsurgical period. A multidisciplinary team approach with psychiatry, ophthalmology, ear, nose, and throat, plastic surgery, radiation oncology, oncology, legal, and bioethics specialties is required in patients with cognitive disabilities. Curative treatment requires complete excision, reconstruction, and proper postoperative care, which can be prohibitive in a schizophrenic patient from a surgical and ethical perspective. Staging of this condition after proper informed consent with biopsy, computed tomography, and magnetic resonance imaging is presented. The options for management are discussed, including surgical intervention and palliative care. PMID:23235512

  18. Possible recurrence of keratocyst in nevoid basal cell carcinoma syndrome: A review of literature

    PubMed Central

    Tarakji, Bassel; Baroudi, Kusai; Hanouneh, Salah; Azzeghaiby, Saleh Naser; Nassani, Mohammad Zakaria

    2013-01-01

    This review will highlight some current areas of difficulty or controversy in diagnosis and treatment of nevoid basal cell carcinoma syndrome (NBCCS). The odontogenic keratocyst (OKC) has significant growth capacity and recurrence potential and is occasionally indicative of the NBCCS. The objective of this study is to clarify the causes of the recurrence of OKC in NBCCS. A literature search was conducted using Medline, accessed via the National Library of Medicine PubMed interface, searching for articles relating to the cause of recurrence of keratocyst in NBCCS written in English. This study has described the previous and the current outcomes of the treatment of OKC (recurrent cause). A protocol was then agreed to search for the possible causes of keratocyst recurrence in NBCCS. The general treatment of other manifestation of NBCCS has excluded from this study. Studies describing cohort, case series and miscellaneous clinical reports were retrieved and evaluated from 2010 to 2012. PMID:24966720

  19. Basal cell carcinoma: clues to its presence in histologic sections when the initial slide is nondiagnostic.

    PubMed

    Haupt, H M; Stern, J B; Dilaimy, M S

    2000-09-01

    Initial sections of skin biopsies may not be diagnostic of basal cell carcinoma (BCC). Are there histologic predictors of BCC that should prompt deeper sections? Ninety-four cases in which the clinical diagnosis was BCC or "rule-out BCC," and the initial histologic slides were nondiagnostic, were submitted for deeper sections on three additional slides. Of the 94 cases, 50 (53%) demonstrated BCC on deeper sections. This relatively high incidence suggests that deeper sections should be taken in all cases of clinically suspected BCCs unless alternate histologic findings adequately account for the clinical lesion. The results of this study suggest that additional sections are more likely to yield BCC when the initial nondiagnostic slide demonstrates focal epidermal atypia, equivocal adnexae, stromal fibrosis, empty dermal space, and microcalcifications, criteria which may be useful in determining the need to do deeper sections in cases in which BCC is not clinically suspected. PMID:10976705

  20. Tumor suppression in basal keratinocytes via dual non-cell-autonomous functions of a Na,K-ATPase beta subunit.

    PubMed

    Hatzold, Julia; Beleggia, Filippo; Herzig, Hannah; Altmüller, Janine; Nürnberg, Peter; Bloch, Wilhelm; Wollnik, Bernd; Hammerschmidt, Matthias

    2016-01-01

    The molecular pathways underlying tumor suppression are incompletely understood. Here, we identify cooperative non-cell-autonomous functions of a single gene that together provide a novel mechanism of tumor suppression in basal keratinocytes of zebrafish embryos. A loss-of-function mutation in atp1b1a, encoding the beta subunit of a Na,K-ATPase pump, causes edema and epidermal malignancy. Strikingly, basal cell carcinogenesis only occurs when Atp1b1a function is compromised in both the overlying periderm (resulting in compromised epithelial polarity and adhesiveness) and in kidney and heart (resulting in hypotonic stress). Blockade of the ensuing PI3K-AKT-mTORC1-NFκB-MMP9 pathway activation in basal cells, as well as systemic isotonicity, prevents malignant transformation. Our results identify hypotonic stress as a (previously unrecognized) contributor to tumor development and establish a novel paradigm of tumor suppression. PMID:27240166

  1. Basal Cell Carcinoma in Gorlin’s Patients: a Matter of Fibroblasts-Led Protumoral Microenvironment?

    PubMed Central

    Gache, Yannick; Brellier, Florence; Rouanet, Sophie; Al-Qaraghuli, Sahar; Goncalves-Maia, Maria; Burty-Valin, Elodie; Barnay, Stéphanie; Scarzello, Sabine; Ruat, Martial; Sevenet, Nicolas; Avril, Marie-Françoise; Magnaldo, Thierry

    2015-01-01

    Basal cell carcinoma (BCC) is the commonest tumor in human. About 70% sporadic BCCs bear somatic mutations in the PATCHED1 tumor suppressor gene which encodes the receptor for the Sonic Hedgehog morphogen (SHH). PATCHED1 germinal mutations are associated with the dominant Nevoid Basal Cell Carcinoma Syndrome (NBCCS), a major hallmark of which is a high susceptibility to BCCs. Although the vast majority of sporadic BCCs arises exclusively in sun exposed skin areas, 40 to 50% BCCs from NBCCS patients develop in non photo-exposed skin. Since overwhelming evidences indicate that microenvironment may both be modified by- and influence the- epithelial tumor, we hypothesized that NBCCS fibroblasts could contribute to BCCs in NBCCS patients, notably those developing in non photo-exposed skin areas. The functional impact of NBCCS fibroblasts was then assessed in organotypic skin cultures with control keratinocytes. Onset of epidermal differentiation was delayed in the presence of primary NBCCS fibroblasts. Unexpectedly, keratinocyte proliferation was severely reduced and showed high levels of nuclear P53 in both organotypic skin cultures and in fibroblast-led conditioning experiments. However, in spite of increased levels of senescence associated β-galactosidase activity in keratinocytes cultured in the presence of medium conditioned by NBCCS fibroblasts, we failed to observe activation of P16 and P21 and then of bona fide features of senescence. Constitutive extinction of P53 in WT keratinocytes resulted in an invasive phenotype in the presence of NBCCS fibroblasts. Finally, we found that expression of SHH was limited to fibroblasts but was dependent on the presence of keratinocytes. Inhibition of SHH binding resulted in improved epidermal morphogenesis. Altogether, these data suggest that the repertoire of diffusible factors (including SHH) expressed by primary NBCCS fibroblasts generate a stress affecting keratinocytes behavior and epidermal homeostasis. Our findings

  2. Progesterone generates cancer stem cells through membrane progesterone receptor-triggered signaling in basal-like human mammary cells.

    PubMed

    Vares, Guillaume; Sai, Sei; Wang, Bing; Fujimori, Akira; Nenoi, Mitsuru; Nakajima, Tetsuo

    2015-07-01

    Ionizing radiation and cumulative exposure to steroid hormones are known risk factors for breast cancer. There is increasing evidence that breast tumors are driven by a subpopulation of tumor-initiating cancer stem cells (CSCs). In MCF10A non-cancerous basal-like PR(-) cells, progesterone treatment and X-rays generated ALDH(+) and CD44(+)/CD24(-) CSCs. Here, we report that in irradiated MCF10A cells, progesterone activated the PI3K/Akt pathway via membrane progesterone receptor (mPR). Inhibition of the PI3K/Akt pathway counteracted the generation of CSCs by progesterone and irradiation. The stimulation of PI3K/Akt via mPR resulted in the inactivation of FOXO transcriptional activity, the upregulation of snail and slug expression and a downregulation of miR-29 expression, which led to increased levels of KLF4, a transcription factor required for breast CSC maintenance. Stabilization of miR-29 expression impeded the generation of CSCs, while its inhibition alone was sufficient to generate CSCs. This study provides a new mechanistic basis for progesterone and radiation-induced breast cancer risk in basal cells. In addition, the elucidation of new pathways and miRNA regulations involved in CSC generation and maintenance may open the door to potential novel anti-CSC strategies. PMID:25819032

  3. Basal and inducible anti-inflammatory epoxygenase activity in endothelial cells

    SciTech Connect

    Askari, Ara A.; Thomson, Scott; Edin, Matthew L.; Lih, Fred B.; Zeldin, Darryl C.; Bishop-Bailey, David

    2014-04-04

    Highlights: • We examined epoxygenase product formation and regulation in endothelial cells. • The epoxygenase CYP2J2 is an LPS (TLR-4) inducible enzyme in endothelial cells. • The endothelial cell line EA.Hy926 synthesises epoxygenase products. • Inhibition of endothelial epoxygenases increases TNFα secretion. • Soluble epoxide hydrolase inhibitors reduce inflammation-induced TNFα and NFκB. - Abstract: The roles of CYP lipid-metabolizing pathways in endothelial cells are poorly understood. Human endothelial cells expressed CYP2J2 and soluble epoxide hydrolase (sEH) mRNA and protein. The TLR-4 agonist LPS (1 μg/ml; 24 h) induced CYP2J2 but not sEH mRNA and protein. LC–MS/MS analysis of the stable commonly used human endothelial cell line EA.Hy926 showed active epoxygenase and epoxide hydrolase activity: with arachidonic acid (stable epoxide products 5,6-DHET, and 14,15-DHET), linoleic acid (9,10-EPOME and 12,13-EPOME and their stable epoxide hydrolase products 9,10-DHOME and 12,13-DHOME), docosahexaenoic acid (stable epoxide hydrolase product 19,20-DiHDPA) and eicosapentaenoic acid (stable epoxide hydrolase product 17,18-DHET) being formed. Inhibition of epoxygenases using either SKF525A or MS-PPOH induced TNFα release, but did not affect LPS, IL-1β, or phorbol-12-myristate-13-acetate (PMA)-induced TNFα release. In contrast, inhibition of soluble epoxide hydrolase by AUDA or TPPU inhibited basal, LPS, IL-1β and PMA induced TNFα release, and LPS-induced NFκB p65 nuclear translocation. In conclusion, human endothelial cells contain a TLR-4 regulated epoxygenase CYP2J2 and metabolize linoleic acid > eicosapentaenoic acid > arachidonic acid > docosahexaenoic acid to products with anti-inflammatory activity.

  4. Human sunlight-induced basal-cell-carcinoma-associated dendritic cells are deficient in T cell co-stimulatory molecules and are impaired as antigen-presenting cells.

    PubMed Central

    Nestle, F. O.; Burg, G.; Fäh, J.; Wrone-Smith, T.; Nickoloff, B. J.

    1997-01-01

    Immune surveillance of skin cancer involves the stimulation of effector T cells by tumor-derived antigens and antigen-presenting cells (APCs). An effective APC must not only display processed antigen in the context of MHC molecules but also express co-stimulatory molecules that are required to fully activate T cells. One of the most common cutaneous neoplasms is basal cell carcinoma. To investigate expression of the co-stimulatory molecules CD80 (B7-1) and CD86 (B7-2) on tumor-associated dendritic cells (TADCs), cryosections from basal cell carcinomas were immunostained. In basal cell carcinomas, only 1 to 2% of intratumor and 5 to 10% of peritumor APCs expressed CD80 or CD86. In contrast, biopsies of immunological/inflammatory dermatoses revealed that 38 to 73% of APCs expressed CD80 and CD86. To further evaluate their phenotype and function, TADCs were isolated from tissue samples of basal cell carcinomas; they were non-adherent to plastic, displayed a typical dendritic morphology, and expressed high levels of major histocompatibility class II molecules on their surface. When TADCs were compared with dendritic cells from blood for presentation of superantigens (staphylococcal enterotoxins A and B) to resting autologous T cells, TADCs were consistently weaker stimulators of T cell proliferation than blood dendritic cells. When analyzed by flow cytometry, TADCs expressed high levels of HLA-DR, but only 5 to 10% co-expressed CD80 or CD86. A 3-day culture in granulocyte/macrophage colony-stimulating factor-containing medium partially reconstituted the TADC expression of CD80 and CD86 as well as their immunostimulatory capacity. Thus, in this common skin cancer, although there are prominent collections of HLA-DR-positive APCs in and around tumor cells, the TADCs are deficient in important co-stimulatory molecules as well as being weak stimulators of T cell proliferation. The paucity of co-stimulatory molecule expression and functional activity of TADCs may explain why

  5. Multiple metastatic basal cell carcinoma with concurrent metastatic pleomorphic sarcoma in chronic lymphedema area--case report.

    PubMed

    Oliveira, Giuliano da Paz; Girão, Régio José Santiago; Soares, Cléverson Teixeira; Mello Junior, Edgard Jose Franco

    2012-01-01

    Chronic lymphedema presents as interstitial fluid retention due to a failure in the lymphatic system drainage. The affected region becomes more vulnerable immunologically and predisposed to the onset of neoplasms. Basal Cell Carcinoma is the most common sort of neoplasm, nevertheless it rarely metastisizes. Sarcomas are malignant mesenchymal neoplasms, locally aggressive, which can spread. Here is reported an infrequent case of multiple basal cell carcinoma, synchronous to a poorly differentiated pleomorphic sarcoma, both spreading to lymph nodes and arising from tissue compromised by chronic lymphedema. PMID:23197211

  6. Differential senescence capacities in meibomian gland carcinoma and basal cell carcinoma.

    PubMed

    Zhang, Leilei; Huang, Xiaolin; Zhu, Xiaowei; Ge, Shengfang; Gilson, Eric; Jia, Renbing; Ye, Jing; Fan, Xianqun

    2016-03-15

    Meibomian gland carcinoma (MGC) and basal cell carcinoma (BCC) are common eyelid carcinomas that exhibit highly dissimilar degrees of proliferation and prognoses. We address here the question of the differential mechanisms between these two eyelid cancers that explain their different outcome. A total of 102 confirmed MGC and 175 diagnosed BCC cases were analyzed. Twenty confirmed MGC and twenty diagnosed BCC cases were collected to determine the telomere length, the presence of senescent cells, and the expression levels of the telomere capping shelterin complex, P53, and the E3 ubiquitin ligase Siah1. Decreased protein levels of the shelterin subunits, shortened telomere length, over-expressed Ki-67, and Bcl2 as well as mutations in P53 were detected both in MGC and BCC. It suggests that the decreased protein levels of the shelterin complex and the shortened telomere length contribute to the tumorigenesis of MGC and BCC. However, several parameters distinguish MGC from BCC samples: (i) the mRNA level of the shelterin subunits decreased in MGC but it increased in BCC; (ii) P53 was more highly mutated in MGC; (iii) Siah1 mRNA was over-expressed in BCC; (iv) BCC samples contain a higher level of senescent cells; (v) Ki-67 and Bcl2 expression were lower in BCC. These results support a model where a preserved P53 checkpoint in BCC leads to cellular senescence and reduced tumor proliferation as compared to MGC. PMID:26437300

  7. Lutheran/basal cell adhesion molecule accelerates progression of crescentic glomerulonephritis in mice

    PubMed Central

    Huang, Jin; Filipe, Anne; Rahuel, Cécile; Bonnin, Philippe; Mesnard, Laurent; Guérin, Coralie; Wang, Yu; Le Van Kim, Caroline; Colin, Yves; Tharaux, Pierre-Louis

    2014-01-01

    Migration of circulating leukocytes from the vasculature into the surrounding tissue is an important component of the inflammatory response. Among the cell surface molecules identified as contributing to leukocyte extravasation is VCAM-1, expressed on activated vascular endothelium, which participates in all stages of leukocyte–endothelial interaction by binding to leukocyte surface expressed integrin VLA-4. However, not all VLA-4-mediated events can be linked to VCAM-1. A novel interaction between VLA-4 and endothelial Lutheran (Lu) blood group antigens and basal cell adhesion molecule (BCAM) proteins has been recently shown, suggesting that Lu/BCAM may have a role in leukocyte recruitments in inflamed tissues. Here, we assessed the participation of Lu/BCAM in the immunopathogenesis of crescentic glomerulonephritis. High expression of Lu/BCAM in glomeruli of mice with rapidly progressive glomerulonephritis suggests a potential role for the local expression of Lu/BCAM in nephritogenic recruitment of leukocytes. Genetic deficiency of Lu/BCAM attenuated glomerular accumulation of T cells and macrophages, crescent formation, and proteinuria, correlating with reduced fibrin and platelet deposition in glomeruli. Furthermore, we found a pro-adhesive interaction between human monocyte α4β1 integrin and Lu/BCAM proteins. Thus, Lu/BCAM may have a critical role in facilitating the accumulation of monocytes and macrophages, thereby exacerbating renal injury. PMID:24429403

  8. Higher sensitivity to cadmium induced cell death of basal forebrain cholinergic neurons: a cholinesterase dependent mechanism.

    PubMed

    Del Pino, Javier; Zeballos, Garbriela; Anadon, María José; Capo, Miguel Andrés; Díaz, María Jesús; García, Jimena; Frejo, María Teresa

    2014-11-01

    Cadmium is an environmental pollutant, which is a cause of concern because it can be greatly concentrated in the organism causing severe damage to a variety of organs including the nervous system which is one of the most affected. Cadmium has been reported to produce learning and memory dysfunctions and Alzheimer like symptoms, though the mechanism is unknown. On the other hand, cholinergic system in central nervous system (CNS) is implicated on learning and memory regulation, and it has been reported that cadmium can affect cholinergic transmission and it can also induce selective toxicity on cholinergic system at peripheral level, producing cholinergic neurons loss, which may explain cadmium effects on learning and memory processes if produced on central level. The present study is aimed at researching the selective neurotoxicity induced by cadmium on cholinergic system in CNS. For this purpose we evaluated, in basal forebrain region, the cadmium toxic effects on neuronal viability and the cholinergic mechanisms related to it on NS56 cholinergic mourine septal cell line. This study proves that cadmium induces a more pronounced, but not selective, cell death on acetylcholinesterase (AChE) on cholinergic neurons. Moreover, MTT and LDH assays showed a dose dependent decrease of cell viability in NS56 cells. The ACh treatment of SN56 cells did not revert cell viability reduction induced by cadmium, but siRNA transfection against AChE partially reduced it. Our present results provide new understanding of the mechanisms contributing to the harmful effects of cadmium on the function and viability of neurons, and the possible relevance of cadmium in the pathogenesis of neurodegenerative diseases. PMID:25201352

  9. Glucocorticoids Inhibit Basal and Hormone-Induced Serotonin Synthesis in Pancreatic Beta Cells

    PubMed Central

    Hasni Ebou, Moina; Singh-Estivalet, Amrit; Launay, Jean-Marie; Callebert, Jacques; Tronche, François; Ferré, Pascal; Gautier, Jean-François; Guillemain, Ghislaine; Bréant, Bernadette

    2016-01-01

    Diabetes is a major complication of chronic Glucocorticoids (GCs) treatment. GCs induce insulin resistance and also inhibit insulin secretion from pancreatic beta cells. Yet, a full understanding of this negative regulation remains to be deciphered. In the present study, we investigated whether GCs could inhibit serotonin synthesis in beta cell since this neurotransmitter has been shown to be involved in the regulation of insulin secretion. To this aim, serotonin synthesis was evaluated in vitro after treatment with GCs of either islets from CD1 mice or MIN6 cells, a beta-cell line. We also explored the effect of GCs on the stimulation of serotonin synthesis by several hormones such as prolactin and GLP 1. We finally studied this regulation in islet in two in vivo models: mice treated with GCs and with liraglutide, a GLP1 analog, and mice deleted for the glucocorticoid receptor in the pancreas. We showed in isolated islets and MIN6 cells that GCs decreased expression and activity of the two key enzymes of serotonin synthesis, Tryptophan Hydroxylase 1 (Tph1) and 2 (Tph2), leading to reduced serotonin contents. GCs also blocked the induction of serotonin synthesis by prolactin or by a previously unknown serotonin activator, the GLP-1 analog exendin-4. In vivo, activation of the Glucagon-like-Peptide-1 receptor with liraglutide during 4 weeks increased islet serotonin contents and GCs treatment prevented this increase. Finally, islets from mice deleted for the GR in the pancreas displayed an increased expression of Tph1 and Tph2 and a strong increased serotonin content per islet. In conclusion, our results demonstrate an original inhibition of serotonin synthesis by GCs, both in basal condition and after stimulation by prolactin or activators of the GLP-1 receptor. This regulation may contribute to the deleterious effects of GCs on beta cells. PMID:26901633

  10. Defined conditions for the isolation and expansion of basal prostate progenitor cells of mouse and human origin.

    PubMed

    Höfner, Thomas; Eisen, Christian; Klein, Corinna; Rigo-Watermeier, Teresa; Goeppinger, Stephan M; Jauch, Anna; Schoell, Brigitte; Vogel, Vanessa; Noll, Elisa; Weichert, Wilko; Baccelli, Irène; Schillert, Anja; Wagner, Steve; Pahernik, Sascha; Sprick, Martin R; Trumpp, Andreas

    2015-03-10

    Methods to isolate and culture primary prostate epithelial stem/progenitor cells (PESCs) have proven difficult and ineffective. Here, we present a method to grow and expand both murine and human basal PESCs long term in serum- and feeder-free conditions. The method enriches for adherent mouse basal PESCs with a Lin(-)SCA-1(+)CD49f(+)TROP2(high) phenotype. Progesterone and sodium selenite are additionally required for the growth of human Lin(-)CD49f(+)TROP2(high) PESCs. The gene-expression profiles of expanded basal PESCs show similarities to ESCs, and NF-kB function is critical for epithelial differentiation of sphere-cultured PESCs. When transplanted in combination with urogenital sinus mesenchyme, expanded mouse and human PESCs generate ectopic prostatic tubules, demonstrating their stem cell activity in vivo. This novel method will facilitate the molecular, genomic, and functional characterization of normal and pathologic prostate glands of mouse and human origin. PMID:25702639

  11. Role of urokinase and its receptor in basal and stimulated colonic epithelial cell migration in vitro

    PubMed Central

    Wilson, A; Gibson, P

    2000-01-01

    BACKGROUND—Migration of colonic epithelial cells is important for mucosal repair following injury. The urokinase (u-PA) system regulates migration in other cell types.
AIM—To examine the role of u-PA and its receptor (u-PAR) in colonic epithelial cell migration.
METHODS—Migration was assessed over 24 hours in circular wounds made in confluent monolayers of LIM1215 and Caco-2 human colon cancer cells. The function of u-PA and u-PAR was ablated with antisense oligonucleotides to block expression, with synthetic u-PA peptides to block interaction, and with aprotinin to block u-PA mediated proteolysis.
RESULTS—Migration was stimulated two to threefold by exogenous u-PA, an effect dependent on u-PAR binding but independent of u-PA mediated mitogenesis and proteolysis. Expression of u-PA and u-PAR was inhibited by 80% by the appropriate antisense oligonucleotide. Basal migration and the motogenic effects of butyrate, epidermal growth factor, and phorbol-12-myristate-13-acetate were suppressed by the u-PAR antisense oligonucleotide (40-60%) but were at best minimally affected following inhibition of u-PA expression and binding. 
CONCLUSIONS—In an in vitro model of wounded colonic epithelium, u-PAR promotes cell migration through mechanisms that are not exclusively dependent on u-PA binding. Therefore, u-PA and u-PAR may contribute to colonic mucosal repair in vivo.


Keywords: colon; migration; urokinase; urokinase receptor; epidermal growth factor; butyrate; protein kinase C PMID:10861271

  12. Interaction of basal positive and negative transcription elements controls repression of the proximal rat prolactin promoter in nonpituitary cells.

    PubMed Central

    Jackson, S M; Keech, C A; Williamson, D J; Gutierrez-Hartmann, A

    1992-01-01

    The proximal rat prolactin (rPRL) promoter contains three cell-specific elements, designated footprints I, III, and IV, which restrict rPRL gene expression to anterior pituitary lactotroph cells. Footprint II (-130 to -120) binds a factor, which we have termed F2F, present in pituitary and nonpituitary cell types. Here we demonstrate that a key role of the footprint II site is to inhibit rPRL promoter activity in nonpituitary cells, specifically, by interfering with the basal activating function of a vicinal element. Gene transfer analysis revealed 20-fold activation of the rPRL promoter in nonpituitary cell types when footprint II was either deleted or specifically mutated. Similar activation of the intact rPRL promoter was obtained by in vivo F2F titration studies. In GH4 rat pituitary cells, the footprint II inhibitory activity was masked by the redundant, positively acting cell-specific elements and was inhibitory only if the two upstream sites, footprints III and IV, were deleted. Deletion of the -112 to -80 region in the footprint II site-specific mutant background resulted in complete loss of rPRL promoter activity in both pituitary and nonpituitary cell types, mapping a basal activating element that is operative irrespective of cell type to this region. While the basal activating element imparted an activating function in a heterologous promoter assay, the footprint II sequence did not display any inherent repressor function and actually induced several minimal heterologous promoters. However, the inhibitory activity of the footprint II site was detected only if it was in context with the basal activating element. These data underscore the importance of ubiquitous activating and inhibitory factors in establishing cell-specific gene expression and further emphasize the complexity of the molecular mechanisms which restrict gene expression to specific cell types. We provide a novel paradigm to study rPRL promoter function and hormone responsiveness

  13. Germline BAP1 mutations predispose also to multiple basal cell carcinomas.

    PubMed

    de la Fouchardière, A; Cabaret, O; Savin, L; Combemale, P; Schvartz, H; Penet, C; Bonadona, V; Soufir, N; Bressac-de Paillerets, B

    2015-09-01

    The BRCA1-associated protein 1 (BAP1) gene encodes a nuclear deubiquitin enzyme which acts as a tumour suppressor. Loss of function germline mutations of BAP1 have been associated with an enhanced risk of uveal and cutaneous melanomas, mesothelioma, clear cell renal cancer and atypical cutaneous melanocytic proliferations. In two independent BAP1 families, we noticed an unusual frequency of basal cell carcinomas (BCCs). Indeed, 19 BCCs were diagnosed in four patients, either of superficial (13/19) or nodular (6/19) subtype; they were all located in chronic sun-exposed areas (limbs, head or neck). Immunohistochemistry (IHC) identified in the 19 tumours, complete or partial loss of BAP1 protein nuclear expression, restricted to the BCC nests. A control study was conducted in 22 sporadic BCCs in 22 subjects under 65 without known associated BAP1 tumours: no loss of BAP1 expression was found. Overall, our observations suggest that BCCs are part of the BAP1 cancer syndrome, perhaps in relation with chronic sun exposure and melanocortin 1 receptor (MC1R) variants. In conclusion, cutaneous follow-up of BAP1 carriers should not only aim to detect melanocytic neoplasms but also BCCs. PMID:25080371

  14. Molecular classification of basal cell carcinoma of skin by gene expression profiling.

    PubMed

    Jee, Byul A; Lim, Hyoseob; Kwon, So Mee; Jo, Yuna; Park, Myong Chul; Lee, Il Jae; Woo, Hyun Goo

    2015-12-01

    Non-melanoma skin cancers (NMSC) including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are more common kinds of skin cancer. Although these tumors share common pathological and clinical features, their similarity and heterogeneity at molecular levels are not fully elaborated yet. Here, by performing comparative analysis of gene expression profiling of BCC, SCC, and normal skin tissues, we could classify the BCC into three subtypes of classical, SCC-like, and normal-like BCCs. Functional enrichment and pathway analyses revealed the molecular characteristics of each subtype. The classical BCC showed the enriched expression and transcription signature with the activation of Wnt and Hedgehog signaling pathways, which were well known key features of BCC. By contrast, the SCC-like BCC was enriched with immune-response genes and oxidative stress-related genes. Network analysis revealed the PLAU/PLAUR as a key regulator of SCC-like BCC. The normal-like BCC showed prominent activation of metabolic processes particularly the fatty acid metabolism. The existence of these molecular subtypes could be validated in an independent dataset, which demonstrated the three subgroups of BCC with distinct functional enrichment. In conclusion, we suggest a novel molecular classification of BCC providing insights on the heterogeneous progression of BCC. PMID:25328065

  15. Nanostructured lipid carrier in photodynamic therapy for the treatment of basal-cell carcinoma.

    PubMed

    Qidwai, Afreen; Khan, Saba; Md, Shadab; Fazil, Mohammad; Baboota, Sanjula; Narang, Jasjeet K; Ali, Javed

    2016-05-01

    Topical photodynamic therapy (PDT) is a promising alternative for malignant skin diseases such as basal-cell carcinoma (BCC), due to its simplicity, enhanced patient compliance, and localization of the residual photosensitivity to the site of application. However, insufficient photosensitizer penetration into the skin is the major issue of concern with topical PDT. Therefore, the aim of the present study was to enable penetration of photosensitizer to the different strata of the skin using a lipid nanocarrier system. We have attempted to develop a nanostructured lipid carrier (NLC) for the topical delivery of second-generation photosensitizer, 5-amino levulinic acid (5-ALA), whose hydrophilicity and charge characteristic limit its percutaneous absorption. The microemulsion technique was used for preparing 5-ALA-loaded NLC. The mean particle size, polydispersity index, and entrapment efficiency of the optimized NLC of 5-ALA were found to be 185.2 ± 1.20, 0.156 ± 0.02, and 76.8 ± 2.58%, respectively. The results of in vitro release and in vitro skin permeation studies showed controlled drug release and enhanced penetration into the skin, respectively. Confocal laser scanning microscopy and cell line studies respectively demonstrated that encapsulation of 5-ALA in NLC enhanced its ability to reach deeper skin layers and consequently, increased cytotoxicity. PMID:26978275

  16. Significance of androgen receptor and CD10 expression in cutaneous basal cell carcinoma and trichoepithelioma

    PubMed Central

    ASTARCI, HESNA M.; GURBUZ, GULFEM A.; SENGUL, DEMET; HUCUMENOGLU, SEMA; KOCER, UGUR; USTUN, HUSEYIN

    2015-01-01

    Differential diagnosis of trichoepithelioma (TE) and basal cell carcinoma (BCC) on the basis of clinical symptoms and laboratory investigations may be difficult in certain patients. The aim of the present study was to compare cluster of differentiation 10 (CD10) and androgen receptor (AR) expression patterns in BCC and TE, to investigate the predictive power of these proteins as markers of the two conditions. A total of 39 cases of BCC and 15 cases of TE were retrieved from the pathology department archives. AR and CD10 immunohistochemistry was performed on all of the specimens; 23 BCC cases displayed focal nuclear AR staining, however, none of the cases demonstrated diffuse nuclear staining and 16 BCC cases were negative for AR staining. Stromal CD10 staining was more common in TE cases than in BCC cases, and peripheral CD10 staining was more common in BCC cases than in TE cases. AR immunostaining of the BCC samples typically appeared as scattered clusters and individual cells. In addition, AR and CD10 staining exhibited varying staining intensities within each samples. Incisional punch biopsy specimens have the potential to present false-negative results. Therefore, AR and CD10 staining of total excision biopsies provides a more accurate differential diagnosis of BCC and TE for cases with difficulties in the histopathological analysis. PMID:26788151

  17. Gene Expression and Proteome Analysis as Sources of Biomarkers in Basal Cell Carcinoma

    PubMed Central

    Ghita, Mihaela Adriana; Voiculescu, Suzana; Rosca, Adrian E.; Moraru, Liliana; Greabu, Maria

    2016-01-01

    Basal cell carcinoma (BCC) is the world's leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC. PMID:27578920

  18. Oocyte glycoproteins regulate the form and function of the follicle basal lamina and theca cells.

    PubMed

    Christensen, Alice P; Patel, Saloni H; Grasa, Patricia; Christian, Helen C; Williams, Suzannah A

    2015-05-15

    Maintaining follicle integrity during development, whereby each follicle is a functional unit containing a single oocyte, is essential for the generation of healthy oocytes. However, the mechanisms that regulate this critical function have not been determined. In this paper we investigate the role of the oocyte in maintaining follicle development. To investigate this role, we use a mouse model with oocyte-specific deletion of C1galt1 which is required for the generation of core 1-derived O-glycans. The loss of oocyte-generated O-glycans results in the joining of follicles and the generation of Multiple-Oocyte Follicles (MOFs). The aim was to determine how Mutant follicle development is modified thus enabling follicles to join. Extracellular matrix and follicle permeability were studied using histology, immunohistochemistry and electron microscopy (EM). In ovaries containing Mutant Oocytes, the Follicle basal lamina (FBL) is altered both functionally and structurally from the primary stage onwards with Mutant follicles possessing unexpectedly thicker FBL. In Mutant ovaries, the theca cell layer is also modified with intermingling of theca between adjacent follicles. MOF function was analysed but despite increased numbers of preantral MOFs in Mutants, these do not reach the preovulatory stage after gonadotrophin stimulation. We propose a model describing how oocyte initiated changes in FBL and theca cells result in follicles joining. These data reveal new and important roles for the oocyte in follicle development and follicle integrity. PMID:25557622

  19. Diagnosis of basal cell carcinoma by two photon excited fluorescence combined with lifetime imaging

    NASA Astrophysics Data System (ADS)

    Fan, Shunping; Peng, Xiao; Liu, Lixin; Liu, Shaoxiong; Lu, Yuan; Qu, Junle

    2014-02-01

    Basal cell carcinoma (BCC) is the most common type of human skin cancer. The traditional diagnostic procedure of BCC is histological examination with haematoxylin and eosin staining of the tissue biopsy. In order to reduce complexity of the diagnosis procedure, a number of noninvasive optical methods have been applied in skin examination, for example, multiphoton tomography (MPT) and fluorescence lifetime imaging microscopy (FLIM). In this study, we explored two-photon optical tomography of human skin specimens using two-photon excited autofluorescence imaging and FLIM. There are a number of naturally endogenous fluorophores in skin sample, such as keratin, melanin, collagen, elastin, flavin and porphyrin. Confocal microscopy was used to obtain structures of the sample. Properties of epidermic and cancer cells were characterized by fluorescence emission spectra, as well as fluorescence lifetime imaging. Our results show that two-photon autofluorescence lifetime imaging can provide accurate optical biopsies with subcellular resolution and is potentially a quantitative optical diagnostic method in skin cancer diagnosis.

  20. Gene Expression and Proteome Analysis as Sources of Biomarkers in Basal Cell Carcinoma.

    PubMed

    Lupu, Mihai; Caruntu, Constantin; Ghita, Mihaela Adriana; Voiculescu, Vlad; Voiculescu, Suzana; Rosca, Adrian E; Caruntu, Ana; Moraru, Liliana; Popa, Iris Maria; Calenic, Bogdan; Greabu, Maria; Costea, Daniela Elena

    2016-01-01

    Basal cell carcinoma (BCC) is the world's leading skin cancer in terms of frequency at the moment and its incidence continues to rise each year, leading to profound negative psychosocial and economic consequences. UV exposure is the most important environmental factor in the development of BCC in genetically predisposed individuals, this being reflected by the anatomical distribution of lesions mainly on sun-exposed skin areas. Early diagnosis and prompt management are of crucial importance in order to prevent local tissue destruction and subsequent disfigurement. Although various noninvasive or minimal invasive techniques have demonstrated their utility in increasing diagnostic accuracy of BCC and progress has been made in its treatment options, recurrent, aggressive, and metastatic variants of BCC still pose significant challenge for the healthcare system. Analysis of gene expression and proteomic profiling of tumor cells and of tumoral microenvironment in various tissues strongly suggests that certain molecules involved in skin cancer pathogenic pathways might represent novel predictive and prognostic biomarkers in BCC. PMID:27578920

  1. Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

    PubMed Central

    Savoia, Paola; Deboli, Tommaso; Previgliano, Alberto; Broganelli, Paolo

    2015-01-01

    Basal cell carcinoma (BCC) is the most common cancer in individuals with fair skin type (I–II) and steadily increasing in incidence (70% of skin malignancy). It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT) has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC. PMID:26426005

  2. Stochastic homeostasis in human airway epithelium is achieved by neutral competition of basal cell progenitors

    PubMed Central

    Teixeira, Vitor H; Nadarajan, Parthiban; Graham, Trevor A; Pipinikas, Christodoulos P; Brown, James M; Falzon, Mary; Nye, Emma; Poulsom, Richard; Lawrence, David; Wright, Nicholas A; McDonald, Stuart; Giangreco, Adam; Simons, Benjamin D; Janes, Sam M

    2013-01-01

    Lineage tracing approaches have provided new insights into the cellular mechanisms that support tissue homeostasis in mice. However, the relevance of these discoveries to human epithelial homeostasis and its alterations in disease is unknown. By developing a novel quantitative approach for the analysis of somatic mitochondrial mutations that are accumulated over time, we demonstrate that the human upper airway epithelium is maintained by an equipotent basal progenitor cell population, in which the chance loss of cells due to lineage commitment is perfectly compensated by the duplication of neighbours, leading to “neutral drift” of the clone population. Further, we show that this process is accelerated in the airways of smokers, leading to intensified clonal consolidation and providing a background for tumorigenesis. This study provides a benchmark to show how somatic mutations provide quantitative information on homeostatic growth in human tissues, and a platform to explore factors leading to dysregulation and disease. DOI: http://dx.doi.org/10.7554/eLife.00966.001 PMID:24151545

  3. Usefulness of (18)F-FDG PET/CT in recurrent basal cell carcinoma: Report of a case.

    PubMed

    Ayala, S; Perlaza, P; Puig, S; Prats, E; Vidal-Sicart, S

    2016-01-01

    We analyze the case of a patient with left periorbital infiltrating basal cell carcinoma treated with surgical excision in October 2010. Surgery included orbital exenteration and reconstruction using skin graft and radiotherapy. In May 2013 a MR imaging showed a mass in the left orbital fossa, suggesting a recurrence in the graft. A basal cell carcinoma recurrence with perineural invasion was confirmed in the biopsy. On (18)F-FDG PET/CT performed, a hypermetabolic activity was observed in the left periorbital area with extension to surrounding sinus and bones. The use of (18)F-FDG PET/CT in patients with advanced basal cell carcinoma has not been fully explored due to the rarity of this entity. This case demonstrates the usefulness of this technique to determine the extent of non-melanocytic recurrent skin tumors, and its value in the staging and treatment control, supporting the incorporation of (18)F-FDG PET/CT in the management of advanced basal cell carcinoma. PMID:26522004

  4. Basal and inducible anti-inflammatory epoxygenase activity in endothelial cells

    PubMed Central

    Askari, Ara A.; Thomson, Scott; Edin, Matthew L.; Lih, Fred B.; Zeldin, Darryl C.; Bishop-Bailey, David

    2014-01-01

    The roles of CYP lipid-metabolizing pathways in endothelial cells are poorly understood. Human endothelial cells expressed CYP2J2 and soluble epoxide hydrolase (sEH) mRNA and protein. The TLR-4 agonist LPS (1 μg/ml; 24 h) induced CYP2J2 but not sEH mRNA and protein. LC–MS/MS analysis of the stable commonly used human endothelial cell line EA.Hy926 showed active epoxygenase and epoxide hydrolase activity: with arachidonic acid (stable epoxide products 5,6-DHET, and 14,15-DHET), linoleic acid (9,10-EPOME and 12,13-EPOME and their stable epoxide hydrolase products 9,10-DHOME and 12,13-DHOME), docosahexaenoic acid (stable epoxide hydrolase product 19,20-DiHDPA) and eicosapentaenoic acid (stable epoxide hydrolase product 17,18-DHET) being formed. Inhibition of epoxygenases using either SKF525A or MS-PPOH induced TNFα release, but did not affect LPS, IL-1β, or phorbol-12-myristate-13-acetate (PMA)-induced TNFα release. In contrast, inhibition of soluble epoxide hydrolase by AUDA or TPPU inhibited basal, LPS, IL-1β and PMA induced TNFα release, and LPS-induced NFκB p65 nuclear translocation. In conclusion, human endothelial cells contain a TLR-4 regulated epoxygenase CYP2J2 and metabolize linoleic acid > eicosapentaenoic acid > arachidonic acid > docosahexaenoic acid to products with anti-inflammatory activity. PMID:24631907

  5. A case of multiple atypical nevi with co-localized Basal cell carcinomas on the scalp: insight into the pathogenesis.

    PubMed

    Ellis, Lixia Z; Cohen, Joel L; High, Whitney; Scholz, Theresa A

    2015-05-01

    The authors report a case of a 29-year-old female with multiple lesions on the scalp containing an atypical nevus and a co-localized basal cell carcinoma (BCC) in the same specimen. This is the first description of such a case in the literature. The peculiar co-existence of these 2 neoplasms in the same specimen in multiple skin lesions raises the possibility of an unknown mutation(s) that increases the risk of developing both conditions; and this case illustrates that the signaling pathways mediating the development of atypical nevi may interact with those associated with BCCs. Additionally, crosstalk between melanocytes and basal keratinocytes, which are both located in the basal layer of the epidermis, may contribute to the development of these coexisting neoplasms. PMID:25942670

  6. Basal Glutathionylation of Na,K-ATPase α-Subunit Depends on Redox Status of Cells during the Enzyme Biosynthesis

    PubMed Central

    Mitkevich, Vladimir A.; Petrushanko, Irina Yu.; Poluektov, Yuri M.; Burnysheva, Ksenia M.; Lakunina, Valentina A.; Anashkina, Anastasia A.; Makarov, Alexander A.

    2016-01-01

    Many viruses induce oxidative stress and cause S-glutathionylation of Cys residues of the host and viral proteins. Changes in cell functioning during viral infection may be associated with glutathionylation of a number of key proteins including Na,K-ATPase which creates a gradient of sodium and potassium ions. It was found that Na,K-ATPase α-subunit has a basal glutathionylation which is not abrogated by reducing agent. We have shown that acute hypoxia leads to increase of total glutathionylation level of Na,K-ATPase α-subunit; however, basal glutathionylation of α-subunit increases under prolonged hypoxia only. The role of basal glutathionylation in Na,K-ATPase function remains unclear. Understanding significance of basal glutathionylation is complicated by the fact that there are no X-ray structures of Na,K-ATPase with the identified glutathione molecules. We have analyzed all X-ray structures of the Na,K-ATPase α-subunit from pig kidney and found that there are a number of isolated cavities with unresolved electron density close to the relevant cysteine residues. Analysis of the structures showed that this unresolved density in the structure can be occupied by glutathione associated with cysteine residues. Here, we discuss the role of basal glutathionylation of Na,K-ATPase α-subunit and provide evidence supporting the view that this modification is cotranslational. PMID:27239254

  7. Effect of intercalated cell-specific Rh C glycoprotein deletion on basal and metabolic acidosis-stimulated renal ammonia excretion

    PubMed Central

    Lee, Hyun-Wook; Verlander, Jill W.; Bishop, Jesse M.; Nelson, Raoul D.; Handlogten, Mary E.

    2010-01-01

    Rh C glycoprotein (Rhcg) is an NH3-specific transporter expressed in both intercalated cells (IC) and principal cells (PC) in the renal collecting duct. Recent studies show that deletion of Rhcg from both intercalated and principal cells inhibits both basal and acidosis-stimulated renal ammonia excretion. The purpose of the current studies was to better understand the specific role of Rhcg expression in intercalated cells in basal and metabolic acidosis-stimulated renal ammonia excretion. We generated mice with intercalated cell-specific Rhcg deletion (IC-Rhcg-KO) using Cre-loxP techniques; control (C) mice were floxed Rhcg but Cre negative. Under basal conditions, IC-Rhcg-KO and C mice excreted urine with similar ammonia content and pH. Mice were then acid loaded by adding HCl to their diet. Ammonia excretion after acid loading increased similarly in IC-Rhcg-KO and C mice during the first 2 days of acid loading but on day 3 was significantly less in IC-Rhcg-KO than in C mice. During the first 2 days of acid loading, urine was significantly more acidic in IC-Rhcg-KO mice than in C mice; there was no difference on day 3. In IC-Rhcg-KO mice, acid loading increased principal cell Rhcg expression in both the cortex and outer medulla as well as expression of another ammonia transporter, Rh glycoprotein B (Rhbg), in principal cells in the outer medulla. We conclude that 1) Rhcg expression in intercalated cells is necessary for the normal renal response to metabolic acidosis; 2) principal cell Rhcg contributes to both basal and acidosis-stimulated ammonia excretion; and 3) adaptations in Rhbg expression occur in response to acid-loading. PMID:20462967

  8. Genetic factors associated with naevus count and dermoscopic patterns: preliminary results from the Study of Nevi in Children (SONIC)

    PubMed Central

    Orlow, I; Satagopan, JM; Berwick, M; Enriquez, HL; White, KAM; Cheung, K; Dusza, SW; Oliveria, SA; Marchetti, MA; Scope, A; Marghoob, AA; Halpern, AC

    2015-01-01

    Background Melanocytic naevi are an important risk factor for melanoma. Naevi with distinct dermoscopic patterns can differ in size, distribution and host pigmentation characteristics. Objectives We examined MC1R and 85 other candidate loci in a cohort of children to test the hypothesis that the development and dermoscopic type of naevi are modulated by genetic variants. Methods Buccal DNAs were obtained from a cohort of 353 fifth graders (mean age 10·4 years). Polymorphisms were chosen based on a known or anticipated role in naevi and melanoma. Associations between single-nucleotide polymorphisms (SNPs) and baseline naevus count were determined by multivariate regression adjusting for sex, race/ethnicity and sun sensitivity. Dermoscopic images were available for 853 naevi from 290 children. Associations between SNPs and dermoscopic patterns were determined by polytomous regression. Results Four SNPs were significantly associated with increasing (IRF4) or decreasing (PARP1, CDK6 and PLA2G6) naevus count in multivariate shrinkage analyses with all SNPs included in the model; IRF4 rs12203952 showed the strongest association with log naevus count (relative risk 1·56, P < 0·001). Using homogeneous naevi as the reference, IRF4 rs12203952 and four other SNPs in TERT, CDKN1B, MTAP and PARP1 were associated with either globular or reticular dermoscopic patterns (P < 0·05). Conclusions Our results provide evidence that subsets of naevi defined by dermoscopic patterns differ in their associations with germline genotypes and support the hypothesis that dermoscopically defined subsets of naevi are biologically distinct. These results require confirmation in larger cohorts. If confirmed, these findings will improve the current knowledge of naevogenesis and assist in the identification of individuals with high-risk phenotypes. PMID:25307738

  9. Conditional cell ablation via diphtheria toxin reveals distinct requirements for the basal plate in the regional identity of diencephalic subpopulations.

    PubMed

    Lee, Bumwhee; Lam, Duc Tri; Baek, Kwanghee; Yoon, Jaeseung; Jeong, Yongsu

    2015-06-01

    The mammalian diencephalon is the caudal derivative of the embryonic forebrain. Early events in diencephalic regionalization include its subdivision along the dorsoventral and anteroposterior axes. The prosomeric model by Puelles and Rubenstein (1993) suggests that the alar plate of the posterior diencephalon is partitioned into three different prosomeres (designated p1-p3), which develop into the pretectum, thalamus, and prethalamus, respectively. Here, we report the developmental consequences of genetic ablation of cell populations from the diencephalic basal plate. The strategy for conditionally regulated cell ablation is based on the targeted expression of the diphtheria toxin gene (DTA) to the diencephalic basal plate via tamoxifen- induced, Cre-mediated recombination of the ROSA(DTA) allele. We show that activation of DTA leads to specific cell loss in the basal plate of the posterior diencephalon, and disrupted early regionalization of distinct alar territories. In the basal plate-deficient embryos, the p1 alar plate exhibited reduced expression of subtype-specific markers in the pretectum, whereas p2 alar plate failed to further subdivide into two discrete thalamic subpopulations. We also show that these defects lead to abnormal nuclear organization at later developmental stages. Our data have implications for increased understanding of the interactive roles between discrete diencephalic compartments. PMID:25950659

  10. Rab35 GTPase couples cell division with initiation of epithelial apico-basal polarity and lumen opening

    PubMed Central

    Klinkert, Kerstin; Rocancourt, Murielle; Houdusse, Anne; Echard, Arnaud

    2016-01-01

    Establishment and maintenance of apico-basal polarity in epithelial organs must be tightly coupled with cell division, but the underlying molecular mechanisms are largely unknown. Using 3D cultures of renal MDCK cells (cysts), we found that the Rab35 GTPase plays a crucial role in polarity initiation and apical lumen positioning during the first cell division of cyst development. At the molecular level, Rab35 physically couples cytokinesis with the initiation of apico-basal polarity by tethering intracellular vesicles containing key apical determinants at the cleavage site. These vesicles transport aPKC, Cdc42, Crumbs3 and the lumen-promoting factor Podocalyxin, and are tethered through a direct interaction between Rab35 and the cytoplasmic tail of Podocalyxin. Consequently, Rab35 inactivation leads to complete inversion of apico-basal polarity in 3D cysts. This novel and unconventional mode of Rab-dependent vesicle targeting provides a simple mechanism for triggering both initiation of apico-basal polarity and lumen opening at the centre of cysts. PMID:27040773