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Sample records for adenocarcinoma vesical presentacion

  1. Mustards and Vesicants

    SciTech Connect

    Young, Robert A; Bast, Cheryl B

    2009-01-01

    Vesicants (sulfur mustards, lewisite, and nitrogen mustards) are chemicals that cause blistering of the skin. Developed as chemical warfare agents, their biological activity is complex and not fully understood. These vesicants in liquid or vapor form are capable of causing injury to most any tissue. Contact with the skin results in erythema and blistering. Exposure to vapors produces ocular and respiratory effects which occur at exposures below those causing dermal effects. Systemic and long-lasting effects may occur, especially following acute exposures that result in severe injury. Multi-organ involvement and fluid loss shock resulting in death may follow severe exposures. As alkylating agents, all of the mustards are known or potential carcinogens. The carcinogenic potential of lewisite in humans is equivocal. Toxicity data in animals are available for the vesicants although data on sulfur mustard and lewisite are more extensive than for the nitrogen mustards. Data from tests with human volunteers and occupational exposure information are also available. These data collectively have provided a basis for the development of exposure standards, guidelines, and criteria for use in emergency planning and emergency response, and remediation efforts. The mode of action of the vesicants is complex, not fully understood, and represents an ongoing area of investigation especially with respect to treatment of vesicant-induced injury. Prevention of exposure and decontamination are critical initial steps in eliminating or minimizing injury. With the exception of arsenic chelating antidotes (e.g., British anti-lewisite; BAL) for lewisite, no antidotes exist for the vesicant agents. Medical management currently focuses on palliative treatment of signs and symptoms.

  2. Vesicant chemotherapy extravasation antidotes and treatments.

    PubMed

    Schulmeister, Lisa

    2009-08-01

    Oncology nurses and pharmacists often are given the responsibility of developing or updating institutional policies to manage vesicant chemotherapy extravasations. Antidote and treatment recommendations of vesicant chemotherapy manufacturers, antidotes and treatments approved by the U.S. Food and Drug Administration (FDA), and guidelines and recommendations made by professional oncology organizations are useful resources in this process. This article describes manufacturers' recommendations, lists antidotes and treatments approved by the FDA, and reviews published guidelines and recommendations. Available antidote and treatment formulations and their preparation and administration also are discussed.

  3. Proceedings of the Vesicant Workshop, February 1987

    DTIC Science & Technology

    1987-12-01

    Rapid detection and decontamination, therefore, become essential in order to permit reduction of MOPP levels. The medical intensity inherent in vesicant...I ~ i Y I " Paipirueister Sum$ary of Presentation I Induction of Glutathione S-Transferase Enhances Detoxification of Aflatoxin I B Control <®, RzW...profiles are shown for aflatoxin B (AFB ) adducts of rat liver DNA. Rats fed 3 control or ethoxyquin-sup~lemented diets were gavaged with I H]AFB 1

  4. Vesical nephrogenic adenoma: an unusual presentation of a bladder tumour

    PubMed Central

    Martínez-Sanchíz, Carlos; Martínez-Ruiz, Jesús; Anguita-Fernandez, Pedro J.; Giménez-Bachs, José M.; Atiénzar-Tobarra, Manuel; Rodríguez, Julio Antonio Virseda; Salinas-Sánchez, Antonio S.

    2011-01-01

    Vesical nephrogenic adenoma is a rare, benign entity that appears most commonly in middle-aged males. Its etiology is unknown, but it has been linked to chronic irritating factors, such as infection, trauma, urological surgery, kidney stones, foreign bodies and chemical agents, such as Bacille Calmette-Guerin. We report 2 new cases with a history of transurethral resection of the bladder and the prostate and a history of prolonged voiding symptoms. In both cases, the findings of encysted tubular structures lined with flattened cuboidal cells without atypia were consistent with the diagnosis of vesical nephrogenic adenoma. PMID:21989174

  5. Urinary Bladder Adenocarcinoma Metastatic to the Abdominal Wall: Report of a Case with Cytohistologic Correlation

    PubMed Central

    Baliga, Mithra

    2016-01-01

    We report a case of adenocarcinoma metastatic to the abdominal wall in a 71-year-old man with a history of primary bladder adenocarcinoma. CT-guided core biopsy was performed; imprints and histologic sections showed malignant glands lined by tumor cells with hyperchromatic nuclei and prominent nucleoli, infiltrating through skeletal muscle. Immunohistochemistry revealed positivity for CK7, membranous/cytoplasmic β-catenin, caudal-type homeobox transcription factor 2 (CDX2), and α-methylacyl coenzyme A racemase and negativity for CK20, p63, prostate-specific antigen (PSA), and prostate-specific acid phosphatase (PSAP). These findings were interpreted as metastatic adenocarcinoma, consistent with bladder primary. Primary bladder adenocarcinoma is a rare malignancy arising within glandular metaplasia and is associated with cystitis cystica and cystitis glandularis. Predisposing factors include bladder exstrophy, schistosomiasis, and other causes of chronic bladder irritation. This tumor is divided into intestinal, clear cell, and signet ring cell subtypes. Treatment involves radical cystectomy with pelvic lymph node dissection, and prognosis is unfavorable. Primary bladder adenocarcinoma should be differentiated from urachal adenocarcinoma, which arises from urachal remnants near the bladder dome, and secondary adenocarcinoma, or vesical involvement by adenocarcinoma from a different primary. CK7, CK20, CDX2, thrombomodulin, and β-catenin can help distinguish primary bladder adenocarcinoma from colonic adenocarcinoma; PSA and PSAP can help distinguish primary bladder adenocarcinoma from prostate adenocarcinoma. PMID:27006847

  6. Mustard vesicant-induced lung injury: Advances in therapy.

    PubMed

    Weinberger, Barry; Malaviya, Rama; Sunil, Vasanthi R; Venosa, Alessandro; Heck, Diane E; Laskin, Jeffrey D; Laskin, Debra L

    2016-08-15

    Most mortality and morbidity following exposure to vesicants such as sulfur mustard is due to pulmonary toxicity. Acute injury is characterized by epithelial detachment and necrosis in the pharynx, trachea and bronchioles, while long-term consequences include fibrosis and, in some instances, cancer. Current therapies to treat mustard poisoning are primarily palliative and do not target underlying pathophysiologic mechanisms. New knowledge about vesicant-induced pulmonary disease pathogenesis has led to the identification of potentially efficacious strategies to reduce injury by targeting inflammatory cells and mediators including reactive oxygen and nitrogen species, proteases and proinflammatory/cytotoxic cytokines. Therapeutics under investigation include corticosteroids, N-acetyl cysteine, which has both mucolytic and antioxidant properties, inducible nitric oxide synthase inhibitors, liposomes containing superoxide dismutase, catalase, and/or tocopherols, protease inhibitors, and cytokine antagonists such as anti-tumor necrosis factor (TNF)-α antibody and pentoxifylline. Antifibrotic and fibrinolytic treatments may also prove beneficial in ameliorating airway obstruction and lung remodeling. More speculative approaches include inhibitors of transient receptor potential channels, which regulate pulmonary epithelial cell membrane permeability, non-coding RNAs and mesenchymal stem cells. As mustards represent high priority chemical threat agents, identification of effective therapeutics for mitigating toxicity is highly significant.

  7. Spontaneous bladder rupture caused by a giant vesical calculus.

    PubMed

    Kaur, Navneet; Attam, Amit; Gupta, Ashish; Amratash

    2006-01-01

    Spontaneous rupture of the urinary bladder is an uncommon occurrence. A 36-year-old man had complaints of pain and progressive distension of abdomen and anuria for 2 days. His abdomen was tense, tender and distended with free fluid. Blood urea was 340 mg% and ascitic fluid urea was 337 mg%. An USG showed massive ascitis, a large vesical calculus and a left renal calculus. The urinary bladder could not be catheterized. Patient underwent hemodialysis and placement of abdominal drains. About 2 l of yellow turbid fluid was drained. Cystolithotomy showed a 6 cm size impacted calculus with a rent in the dome of the bladder, which was repaired. Subsequently patient underwent percutaneous nephrolithotrypsy for left staghorn renal calculus and nephrectomy for right non-functioning kidney.

  8. Molecular Mechanisms of Sulfur Mustard Vesicant-Induced Cell Death: Early and Late Cell Responses

    DTIC Science & Technology

    2005-10-01

    Mechanisms of Sulfur Mustard Vesicant-Induced Cell Death : Early and late cell responses 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...It possess mutagenic, carcinogenic, cytotoxic, vesicating effects, and results in cell death . However, the biomedical mechanism of cell death induced... cell death via apoptosis: • In early stage, It induces JNK activity and then triggers apoptosis pathway. • In late stage, sulphur mustard attacks the

  9. [Adenocarcinoma mucoproductor in Meckel's diverticulum. Case report and review].

    PubMed

    Ramírez-González, Luis Ricardo; Leonher-Ruezga, Karla Lisseth; Plascencia-Posadas, Francisco Javier; Jiménez-Gómez, José Alfredo; López-Zamudio, José; Fuentes-Orozco, Clotilde

    2014-01-01

    Antecedentes: el divertículo de Meckel es la anomalía congénita más frecuente en el intestino delgado, que resulta de la obliteración incompleta del conducto onfalomesentérico; su diagnóstico suele ser incidental, pocas veces con sangrado, obstrucción, diverticulitis o en casos raros una neoplasia. Caso clínico: paciente femenina de 67 años de edad, que inició su padecimiento con síntomas urinarios (disuria, polaquiuria, pujo y tenesmo vesical). El cistograma demostró: defecto en el domo de la vejiga, bordes irregulares y efecto de compresión. La tomografía computada reportó: vejiga con lesión hipodensa infiltrante en el domo vesical, al resecarla se encontró un divertículo de Meckel con un tumor infiltrante; el estudio histopatológico confirmó el diagnóstico y demostró los bordes libres; todos los estudios de extensión resultaron sin actividad tumoral. Conclusiones: el adenocarcinoma mucoproductor derivado de un divertículo de Meckel es una entidad clínica que debido a sus síntomas inespecíficos y variabilidad de presentación sólo se diagnostica por lo que se aprecia en las imágenes radiológicas. Este adenocarcinoma tiene un alto índice de mortalidad pero baja prevalencia.

  10. Doxycycline loaded poly(ethylene glycol) hydrogels for healing vesicant-induced ocular wounds

    PubMed Central

    Anumolu, SivaNaga S; DeSantis, Andrea S; Menjoge, Anupa R; Hahn, Rita A; Beloni, John A; Gordon, Marion K; Sinko, Patrick J

    2015-01-01

    Half mustard (CEES) and nitrogen mustard (NM) are commonly used surrogates and vesicant analogs of the chemical warfare agent sulfur mustard. In the current study, in situ forming poly(ethylene glycol) (PEG)-based doxycycline hydrogels are developed and evaluated for their wound healing efficacy in CEES and NM exposed rabbit corneas in organ culture. The hydrogels, characterized by UV-Vis spectrophotometry, rheometry, and swelling kinetics, showed that the hydrogels are optically transparent, have good mechanical strength and a relatively low degree of swelling (<7%). In vitro doxycycline release from the hydrogel disks (0.25% w/v) was found to be biphasic with release half times of ~12 and 72 h, respectively, with 80–100% released over a 7-day period. Permeation of doxycycline through vesicant wounded corneas was found to be 2.5 to 3.4 fold higher than non-wounded corneas. Histology and immunofluorescence studies showed a significant reduction of matrix metalloproteinase-9 (MMP-9) and improved healing of vesicant exposed corneas by doxycycline hydrogels compared to a similar dose of doxycycline delivered in phosphate buffered saline (PBS, pH 7.4). In conclusion, the current studies demonstrate that the doxycycline-PEG hydrogels accelerate corneal wound healing after vesicant injury offering a therapeutic option for ocular mustard injuries. PMID:19853296

  11. Doxycycline loaded poly(ethylene glycol) hydrogels for healing vesicant-induced ocular wounds.

    PubMed

    Anumolu, SivaNaga S; DeSantis, Andrea S; Menjoge, Anupa R; Hahn, Rita A; Beloni, John A; Gordon, Marion K; Sinko, Patrick J

    2010-02-01

    Half mustard (CEES) and nitrogen mustard (NM) are commonly used surrogates and vesicant analogs of the chemical warfare agent sulfur mustard. In the current study, in situ forming poly(ethylene glycol) (PEG)-based doxycycline hydrogels are developed and evaluated for their wound healing efficacy in CEES and NM-exposed rabbit corneas in organ culture. The hydrogels, characterized by UV-Vis spectrophotometry, rheometry, and swelling kinetics, showed that the hydrogels are optically transparent, have good mechanical strength and a relatively low degree of swelling (<7%). In vitro doxycycline release from the hydrogel disks (0.25% w/v) was found to be biphasic with release half times of approximately 12 and 72h, respectively, with 80-100% released over a 7-day period. Permeation of doxycycline through vesicant wounded corneas was found to be 2.5 to 3.4 fold higher than non-wounded corneas. Histology and immunofluorescence studies showed a significant reduction of matrix metalloproteinase-9 (MMP-9) and improved healing of vesicant-exposed corneas by doxycycline hydrogels compared to a similar dose of doxycycline delivered in phosphate buffered saline (PBS, pH 7.4). In conclusion, the current studies demonstrate that the doxycycline-PEG hydrogels accelerate corneal wound healing after vesicant injury offering a therapeutic option for ocular mustard injuries.

  12. Mustard vesicating agent-induced toxicity in the skin tissue and silibinin as a potential countermeasure.

    PubMed

    Tewari-Singh, Neera; Agarwal, Rajesh

    2016-06-01

    Exposure to the vesicating agents sulfur mustard (SM) and nitrogen mustard (NM) causes severe skin injury with delayed blistering. Depending upon the dose and time of their exposure, edema and erythema develop into blisters, ulceration, necrosis, desquamation, and pigmentation changes, which persist weeks and even years after exposure. Research advances have generated data that have started to explain the probable mechanism of action of vesicant-induced skin toxicity; however, despite these advances, effective and targeted therapies are still deficient. This review highlights studies on two SM analogs, 2-chloroethyl ethyl sulfide (CEES) and NM, and CEES- and NM-induced skin injury mouse models that have substantially added to the knowledge on the complex pathways involved in mustard vesicating agent-induced skin injury. Furthermore, employing these mouse models, studies under the National Institutes of Health Countermeasures Against Chemical Threats program have identified the flavanone silibinin as a novel therapeutic intervention with the potential to be developed as an effective countermeasure against skin injury following exposure to mustard vesicating agents.

  13. Primary appendiceal mucinous adenocarcinoma.

    PubMed

    Behera, Prativa Kumari; Rath, Pramod Kumar; Panda, Rabiratna; Satpathi, Sanghamitra; Behera, Rajan

    2011-04-01

    Primary Adenocarcinomas of the appendix are extremely rare tumor. We report a case of primary mucinous adenocarcinoma in a 40 year old lady misdiagnosed as having acute appendicitis. All the routine investigations were within normal limit. USG of abdomen showed dilated appendix with little fluid collection adjacent to it and no other abnormality was seen which suggested acute appendicitis. Appendicectomy was done and excised appendix was sent for histopathological examination. Mucinous Adenocarcinoma of the appendix was confirmed after histopathological examination. Right hemicolectomy was done as a second stage procedure. As some cases are incidentally discovered, this case emphasizes that histological examination of all appendicectomy specimens is mandatory.

  14. Small Bowel Adenocarcinoma.

    PubMed

    Aparicio, Thomas; Zaanan, Aziz; Mary, Florence; Afchain, Pauline; Manfredi, Sylvain; Evans, Thomas Ronald Jeffry

    2016-09-01

    Small bowel adenocarcinomas (SBAs) are rare tumors, but their incidence is increasing. The most common primary location is the duodenum. Even though SBAs are more often sporadic, some diseases are risk factors. Early diagnosis of small bowel adenocarcinoma remains difficult, despite significant radiologic and endoscopic progress. After R0 surgical resection, the main prognostic factor is lymph node invasion. An international randomized trial (BALLAD [Benefit of Adjuvant Chemotherapy For Small Bowel Adenocarcinoma] study) will evaluate the benefit of adjuvant chemotherapy. For metastatic disease, retrospectives studies suggest that platinum-based chemotherapy is the most effective treatment. Phase II studies are ongoing to evaluate targeted therapy in metastatic SBA.

  15. Adenocarcinoma of the urinary bladder.

    PubMed

    Dadhania, Vipulkumar; Czerniak, Bogdan; Guo, Charles C

    2015-01-01

    Adenocarcinoma is an uncommon malignancy in the urinary bladder which may arise primarily in the bladder as well as secondarily from a number of other organs. Our aim is to provide updated information on primary and secondary bladder adenocarcinomas, with focus on pathologic features, differential diagnosis, and clinical relevance. Primary bladder adenocarcinoma exhibits several different growth patterns, including enteric, mucinous, signet-ring cell, not otherwise specified, and mixed patterns. Urachal adenocarcinoma demonstrates similar histologic features but it can be distinguished from bladder adenocarcinoma on careful pathologic examination. Secondary bladder adenocarcinomas may arise from the colorectum, prostate, endometrium, cervix and other sites. Immunohistochemical study is valuable in identifying the origin of secondary adenocarcinomas. Noninvasive neoplastic glandular lesions, adenocarcinoma in situ and villous adenoma, are frequently associated with bladder adenocarcinoma. It is also important to differentiate bladder adenocarcinoma from a number of nonneoplastic lesions in the bladder. Primary bladder adenocarcinoma has a poor prognosis largely because it is usually diagnosed at an advanced stage. Urachal adenocarcinoma shares similar histologic features with bladder adenocarcinoma, but it has a more favorable prognosis than bladder adenocarcinoma, partly due to the relative young age of patients with urachal adenocarcinoma.

  16. Adenocarcinoma of the urinary bladder

    PubMed Central

    Dadhania, Vipulkumar; Czerniak, Bogdan; Guo, Charles C

    2015-01-01

    Adenocarcinoma is an uncommon malignancy in the urinary bladder which may arise primarily in the bladder as well as secondarily from a number of other organs. Our aim is to provide updated information on primary and secondary bladder adenocarcinomas, with focus on pathologic features, differential diagnosis, and clinical relevance. Primary bladder adenocarcinoma exhibits several different growth patterns, including enteric, mucinous, signet-ring cell, not otherwise specified, and mixed patterns. Urachal adenocarcinoma demonstrates similar histologic features but it can be distinguished from bladder adenocarcinoma on careful pathologic examination. Secondary bladder adenocarcinomas may arise from the colorectum, prostate, endometrium, cervix and other sites. Immunohistochemical study is valuable in identifying the origin of secondary adenocarcinomas. Noninvasive neoplastic glandular lesions, adenocarcinoma in situ and villous adenoma, are frequently associated with bladder adenocarcinoma. It is also important to differentiate bladder adenocarcinoma from a number of nonneoplastic lesions in the bladder. Primary bladder adenocarcinoma has a poor prognosis largely because it is usually diagnosed at an advanced stage. Urachal adenocarcinoma shares similar histologic features with bladder adenocarcinoma, but it has a more favorable prognosis than bladder adenocarcinoma, partly due to the relative young age of patients with urachal adenocarcinoma. PMID:26309895

  17. Prostate Ductal Adenocarcinoma.

    PubMed

    Amin, Ali

    2017-03-30

    Prostate ductal adenocarcinoma (PDA) is a rare subtype of prostate adenocarcinoma that shows more aggressive behavior than conventional prostatic acinar adenocarcinoma. PDA demonstrates similar clinical and paraclinical features such as prostatic acinar adenocarcinoma; therefore, clinical distinction of the 2 entities is very difficult (if not impossible) and histopathology plays an important role in the diagnosis of the disease. This review discusses all the necessary information needed for the diagnosis and prognosis of PDA including the morphologic features of PDA, an introduction about the known variants of PDA with helpful hints in grading of each variant, tips on differential diagnosis of PDA from the common morphologic mimickers, a detailed discussion on the value of immunohistochemistry in the diagnosis of PDA, and pathologic features that are helpful in determining the outcome.

  18. Sulfur mustard induces an endoplasmic reticulum stress response in the mouse ear vesicant model

    SciTech Connect

    Chang, Yoke-Chen; Wang, James D.; Svoboda, Kathy K.; Casillas, Robert P.; Laskin, Jeffrey D.; Gordon, Marion K.; Gerecke, Donald R.

    2013-04-15

    The endoplasmic reticulum (ER) stress response is a cell survival pathway upregulated when cells are under severe stress. Severely damaged mouse ear skin exposed to the vesicant, sulfur mustard (bis-2-chloroethyl sulfide, SM), resulted in increased expression of ER chaperone proteins that accompany misfolded and incorrectly made proteins targeted for degradation. Time course studies with SM using the mouse ear vesicant model (MEVM) showed progressive histopathologic changes including edema, separation of the epidermis from the dermis, persistent inflammation, upregulation of laminin γ2 (one of the chains of laminin-332, a heterotrimeric skin glycoprotein required for wound repair), and delayed wound healing from 24 h to 168 h post exposure. This was associated with time related increased expression of the cell survival ER stress marker, GRP78/BiP, and the ER stress apoptosis marker, GADD153/CHOP, suggesting simultaneous activation of both cell survival and non-mitochondrial apoptosis pathways. Dual immunofluorescence labeling of a keratinocyte migration promoting protein, laminin γ2 and GRP78/BIP, showed colocalization of the two molecules 72 h post exposure indicating that the laminin γ2 was misfolded after SM exposure and trapped within the ER. Taken together, these data show that ER stress is induced in mouse skin within 24 h of vesicant exposure in a defensive response to promote cell survival; however, it appears that this response is rapidly overwhelmed by the apoptotic pathway as a consequence of severe SM-induced injury. - Highlights: ► We demonstrated ER stress response in the mouse ear vesicant model. ► We described the asymmetrical nature of wound repair in the MEVM. ► We identified the distribution of various ER stress markers in the MEVM.

  19. Sulfur mustard induces an endoplasmic reticulum stress response in the mouse ear vesicant model

    PubMed Central

    Chang, Yoke-Chen; Wang, James D.; Svoboda, Kathy K.; Casillas, Robert P.; Laskin, Jeffrey D.; Gordon, Marion K.; Gerecke, Donald R.

    2013-01-01

    The endoplasmic reticulum (ER) stress response is a cell survival pathway upregulated when cells are under severe stress. Severely damaged mouse ear skin exposed to the vesicant, sulfur mustard (bis-2-chloroethyl sulfide, SM), resulted in increased expression of ER chaperone proteins that accompany misfolded and incorrectly made proteins targeted for degradation. Time course studies with SM using the mouse ear vesicant model (MEVM) showed progressive histopathologic changes including edema, separation of the epidermis from the dermis, persistent inflammation, upregulation of laminin γ2 (one of the chains of laminin-332, a heterotrimeric skin glycoprotein required for wound repair), and delayed wound healing from 24 h to 168 h post exposure. This was associated with time related increased expression of the cell survival ER stress marker, GRP78/BiP, and the ER stress apoptosis marker, GADD153/CHOP, suggesting simultaneous activation of both cell survival and non-mitochondrial apoptosis pathways. Dual immunofluorescence labeling of a keratinocyte migration promoting protein, laminin γ2 and GRP78/BIP, showed colocalization of the two molecules 72 h post exposure indicating that the laminin γ2 was misfolded after SM exposure and trapped within the ER. Taken together, these data show that ER stress is induced in mouse skin within 24 h of vesicant exposure in a defensive response to promote cell survival; however, it appears that this response is rapidly overwhelmed by the apoptotic pathway as a consequence of severe SM-induced injury. PMID:23357548

  20. Evaluation of the vesicating properties of neutralized chemical agent identification sets. Final report, November 1995-August 1997

    SciTech Connect

    Olajos, E.J.; Salem, H.; Gieseking, J.K.

    1997-08-01

    Vesication and skin irritation studies were conducted in hairless guinea-pigs to determine the vesicant and skin irritation potential of Chemical Agent Identification Sets (CAIS). Guinea-pigs were topically dosed with `test article` NEAT HD, 10% agent/chloroform solutions, or product solutions (wastestreams) and evaluated for skin-damaging effects (gross and light microscopic). Product solutions from the chemical neutralization of neat sulfur mustard resulted in microvesicle formation (vesication). All agent-dosed (agent/chloroform solutions or HD) sites exhibited microblisters, as well as other histopathologic lesions of the skin. Wastestreams from the neutalization of agent (agent/chloroform; agent on charcoal) were devoid of microvesicant activity. Dermal irritant effects (erythema and edema) were consistent with the skin-injurious activity associated with the neutralizing reagent 1,3-dichloro-5,5-dimethylhydantoin (DCDMH).

  1. Silibinin, Dexamethasone, and Doxycycline as Potential Therapeutic Agents for Treating Vesicant-Inflicted Ocular Injuries

    PubMed Central

    Tewari-Singh, Neera; Jain, Anil K; Inturi, Swetha; Ammar, David A; Agarwal, Chapla; Tyagi, Puneet; Kompella, Uday B; Enzenauer, Robert W; Petrash, J Mark; Agarwal, Rajesh

    2014-01-01

    There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 µg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. PMID:22841772

  2. Silibinin, dexamethasone, and doxycycline as potential therapeutic agents for treating vesicant-inflicted ocular injuries

    SciTech Connect

    Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; Ammar, David A.; Agarwal, Chapla; Tyagi, Puneet; Kompella, Uday B.; Enzenauer, Robert W.; Petrash, J. Mark; Agarwal, Rajesh

    2012-10-01

    There are no effective and approved therapies against devastating ocular injuries caused by vesicating chemical agents sulfur mustard (SM) and nitrogen mustard (NM). Herein, studies were carried out in rabbit corneal cultures to establish relevant ocular injury biomarkers with NM for screening potential efficacious agents in laboratory settings. NM (100 nmol) exposure of the corneas for 2 h (cultured for 24 h), showed increases in epithelial thickness, ulceration, apoptotic cell death, epithelial detachment microbullae formation, and the levels of VEGF, cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9). Employing these biomarkers, efficacy studies were performed with agent treatments 2 h and every 4 h thereafter, for 24 h following NM exposure. Three agents were evaluated, including prescription drugs dexamethasone (0.1%; anti-inflammatory steroid) and doxycycline (100 nmol; antibiotic and MMP inhibitor) that have been studied earlier for treating vesicant-induced eye injuries. We also examined silibinin (100 μg), a non-toxic natural flavanone found to be effective in treating SM analog-induced skin injuries in our earlier studies. Treatments of doxycycline + dexamethasone, and silibinin were more effective than doxycycline or dexamethasone alone in reversing NM-induced epithelial thickening, microbullae formation, apoptotic cell death, and MMP-9 elevation. However, dexamethasone and silibinin alone were more effective in reversing NM-induced VEGF levels. Doxycycline, dexamethasone and silibinin were all effective in reversing NM-induced COX-2 levels. Apart from therapeutic efficacy of doxycycline and dexamethasone, these results show strong multifunctional efficacy of silibinin in reversing NM-induced ocular injuries, which could help develop effective and safe therapeutics against ocular injuries by vesicants. -- Highlights: ► Established injury biomarkers in rabbit corneal culture with nitrogen mustard (NM) ► This NM model is a cost effective

  3. General guidelines for medically screening mixed population groups potentially exposed to nerve or vesicant agents

    SciTech Connect

    Watson, A.P.; Munro, N.B. ); Sidell, F.R. ); Leffingwell, S.S. . Center for Environmental Health and Injury Control)

    1992-01-01

    A number of state and local planners have requested guidance on screening protocols and have expressed interest in sampling body fluids from exposed or potentially exposed individuals as a means of estimating agent dose. These guidelines have been developed to provide a clear statement that could be used by state and local emergency response personnel in the event of a nerve or vesicant agent incident resulting in off-post contamination; maximum protection from harm is the goal. The assumption is that any population group so exposed would be heterogeneous for age, gender, reproductive status, and state of health.

  4. Mechanisms Mediating the Vesicant Actions of Sulfur Mustard after Cutaneous Exposure

    PubMed Central

    Shakarjian, Michael P.; Heck, Diane E.; Gray, Joshua P.; Sinko, Patrick J.; Gordon, Marion K.; Casillas, Robert P.; Heindel, Ned D.; Gerecke, Donald R.; Laskin, Debra L.; Laskin, Jeffrey D.

    2010-01-01

    Sulfur mustard (SM), a chemical weapon first employed during World War I, targets the skin, eyes, and lung. It remains a significant military and civilian threat. The characteristic response of human skin to SM involves erythema of delayed onset, followed by edema with inflammatory cell infiltration, the appearance of large blisters in the affected area, and a prolonged healing period. Several in vivo and in vitro models have been established to understand the pathology and investigate the mechanism of action of this vesicating agent in the skin. SM is a bifunctional alkylating agent which reacts with many targets including lipids, proteins, and DNA, forming both intra- and intermolecular cross-links. Despite the relatively nonselective chemical reactivity of this agent, basal keratinocytes are more sensitive, and blistering involves detachment of these cells from their basement membrane adherence zones. The sequence and manner in which these cells die and detach is still unresolved. Much has been discovered over the past two decades with respect to the mechanisms of SM-induced cytotoxicity and the intracellular and extracellular targets of this vesicant. In this review, the effects of SM exposure on the skin are described, as well as potential mechanisms mediating its actions. Successful therapy for SM poisoning will depend on following new mechanistic leads to develop drugs that target one or more of its sites of action. PMID:19833738

  5. Toxicity of vesicant agents scheduled for destruction by the Chemical Stockpile Disposal Program.

    PubMed Central

    Watson, A P; Griffin, G D

    1992-01-01

    The vesicant agents of the unitary chemical munitions stockpile include various formulations of sulfur mustard [bis-(2-chloroethyl) sulfide; agents H, HD, and HT] and small quantities of the organic arsenical Lewisite [dichloro(2-chlorovinyl) arsine; agent L]. These agents can be dispersed in liquid, aerosol, or vapor form and are capable of producing severe chemical burns upon direct contact with tissue. Moist tissues such as the eyes, respiratory tract, and axillary areas are particularly affected. Available data summarizing acute dose response in humans and laboratory animals are summarized. Vesicant agents are also capable of generating delayed effects such as chronic bronchitis, carcinogenesis, or keratitis/keratopathy of the eye under appropriate conditions of exposure and dose. These effects may not become manifest until years following exposure. Risk analysis derived from carcinogenesis data indicates that sulfur mustard possesses a carcinogenic potency similar to that of benzo[a]pyrene. Because mustard agents are alkylating compounds, they destroy individual cells by reaction with cellular proteins, enzymes, RNA, and DNA. Once begun, tissue reaction is irreversible. Mustard agents are mutagenic; data for cellular and laboratory animal assays are presented. Reproductive effects have not been demonstrated in the offspring of laboratory rats. Acute Lewisite exposure has been implicated in cases of Bowen's disease, an intraepidermal squamous cell carcinoma. Lewisite is not known to generate reproductive or teratogenic effects. PMID:1486858

  6. Toxicity of vesicant agents scheduled for destruction by the chemical stockpile disposal program

    SciTech Connect

    Watson, A.P.; Griffin, G.D. )

    1992-11-01

    The vesicant agents of the unitary chemical munitions stockpile include various formulations of sulfur mustard [bis-(2-chloroethyl) sulfide; agents H, HD, and HT] and small quantities of the organic arsenical Lewisite [dichloro(2-chlorovinyl)arsine; agent L]. These agents can be dispersed in liquid, aerosol, or vapor form and are capable of producing severe chemical burns upon direct contact with tissue. Moist tissues such as the eyes, respiratory tract, and axillary areas are particularly affected. Available data summarizing acute dose response in humans and laboratory animals are summarized. Vesicant agents are also capable of generating delayed effects such as chronic bronchitis, carcinogenesis, or keratitis/keratopathy of the eye under appropriate conditions of exposure and dose. These effects may not become manifest until years following exposure. Risk analysis derived from carcinogenesis data indicates that sulfur mustard possesses a carcinogenic potency similar to that of benzo[a]pyrene. Because mustard agents are alkylating compounds, they destroy individual cells by reaction with cellular proteins, enzymes, RNA, and DNA. Once begun, tissue reaction is irreversible. Mustard agents are mutagenic; data for cellular and laboratory animal assays are presented. Reproductive effects have not been demonstrated in the offspring of laboratory rats. Acute Lewisite exposure has been implicated in cases of Bowen's disease, an intraepidermal squamous cell carcinoma. Lewisite is not known to generate reproductive or teratogenic effects. 112 refs., 1 fig., 6 tabs.

  7. Evaluation of protective ointments used against dermal effects of nitrogen mustard, a vesicant warfare agent.

    PubMed

    Kenar, Levent; Karayilanoğlu, Turan; Yuksel, Altan; Gunhan, Omer; Kose, Songul; Kurt, Bulent

    2005-01-01

    Mustard, a vesicant warfare agent, has cytotoxic, mutagenic, and cytostatic effects via alkylation of DNA and inhibition of DNA replication. Since symptoms appear following a latent period, it can cause some subacute and chronic effects to occur and delay in the treatment. Therefore, the main approach should be the use of protective preparation to reduce the skin toxicity. Thus, this study was conducted in guinea pigs (350-400 g) shaved in areas of 10 x 10 cm. Mechlorethamine HCl (100 mg), a nitrogen mustard derivative, in ethanol was applied by spraying on hairless regions where previously prepared pharmaceutical topical formulations were medicated before. The experimental regions of the animals were kept preserved from environmental factors. Forty-eight hours after the application of the protective ointments and mechlorethamine consecutively, skin-damaging effects were macroscopically evaluated in terms of erythema formation, ulceration, necrosis, and inflammation occurrences. Then, punch biopsy was performed from these damaged sites for histopathological evaluation. Although numerous topical formulations were prepared and tested for protection, according to microscopic examination of the pathologic sections, tissue specimen treated with the ointment containing the mixture of zinc oxide, zinc chloride, dimethylpolysiloxane in a base of petroleum jelly was determined as being the most effective protective against skin injury caused by the vesicant agent.

  8. Villoglandular papillary adenocarcinoma: case report

    PubMed Central

    Salek, Ghizlane; Lalya, Issam; Rahali, Driss Moussaoui; Dehayni, Mohamed

    2016-01-01

    Villoglandular papillary adenocarcinoma (VPA) is a very rare subtype of adenocarcinoma of the uterine cervix, but a well-recognized variant of cervical adenocarcinoma with a favorable prognosis and generally occurring in women of child-bearing age. Herein, we report a case of VPA diagnosed and managed successfully with conservative measure. This management is particularly desirable in young women to preserve reproductive capability. PMID:28293348

  9. Symptomatic treatment of ascites with a peritoneo-vesical automated fluid shunt system in a dog.

    PubMed

    Venzin, C; Kook, P; Jenni, S; Wilhelm, S; Degen, T; Braun, A; Rütten, M; Glaus, T M

    2012-02-01

    A six-year-old Rottweiler with chronic ascites and moderate panhypoproteinaemia that had been treated with large volume paracentesis over several months duration was diagnosed with a large bi-atrial mass and hepatic fibrosis. For palliative treatment, a peritoneo-vesical automated fluid shunt system with an integrated chargeable battery and an integrated computer to control pump function and to transmit data transcutaneously was implanted by coeliotomy. The pump was left in place for 10 weeks, eliminating the need for further paracentesis during this time. At the end of this period, no ascites was discernible and serum protein concentrations had returned to their respective reference intervals. As a complication, decubitus with skin perforation had developed above the pump. Besides palliative treatment of chronic refractory ascites, this pump may have application in other conditions characterised by chronic cavity effusion or in peritoneal dialysis.

  10. The role of climate on prevalence or eradication of vesical schistosomiasis in Khuzestan Province of Iran.

    PubMed

    Hamidinia, Dariush; Maraghi, Sharif; Azimi, Farideh; Ai, Armin; Shirian, Sadegh

    2016-06-01

    Climate is defined as the combination of climate and air elements of a given region which is usually measured for a period of decades. De-marton climate classification has been established based on many factors, including elements such as temperature and rainfall. Vesicle schistosomiasis is a parasitic disease caused by Schistosoma haematobium. This parasite lives in the blood vessels of the bladder. The parasite can cause hematuria in human and if not treated properly can lead to vesicale carcinoma. The parasite is distributed only in certain parts of the province and it is highly dispersed along the rivers of Dez, Karkheh and Karun with high emissions. In 1970, the prevalence of infection in infected foci was 23.8 %. Campaign against the parasite began in 1958 but it did not encompass all centers of infection. Preventive measures include diagnosis and treatment of patients, public health promotion, health education, drying swamps and ponds, improving the environment, cementing the irrigation canals, and the use of moluscocide eventually leads to changing the ecological and conditions of parasite and snail inhabits. Application of preventive measures resulted in the reduction of infection level to 0.7 % in 1979. By continuing struggle and intensifying preventive measures and changing ecological and climatic environment, in 2008, the examination of 3400 urine samples of students in Andimeshk district revealed no cases of the vesical schistosomiasis. It is concluded that S. haematobium and vesical schistosomiasis is eliminated from Khuzestan province southwest Iran, but the disease is still prevalent in neighboring Iran's western border country (Iraq) and due to the special conditions of its facilities and the traffic between the two countries, it is necessary to control and eradicate the disease in Iraq by using the experiences of Iran in eliminating the disease.

  11. Mucoadhesion on pig vesical mucosa: influence of polycarbophil/calcium interactions.

    PubMed

    Kerec, M; Bogataj, M; Mugerle, B; Gasperlin, M; Mrhar, A

    2002-07-08

    The influence of polycarbophil/calcium interactions on the mucoadhesive properties of polycarbophil has been examined. Polycarbophil dispersions and films with different concentrations of calcium or sodium ions were prepared and the following parameters were measured: detachment force on pig vesical mucosa, zeta potential, pH and viscosity. Polycarbophil detachment force decreased significantly in the presence of calcium but not sodium. Both ions decrease the pH of polycarbophil dispersions. On the other hand, altering the pH of hydrated polycarbophil films in the absence of added ions had an insignificant effect on detachment force. Both ions reduce the absolute values of polycarbophil zeta potential, calcium more efficiently than sodium. We could conclude that decreased mucoadhesion strength of polycarbophil in the presence of calcium is due to the chelation of polycarbophil carboxylic groups by calcium and crosslinking of polymer. The crosslinked polymer chains would be expected to be less flexible, and therefore, interpenetrate to a lesser extent with the glycosaminoglycans of mucus. Additionally, the interactions between functional groups of polycarbophil and mucus glycosaminoglycans are lowered due to the calcium, blocking the carboxylic groups. The mechanism of calcium influence on viscosity of polycarbophil dispersions appears to be different: repulsion between ionised carboxylic groups of polycarbophil prevails over the crosslinking of polycarbophil by calcium.

  12. The correlation between zeta potential and mucoadhesion strength on pig vesical mucosa.

    PubMed

    Bogataj, Marija; Vovk, Tomaz; Kerec, Mojca; Dimnik, Ales; Grabnar, Iztok; Mrhar, Ales

    2003-05-01

    The detachment forces of various polymers are frequently measured to determine their mucoadhesion strength. As the process of mucoadhesion is a consequence of interactions between the mucus layer on mucosa and mucoadhesive polymers, it is greatly dependent on mucus and polymer structure including their charge. It is also known that the glycosaminoglycan layer, which covers the urinary bladder mucosa surface, is highly negatively charged. Therefore, by measuring the zeta potential of polymer dispersions and mucosal homogenates an insight into electrostatic interactions during mucoadhesion can be obtained. In our experiments we chose three polymers, two anionic (polycarbophil, PC; sodium carboxymethyl cellulose, CMCNa) and one cationic (chitosan hydrochloride, CH), for which we expected different zeta potential values and different mucoadhesion strengths. The correlation between the zeta potential and the detachment force was determined. In addition to that, the zeta potential of the scraped surface layer of pig urinary bladders was measured to confirm its negative value. The mucoadhesion strength decreased in the following order: CH>CMCNa=PC. The zeta potentials for all three polymers and for porcine vesical mucosal homogenates were measured in Tyrode solution and two NaCl solutions with different ionic strengths. The lower values of the detachment force correlated well with the more negative zeta potential of the polymer, which might be a consequence of the greater repulsion between negative charges of polymers and glycosaminoglycans.

  13. Hematological profile of the euthymic hairless guinea pig following sulfur mustard vesicant exposure.

    PubMed

    Gold, M B; Scharf, B A

    1995-01-01

    Sulfur mustard (HD) is a potent vesicating agent of military importance, with known radiomimetic properties. The euthymic hairless guinea pig (EHGP) (Cavia porcellus) is emerging as the animal model of choice for cutaneous HD study. With elucidation of the systemic effects, we may better utilize this animal for all HD toxicity work. To this end, studies were conducted to determine the definitive median lethal dose (MLD) of subcutaneously applied sulfur mustard (HD) in the EHGP, and to correlate the induced hematological changes. Eight groups of two animals each were dosed at 0.3 log intervals from an extrapolated expected dose, deriving a tentative mean around which five groups of six animals each were dosed at 0.1 log intervals, resulting in a definitive MLD of 48.17 mg kg(-1). Sulfur mustard was then administered to seven groups of six animals each at a dose of 30 mg kg(-1) and hematology performed. Significant leukocyte count suppression was found to occur on days 4, 5 and 6, following a leukocyte elevation on day 1 after exposure. Serum potassium levels were found to be elevated all 7 days after HD exposure. Establishing the MLD for subcutaneously applied HD and the pattern of induced leukocyte suppression allows for more definitive evaluation of successful toxicity counter-measures.

  14. Nd:YAG laser incision of the vesical neck in obstructive BPH

    NASA Astrophysics Data System (ADS)

    Gilbert, Peter T. O.

    2003-06-01

    From February, 1995 through June, 2002, 68 patients underwent laser incision of the prostate at our clinic. By means of a 23 F cytoscope and a 600 micrometer lateral firing quartz fiber the vesical neck was incised at the 5 and 7 o'clock position at 60 W power. Total energy averaged 13648 J. Operative time did not exceed 15 minutes. General anesthesia was employed in all but one patient. 38 patients remained catheter-free whereas 30 patients were catheterized for two hours. Except for three cases, all patients were discharged on the same day, usually after the first micturition. Anti-inflammatory treatment was administered for two weeks, Cotrimoxazole for 5 days. No serious complications were encountered. Minor side effects included urinary retention (1 pat.), urinary infection (3 pat.) and retrograde ejaculation (1 pat.). Considering a mean follow-up of 21 months, the average Qmax improved enormously (25.4 ml/s versus 10.9 ml/s), as did residual urine volume (35 ml versus 95 ml) and IPSS (7.1 versus 20.5). Three patients required TUR-P 2-3 years after laser surgery and one patient underwent radical retropubic prostatectomy for prostate cancer 2 years later. In conclusion, Nd:YAG laser incision of the prostate is a simple, safe, reliable and cost-effective outpatient procedure.

  15. [Endoscopic diagnosis of Barrett's adenocarcinoma].

    PubMed

    Yoshio, H; Takashi, Y; Mitsuyo, H; Nobuhiko, Y; Tatsurou, T; Kazuhiko, S; Yoko, H; Shigemasa, I; Hisanaga, M; Osamu, H; Katsuyoshi, S; Seishi, U; Matsushita, H; Masahiko, T

    1999-03-01

    Biopsy specimens can reveal that esophageal cancer is an adenocarcinoma but they cannot show that its origin is Barrett's mucosa. Therefore we must show during endoscopy that the tumor exists in Barrett's mucosa. We reported that Barrett's esophagus could be clearly diagnosed at endoscopy as the columnar mucosa lying on the longitudinal vessels in the lower esophagus. We define Barrett's esophagus as "the columnar mucosa in the esophagus which exists continuously more than 2 cm in circumference from the stomach." Short-segment Barrett's esophagus (SSBE) is "the columnar mucosa which exists in the esophagus continuously from the stomach but its length has a part under 2 cm in length." Endoscopically Barrett's adenocarcinoma is visualized as a lesion with a reddish and uneven mucosal surface. Barrett's adenocarcinomas occur in the SSBE as well. Endoscopic observation at periodic intervals is necessary not only for cases with Barrett's esophagus but also with SSBE. A further examination is necessary to determine the application of EMR for superficial Barrett's adenocarcinoma.

  16. Hepatoid Adenocarcinoma of the Urachus

    PubMed Central

    Jimenez, Carlos Andrés; Carrascal, Edwin

    2016-01-01

    Hepatoid adenocarcinoma of the urachus is a rare condition. We present the case of a 51-year-old female who developed abdominal pain and hematuria. Pelvic magnetic resonance imaging (MRI) reported an urachal mass with invasion to the bladder that was resected by partial cystectomy. On light microscopy the tumor resembled liver architecture, with polygonal atypical cells in nest formation and trabecular structures. Immunochemistry was positive for alfa-fetoprotein (AFP) and serum AFP was elevated. Hepatoid adenocarcinomas have been reported in multiple organs, being most commonly found in the stomach and the ovaries. Bladder compromise has been rarely described in the literature, and it has been associated with poor prognosis, low remission rates, and early metastasis. PMID:27803830

  17. Oncocytic Adenocarcinoma of the Orbit.

    PubMed

    Harris, Gerald J; Paul, Sean; Hunt, Bryan C

    Oncocytic adenocarcinoma of the orbit is a rare tumor, with 1 case of nonlacrimal sac, nonlacrimal gland origin, and a poor outcome previously reported. An 85-year-old man with a 2-month history of left-sided epiphora, enlarging eyelid nodules, and diplopia in left gaze was found on imaging to have a poorly circumscribed, nodular mass of uniform radiodensity in the inferomedial orbit. Incisional biopsy revealed morphologic and immunohistochemical features of oncocytic adenocarcinoma with origin in the caruncle suspected, and CT of the neck, chest, abdomen, and pelvis showed no metastases or remote primary tumor source. Based on multidisciplinary consensus, orbital exenteration with adjuvant radiation therapy was performed, and there was no evidence of residual or recurrent tumor 2 years after treatment.

  18. Optimal lymphadenectomy for esophageal adenocarcinoma.

    PubMed

    Oezcelik, A

    2013-08-01

    Recently published data have shown that an extended lymphadenectomy during the en bloc esophagectomy leads to a significant increased long-term survival for esophageal adenocarcinoma. On the other hand some studies indicate that the increased survival is based on stage migration and that the surgical complication rate is increased after extended lymphadenectomy. The aim of this review was to give an overview about all aspects of an extended lymphadenectomy in patients with esophageal adenocarcinoma. The review of the literature shows clearly that the number of involved lymph nodes is an independent prognostic factor in patients with esophageal adenocarcinoma. Furthermore, an extended lymphadenectomy leads to an increased long-term survival. Some studies describe that 23 lymph nodes should be removed to predict survival; other studies 18 lymph nodes or 15 lymph nodes. Opponents indicate that the survival benefit is based on stage migration. The studies with a large study population have performed a Cox regression analyzes and identified the number of lymph nodes removed as an independent factor for improved survival, which means it is significant independently from other parameters. Under these circumstances is stage migration not an option to explain the survival benefit. An important difficulty is, that there is no standardized definition of an extended lymphadenectomy, which means the localization and number of removed lymph nodes differ depending from the performing centre. The controversies regarding the survival benefit of the lymphadenectomy is based on the lack of standardisation of the lymphadenectomy. The main goal of further studies should be to generate a clear definition of an extended lymphadenectomy in patients with esophageal adenocarcinoma.

  19. Metastatic adenocarcinoma of unknown primary origin.

    PubMed

    Hammar, S P

    1998-12-01

    Adenocarcinomas account for up to 60% of all metastatic neoplasms of unknown primary origin. In general, adenocarcinomas are the most difficult metastatic tumor to accurately identify the primary site. Some metastatic adenocarcinomas have distinctive histological features that allow for their site determination (eg, colonic adenocarcinoma, bronchioloalveolar cell carcinoma), although the majority of metastatic adenocarcinomas have histological features that are not distinctive enough to allow for a specific diagnosis of their origin. For this reason, electron microscopy and immunohistochemistry have been used to help identify the exact type (origin) of metastatic adenocarcinomas. Relatively specific ultrastructural features used to diagnose metastatic adenocarcinomas of unknown primary origin include tubular myelin, intranuclear surfactant apoprotein tubular inclusions, Clara cell granules, uniform short microvilli with filamentous cores and core rootlets, Langerhans cells associated with neoplastic cells, cytoplasmic hyaline globules, lipid droplets, glycogen, and cytoplasmic crystals. Only a few of these ultrastructural features are absolutely specific. Relatively specific immunohistochemical tests used to diagnose metastatic adenocarcinomas of unknown primary origin include prostate-specific antigen, thyroglobulin, estrogen and progesterone receptor proteins, thyroid transcription factor-I, and surfactant apoproteins. Of these, prostate-specific antigen and thyroglobulin are the most specific. The purpose of this article is to discuss the use of electron microscopy and immunohistochemistry in the site-specific diagnosis of metastatic adenocarcinomas of unknown primary origin.

  20. Transcriptomic Microenvironment of Lung Adenocarcinoma.

    PubMed

    Bossé, Yohan; Sazonova, Olga; Gaudreault, Nathalie; Bastien, Nathalie; Conti, Massimo; Pagé, Sylvain; Trahan, Sylvain; Couture, Christian; Joubert, Philippe

    2017-03-01

    Background: Tissues surrounding tumors are increasingly studied to understand the biology of cancer development and identify biomarkers.Methods: A unique geographic tissue sampling collection was obtained from patients that underwent curative lobectomy for stage I pulmonary adenocarcinoma. Tumor and nontumor lung samples located at 0, 2, 4, and 6 cm away from the tumor were collected. Whole-genome gene expression profiling was performed on all samples (n = 5 specimens × 12 patients = 60). Analyses were carried out to identify genes differentially expressed in the tumor compared with adjacent nontumor lung tissues at different distances from the tumor as well as to identify stable and transient genes in nontumor tissues with respect to tumor proximity.Results: The magnitude of gene expression changes between tumor and nontumor sites was similar with increasing distance from the tumor. A total of 482 up- and 843 downregulated genes were found in tumors, including 312 and 566 that were consistently differentially expressed across nontumor sites. Twenty-nine genes induced and 34 knocked-down in tumors were also identified. Tumor proximity analyses revealed 15,700 stable genes in nontumor lung tissues. Gene expression changes across nontumor sites were subtle and not statistically significant.Conclusions: This study describes the transcriptomic microenvironment of lung adenocarcinoma and adjacent nontumor lung tissues collected at standardized distances relative to the tumor.Impact: This study provides further insights about the molecular transitions that occur from normal tissue to lung adenocarcinoma and is an important step to develop biomarkers in nonmalignant lung tissues. Cancer Epidemiol Biomarkers Prev; 26(3); 389-96. ©2016 AACR.

  1. Uterine adenocarcinoma with feline leukemia virus infection.

    PubMed

    Cho, Sung-Jin; Lee, Hyun-A; Hong, Sunhwa; Kim, Okjin

    2011-12-01

    Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virus infection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virus infection.

  2. MLN0264 in Previously Treated Asian Participants With Advanced Gastrointestinal Carcinoma or Metastatic or Recurrent Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Guanylyl Cyclase C

    ClinicalTrials.gov

    2017-02-08

    Advanced Gastrointestinal Carcinoma; Gastroesophageal Junction Adenocarcinoma; Recurrent Gastric Adenocarcinoma; Recurrent Gastroesophageal Junction Adenocarcinoma; Metastatic Gastric Adenocarcinoma; Metastatic Gastroesophageal Junction Adenocarcinoma; Recurrent Gastrointestinal Carcinoma

  3. Expression of proliferative and inflammatory markers in a full-thickness human skin equivalent following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

    SciTech Connect

    Black, Adrienne T.; Hayden, Patrick J.; Casillas, Robert P.; Heck, Diane E.; Gerecke, Donald R.; Sinko, Patrick J.; Laskin, Debra L.; Laskin, Jeffrey D.

    2010-12-01

    Sulfur mustard is a potent vesicant that induces inflammation, edema and blistering following dermal exposure. To assess molecular mechanisms mediating these responses, we analyzed the effects of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide, on EpiDerm-FT{sup TM}, a commercially available full-thickness human skin equivalent. CEES (100-1000 {mu}M) caused a concentration-dependent increase in pyknotic nuclei and vacuolization in basal keratinocytes; at high concentrations (300-1000 {mu}M), CEES also disrupted keratin filament architecture in the stratum corneum. This was associated with time-dependent increases in expression of proliferating cell nuclear antigen, a marker of cell proliferation, and poly(ADP-ribose) polymerase (PARP) and phosphorylated histone H2AX, markers of DNA damage. Concentration- and time-dependent increases in mRNA and protein expression of eicosanoid biosynthetic enzymes including COX-2, 5-lipoxygenase, microsomal PGE{sub 2} synthases, leukotriene (LT) A{sub 4} hydrolase and LTC{sub 4} synthase were observed in CEES-treated skin equivalents, as well as in antioxidant enzymes, glutathione S-transferases A1-2 (GSTA1-2), GSTA3 and GSTA4. These data demonstrate that CEES induces rapid cellular damage, cytotoxicity and inflammation in full-thickness skin equivalents. These effects are similar to human responses to vesicants in vivo and suggest that the full thickness skin equivalent is a useful in vitro model to characterize the biological effects of mustards and to develop potential therapeutics.

  4. Inhibition of NADPH cytochrome P450 reductase by the model sulfur mustard vesicant 2-chloroethyl ethyl sulfide is associated with increased production of reactive oxygen species

    SciTech Connect

    Gray, Joshua P.; Mishin, Vladimir; Heck, Diane E.; Laskin, Debra L.; Laskin, Jeffrey D.

    2010-09-01

    Inhalation of vesicants including sulfur mustard can cause significant damage to the upper airways. This is the result of vesicant-induced modifications of proteins important in maintaining the integrity of the lung. Cytochrome P450s are the major enzymes in the lung mediating detoxification of sulfur mustard and its metabolites. NADPH cytochrome P450 reductase is a flavin-containing electron donor for cytochrome P450. The present studies demonstrate that the sulfur mustard analog, 2-chloroethyl ethyl sulfide (CEES), is a potent inhibitor of human recombinant cytochrome P450 reductase, as well as native cytochrome P450 reductase from liver microsomes of saline and {beta}-naphthoflavone-treated rats, and cytochrome P450 reductase from type II lung epithelial cells. Using rat liver microsomes from {beta}-naphthoflavone-treated rats, CEES was found to inhibit CYP 1A1 activity. This inhibition was overcome by microsomal cytochrome P450 reductase from saline-treated rats, which lack CYP 1A1 activity, demonstrating that the CEES inhibitory activity was selective for cytochrome P450 reductase. Cytochrome P450 reductase also generates reactive oxygen species (ROS) via oxidation of NADPH. In contrast to its inhibitory effects on the reduction of cytochrome c and CYP1A1 activity, CEES was found to stimulate ROS formation. Taken together, these data demonstrate that sulfur mustard vesicants target cytochrome P450 reductase and that this effect may be an important mechanism mediating oxidative stress and lung injury.

  5. [An unusual secondary localization of bronchial adenocarcinoma].

    PubMed

    Mirallie, E; Courant, O; Sagan, C; Letessier, E; Paineau, J; Visset, J

    1993-01-01

    The authors report a rare case of metastatic carcinoma of the large bowel, secondary to a primary bronchogenic adenocarcinoma. Abdominal pain developed in a 44-year old man 5 months after lobectomy for lung adenocarcinoma. The diagnosis of a large caecal extraluminal mass was established by means of sonography, scanner and laparoscopy. Palliative resection (brain metastases) was performed. Postoperative histological examination revealed the resected tumor to be identical to the lung adenocarcinoma. The patient eventually died 4 months after resection (complication of intracranial hypertension). Diagnosis and therapeutic features of metastatic extra-thoracic lung carcinoma are discussed.

  6. [Mesocolic excision for colonic adenocarcinoma].

    PubMed

    Debove, Clotilde; Lefèvre, Jérémie H; Parc, Yann

    2017-02-01

    On the same principle than total mesorectal excision in rectal cancer, the effect of complete mesocolic excision on short and long-term outcomes is actually evaluated for colonic adenocarcinoma. This method, usually performed for left colectomy, offers a surgical specimen of higher quality, with a larger number of lymph nodes harvested. For right colectomy, surgical specifications make it less common complete mesocolic excision and conventional surgery offer comparable outcomes, as regards to postoperative morbidity and mortality rates. No differences are identified between laparoscopic and open surgery. On oncologic outcomes, only two studies report a higher free-disease survival after complete mesocolic excision. Then, there is evidence that complete mesocolic excision offers a higher rate of specimen with extensive lymph node resection, without increased morbidity rate. However, there is limited evidence that it leads to improve long-term oncological outcomes.

  7. Colonic adenocarcinoma with metastasis to the gingiva.

    PubMed

    Alvarez-Alvarez, Carlos; Iglesias-Rodríguez, Begoña; Pazo-Irazu, Susana; Delgado-Sánchez-Gracián, Carlos

    2006-01-01

    Metastatic tumors involve the oral cavity, and the most common primary sites are the breast and lung. Most cases affect the mandible and maxilla in that order, although some of them can be located in the soft perioral tissues. We report the case of a 62-year-old male who had been diagnosed with sigmoid adenocarcinoma with nodal and liver metastasis, who presented 6 months later with a gingival polypoid tumor, at first considered as a primary neoplasm of gingiva, that was diagnosed in a biopsy as metastatic intestinal adenocarcinoma. The histological evaluation is essential to separate adenocarcinoma from the commoner in this site squamous cell carcinoma, and the immunohistochemical techniques are useful to distinguish metastatic tumor versus primary adenocarcinoma from the minor salivary glands of the area. The intraoral spread of a disseminated neoplasm is generally a sign of bad prognosis, although a longer survival can be expected if a radical surgical treatment of a solitary metastasis is carried out.

  8. Pathologic classification of adenocarcinoma of lung.

    PubMed

    Van Schil, Paul E; Sihoe, Alan D L; Travis, William D

    2013-10-01

    Recently, the 1999/2004 World Health Organization (WHO) classification of adenocarcinoma became less useful from a clinical standpoint as most adenocarcinomas belonged to the mixed subtype and the term bronchioloalveolar carcinoma (BAC) gave rise to much confusion among clinicians. For these reasons a new adenocarcinoma classification was introduced in 2011 by a joint working group of the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS). This represents an international, multidisciplinary effort joining pathologists, molecular biologists, pulmonary physicians, thoracic oncologists, radiologists, and thoracic surgeons. Currently, a distinction is made between pre-invasive lesions, minimally invasive and invasive lesions. The confusing term BAC is not used anymore and new subcategories include adenocarcinoma in situ and minimally invasive adenocarcinoma. Several aspects of this classification are discussed with main emphasis on its correlation with imaging techniques and its impact on diagnosis, treatment and prognosis. On chest computed tomography (CT) a distinction is made between solid and subsolid nodules, the latter comprising ground glass opacities (GGO), and partly solid lesions. Several studies incorporating CT and positron emission tomographic (PET) data show a good imaging-pathologic correlation. With the implementation of screening programs early lung cancer has become a hotly debated topic and sublobar resection is currently reconsidered for early lesions without lymph node involvement. This new classification will also have an impact on the TNM classification. Thoracic surgeons will continue to play a major role in the application, evaluation and further refinement of this new adenocarcinoma classification.

  9. Molecular analysis of the fragile histidine triad (FHIT) tumor suppressor gene in vesical tumors of cattle with chronic enzootic hematuria (CEH).

    PubMed

    Guidi, E; Uboldi, C; Ferretti, L

    2008-01-01

    The FHIT (fragile histidine triad) gene is a tumor suppressor gene known to be inactivated in many tumors including bladder tumors and is spanning FRA3B, a very active common fragile site in the human genome. We have recently isolated the bovine gene, and the aim of this study was to test whether FHIT presents altered expression patterns in vesical tumors of cattle with CEH (chronic enzootic hematuria). CEH is a common syndrome affecting Mediterranean cattle: clastogenic, mutagenic and cancerogenic substances released by the bracken fern (Pteridium spp) grazed by animals induce the formation of neoplastic lesions, among which bladder tumors have a high incidence. We analysed FHIT in 23 bladder tumors of CEH cattle looking at: 1) the methylation status of the CpG island comprising the promoter and part of exon 1; 2) the presence of altered FHIT transcripts; 3) the mRNA expression levels measured with a quantitative real time PCR (QRT-PCR) approach. Our results suggest that unlike in human tumors, FHIT in vesical tumors of CEH cattle is largely unmethylated. Furthermore, the same mRNA isoforms of FHIT were detected in tumors and in healthy tissues, including a novel isoform that was found in this study. Finally, QRT-PCR data did not reveal significantly altered expression profiles of FHIT transcripts. Further studies and larger sets of cases will be useful to confirm this finding, but the data seem to suggest that epigenetic modifications of FHIT and altered expression profiles are not a hallmark of bovine vesical tumors like they are in human tumors.

  10. What Happens After Treatment for Small Intestine Adenocarcinoma?

    MedlinePlus

    ... After Treatment What Happens After Treatment for Small Intestine Adenocarcinoma? For some people with small intestine cancer, ... Small Intestine Adenocarcinoma Stops Working More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  11. What Should You Ask Your Doctor About Small Intestine Adenocarcinoma?

    MedlinePlus

    ... What Should You Ask Your Doctor About Small Intestine Adenocarcinoma? It’s important to have honest, open discussions ... Doctor About Small Intestine Adenocarcinoma? More In Small Intestine Cancer About Small Intestine Cancer Causes, Risk Factors, ...

  12. Role of reactive nitrogen species generated via inducible nitric oxide synthase in vesicant-induced lung injury, inflammation and altered lung functioning

    SciTech Connect

    Sunil, Vasanthi R.; Shen, Jianliang; Patel-Vayas, Kinal; Gow, Andrew J.; Laskin, Jeffrey D.; Laskin, Debra L.

    2012-05-15

    Pulmonary toxicity induced by sulfur mustard and related vesicants is associated with oxidative stress. In the present studies we analyzed the role of reactive nitrogen species (RNS) generated via inducible nitric oxide synthase (iNOS) in lung injury and inflammation induced by vesicants using 2-chloroethyl ethyl sulfide (CEES) as a model. C57Bl/6 (WT) and iNOS −/− mice were sacrificed 3 days or 14 days following intratracheal administration of CEES (6 mg/kg) or control. CEES intoxication resulted in transient (3 days) increases in bronchoalveolar lavage (BAL) cell and protein content in WT, but not iNOS −/− mice. This correlated with expression of Ym1, a marker of oxidative stress in alveolar macrophages and epithelial cells. In contrast, in iNOS −/− mice, Ym1 was only observed 14 days post-exposure in enlarged alveolar macrophages, suggesting that they are alternatively activated. This is supported by findings that lung tumor necrosis factor and lipocalin Lcn2 expression, mediators involved in tissue repair were also upregulated at this time in iNOS −/− mice. Conversely, CEES-induced increases in the proinflammatory genes, monocyte chemotactic protein-1 and cyclooxygenase-2, were abrogated in iNOS −/− mice. In WT mice, CEES treatment also resulted in increases in total lung resistance and decreases in compliance in response to methacholine, effects blunted by loss of iNOS. These data demonstrate that RNS, generated via iNOS play a role in the pathogenic responses to CEES, augmenting oxidative stress and inflammation and suppressing tissue repair. Elucidating inflammatory mechanisms mediating vesicant-induced lung injury is key to the development of therapeutics to treat mustard poisoning. -- Highlights: ► Lung injury, inflammation and oxidative stress are induced by the model vesicant CEES ► RNS generated via iNOS are important in the CEES-induced pulmonary toxicity ► iNOS −/− mice are protected from CEES-induced lung toxicity and

  13. Adenocarcinoma of Meckel's cave: case report.

    PubMed

    Tacconi, L; Arulampalam, T; Johnston, F; Symon, L

    1995-12-01

    A rare localization of adenocarcinoma in Meckel's cave is reported in a 58-year-old woman, who had a 5-month history of pain and altered sensation in the second division of the left trigeminal nerve. Removal of the lesion was achieved by a subtemporal route. Histology showed this to be an adenocarcinoma. The patient underwent investigations for a primary tumor; the investigations were all negative, and the patient was subsequently treated with a course of radiotherapy. At 4-month follow-up, there was no evidence of recurrence, and she remains symptomatically well. The various mechanisms of secondary localization are discussed.

  14. Aggressive digital papillary adenoma-adenocarcinoma.

    PubMed

    Keramidas, Evangelos G; Miller, Gavin; Revelos, Kyriakos; Kitsanta, Panagiota; Page, Robert E

    2006-01-01

    Aggressive digital papillary adenocarcinoma and aggressive digital papillary adenoma are rare tumours of the sweat glands. They are most common in the most distal part of the fingers and are locally aggressive with a 50% local recurrence rate; 14% of tumours metastasize. We present two cases.

  15. Adenocarcinoma - chest x-ray (image)

    MedlinePlus

    This chest x-ray shows adenocarcinoma of the lung. There is a rounded light spot in the right upper lung (left side ... density. Diseases that may cause this type of x-ray result would be tuberculous or fungal granuloma, and ...

  16. MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma.

    PubMed

    Schultz, Nicolai A; Werner, Jens; Willenbrock, Hanni; Roslind, Anne; Giese, Nathalia; Horn, Thomas; Wøjdemann, Morten; Johansen, Julia S

    2012-12-01

    MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced). Several of these microRNAs have not before been related to diagnosis of pancreatic cancer (eg, miR-492, miR-614, miR-622). MiR-614, miR-492, miR-622, miR-135b and miR-196 were most differently expressed. MicroRNA profiles of pancreatic and ampullary adenocarcinomas were correlated (0.990). MicroRNA expression profiles for pancreatic cancer described in the literature were consistent with our findings, and the microRNA profile for pancreatic adenocarcinoma (miR-196b-miR-217) was validated. We identified a more significant expression profile, the difference between miR-411 and miR-198 (P=2.06 × 10(-54)) and a diagnostic LASSO classifier using 19 microRNAs (sensitivity 98.5%; positive predictive value 97.8%; accuracy 97.0%). We also identified microRNA profiles to subclassify ampullary adenocarcinomas into pancreatobiliary or intestinal type. In conclusion, we found that combinations of two microRNAs could roughly separate neoplastic from non-neoplastic samples. A diagnostic 19 microRNA classifier was constructed which without micro-dissection could discriminate pancreatic

  17. FOLFOX-6 Induction Chemotherapy Followed by Esophagectomy and Post-operative Chemoradiotherapy in Patients With Esophageal Adenocarcinoma

    ClinicalTrials.gov

    2016-09-15

    Adenocarcinoma of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Adenocarcinoma of the Gastric Cardia; Stage IIIA Esophageal Cancer; Stage IIIB Esophageal Cancer; Stage IIIC Esophageal Cancer

  18. Crohn enteritis-associated small bowel adenocarcinomas exhibit gastric differentiation.

    PubMed

    Whitcomb, Emma; Liu, Xiuli; Xiao, Shu-Yuan

    2014-02-01

    Primary small bowel adenocarcinoma is rare. Although generally similar to colonic adenocarcinoma, some small bowel adenocarcinomas exhibit unique morphologic features, particularly those arising in association with Crohn disease. In this study, 15 sporadic small bowel adenocarcinomas and 11 Crohn enteritis-associated small bowel adenocarcinomas were examined for histology and immunohistochemical profile including cytokeratins (CK) 7 and 20, intestinal markers CDX2 and MUC2, and gastric epithelial markers MUC5AC and MUC6. We found that Crohn enteritis-associated small bowel adenocarcinomas frequently resemble gastric tubular adenocarcinoma histologically. In addition, when compared to sporadic small bowel adenocarcinoma, the former expressed MUC5AC and MUC6 with much higher frequency (82% vs. 7% and 73% vs. 0%, respectively). Ten of 11 Crohn enteritis-associated small bowel adenocarcinomas (91%) were positive for at least one gastric-type marker (MUC5AC or MUC6). Expression of CK7 was also more frequent in Crohn enteritis-associated small bowel adenocarcinoma (73% versus 27%) while expression of CK20 was less frequent (64% vs. 100%). There was no difference between sporadic and Crohn enteritis-associated small bowel adenocarcinoma in expression of CDX2 (100% vs. 91%) and MUC2 (93% vs. 73%). These observations suggest that there is a difference in the morphologic and immunohistochemical characteristics of sporadic versus Crohn enteritis-associated small bowel adenocarcinoma, particularly in their expression of gastric-type mucin. The findings also suggest that gastric differentiation in Crohn enteritis-associated small bowel adenocarcinoma is related to gastric metaplasia, a common phenomenon in Crohn disease.

  19. Pancreatic Adenocarcinoma, Version 2.2012

    PubMed Central

    Tempero, Margaret A.; Arnoletti, J. Pablo; Behrman, Stephen W.; Ben-Josef, Edgar; Benson, Al B.; Casper, Ephraim S.; Cohen, Steven J.; Czito, Brian; Ellenhorn, Joshua D. I.; Hawkins, William G.; Herman, Joseph; Hoffman, John P.; Ko, Andrew; Komanduri, Srinadh; Koong, Albert; Ma, Wen Wee; Malafa, Mokenge P.; Merchant, Nipun B.; Mulvihill, Sean J.; Muscarella, Peter; Nakakura, Eric K.; Obando, Jorge; Pitman, Martha B.; Sasson, Aaron R.; Tally, Anitra; Thayer, Sarah P.; Whiting, Samuel; Wolff, Robert A.; Wolpin, Brian M.; Freedman-Cass, Deborah A.; Shead, Dorothy A.

    2013-01-01

    The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting. PMID:22679115

  20. [Atypical metastatic site of lung adenocarcinoma].

    PubMed

    Sakhri, L; Mennecier, B; Jacqmin, D; Di Marco, A; Schumacher, C; Chenard, M-P; Bergmann, E; Quoix, E

    2011-12-01

    The case concerns a 40 years old smoker male, treated for an adenocarcinoma of the left upper lobe, metastatic in muscle extended to the right femur cortex. The patient had first a surgical excision of the mass of the thigh, an intramedullary femoral nailing, and six courses of chemotherapy (cisplatin-vinorelbine) with concurrent thoracic radiotherapy. This treatment led to disease stability. One year later, hematuria revealed a bladder tumor. Cystoscopy with biopsy concluded to an adenocarcinoma pulmonary origin. The PET-scanner showed an uptake of the bladder mass, a hypermetabolic right adrenal gland and subcutaneous left shoulder nodule. The patient had a partial cystectomy associated with enterocystoplasty and left ureteral reimplantation, plus excision of the subcutaneous nodule located in the left shoulder and a right adrenalectomy during the same time. All of the sites were metastasis from adenocarcinoma of pulmonary origin. A salvage chemotherapy was initiated. In the vast majority of cases, bladder metastasis as primary bladder tumours is revealed by hematuria, cystitis or sometimes vague pelvic pain. Our case is a very unusual bladder metastatic site from lung cancer. We will discuss the different procedures and the therapeutic strategies on the basis of the published data.

  1. Laparoscopy in the management of gastric adenocarcinoma.

    PubMed Central

    Burke, E C; Karpeh, M S; Conlon, K C; Brennan, M F

    1997-01-01

    OBJECTIVE: The authors determined the accuracy of laparoscopy in detecting metastatic disease in patients with gastric adenocarcinoma. SUMMARY BACKGROUND DATA: The majority of patients with gastric adenocarcinoma in the United States present with advanced disease. They are at high risk for intraabdominal metastatic spread. METHODS: One hundred eleven patients with gastric adenocarcinoma underwent laparoscopy at Memorial-Sloan Kettering Cancer Center from December 1991 to December 1995. All were judged to be free of intra-abdominal metastatic disease on preoperative computed tomographic scan imaging. RESULTS: Laparoscopic exploration was successful in 110 of 111 patients and accurately staged 94% of the patients with respect to metastatic disease with a sensitivity of 84% and a specificity of 100%. The prevalence rate of metastatic disease was 37%. Twenty-four patients underwent laparoscopy only and were discharged in an average 1.4 days versus 6.5 days in patients undergoing exploratory laparotomy without resection (p < 0.05). No patients undergoing laparoscopy only have returned for palliative surgery. CONCLUSIONS: Laparoscopy should be performed in nonobstructed, nonbleeding patients with advanced gastric cancer in the United States. More than one third of these patients have unsuspected metastatic disease at time of operation. Laparoscopy is highly accurate in detecting occult metastases and identifies a unique population of stage IV patients who may benefit from newer induction chemotherapeutic approaches while avoiding unnecessary laparotomy. Images Figure 4. PMID:9060581

  2. Carcinogenesis of Pancreatic Adenocarcinoma: Precursor Lesions

    PubMed Central

    Gnoni, Antonio; Licchetta, Antonella; Scarpa, Aldo; Azzariti, Amalia; Brunetti, Anna Elisabetta; Simone, Gianni; Nardulli, Patrizia; Santini, Daniele; Aieta, Michele; Delcuratolo, Sabina; Silvestris, Nicola

    2013-01-01

    Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lead cancer cells not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes include: genetic alterations in oncogenes and cancer suppressor genes; changes in the cell cycle and pathways leading to apoptosis; and also changes in epithelial to mesenchymal transition. The most common alterations involve the epidermal growth factor receptor (EGFR) gene, the HER2 gene, and the K-ras gene. In particular, the loss of function of tumor-suppressor genes has been documented in this tumor, especially in CDKN2a, p53, DPC4 and BRCA2 genes. However, other molecular events involved in pancreatic adenocarcinoma pathogenesis contribute to its development and maintenance, specifically epigenetic events. In fact, key tumor suppressors that are well established to play a role in pancreatic adenocarcinoma may be altered through hypermethylation, and oncogenes can be upregulated secondary to permissive histone modifications. Indeed, factors involved in tumor invasiveness can be aberrantly expressed through dysregulated microRNAs. This review summarizes current knowledge of pancreatic carcinogenesis from its initiation within a normal cell until the time that it has disseminated to distant organs. In this scenario, highlighting these molecular alterations could provide new clinical tools for early diagnosis and new effective therapies for this malignancy. PMID:24084722

  3. Intraoperative molecular imaging to identify lung adenocarcinomas

    PubMed Central

    Newton, Andrew D.; Kennedy, Gregory T.; Predina, Jarrod D.; Low, Philip S.

    2016-01-01

    Intraoperative molecular imaging is a promising new technology with numerous applications in lung cancer surgery. Accurate identification of small nodules and assessment of tumor margins are two challenges in pulmonary resections for cancer, particularly with increasing use of video-assisted thoracoscopic surgery (VATS). One potential solution to these problems is intraoperative use of a fluorescent contrast agent to improve detection of cancer cells. This technology requires both a targeted fluorescent dye that will selectively accumulate in cancer cells and a specialized imaging system to detect the cells. In several studies, we have shown that intraoperative imaging with indocyanine green (ICG) can be used to accurately identify indeterminate pulmonary nodules. The use of a folate-tagged fluorescent molecule targeted to the folate receptor-α (FRα) further improves the sensitivity and specificity of detecting lung adenocarcinomas. We have demonstrated this technology can be used as an “optical biopsy” to differentiate adenocarcinoma versus other histological subtypes of pulmonary nodules. This strategy has potential applications in assessing bronchial stump margins, identifying synchronous or metachronous lesions, and rapidly assessing lymph nodes for lung adenocarcinoma. PMID:28066672

  4. Comprehensive molecular profiling of lung adenocarcinoma

    PubMed Central

    2014-01-01

    Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis. PMID:25079552

  5. Comprehensive molecular profiling of lung adenocarcinoma.

    PubMed

    2014-07-31

    Adenocarcinoma of the lung is the leading cause of cancer death worldwide. Here we report molecular profiling of 230 resected lung adenocarcinomas using messenger RNA, microRNA and DNA sequencing integrated with copy number, methylation and proteomic analyses. High rates of somatic mutation were seen (mean 8.9 mutations per megabase). Eighteen genes were statistically significantly mutated, including RIT1 activating mutations and newly described loss-of-function MGA mutations which are mutually exclusive with focal MYC amplification. EGFR mutations were more frequent in female patients, whereas mutations in RBM10 were more common in males. Aberrations in NF1, MET, ERBB2 and RIT1 occurred in 13% of cases and were enriched in samples otherwise lacking an activated oncogene, suggesting a driver role for these events in certain tumours. DNA and mRNA sequence from the same tumour highlighted splicing alterations driven by somatic genomic changes, including exon 14 skipping in MET mRNA in 4% of cases. MAPK and PI(3)K pathway activity, when measured at the protein level, was explained by known mutations in only a fraction of cases, suggesting additional, unexplained mechanisms of pathway activation. These data establish a foundation for classification and further investigations of lung adenocarcinoma molecular pathogenesis.

  6. Solitary Psoas Muscle Metastasis of Gastroesphageal Junction Adenocarcinoma

    PubMed Central

    Azadeh, Payam; Yaghobi Joybari, Ali; Sarbaz, Samaneh; Ghiasi, Hosein Ali; Farasatinasab, Maryam

    2016-01-01

    Metastasis of gastroesphageal junction (GEJ) adenocarcinoma in skeletal muscle is rare and primary sites for skeletal muscle metastases are usually lung, renal and colorectal cancer. We have encountered with the first case report of solitary psoas muscle metastasis of GEJ adenocarcinoma. Here we describe a 65 years old man was diagnosed with GEJ adenocarcinoma in Gastroenterology Department, Imam Hussein Hospital, Tehran, Iran in February 2014. We were not able to use PET techniques due to lack of access. Staging CT scans demonstrated a small mass lateral to right psoas muscle. A CT-guided core needle biopsy of right psoas muscle was performed that supported a diagnosis of adenocarcinoma consistent with primary adenocarcinoma of the GEJ. Distant metastasis to skeletal muscle rarely occurs in patients with GEJ adenocarcinoma, but heightened awareness to these soft tissue lesions is warranted. CT or MR imaging could show findings suggestive of metastatic disease, although PET is preferable modality. PMID:26870148

  7. Mechanism of Cutaneous Vesication

    DTIC Science & Technology

    1994-02-17

    neurofilibroma. J. Invest. Dermatol. 85:54- 59. Foidart, J.M., Bere, E.W., Yaar, M ., Rennard, S.I., Gullino , M ., Martin, G.R., and Katz, S.I. (1980). Distribution...of animal models for predicting skin penetration in man. Fundam. Appl. Toxicol. 4:S224-S230. Requena, L ., Requena, C., Sanchez, M ., Jaqueti, G...H., Gullino , M ., and Katz, S.I. (1976). Herpes gestationis. Ultrastructure and ultrastructural localization of in vivo-bound complement: Modified

  8. Ductal Adenocarcinoma of the Prostate: A Case Report

    PubMed Central

    Hayashi, Yutaro; Kawahara, Takashi; Iwashita, Hiromichi; Shimokihara, Kota; Tsutsumi, Sohgo; Takamoto, Daiji; Mochizuki, Taku; Hattori, Yusuke; Teranishi, Jun-ichi; Miyoshi, Yasuhide; Yumura, Yasushi; Yao, Masahiro; Inayama, Yoshiaki; Uemura, Hiroji

    2016-01-01

    Ductal adenocarcinoma is an unusual variant of adenocarcinoma of the prostate. A 73-year-old male was referred to our hospital for the further examination of an elevated prostate-specific antigen level of 23.4 ng/mL. Radical prostatectomy (RP) was performed based on the diagnosis obtained by a prostate needle biopsy. The RP specimen revealed ductal adenocarcinoma of the prostate with positive capsular penetration. We herein report a rare case of ductal adenocarcinoma of the prostate. PMID:28101029

  9. Laparoscopic Diagnosis of Adenocarcinoma of the Appendix Mimicking Serous Papillary Adenocarcinoma of the Peritoneum

    PubMed Central

    Yoshimura, Mayumi; Terai, Yoshito; Konishi, Hiromi; Tanaka, Yoshimichi; Tanaka, Tomohito; Sasaki, Hiroshi; Ohmichi, Masahide

    2013-01-01

    Primary carcinoma of the vermiform appendix is a rare disease with few clinical symptoms. Accordingly, preoperative diagnosis of appendiceal cancer is challenging because of the lack of specific symptoms. We herein report a case of appendicular adenocarcinoma found unexpectedly during laparoscopic surgery in a 69-year-old Japanese female patient diagnosed with serous papillary adenocarcinoma, in order to determine whether optimal cytoreduction could successfully be achieved at the time of primary surgery. We performed diagnostic laparoscopic surgery in order to make a correct diagnosis based on the histological tissue. The vermiform appendix was found to contain a tumor measuring 1.5 cm wide and 4.5 cm long. Laparoscopic appendectomy, partial omentectomy, and partial resection of the lesion in the peritoneum were performed. The histological diagnosis was mucinous adenocarcinoma of the vermiform appendix, and the stage was T4NxM1. The patient received adjuvant chemotherapy with mFOLFOX 6 (5FU, leucovorin, and oxaliplatin). She achieved stable disease and was alive with disease eleven months after surgery. We therefore recommend that gynecologists should not rule out the possibility of appendiceal cancer, even in cases with preoperative findings similar to those of serous papillary adenocarcinoma of the peritoneum with peritoneal disseminated tumors. PMID:24383020

  10. Intensity-Modulated Radiotherapy for Pancreatic Adenocarcinoma

    SciTech Connect

    Abelson, Jonathan A.; Murphy, James D.; Minn, Ann Yuriko; Chung, Melody; Fisher, George A.; Ford, James M.; Kunz, Pamela; Norton, Jeffrey A.; Visser, Brendan C.; Poultsides, George A.; Koong, Albert C.; Chang, Daniel T.

    2012-03-15

    Purpose: To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma. Methods and Materials: Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively. Results: The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%). Conclusions: Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity.

  11. Endometrial Adenocarcinoma Presenting in a Premenopausal Patient with Tuberous Sclerosis

    ERIC Educational Resources Information Center

    Jaffe, J. S.; Chambers, J. T.

    2005-01-01

    Background: Endometrial adenocarcinoma is very uncommon in women under 40 years of age. Case: A 39-year-old woman with tuberous sclerosis and severe intellectual disability presented with irregular bleeding unresponsive to oral contraceptive therapy. She was subsequently found to have a deeply invasive endometrial adenocarcinoma. Conclusion:…

  12. Eccrine adenocarcinoma of the footpads in 2 cats.

    PubMed Central

    Fuentealba, I C; Illanes, O G; Haines, D M

    2000-01-01

    Adenocarcinoma of sweat glands of the footpads was diagnosed in 2 cats. Clinical signs included lameness and swelling of multiple digits. Pulmonary metastasis was detected in one case. Diagnosis was based on histopathological and immunohistochemical findings. Eccrine adenocarcinoma should be included in the differential diagnosis of footpads lesions in aged cats. Images Figure 1. Figure 2. PMID:10816835

  13. Laparoscopic treatment of mucinous urachal adenocarcinoma with mucocele.

    PubMed

    Oberndoerfer, Marine; Bucher, Pascal; Caviezel, Alessandro; Platon, Alexandra; Ott, Vincent; Egger, Jean-François; Morel, Philippe

    2009-02-01

    We present a case of an asymptomatic 76-year-old woman treated laparoscopically for an urachal mucocele owing to a nonmetastatic urachal mucinous adenocarcinoma. Since laparoscopic en bloc resection of the urachus and partial cystectomy, the patient has been healthy and disease-free for 12 months. Modern surgical treatment of urachal adenocarcinoma is discussed in the light of this case.

  14. Neoadjuvant treatment for resectable pancreatic adenocarcinoma

    PubMed Central

    Wong, John; Solomon, Naveenraj L; Hsueh, Chung-Tsen

    2016-01-01

    Pancreatic adenocarcinoma is the fourth leading cause of cancer mortality in the United States in both men and women, with a 5-year survival rate of less than 5%. Surgical resection remains the only curative treatment, but most patients develop systemic recurrence within 2 years of surgery. Adjuvant treatment with chemotherapy or chemoradiotherapy has been shown to improve overall survival, but the delivery of treatment remains problematic with up to 50% of patients not receiving postoperative treatment. Neoadjuvant therapy can provide benefits of eradication of micrometastasis and improved delivery of intended treatment. We have reviewed the findings from completed neoadjuvant clinical trials, and discussed the ongoing studies. Combinational cytotoxic chemotherapy such as fluorouracil, leucovorin, irinotecan, and oxaliplatin and gemcitabine plus nanoparticle albumin-bound (nab)-paclitaxel, active in the metastatic setting, are being studied in the neoadjuvant setting. In addition, novel targeted agents such as inhibitor of immune checkpoint are incorporated with cytotoxic chemotherapy in early-phase clinical trial. Furthermore we have explored the utility of biomarkers which can personalize treatment and select patients for target-driven therapy to improve treatment outcome. The treatment of resectable pancreatic adenocarcinoma requires multidisciplinary approach and novel strategies including innovative trials to make progress. PMID:26862486

  15. Aggressive papillary adenocarcinoma on atypical localization

    PubMed Central

    Balci, Mecdi Gurhan; Tayfur, Mahir; Deger, Ayse Nur; Cimen, Orhan; Eken, Huseyin

    2016-01-01

    Abstract Introduction: Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland tumor that is found on the fingers, toes, and the digits. To date, <100 cases have been reported in the literature. Apart from 1 case reported in the thigh, all of them were on digital or nondigital acral skin. Case presentation: A 67-year-old Caucasian woman was admitted to the hospital due to a mass on the scalp. This lesion was present for almost a year. It was a semimobile cyctic mass that elevated the scalp. There was no change in the skin color. Its dimensions were 1.5 × 1 × 0.6 cm. The laboratory, clinic, and radiologic findings (head x-ray) of the patient were normal. It was evaluated as a benign lesion such as lipoma or epidermal cyst by a surgeon due to a small semimobile mass and no erosion of the skull. It was excised by a local surgery excision. The result of the pathologic examination was aggressive papillary adenocarcinoma. This diagnosis is synonymous with ADPA. Conclusion: In our case, localization was scalp. This localization is the first for this tumor in the literature. In addition, another atypical localization of this tumor (ADPA) is thigh in the literature. This case was presented due to both the rare and atypical localizations. That is why, in our opinion, revision of “digital” term in ADPA is necessary due to seem in atypical localizations like thigh and scalp. PMID:27428196

  16. Metastasis of Prostate Adenocarcinoma to the Testis

    PubMed Central

    Campara, Zoran; Simic, Dejan; Aleksic, Predrag; Spasic, Aleksandar; Milicevic, Snjezana

    2016-01-01

    Introduction: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease. Case report: This work presents a 48-year-old patient, to whom an adenocarcinoma of the prostate has been proven by the pathohistological finding of transrectal biopsy, performed due to the elevated level of prostate-specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy and right orchectomy were performed. Metastatic dissemination of prostate adenocarcinoma into a testis was determined by a pathohistological analysis of the left testis. Conclusion: The metastasis of the prostate carcinoma into a testis, as a rare localization of the metastatic dissemination, after additionally performed orchectomy along with further oncological therapy, can provide a continuation of a good life quality as well as a control of the disease in a longer time period. PMID:27703299

  17. Clinicopathologic features and prognosis of duodenal adenocarcinoma and comparison with ampullary and pancreatic ductal adenocarcinoma.

    PubMed

    Zenali, Maryam; Overman, Michael J; Rashid, Asif; Broaddus, Russell B; Wang, Hua; Katz, Matthew H; Fleming, Jason B; Abbruzzese, James L; Wang, Huamin

    2013-12-01

    Because of the rarity of duodenal adenocarcinoma (DAC), the clinicopathologic features and prognostication data for DAC are limited. There are no published studies directly comparing the prognosis of DAC to that of ampullary adenocarcinoma (AA) and of pancreatic ductal adenocarcinoma (PDA) after resection. In this study, we examined the clinicopathologic features of 68 patients with DAC, 92 patients with AA, and 126 patients with PDA who underwent resection. Patient clinicopathologic and survival information were extracted from medical records. Statistical analysis was performed using Statistical Package for the Social Sciences with 2-sided significance level of .05. Patients with DAC had higher American Joint Committee on Cancer (AJCC) stage than AA patients (P = .001). Lymph node metastasis (P = .013) and AJCC stage (P = .02) correlated with overall survival in DAC patients. Patients with DAC or AA had lower frequencies of lymph node metastasis and positive margin and better survival than those with PDA (P < .05). However, no differences in nodal metastasis, margin status, or survival were observed between DAC patients and those with AA. Our study showed that lymph node metastasis and AJCC stage are important prognostic factors for overall survival in DAC patients. Patients with DAC had less frequent nodal metastasis and better prognosis than those with PDA. There was no significant difference in prognosis between DAC and AA.

  18. Abiraterone Acetate and Castration Resistant Ductal Adenocarcinoma of the Prostate

    PubMed Central

    Linden-Castro, Edgar; Pelayo-Nieto, Marcela; Alias-Melgar, Alejandro; Espinosa-Perezgrovas, Daniel; Ramirez-Galindo, Ivan; Catalan-Quinto, Gabriel

    2014-01-01

    Ductal adenocarcinoma of the prostate is a rare histological variant that only represents <1% of prostate tumors. This histological variant has several important clinical implications with respect to their evolution, clinical prognosis, and treatment. We report the case of a 64-year-old patient with ductal adenocarcinoma of the prostate, which progresses to castration-resistant prostate cancer, that was treated with abiraterone acetate with good clinical response, to our knowledge, the first case of ductal adenocarcinoma of the prostate in treatment with abiraterone acetate. PMID:24891969

  19. Primary Adenocarcinoma of an Ileostomy in Crohn's Disease

    PubMed Central

    Prasad, Meena A.; Lo, Amy; Bellaguarda, Emanuelle; Strong, Scott; Hanauer, Stephen B.

    2016-01-01

    Although Crohn's disease has been associated with an increased risk of small bowel adenocarcinoma, primary adenocarcinoma arising from an ileostomy is a complication that has been rarely documented in Crohn's disease. Chronic small bowel inflammation may lead to development of malignancy through the dysplasia-carcinoma sequence. We report a case of a 61-year-old woman with Crohn's ileocolitis diagnosed with a primary adenocarcinoma at the ileostomy with metastases to the liver 47 years after proctocolectomy, and review the literature. PMID:27622191

  20. [Secondary neoplasms of the larynx from a colonic adenocarcinoma].

    PubMed

    Dadkhah, Naser; Hahn, Christoffer

    2015-01-26

    Secondary neoplasms of the larynx are rare and account for 0.09-0,4% of all laryngeal tumours. Cutaneous melanomas are the preponderant primaries metastasizing to the larynx, followed by renal cell carcinomas, breast and lung carcinomas. Colonic adenocarcinoma metastases to the larynx are extremely rare. Tumours spreading to the larynx may be asymptomatic or may result in hoarseness, stridor or airway obstruction. Patients with metastasis of colonic adenocarcinoma to the larynx usually present with disseminated disease. We present a case of an isolated laryngeal metastasis from a colonic adenocarcinoma. The patient was treated with endoscopic surgery and radiation.

  1. Duodenal adenocarcinoma presenting as a mass with aneurismal dilatation.

    PubMed

    Mama, Nadia; Ben Slama, Aïda; Arifa, Nadia; Kadri, Khaled; Sriha, Badreddine; Ksiaa, Mehdi; Jemni, Hela; Tlili-Graiess, Kalthoum

    2014-01-01

    Duodenal adenocarcinoma is frequent. Aneurysmal dilatation of the small bowel is reported to be a lymphoma characteristic imaging finding. A 57-year-old male was found to have a duodenal adenocarcinoma with aneurismal dilatation on imaging which is an exceptional feature. On laparotomy, the wall thickening of the dilated duodenum extended to the first jejunal loop, with multiple mesenteric lymph nodes and ascites. Segmental palliative resection with gastro-entero-anastomosis was done. Histopathology revealed a moderately differentiated adenocarcinoma with neuro-endocrine differentiation foci. Wide areas of necrosis and vascular emboli were responsible for the radiological feature of the dilated duodenum with wall thickening.

  2. Biomarkers in pancreatic adenocarcinoma: current perspectives

    PubMed Central

    Swords, Douglas S; Firpo, Matthew A; Scaife, Courtney L; Mulvihill, Sean J

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC. PMID:28003762

  3. Preclinical models of pancreatic ductal adenocarcinoma.

    PubMed

    Hwang, Chang-Il; Boj, Sylvia F; Clevers, Hans; Tuveson, David A

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDA) is one of the most difficult human malignancies to treat. The 5-year survival rate of PDA patients is 7% and PDA is predicted to become the second leading cancer-related cause of death in the USA. Despite intensive efforts, the translation of findings in preclinical studies has been ineffective, due partially to the lack of preclinical models that faithfully recapitulate features of human PDA. Here, we review current preclinical models for human PDA (eg human PDA cell lines, cell line-based xenografts and patient-derived tumour xenografts). In addition, we discuss potential applications of the recently developed pancreatic ductal organoids, three-dimensional culture systems and organoid-based xenografts as new preclinical models for PDA.

  4. Targeting Pancreatic Ductal Adenocarcinoma Acidic Microenvironment

    NASA Astrophysics Data System (ADS)

    Cruz-Monserrate, Zobeida; Roland, Christina L.; Deng, Defeng; Arumugam, Thiruvengadam; Moshnikova, Anna; Andreev, Oleg A.; Reshetnyak, Yana K.; Logsdon, Craig D.

    2014-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death in the USA, accounting for ~40,000 deaths annually. The dismal prognosis for PDAC is largely due to its late diagnosis. Currently, the most sensitive diagnosis of PDAC requires invasive procedures, such as endoscopic ultrasonography, which has inherent risks and accuracy that is highly operator dependent. Here we took advantage of a general characteristic of solid tumors, the acidic microenvironment that is generated as a by-product of metabolism, to develop a novel approach of using pH (Low) Insertion Peptides (pHLIPs) for imaging of PDAC. We show that fluorescently labeled pHLIPs can localize and specifically detect PDAC in human xenografts as well as PDAC and PanIN lesions in genetically engineered mouse models. This novel approach may improve detection, differential diagnosis and staging of PDAC.

  5. Clinically-Relevant Cutaneous Lesions by Nitrogen Mustard: Useful Biomarkers of Vesicants Skin Injury in SKH-1 Hairless and C57BL/6 Mice

    PubMed Central

    Tewari-Singh, Neera; Jain, Anil K.; Inturi, Swetha; White, Carl W.; Agarwal, Rajesh

    2013-01-01

    A paucity of clinically applicable biomarkers to screen therapies in laboratory is a limitation in the development of countermeasures against cutaneous injuries by chemical weapon, sulfur mustard (SM), and its analog nitrogen mustard (NM). Consequently, we assessed NM-caused progression of clinical cutaneous lesions; notably, skin injury with NM is comparable to SM. Exposure of SKH-1 hairless and C57BL/6 (haired) mice to NM (3.2 mg) for 12–120 h caused clinical sequelae of toxicity, including microblister formation, edema, erythema, altered pigmentation, wounding, xerosis and scaly dry skin. These toxic effects of NM were similar in both mouse strains, except that wounding and altered pigmentation at 12–24 h and appearance of dry skin at 24 and 72 h post-NM exposure were more pronounced in C57BL/6 compared to SKH-1 mice. Conversely, edema, erythema and microblister formation were more prominent in SKH-1 than C57BL/6 mice at 24–72 h after NM exposure. In addition, 40–60% mortality was observed following 120 h of NM exposure in the both mouse strains. Overall, these toxic effects of NM are comparable to those reported in humans and other animal species with SM, and thus represent clinically-relevant cutaneous injury endpoints in screening and optimization of therapies for skin injuries by vesicating agents. PMID:23826320

  6. Human chorionic gonadotropin and CA 15-3 producing adenocarcinoma.

    PubMed

    Uçkaya, G; Ozet, A; Arpaci, A; Kömürcü, S

    1998-01-01

    50 years old man suffering from primary lung adenocarcinoma presented with high levels of both beta subunit human chorionic gonadotropin (beta HCG) and cancer antigen 15-3 (CA 15-3) in the absence of elevated carcinoembrionic antigen (CEA), alfa fetoprotein (AFP) and carbohydrate antigen 19-9 (CA 19-9). Although beta HCG or CA 15-3 high levels were reported in adenocarcinoma of lung, this is the first report of a patient with high levels of both markers.

  7. Metachronous Colon Metastases from Gastric Adenocarcinoma: A Case Report

    PubMed Central

    Pace, Ugo; Contino, Gianmarco; Chiappa, Antonio; Bertani, Emilio; Bianchi, Paolo P.; Fazio, Nicola; Renne, Giuseppe; Di Meglio, Giovanni; Andreoni, Bruno

    2009-01-01

    The colon is a very rare metastatic localization. Here we report a case of colonic metastases from gastric adenocarcinoma whose clinical presentation was suggestive of a de novo adenocarcinoma of the ascending colon. The authors discuss that in the presence of a previous history of gastric cancer, immunohistochemical analysis on endoscopic biopsies may help in the definition of a differential diagnosis. Furthermore, this rare metastatic localization might suggest a poor prognosis and a more accurate diagnostic work-up. PMID:20740169

  8. [Gastric signet ring cell adenocarcinoma: A distinct entity].

    PubMed

    Tabouret, Tessa; Dhooge, Marion; Rouquette, Alexandre; Brezault, Catherine; Beuvon, Frédéric; Chaussade, Stanislas; Coriat, Romain

    2014-04-01

    Gastric signet ring cell carcinoma (GSRC) is a distinct entity. Their incidence is increasing. The pathologist plays a central role in the identification of this entity. Diagnosis is based on an adenocarcinoma containing a majority of signet ring cells (above 50 %). The prognosis of GSRC is the same as gastric adenocarcinoma while GSRC appeared more aggressive. Signet ring cells present a low sensitivity to chemotherapy. This review aimed to discuss the histological, the prognostic and the therapeutic aspect of this entity.

  9. The Management and Prognostic Prediction of Adenocarcinoma of Appendix

    PubMed Central

    Xie, Xin; Zhou, Zhangjian; Song, Yongchun; Li, Wenhan; Diao, Dongmei; Dang, Chengxue; Zhang, Hao

    2016-01-01

    Malignant tumours of the appendix are quite rare, especially appendiceal adenocarcinomas, which may be difficult to detect preoperatively or intraoperatively. We collected data for 1404 patients with adenocarcinoma of the appendix from the Surveillance, Epidemiology, and End Results Program (SEER) database to explore the potential associations between clinicopathological factors and overall survival. Furthermore, a novel nomogram for predicting prognosis was developed based on our analysis of the SEER data. The nomogram prediction model included seven prognostic factors derived based on different clinical estimates. When compared with the traditional tumour-node-metastasis (TNM) staging system, the nomogram prediction model showed superior discriminatory power (Harrell’s C-index, 0.741 vs. 0.686) and a greater degree of similarity to actual 5-year overall survival after calibration (Akaike Information Criterion index, 5270.781 vs. 5430.141). Finally, we provide recommendations for the management of patients with adenocarcinoma of the appendix. Notably, we found the depth of adenocarcinoma invasion may be used as an indicator to determine the optimal surgical approach. For mucinous adenocarcinomas of the appendix, because these tumours are characterized by unique biological behaviour, intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is recommended. However, whether systematic chemotherapy should be administered to patients with adenocarcinoma of the appendix requires further investigation. PMID:27982068

  10. Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin.

    PubMed

    Park, Won Young; Kim, Mi Hyun; Shin, Dong Hoon; Lee, Jung Hee; Choi, Kyung Un; Kim, Jee Yeon; Park, Do Youn; Lee, Chang Hun; Sol, Mee Young

    2012-09-01

    Whereas most carcinomas occur through a sequential step, atypical adenomatous hyperplasia and bronchioloalveolar carcinoma pathway is known for pulmonary adenocarcinoma. This type is known as terminal respiratory unit adenocarcinoma. Based on our observation of transitions from normal ciliated columnar cells to adenocarcinoma via dysplastic mucous columnar cells, we reviewed our archive of pulmonary adenocarcinoma. Terminal respiratory unit type adenocarcinoma was defined as adenocarcinoma with type II pneumocyte, Clara cell, or bronchiolar cell morphology according to previous reports. Among 157 cases, 121 cases have been identified as terminal respiratory unit type adenocarcinoma and 36 cases as non-terminal respiratory unit type adenocarcinoma. Among non-terminal respiratory unit type adenocarcinoma, 24 cases revealed mucous columnar cell changes that were continuous with bronchial ciliated columnar cells. The mucous columnar cells became dysplastic showing loss of cilia, disorientation, and enlarged nuclei. Adenocarcinoma arose from these dysplastic mucous columnar cells and, characteristically, this type of adenocarcinoma showed acute inflammation, and honeycombing changes in the background. TTF1 immunostaining was consistently negative. In a case study with 14 males and 10 females, including 12 smokers or ex-smokers, EGFR and KRAS mutations were detected in 3 and 6 patients, respectively. We think that this kind of adenocarcinoma arising through mucous columnar cell change belongs to non-terminal respiratory unit type adenocarcinoma, and mucous columnar cell change is a precursor lesion of pulmonary adenocarcinoma.

  11. Hepatoid adenocarcinoma of the stomach – a different histology for not so different gastric adenocarcinoma: a case report

    PubMed Central

    Gálvez-Muñoz, Elisa; Gallego-Plazas, Javier; Gonzalez-Orozco, Verónica; Menarguez-Pina, Francisco; Ruiz-Maciá, José A; Morcillo, Miguel A

    2009-01-01

    Hepatoid adenocarcinoma is an extrahepatic tumor characterized by morphological similarities to hepatocellular carcinoma. Hepatoid adenocarcinoma of the stomach is a cancer with an extremely poor prognosis with few cases reported. Here, we describe a 75-year-old Spanish man referred to our hospital with a history of abdominal pain, general fatigue, anorexia and sickness. Initial study revealed anemia, and computed tomography scan and abdominal ultrasonography showed multiple metastases to the liver with hepatocellular carcinoma characteristics in a liver with no cirrhotic change. Further study included a serum level of alpha-fetoprotein (AFP), which resulted markedly elevated, and a conclusive esophagogastroduodenoscopy describing an elevated tumour growing through the cardia and gastroesophageal junction with foci of necrosis and haemorrhage. Gastric biopsies of the tumor revealed poorly differenciated adenocarcinoma, with hepatoid differentiation. After a diagnosis of AFP-producing hepatoid adenocarcinoma of the stomach with multiple liver metastases was made, pallitive total gastrectomy, without liver resection, was performed. Patient recovered well after surgery, and entered into a palliative systemich chemotherapy protocol. Although this illness is recognized as having poor prognosis, the patient remains alive 8 months after the operation. Accurate diagnosis of hepatoid adenocarcinoma of the stomach is important, and should be suspected under certain circumstances. We describe this rare case of hepatoid adenocarcinoma of the stomach, and review the literature concerning the clinicopathological aspects. PMID:19674468

  12. Annexin A3 Knockdown Suppresses Lung Adenocarcinoma

    PubMed Central

    Liu, Qing-Qing; Zhang, Yue-Hua; Qiu, Jing-Hua

    2016-01-01

    Our previous study identified an elevated abundance of annexin A3 (Anxa3) as a novel prognostic biomarker of lung adenocarcinoma (LADC) through quantitative proteomics analysis. However, the biological functions of Anxa3 in LADC are not fully clear. In this study, in vitro and in vivo assays were performed to investigate the effects of Anxa3 downregulation on the growth, migration, invasion, metastasis, and signaling pathway activation of LADC cells. After Anxa3 downregulation, the growth of A549 and LTEP-a2 LADC cells was slowed and they showed decreased migration and invasion in vitro. Anxa3 knockdown significantly inhibited tumor formation by A549 cells in vivo; while many metastases were formed by control A549 cells, there were obvious reductions in the numbers of lung, liver, and brain metastases formed by Anxa3 knockdown in A549 cells. Furthermore, Anxa3 knockdown significantly decreased MMP-2 and N-cadherin expression and increased E-cadherin expression both in cell lines in vitro and in tumor nodules examined during in vivo tumorigenesis assays. Interestingly, Anxa3 downregulation reduced the phosphorylated levels of MEK and ERK. In summary, Anxa3 knockdown inhibited the growth, migration, invasion, and metastasis of LADC, decreased the activation of the MEK/ERK signaling pathway, and modulated the expression of MMP-2, E-cadherin, and N-cadherin. PMID:27995049

  13. Pancreatic adenocarcinoma pathology: changing “landscape”

    PubMed Central

    Brosens, Lodewijk A. A.; Hackeng, Wenzel M.; Offerhaus, G. Johan; Hruban, Ralph H.

    2015-01-01

    Pancreatic cancer is a devastating disease. At time of diagnosis the disease is usually advanced and only a minority of patients are eligible for surgical resection. The overall 5-year survival is 6%. However, survival of patients with early stage pancreatic cancer is significantly better. To improve the prognosis of patients with pancreatic cancer, it is essential to diagnose and treat pancreatic cancer in the earliest stage. Prevention of pancreatic cancer by treating noninvasive precursor lesions just before they invade tissues can potentially lead to even better outcomes. Pancreatic carcinogenesis results from a stepwise progression in which accumulating genetic alterations drive neoplastic progression in well-defined precursor lesions, ultimately giving rise to an invasive adenocarcinoma. A thorough understanding of the genetic changes that drive pancreatic carcinogenesis can lead to identification of biomarkers for early detection and targets for therapy. Recent next-generation sequencing (NGS) studies have shed new light on our understanding of the natural history of pancreatic cancer and the precursor lesions that give rise to these cancers. Importantly, there is a significant window of opportunity for early detection and treatment between the first genetic alteration in a cell in the pancreas and development of full-blown pancreatic cancer. The current views on the pathology and genetics of pancreatic carcinogenesis that evolved from studies of pancreatic cancer and its precursor lesions are discussed in this review. PMID:26261723

  14. Emerging therapeutic targets in esophageal adenocarcinoma

    PubMed Central

    Gaur, Puja; Hunt, Clayton R.; Pandita, Tej K.

    2016-01-01

    The incidence of gastro-esophageal disease and associated rate of esophageal adenocarcinoma (EAC) is rising at an exponential rate in the United States. However, research targeting EAC is lagging behind, and much research is needed in the field to identify ways to diagnose EAC early as well as to improve the rate of pathologic complete response (pCR) to systemic therapies. Esophagectomy with subsequent reconstruction is known to be a morbid procedure that significantly impacts a patient's quality of life. If indeed the pCR rate of patients can be improved and those patients destined to be pCR can be identified ahead of time, they may be able to avoid this life-altering procedure. While cancer-specific biological pathways have been thoroughly investigated in other solid malignancies, much remains unexplored in EAC. In this review, we will highlight some of the latest research in the field in regards with EAC, along with new therapeutic targets that are currently being explored. After reviewing conventional treatment and current changes in medical therapy for EAC, we will focus on unchartered grounds such as cancer stem cells, genetics and epigenetics, immunotherapy, and chemoradio-resistant pathways as we simultaneously propose some investigational possibilities that could be applicable to EAC. PMID:27102294

  15. Algenpantucel-L immunotherapy in pancreatic adenocarcinoma.

    PubMed

    Coveler, Andrew L; Rossi, Gabriela R; Vahanian, Nicholas N; Link, Charles; Chiorean, E Gabriela

    2016-02-01

    Pancreatic adenocarcinoma is the 4th leading cause of cancer death in the USA and the EU. A minority of patients presents with surgically resectable and potentially curable disease, but among these, 80% are destined to relapse and overall survival rates with adjuvant chemotherapy average 24 months. Immunotherapy is a promising therapeutic option and a potential paradigm shift in the treatment of patients with pancreatic cancer, and may be particularly effective when used early in the disease course to prevent metastatic spread. Algenpantucel-L (HyperAcute Pancreas, NewLink Genetics, Ames, IA, USA) is a whole-cell immunotherapy consisting of irradiated allogeneic pancreatic cancer cells genetically engineered to express the murine enzyme α-GT, which results in hyperacute rejection of the tumor cells with complement- and antibody-dependent cytotoxicity. Phase II clinical trial data has been encouraging, particularly for patients who demonstrated humoral immunologic responses. Here, we report preliminary results and biomarkers correlations with clinical activity of algenpantucel-L in pancreatic cancer.

  16. Biology and treatment of cervical adenocarcinoma

    PubMed Central

    Takeuchi, Satoshi

    2016-01-01

    Uterine cervical adenocarcinoma (ADC) has been increasing in its prevalence world widely despite the decrease of squamous cell carcinoma (SCC). It comprises nearly 20-25% of the all cervical malignancy in developed countries. The worse biological behavior had been reported in patients with intermediate- and high risk factors after surgery, and in advanced stage over Ⅲ, radiotherapy (RT) alone and concurrent chemo-radiotherapy (CCRT) with cisplatin was not always effective. As for chemotherapy (CT), the induction CT has not established, as well. Further molecular targeted therapy (MTT) has been studied. The targets of oncogenic driver mutations were vascular endothelial growth factor (VEGF) in SCC, or tyrosine kinase (TK) of endothelial growth factor receptor 2 (EGFR2, Her2/neu)-Ras-MAPK-ERK pathway. Bevacizumab (Bev, anti-VEGF monoclonal antibody) is considered as one of key agent with paclitaxel and carboplatin in SCC, but not for ADC. This article focuses on up-to-date knowledge of biology and possible specific therapeutic directions to explore in the management of cervical ADC. PMID:27198186

  17. Comprehensive molecular characterization of gastric adenocarcinoma

    PubMed Central

    Bass, Adam J.; Thorsson, Vesteinn; Shmulevich, Ilya; Reynolds, Sheila M.; Miller, Michael; Bernard, Brady; Hinoue, Toshinori; Laird, Peter W.; Curtis, Christina; Shen, Hui; Weisenberger, Daniel J.; Schultz, Nikolaus; Shen, Ronglai; Weinhold, Nils; Kelsen, David P.; Bowlby, Reanne; Chu, Andy; Kasaian, Katayoon; Mungall, Andrew J.; Robertson, A. Gordon; Sipahimalani, Payal; Cherniack, Andrew; Getz, Gad; Liu, Yingchun; Noble, Michael S.; Pedamallu, Chandra; Sougnez, Carrie; Taylor-Weiner, Amaro; Akbani, Rehan; Lee, Ju-Seog; Liu, Wenbin; Mills, Gordon B.; Yang, Da; Zhang, Wei; Pantazi, Angeliki; Parfenov, Michael; Gulley, Margaret; Piazuelo, M. Blanca; Schneider, Barbara G.; Kim, Jihun; Boussioutas, Alex; Sheth, Margi; Demchok, John A.; Rabkin, Charles S.; Willis, Joseph E.; Ng, Sam; Garman, Katherine; Beer, David G.; Pennathur, Arjun; Raphael, Benjamin J.; Wu, Hsin-Ta; Odze, Robert; Kim, Hark K.; Bowen, Jay; Leraas, Kristen M.; Lichtenberg, Tara M.; Weaver, Stephanie; McLellan, Michael; Wiznerowicz, Maciej; Sakai, Ryo; Getz, Gad; Sougnez, Carrie; Lawrence, Michael S.; Cibulskis, Kristian; Lichtenstein, Lee; Fisher, Sheila; Gabriel, Stacey B.; Lander, Eric S.; Ding, Li; Niu, Beifang; Ally, Adrian; Balasundaram, Miruna; Birol, Inanc; Bowlby, Reanne; Brooks, Denise; Butterfield, Yaron S. N.; Carlsen, Rebecca; Chu, Andy; Chu, Justin; Chuah, Eric; Chun, Hye-Jung E.; Clarke, Amanda; Dhalla, Noreen; Guin, Ranabir; Holt, Robert A.; Jones, Steven J.M.; Kasaian, Katayoon; Lee, Darlene; Li, Haiyan A.; Lim, Emilia; Ma, Yussanne; Marra, Marco A.; Mayo, Michael; Moore, Richard A.; Mungall, Andrew J.; Mungall, Karen L.; Nip, Ka Ming; Robertson, A. Gordon; Schein, Jacqueline E.; Sipahimalani, Payal; Tam, Angela; Thiessen, Nina; Beroukhim, Rameen; Carter, Scott L.; Cherniack, Andrew D.; Cho, Juok; Cibulskis, Kristian; DiCara, Daniel; Frazer, Scott; Fisher, Sheila; Gabriel, Stacey B.; Gehlenborg, Nils; Heiman, David I.; Jung, Joonil; Kim, Jaegil; Lander, Eric S.; Lawrence, Michael S.; Lichtenstein, Lee; Lin, Pei; Meyerson, Matthew; Ojesina, Akinyemi I.; Pedamallu, Chandra Sekhar; Saksena, Gordon; Schumacher, Steven E.; Sougnez, Carrie; Stojanov, Petar; Tabak, Barbara; Taylor-Weiner, Amaro; Voet, Doug; Rosenberg, Mara; Zack, Travis I.; Zhang, Hailei; Zou, Lihua; Protopopov, Alexei; Santoso, Netty; Parfenov, Michael; Lee, Semin; Zhang, Jianhua; Mahadeshwar, Harshad S.; Tang, Jiabin; Ren, Xiaojia; Seth, Sahil; Yang, Lixing; Xu, Andrew W.; Song, Xingzhi; Pantazi, Angeliki; Xi, Ruibin; Bristow, Christopher A.; Hadjipanayis, Angela; Seidman, Jonathan; Chin, Lynda; Park, Peter J.; Kucherlapati, Raju; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Kim, Sang-Bae; Lee, Ju-Seog; Lu, Yiling; Mills, Gordon; Laird, Peter W.; Hinoue, Toshinori; Weisenberger, Daniel J.; Bootwalla, Moiz S.; Lai, Phillip H.; Shen, Hui; Triche, Timothy; Van Den Berg, David J.; Baylin, Stephen B.; Herman, James G.; Getz, Gad; Chin, Lynda; Liu, Yingchun; Murray, Bradley A.; Noble, Michael S.; Askoy, B. Arman; Ciriello, Giovanni; Dresdner, Gideon; Gao, Jianjiong; Gross, Benjamin; Jacobsen, Anders; Lee, William; Ramirez, Ricardo; Sander, Chris; Schultz, Nikolaus; Senbabaoglu, Yasin; Sinha, Rileen; Sumer, S. Onur; Sun, Yichao; Weinhold, Nils; Thorsson, Vésteinn; Bernard, Brady; Iype, Lisa; Kramer, Roger W.; Kreisberg, Richard; Miller, Michael; Reynolds, Sheila M.; Rovira, Hector; Tasman, Natalie; Shmulevich, Ilya; Ng, Santa Cruz Sam; Haussler, David; Stuart, Josh M.; Akbani, Rehan; Ling, Shiyun; Liu, Wenbin; Rao, Arvind; Weinstein, John N.; Verhaak, Roeland G.W.; Mills, Gordon B.; Leiserson, Mark D. M.; Raphael, Benjamin J.; Wu, Hsin-Ta; Taylor, Barry S.; Black, Aaron D.; Bowen, Jay; Carney, Julie Ann; Gastier-Foster, Julie M.; Helsel, Carmen; Leraas, Kristen M.; Lichtenberg, Tara M.; McAllister, Cynthia; Ramirez, Nilsa C.; Tabler, Teresa R.; Wise, Lisa; Zmuda, Erik; Penny, Robert; Crain, Daniel; Gardner, Johanna; Lau, Kevin; Curely, Erin; Mallery, David; Morris, Scott; Paulauskis, Joseph; Shelton, Troy; Shelton, Candace; Sherman, Mark; Benz, Christopher; Lee, Jae-Hyuk; Fedosenko, Konstantin; Manikhas, Georgy; Potapova, Olga; Voronina, Olga; Belyaev, Smitry; Dolzhansky, Oleg; Rathmell, W. Kimryn; Brzezinski, Jakub; Ibbs, Matthew; Korski, Konstanty; Kycler, Witold; ŁaŸniak, Radoslaw; Leporowska, Ewa; Mackiewicz, Andrzej; Murawa, Dawid; Murawa, Pawel; Spychała, Arkadiusz; Suchorska, Wiktoria M.; Tatka, Honorata; Teresiak, Marek; Wiznerowicz, Maciej; Abdel-Misih, Raafat; Bennett, Joseph; Brown, Jennifer; Iacocca, Mary; Rabeno, Brenda; Kwon, Sun-Young; Penny, Robert; Gardner, Johanna; Kemkes, Ariane; Mallery, David; Morris, Scott; Shelton, Troy; Shelton, Candace; Curley, Erin; Alexopoulou, Iakovina; Engel, Jay; Bartlett, John; Albert, Monique; Park, Do-Youn; Dhir, Rajiv; Luketich, James; Landreneau, Rodney; Janjigian, Yelena Y.; Kelsen, David P.; Cho, Eunjung; Ladanyi, Marc; Tang, Laura; McCall, Shannon J.; Park, Young S.; Cheong, Jae-Ho; Ajani, Jaffer; Camargo, M. Constanza; Alonso, Shelley; Ayala, Brenda; Jensen, Mark A.; Pihl, Todd; Raman, Rohini; Walton, Jessica; Wan, Yunhu; Demchok, John A.; Eley, Greg; Mills Shaw, Kenna R.; Sheth, Margi; Tarnuzzer, Roy; Wang, Zhining; Yang, Liming; Zenklusen, Jean Claude; Davidsen, Tanja; Hutter, Carolyn M.; Sofia, Heidi J.; Burton, Robert; Chudamani, Sudha; Liu, Jia

    2014-01-01

    Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies. PMID:25079317

  18. Interventional Nanotheranostics of Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Li, Junjie; Liu, Fengyong; Gupta, Sanjay; Li, Chun

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) accounts for over 90% of all pancreatic cancer. Nanoparticles (NPs) offer new opportunities for image-guided therapy owing to the unique physicochemical properties of the nanoscale effect and the multifunctional capabilities of NPs. However, major obstacles exist for NP-mediated cancer theranostics, especially in PDAC. The hypovascular nature of PDAC may impede the deposition of NPs into the tumor after systemic administration, and most NPs localize predominantly in the mononuclear phagocytic system, leading to a relatively poor tumor-to-surrounding-organ uptake ratio. Image guidance combined with minimally invasive interventional procedures may help circumvent these barriers to poor drug delivery of NPs in PDAC. Interventional treatments allow regional drug delivery, targeted vascular embolization, direct tumor ablation, and the possibility of disrupting the stromal barrier of PDAC. Interventional treatments also have potentially fewer complications, faster recovery, and lower cost compared with conventional therapies. This work is an overview of current image-guided interventional cancer nanotheranostics with specific attention given to their applications for the management of PDAC. PMID:27375787

  19. Regulation of Hsp27 and Hsp70 expression in human and mouse skin construct models by caveolae following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide.

    PubMed

    Black, Adrienne T; Hayden, Patrick J; Casillas, Robert P; Heck, Diane E; Gerecke, Donald R; Sinko, Patrick J; Laskin, Debra L; Laskin, Jeffrey D

    2011-06-01

    Dermal exposure to the vesicant sulfur mustard causes marked inflammation and tissue damage. Basal keratinocytes appear to be a major target of sulfur mustard. In the present studies, mechanisms mediating skin toxicity were examined using a mouse skin construct model and a full-thickness human skin equivalent (EpiDerm-FT™). In both systems, administration of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide (CEES, 100-1000μM) at the air surface induced mRNA and protein expression of heat shock proteins 27 and 70 (Hsp27 and Hsp70). CEES treatment also resulted in increased expression of caveolin-1, the major structural component of caveolae. Immunohistochemistry revealed that Hsp27, Hsp70 and caveolin-1 were localized in basal and suprabasal layers of the epidermis. Caveolin-1 was also detected in fibroblasts in the dermal component of the full thickness human skin equivalent. Western blot analysis of caveolar membrane fractions isolated by sucrose density centrifugation demonstrated that Hsp27 and Hsp70 were localized in caveolae. Treatment of mouse keratinocytes with filipin III or methyl-β-cyclodextrin, which disrupt caveolar structure, markedly suppressed CEES-induced Hsp27 and Hsp70 mRNA and protein expression. CEES treatment is known to activate JNK and p38 MAP kinases; in mouse keratinocytes, inhibition of these enzymes suppressed CEES-induced expression of Hsp27 and Hsp70. These data suggest that MAP kinases regulate Hsp 27 and Hsp70; moreover, caveolae-mediated regulation of heat shock protein expression may be important in the pathophysiology of vesicant-induced skin toxicity.

  20. Regulation of Hsp27 and Hsp70 expression in human and mouse skin construct models by caveolae following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

    SciTech Connect

    Black, Adrienne T.; Hayden, Patrick J.; Casillas, Robert P.; Heck, Diane E.; Gerecke, Donald R.; Sinko, Patrick J.; Laskin, Debra L.; Laskin, Jeffrey D.

    2011-06-01

    Dermal exposure to the vesicant sulfur mustard causes marked inflammation and tissue damage. Basal keratinocytes appear to be a major target of sulfur mustard. In the present studies, mechanisms mediating skin toxicity were examined using a mouse skin construct model and a full-thickness human skin equivalent (EpiDerm-FT{sup TM}). In both systems, administration of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide (CEES, 100-1000 {mu}M) at the air surface induced mRNA and protein expression of heat shock proteins 27 and 70 (Hsp27 and Hsp70). CEES treatment also resulted in increased expression of caveolin-1, the major structural component of caveolae. Immunohistochemistry revealed that Hsp27, Hsp70 and caveolin-1 were localized in basal and suprabasal layers of the epidermis. Caveolin-1 was also detected in fibroblasts in the dermal component of the full thickness human skin equivalent. Western blot analysis of caveolar membrane fractions isolated by sucrose density centrifugation demonstrated that Hsp27 and Hsp70 were localized in caveolae. Treatment of mouse keratinocytes with filipin III or methyl-{beta}-cyclodextrin, which disrupt caveolar structure, markedly suppressed CEES-induced Hsp27 and Hsp70 mRNA and protein expression. CEES treatment is known to activate JNK and p38 MAP kinases; in mouse keratinocytes, inhibition of these enzymes suppressed CEES-induced expression of Hsp27 and Hsp70. These data suggest that MAP kinases regulate Hsp 27 and Hsp70; moreover, caveolae-mediated regulation of heat shock protein expression may be important in the pathophysiology of vesicant-induced skin toxicity.

  1. Regulation of Hsp27 and Hsp70 expression in human and mouse skin construct models by caveolae following exposure to the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide

    PubMed Central

    Black, Adrienne T.; Hayden, Patrick J.; Casillas, Robert P.; Heck, Diane E.; Gerecke, Donald R.; Sinko, Patrick J.; Laskin, Debra L.; Laskin, Jeffrey D.

    2012-01-01

    Dermal exposure to the vesicant sulfur mustard causes marked inflammation and tissue damage. Basal keratinocytes appear to be a major target of sulfur mustard. In the present studies, mechanisms mediating skin toxicity were examined using a mouse skin construct model and a full-thickness human skin equivalent (EpiDerm-FTTM). In both systems, administration of the model sulfur mustard vesicant, 2-chloroethyl ethyl sulfide (CEES, 100–1000 µM) at the air surface induced mRNA and protein expression of heat shock proteins 27 and 70 (Hsp27 and Hsp70). CEES treatment also resulted in increased expression of caveolin-1, the major structural component of caveolae. Immunohistochemistry revealed that Hsp27, Hsp70 and caveolin-1 were localized in basal and suprabasal layers of the epidermis. Caveolin-1 was also detected in fibroblasts in the dermal component of the full thickness human skin equivalent. Western blot analysis of caveolar membrane fractions isolated by sucrose density centrifugation demonstrated that Hsp27 and Hsp70 were localized in caveolae. Treatment of mouse keratinocytes with filipin III or methyl-β-cyclodextrin, which disrupt caveolar structure, markedly suppressed CEES-induced Hsp27 and Hsp70 mRNA and protein expression. CEES treatment is known to activate JNK and p38 MAP kinases; in mouse keratinocytes, inhibition of these enzymes suppressed CEES-induced expression of Hsp27 and Hsp70. These data suggest that MAP kinases regulate Hsp 27 and Hsp70; moreover, caveolae-mediated regulation of heat shock protein expression may be important in the pathophysiology of vesicant-induced skin toxicity. PMID:21457723

  2. Free radical production from the interaction of 2-chloroethyl vesicants (mustard gas) with pyridine nucleotide-driven flavoprotein electron transport systems

    SciTech Connect

    Brimfield, A.A. Mancebo, A.M.; Mason, R.P.; Jiang, J.J.; Siraki, A.G.; Novak, M.J.

    2009-01-01

    The biochemical sequelae to chloroethyl mustard exposure correspond very well to toxic processes initiated by free radicals. Additionally, mustard solutions contain spontaneously formed cyclic onium ions which produce carbon free radicals when reduced electrochemically. Therefore, we hypothesized that the onium ions of sulfur or nitrogen mustards might produce carbon free radicals upon being reduced enzymatically, and that these radicals might constitute a metabolic activation. We set out to document radical production using an in vitro metabolic system and electron paramagnetic resonance (EPR). Our system consisted of NADPH, one of several pyridine nucleotide-driven flavoprotein reductases, cytochrome c as a terminal electron acceptor, various sulfur or nitrogen mustards and the spin trap {alpha}-[4-pyridyl-1-oxide]-N-tert-butylnitrone in buffer. Reactions were started by adding the reductase to the other materials, vortexing and immediately transferring the mixture to a 10 mm EPR flat cell. Repeated scans on a Bruker ESP 300E EPR spectrometer produced a triplet of doublets with hyperfine splitting constants of a{sub N} = 15.483 G and a{sub H} = 2.512 G. The outcome supported our hypothesis that carbon-centered free radicals are produced when mustard-related onium ions are enzymatically reduced. The EPR results varied little with the chloroethyl compound used or with porcine or human cytochrome P450 reductase, the reductase domain of rat brain neuronal nitric oxide synthase or rat liver thioredoxin reductase. Our results offer new insight into the basis for mustard-induced vesication and the outcome of exposure to different mustards. The free radical model provides an explanation for similarities in the lesions arising from mustard exposure and energy-based lesions such as those from heat, ultraviolet and nuclear radiation as well as damage across tissue types such as skin, eyes or airway epithelium.

  3. Multigene deletions in lung adenocarcinomas from irradiated and control mice

    SciTech Connect

    Zhang, Y.; Woloschak, G.E.

    1996-06-01

    K-ras codon 12 point mutations mRb and p53 gene deletions were examined in tissues from 120 normal lungs and lung adenocarcinomas that were Formalin-treated and paraffin-embedded 25 years ago. The results showed that 12 of 60 (20%) lung adenocarcinomas had mRb deletions. All lung adenocarcinomas that were initially found bearing deleted mRb had p53 deletions (15 of 15; 100%). A significantly higher mutation frequency for K-ras codon 12 point mutations was also found in the lung adenocarcinomas from mice exposed to 24 once-weekly neutron irradiation (10 of 10; 100%) compared with those exposed to 24 or 60 once-weekly {gamma}-ray doses (5 of 10; 50%). The data suggested that p53 and K-ras gene alterations were two contributory factors responsible for the increased incidence of lung adenocarcinoma in B6CF{sub 1} male mice exposed to protracted neutron radiation.

  4. Small bowel adenocarcinomas--existing evidence and evolving paradigms.

    PubMed

    Raghav, Kanwal; Overman, Michael J

    2013-09-01

    Small bowel cancers account for 3% of all gastrointestinal malignancies and small bowel adenocarcinomas represent a third of all small bowel cancers. Rarity of small bowel adenocarcinomas restricts molecular understanding and presents unique diagnostic and therapeutic challenges. Better cross-sectional imaging techniques and development of enteroscopy and capsule endoscopy have facilitated earlier and more-accurate diagnosis. Surgical resection remains the mainstay of therapy for locoregional disease. In the metastatic setting, fluoropyrimidine and oxaliplatin-based chemotherapy has shown clinical benefit in prospective non-randomized trials. Although frequently grouped under the same therapeutic umbrella as large bowel adenocarcinomas, small bowel adenocarcinomas are distinct clinical and molecular entities. Recent progress in molecular characterization has aided our understanding of the pathogenesis of these tumours and holds potential for prospective development of novel targeted therapies. Multi-institutional collaborative efforts directed towards cogent understanding of tumour biology and designing sensible clinical trials are essential for developing improved therapeutic strategies. In this Review, we endeavour to outline an evidence-based approach to present-day management of small bowel adenocarcinoma, describe contemporary challenges and uncover evolving paradigms in the management of these rare 'orphan' neoplasias.

  5. Synchronous Multiple Lung Adenocarcinomas: Estrogen Concentration in Peripheral Lung

    PubMed Central

    Shinchi, Yusuke; Sanada, Mune; Motooka, Yamato; Fujino, Kosuke; Mori, Takeshi; Suzuki, Makoto

    2016-01-01

    Background The detection rate of synchronous multiple lung adenocarcinomas (SMLA), which display multiple ground glass opacity nodules in the peripheral lung, is increasing due to advances in high resolution computed tomography. The backgrounds of multicentric development of adenocarcinoma are unknown. In this study, we quantitated estrogen concentration in the peripheral lungs of postmenopausal female patients with SMLA. Methods The tissue concentration of estrogens (estrone [E1] and estdadiol [E2]) in the noncancerous peripheral lung were measured with liquid chromatography/electrospray tandem mass spectrometry in postmenopausal female patients with lung adenocarcinoma. The expression levels of CYP19A1 in the normal lung were also quantitated with real-time PCR. Thirty patients with SMLA and 79 cases of control patients with single lung adenocarcinoma were analyzed. Results The concentrations of E1 and E2 in the noncancerous tissue were significantly higher in SMLA cases than control cases (P = 0.004 and P = 0.02, respectively). The minor allele (A) of single nucleotide polymorphism rs3764221 were significantly associated with higher concentration of E1 and E2 (P = 0.002 and P = 0.01, respectively) and higher CYP19A1 mRNA expression (P = 0.03). Conclusion The tissue estrogen concentration of peripheral lung was significantly higher in SMLA than control cases. The high concentration of estrogen may be one of the causes of multicentric development of peripheral lung adenocarcinomas. PMID:27526096

  6. Gli promotes epithelial-mesenchymal transition in human lung adenocarcinomas

    PubMed Central

    Jin, Joy Q.; Woodard, Gavitt A.; Tolani, Bhairavi; Luh, Thomas M.; Giroux-Leprieur, Etienne; Mo, Minli; Chen, Zhao; Che, Juanjuan; Zhang, Zhenfa; Zhou, Yong; Wang, Lei; Hao, Xishan; Jablons, David; Wang, Changli; He, Biao

    2016-01-01

    Adenocarcinoma is the most common type of lung cancer. Epithelial-mesenchymal transition (EMT) is required for tumor invasion/metastasis and the components that control this process are potential therapeutic targets. This study we examined the role of Gli in lung adenocarcinoma and whether its activation regulates metastasis through EMT in lung adenocarcinoma. We found that tumors with high Gli expression had significantly lower E-Cadherin expression in two independent cohorts of patients with lung adenocarcinoma that we studied. In vitro up-regulation of SHh resulted in increased cell migration while small molecule inhibitors of Smo or Gli significantly reduced cell mobility both in a wound healing assay and in a 3D cell invasion assay. Inhibition of Gli in vivo decreased tumor growth and induced an increase in E-Cadherin expression. Our results indicate that Gli may be critical for lung adenocarcinoma metastasis and that a novel Gli inhibitor shows promise as a therapeutic agent by preventing cell migration and invasion in vitro and significantly reducing tumor growth and increasing E-Cadherin expression in vivo. PMID:27533453

  7. ATM protein is deficient in over 40% of lung adenocarcinomas.

    PubMed

    Villaruz, Liza C; Jones, Helen; Dacic, Sanja; Abberbock, Shira; Kurland, Brenda F; Stabile, Laura P; Siegfried, Jill M; Conrads, Thomas P; Smith, Neil R; O'Connor, Mark J; Pierce, Andrew J; Bakkenist, Christopher J

    2016-09-06

    Lung cancer is the leading cause of cancer-related mortality in the USA and worldwide, and of the estimated 1.2 million new cases of lung cancer diagnosed every year, over 30% are lung adenocarcinomas. The backbone of 1st-line systemic therapy in the metastatic setting, in the absence of an actionable oncogenic driver, is platinum-based chemotherapy. ATM and ATR are DNA damage signaling kinases activated at DNA double-strand breaks (DSBs) and stalled and collapsed replication forks, respectively. ATM protein is lost in a number of cancer cell lines and ATR kinase inhibitors synergize with cisplatin to resolve xenograft models of ATM-deficient lung cancer. We therefore sought to determine the frequency of ATM loss in a tissue microarray (TMA) of lung adenocarcinoma. Here we report the validation of a commercial antibody (ab32420) for the identification of ATM by immunohistochemistry and estimate that 61 of 147 (41%, 95% CI 34%-50%) cases of lung adenocarcinoma are negative for ATM protein expression. As a positive control for ATM staining, nuclear ATM protein was identified in stroma and immune infiltrate in all evaluable cases. ATM loss in lung adenocarcinoma was not associated with overall survival. However, our preclinical findings in ATM-deficient cell lines suggest that ATM could be a predictive biomarker for synergy of an ATR kinase inhibitor with standard-of-care cisplatin. This could improve clinical outcome in 100,000's of patients with ATM-deficient lung adenocarcinoma every year.

  8. Intestinal Type Adenocarcinoma from Inverted Papilloma: A Rare Recurrence

    PubMed Central

    Singh, Garima; Singh, Meeta; Chandana, Mansi; Nargotra, Namrata

    2016-01-01

    Inverted Papilloma (IP) is an uncommon and locally aggressive benign tumour of sinonasal region, which tends to recur after surgical resection. Most tumours are confined to the lateral nasal wall and sinuses, with maxillary sinus being most commonly affected and a male preponderance. It has a known association with in situ and invasive carcinomas with a <10% rate of malignant transformation. Most common association has been seen with squamous cell carcinoma and extremely rare association with adenocarcinoma and small cell carcinoma. A 36-year-old male presented with a left sided polypoidal nasal mass and underwent a polypectomy. Pathology results showed IP with mild dysplasia. The polypoidal growth reappeared on the same side after a period of 10 months and on histopathological examination, the growth revealed features of intestinal type adenocarcinoma. IP recurring as adenocarcinoma is rare and even after exhaustive literature search only few cases could be found. Two studies have described recurrence of adenocarcinoma in existing IP previously. We report an unusual case of inverted papilloma showing malignant transformation into an intestinal type adenocarcinoma in a 36-year-old male patient within 10 months of previous surgery. PMID:28050382

  9. From Reflux Esophagitis to Esophageal Adenocarcinoma.

    PubMed

    Souza, Rhonda F

    Reflux esophagitis causes Barrett's metaplasia, an abnormal esophageal mucosa predisposed to adenocarcinoma. Medical therapy for reflux esophagitis focuses on decreasing gastric acid production with proton pump inhibitors. We have reported that reflux esophagitis in a rat model develops from a cytokine-mediated inflammatory injury, not from a caustic chemical (acid) injury. In this model, refluxed acid and bile stimulate the release of inflammatory cytokines from esophageal squamous cells, recruiting lymphocytes first to the submucosa and later to the luminal surface. Emerging studies on acute reflux esophagitis in humans support this new concept, suggesting that reflux-induced cytokine release may be a future target for medical therapies. Sometimes, reflux esophagitis heals with Barrett's metaplasia, a process facilitated by reflux-related nitric oxide (NO) production and Sonic Hedgehog (Hh) secretion by squamous cells. We have shown that NO reduces expression of genes that promote a squamous cell phenotype, while Hh signaling induces genes that mediate the development of the columnar cell phenotypes of Barrett's metaplasia. Agents targeting esophageal NO production or Hh signaling conceivably could prevent the development of Barrett's esophagus. Persistent reflux promotes cancer in Barrett's metaplasia. We have reported that acid and bile salts induce DNA damage in Barrett's cells. Bile salts also cause NF-x03BA;B activation in Barrett's cells, enabling them to resist apoptosis in the setting of DNA damage and likely contributing to carcinogenesis. Oral treatment with ursodeoxycholic acid prevents the esophageal DNA damage and NF-x03BA;B activation induced by toxic bile acids. Altering bile acid composition might be another approach to cancer prevention.

  10. Perspectives in the treatment of pancreatic adenocarcinoma

    PubMed Central

    Cid-Arregui, Angel; Juarez, Victoria

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is an incurable lethal disease whose incidence rate is growing. There is no effective screening for detection of early stage tumors and, in most cases, PDAC is diagnosed at advanced disease stages, when radical pancreatic resection is not possible. The aggressive nature of pancreatic tumor cells lies in the complex genetic mechanisms behind their uncontrolled capability to grow and metastasize, which involve essential adaptive changes in cellular metabolism, signaling, adhesion and immunoediting. In addition, PDAC cells promote a dense functional stroma that facilitates tumor resistance to chemotherapy and radiation. During the last two decades, gemcitabine has been the reference for the systemic treatment of PDAC. However, recently, a regimen combining fluorouracil, irinotecan, oxaliplatin, and leucovorin (FOLFIRINOX) and another combining albumin-bound paclitaxel with gemcitabine have shown clear therapeutic advantage in advanced PDAC, with survival outcomes of 11.3 and 8.5 mo on phase III trials, respectively, over single-agent gemcitabine. With the pending issue of their higher toxicities, these regimens set the reference for ongoing and future clinical studies in advanced PDAC. In addition, the efficacy of oral fluoropyrimidine (S-1) has been well documented in Asiatic PDAC patients. The development of therapeutic approaches other than cytotoxic drugs has proven difficult in the past, with only one drug (erlotinib) approved to date. Besides, a number of agents targeting signaling pathways in tumor or stroma cells are being investigated. Likewise, immunotherapies that target PDAC in various ways are the subject of a number of clinical trials. The search for reliable biomarkers with diagnostic and prognostic value using genomics and mass spectrometry methods may facilitate monitoring and refinement of therapies. This review focuses on current understanding of the pathogenesis of PDAC and the latest developments in the

  11. Gemcitabine resistance in pancreatic ductal adenocarcinoma.

    PubMed

    Binenbaum, Yoav; Na'ara, Shorook; Gil, Ziv

    2015-11-01

    Pancreatic ductal adenocarcinoma (PDA) ranks fourth among cancer related deaths. The disappointing 5-year survival rate of below 5% stems from drug resistance to all known therapies, as well as from disease presentation at a late stage when PDA is already metastatic. Gemcitabine has been the cornerstone of PDA treatment in all stages of the disease for the last two decades, but gemcitabine resistance develops within weeks of chemotherapy initiation. From a mechanistic perspective, gemcitabine resistance may result from alterations in drug metabolism until the point that the cytidine analog is incorporated into the DNA, or from mitigation of gemcitabine-induced apoptosis. Both of these drug resistance modalities can be either intrinsic to the cancer cell, or influenced by the cancer microenvironment. Mechanisms of intrinsic gemcitabine resistance are difficult to tackle, as many of the genes that drive the carcinogenic process itself also interfere with gemcitabine-induced apoptosis. In this regard, recent understanding of the involvement of microRNAs in gemcitabine resistance may offer new opportunities to overcome intrinsic gemcitabine resistance. The characteristically fibrotic and immune infiltrated stroma of PDA that accompanies tumor inception and expansion is a lush ground for treatments aimed at targeting tumor microenvironment-mediated drug resistance. In the last couple of years, drugs interfering with tumor microenvironment have matured to clinical trials. Although drugs inducing 'stromal depletion' have yet failed to improve survival, they have greatly increased our understanding of tumor microenvironment-mediated drug resistance. In this review we summarize the current knowledge on intrinsic and environment-mediated gemcitabine resistance, and discuss the impact of these pathways on patient screening, and on future treatments aimed to potentiate gemcitabine activity.

  12. Adenocarcinoma in situ, minimally invasive adenocarcinoma, and invasive pulmonary adenocarcinoma--analysis of interobserver agreement, survival, radiographic characteristics, and gross pathology in 296 nodules.

    PubMed

    Boland, Jennifer M; Froemming, Adam T; Wampfler, Jason A; Maldonado, Fabien; Peikert, Tobias; Hyland, Courtney; de Andrade, Mariza; Aubry, Marie Christine; Yang, Ping; Yi, Eunhee S

    2016-05-01

    The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society and 2015 World Health Organization classifications of lung adenocarcinoma recommend designating tumors showing entirely lepidic growth as adenocarcinoma in situ (AIS) and lepidic tumors with invasion less than or equal to 5 mm as minimally invasive adenocarcinoma (MIA), both of which have superior outcome to conventional invasive adenocarcinoma (IA). Data on interobserver variability within this classification are limited, and further validation of the superior survival of AIS and MIA is needed. A total of 296 surgically excised pulmonary adenocarcinomas were reviewed from 254 patients (1997-2009). Slides were independently reviewed by 2 pulmonary pathologists who categorized tumors as AIS, MIA, or IA. Of 296 nodules, 244 (82.4%) were agreed upon by both observers: 10 AIS, 61 MIA, and 173 IA (κ = 0.63, good agreement). In 6 cases (2%), there was disagreement between AIS and MIA; in 45 cases (15%), there was disagreement between MIA and IA; and in 1 case, there was disagreement between AIS and IA. Overall survival was significantly different among categories as determined by both observers. Cases with disagreement between MIA and IA had similar survival to agreed MIA. Disease-specific 10-year survival was 100% for AIS (both observers) and 97.3% and 97.6% for MIA, although this did not reach statistical significance compared to IA for either observer. Good agreement was present between observers when classifying tumors as AIS, MIA, and IA. Significant differences in overall survival were present between the 3 groups for both observers, and interobserver variability was evident. Patients with AIS and MIA experienced excellent DSS.

  13. Medroxyprogesterone in Treating Patients With Endometrioid Adenocarcinoma of the Uterine Corpus

    ClinicalTrials.gov

    2016-03-17

    Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation; Recurrent Uterine Corpus Carcinoma; Stage I Uterine Corpus Cancer; Stage II Uterine Corpus Cancer; Stage III Uterine Corpus Cancer; Stage IV Uterine Corpus Cancer

  14. Dome-type: a distinctive variant of colonic adenocarcinoma.

    PubMed

    Puppa, Giacomo; Molaro, Mariella

    2012-01-01

    Introduction. Ten cases of dome-type adenocarcinoma of the colon have been reported so far. Most of them were presented as early lesions, with endoscopic and microscopic distinguishing features. Methods and Results. A raised plaque was removed from the right colon during colonoscopy in a 56-year-old man. Histopathological examination showed a cancerized adenoma invading the submucosa with several typical features of dome-type adenocarcinoma, in particular the associated prominent lymphoid tissue. Immunohistochemistry showed retention of the mismatch repair proteins MLH-1, MSH-2, MLH-6, and PMS-2. Conclusion. We report an additional case of dome-type adenocarcinoma of the colon as an early, low-risk, and microsatellite stable tumor, indicating that this particular histotype may deserve specific consideration for both classification and management.

  15. Endometrial Adenocarcinoma in a 27-Year-Old Woman

    PubMed Central

    Fadhlaoui, Anis; Ben Hassouna, Jamel; Khrouf, Mohamed; Zhioua, Fethi; Chaker, Anis

    2010-01-01

    Background Endometrial adenocarcinoma usually occurs after menopause, but in 2%–14% of cases, it occurs in young patients (less than 40 years of age) who are eager to preserve their fertility. Its treatment includes hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy, and, in some cases, radiation therapy. Aim To describe a case of endometrial adenocarcinoma occurring in a young woman and to undertake a literature review of risk factors and therapeutic options proposed for young women wishing to preserve their fertility. Case We report a case of endometrial cancer in a 27-year-old woman treated for resistant menorrhagia and cared for in our department as well as in the Salah Azaiez Institute. Conclusion Endometrial adenocarcinoma rarely occurs in young women. In such cases, other therapeutic options can be proposed: progesterone therapy and LH-RH (Luteinzing-Hormone-Releasing-Hormone) agonists therapy in order to preserve fertility in younger patients. PMID:21769252

  16. The revised lung adenocarcinoma classification-an imaging guide.

    PubMed

    Gardiner, Natasha; Jogai, Sanjay; Wallis, Adam

    2014-10-01

    Advances in our understanding of the pathology, radiology and clinical behaviour of peripheral lung adenocarcinomas facilitated a more robust terminology and classification of these lesions. The International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification introduced new terminology to better reflect this heterogeneous group of adenocarcinomas formerly known as bronchoalveolar cell carcinoma (BAC). There is now a clear distinction between pre-invasive, minimally invasive and frankly invasive lesions. The radiographic appearance of these ranges from pure ground glass nodules to solid mass lesions. Radiologists must be aware of the new classification in order to work alongside multidisciplinary colleagues to allow accurate staging and treatment. This article reviews the new classification of lung adenocarcinomas. Management options of these lesions with particular focus on radiological implications of the new classification will be reviewed.

  17. Adenocarcinoma in an ano-vaginal fistula in Crohn's disease

    PubMed Central

    Alfa-Wali, Maryam; Atinga, Angela; Mohsen, Yasser; Anthony, Andrew; Myers, Alistair

    2013-01-01

    INTRODUCTION Fistulas are a relatively common occurrence in Crohn's disease (CD), and often present early in the disease process. Additionally, patients suffering from either CD or ulcerative colitis are shown to have an increased risk of colorectal malignancies compared with the general population. PRESENTATION OF CASE We present a case of adenocarcinoma in an ano-vaginal fistula in a patient with longstanding CD. DISCUSSION Various pathogenic mechanisms for the development of carcinoma in fistulas have been suggested, but there is no consensus and indeed this risk may be cumulative. In this case report, we also discuss the pathogenesis of mucinous adenocarcinoma in fistulas secondary to CD. CONCLUSION Better detection of adenocarcinoma in patients presenting with persistent non-resolving fistulas in the presence of CD should be undertaken with regular biopsies following examinations under anaesthetic of the anorectum. PMID:23702362

  18. Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing.

    PubMed

    Zhang, Jianjun; Fujimoto, Junya; Zhang, Jianhua; Wedge, David C; Song, Xingzhi; Zhang, Jiexin; Seth, Sahil; Chow, Chi-Wan; Cao, Yu; Gumbs, Curtis; Gold, Kathryn A; Kalhor, Neda; Little, Latasha; Mahadeshwar, Harshad; Moran, Cesar; Protopopov, Alexei; Sun, Huandong; Tang, Jiabin; Wu, Xifeng; Ye, Yuanqing; William, William N; Lee, J Jack; Heymach, John V; Hong, Waun Ki; Swisher, Stephen; Wistuba, Ignacio I; Futreal, P Andrew

    2014-10-10

    Cancers are composed of populations of cells with distinct molecular and phenotypic features, a phenomenon termed intratumor heterogeneity (ITH). ITH in lung cancers has not been well studied. We applied multiregion whole-exome sequencing (WES) on 11 localized lung adenocarcinomas. All tumors showed clear evidence of ITH. On average, 76% of all mutations and 20 out of 21 known cancer gene mutations were identified in all regions of individual tumors, which suggested that single-region sequencing may be adequate to identify the majority of known cancer gene mutations in localized lung adenocarcinomas. With a median follow-up of 21 months after surgery, three patients have relapsed, and all three patients had significantly larger fractions of subclonal mutations in their primary tumors than patients without relapse. These data indicate that a larger subclonal mutation fraction may be associated with increased likelihood of postsurgical relapse in patients with localized lung adenocarcinomas.

  19. Duodenal adenocarcinoma: Advances in diagnosis and surgical management

    PubMed Central

    Cloyd, Jordan M; George, Elizabeth; Visser, Brendan C

    2016-01-01

    Duodenal adenocarcinoma is a rare but aggressive malignancy. Given its rarity, previous studies have traditionally combined duodenal adenocarcinoma (DA) with either other periampullary cancers or small bowel adenocarcinomas, limiting the available data to guide treatment decisions. Nevertheless, management primarily involves complete surgical resection when technically feasible. Surgery may require pancreaticoduodenectomy or segmental duodenal resection; either are acceptable options as long as negative margins are achievable and an adequate lymphadenectomy can be performed. Adjuvant chemotherapy and radiation are important components of multi-modality treatment for patients at high risk of recurrence. Further research would benefit from multi-institutional trials that do not combine DA with other periampullary or small bowel malignancies. The purpose of this article is to perform a comprehensive review of DA with special focus on the surgical management and principles. PMID:27022448

  20. Thyroid metastasis from lung adenocarcinoma with EML4-ALK rearrangement

    PubMed Central

    Kawamoto, Hironori; Kaneko, Yugo; Ryu, Kai; Kuwano, Kazuyoshi

    2016-01-01

    Thyroid metastases from lung cancer are very rare. A woman aged 42 years with a tumour in the lower lobe of the right lung was diagnosed as having lung adenocarcinoma positive for echinoderm microtubule-associated proteinlike 4-anaplastic lymphoma kinase. Positron emission tomography demonstrated fluorodeoxyglucose accumulation in the lower lobe of the right lung, the right thyroid lobe and both adrenal glands. We performed fine-needle aspiration biopsy (FNAB) and used reverse transcriptase-PCR (RT-PCR) to diagnose the patient as having metastatic lung adenocarcinoma to the thyroid gland. We believe that FNAB combined with RT-PCR can be an effective method for diagnosing metastatic lung adenocarcinoma to the thyroid gland. PMID:27872133

  1. Numb chin syndrome secondary to leptomeningeal carcinomatosis from gastric adenocarcinoma

    PubMed Central

    Riesgo, Vincent J.; Poveda, Julio; Rammohan, Kottil

    2015-01-01

    Numb chin syndrome (NCS) can be a sign of malignancy. Its association with gastric adenocarcinoma is rare. We report a case of a 27-year-old Hispanic female that presented with complaint of left sided headache associated with numbness of the left side of chin and lower gingiva. Initial brain MRI, whole body gallium scan, high resolution CT of chest and elevated protein in the CSF were suggestive of sarcoidosis. She was treated with IV steroids with transient clinical improvement. Two weeks later, her symptoms worsened and further evaluation revealed the diagnosis of a poorly differentiated metastatic gastric adenocarcinoma with leptomeningeal involvement. This case report aims to emphasize the importance of identifying NCS as a possible indication of an underlying malignant condition. Reported cases of NCS associated with metastatic gastric adenocarcinoma are very rare. PMID:25830044

  2. Mitochondrial genome instability in colorectal adenoma and adenocarcinoma.

    PubMed

    de Araujo, Luiza F; Fonseca, Aline S; Muys, Bruna R; Plaça, Jessica R; Bueno, Rafaela B L; Lorenzi, Julio C C; Santos, Anemari R D; Molfetta, Greice A; Zanette, Dalila L; Souza, Jorge E S; Valente, Valeria; Silva, Wilson A

    2015-11-01

    Mitochondrial dysfunction is regarded as a hallmark of cancer progression. In the current study, we evaluated mitochondrial genome instability and copy number in colorectal cancer using Next Generation Sequencing approach and qPCR, respectively. The results revealed higher levels of heteroplasmy and depletion of the relative mtDNA copy number in colorectal adenocarcinoma. Adenocarcinoma samples also presented an increased number of mutations in nuclear genes encoding proteins which functions are related with mitochondria fusion, fission and localization. Moreover, we found a set of mitochondrial and nuclear genes, which cooperate in the same mitochondrial function simultaneously mutated in adenocarcinoma. In summary, these results support an important role for mitochondrial function and genomic instability in colorectal tumorigenesis.

  3. Absorption spectra of adenocarcinoma and squamous cell carcinoma cervical tissues

    NASA Astrophysics Data System (ADS)

    Ivashko, Pavlo; Peresunko, Olexander; Zelinska, Natalia; Alonova, Marina

    2014-08-01

    We studied a methods of assessment of a connective tissue of cervix in terms of specific volume of fibrous component and an optical density of staining of connective tissue fibers in the stroma of squamous cancer and cervix adenocarcinoma. An absorption spectra of blood plasma of the patients suffering from squamous cancer and cervix adenocarcinoma both before the surgery and in postsurgical periods were obtained. Linear dichroism measurements transmittance in polarized light at different orientations of the polarization plane relative to the direction of the dominant orientation in the structure of the sample of biotissues of stroma of squamous cancer and cervix adenocarcinoma were carried. Results of the investigation of the tumor tissues showed that the magnitude of the linear dichroism Δ is insignificant in the researched spectral range λ=280-840 nm and specific regularities in its change observed short-wave ranges.

  4. Comparative analysis of gene expression profiles of gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma

    PubMed Central

    Song, Bin; Du, Juan; Deng, Neng; Ren, Ji-Chen; Shu, Zhen-Bo

    2016-01-01

    In the present study, gene expression profiles were analyzed to identify the molecular mechanisms underlying gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA). A gene expression dataset (accession number GSE29272) was downloaded from Gene Expression Omnibus, and consisted of 62 GCA samples and 62 normal controls, as well as 72 GNCA samples and 72 normal controls. The two groups of differentially-expressed genes (DEGs) were compared to obtain common and unique DEGs. A differential analysis was performed using the Linear Models for Microarray Data package in R. Functional enrichment analysis was conducted for the DEGs using the Database for Annotation, Visualization and Integrated Discovery. Protein-protein interaction (PPI) networks were constructed for the DEGs with information from the Search Tool for the Retrieval of Interacting Genes. Subnetworks were extracted from the whole network with Cytoscape. Compared with the control, 284 and 268 genes were differentially-expressed in GCA and GNCA, respectively, of which 194 DEGs were common between GCA and GNCA. Common DEGs [e.g., claudin (CLDN)7, CLDN4 and CLDN3] were associated with cell adhesion and digestion. GCA-unique DEGs [e.g., MAD1 mitotic arrest deficient like 1, cyclin (CCN)B1, CCNB2 and CCNE1] were associated with the cell cycle and the regulation of cell proliferation, while GNCA-unique DEGs (e.g., GATA binding protein 6 and hyaluronoglucosaminidase 1) were implicated in cell death. A PPI network with 141 nodes and 446 edges were obtained, from which two subnetworks were extracted. Genes [e.g., fibronectin 1, collagen type I α2 chain (COL1A2) and COL1A1] from the two subnetworks were implicated in extracellular matrix organization. These common DEGs could advance our understanding of the etiology of gastric cancer, while the unique DEGs in GCA and GNCA could better define the properties of specific cancers and provide potential biomarkers for diagnosis, prognosis or therapy

  5. Thyroid adenocarcinoma in a bald eagle (Haliaeetus leukocephalus).

    PubMed

    Bates, G; Tucker, R L; Ford, S; Mattix, M E

    1999-09-01

    Thyroid adenocarcinoma was diagnosed in an adult bald eagle (Haliaeetus leukocephalus) with clinical signs of weakness manifested by inability to fly. Physical examination at the time of admission revealed dried blood in the pharynx and glottis and the presence of pharyngeal trichomonads. Radiographs revealed a large soft tissue mass in the area of the left coracoid and clavicular bones. One month following successful treatment for trichomoniasis, the bird suffered an acute episode of tracheal hemorrhage and died. Necropsy revealed a large mass within the interclavicular air sac. The histologic features were consistent with thyroid adenocarcinoma. This is the first report of thyroid neoplasia in a member of the order Falconiformes.

  6. Esophageal adenocarcinoma and Barrett esophagus in a neurologically impaired teenager.

    PubMed

    Hwang, Jae-Yeon; Lee, Yeoun Joo; Chun, Peter; Shin, Dong Hoon; Park, Jae Hong

    2016-11-01

    Esophageal adenocarcinoma (EAC) accompanied by Barrett esophagus (BE) is rare in patients younger than 20 years old. EAC in the upper esophagus is also rare. We report a rare case of EAC with BE that developed in the upper esophagus after chronic, untreated gastroesophageal reflux disease in a neurologically impaired teenager. A 19-year-old neurologically impaired man underwent endoscopy for evaluation of dysphagia and vomiting, and was diagnosed with EAC with BE. He underwent transthoracic esophagectomy, extensive lymph node dissection, and cervical esophagogastric anastomosis, but the prognosis was poor. Pathology indicated poorly differentiated adenocarcinoma with BE.

  7. Minimal deviation adenocarcinoma of endometrium: A rare entity in a 72-year-old female.

    PubMed

    Renu, Thambi; Siji, Mathew; Shilpa, N; Vijayalakhmi, A

    2016-01-01

    Minimal deviation adenocarcinoma (MDA) of endometrium is considered a differentiated state of endometrioid adenocarcinoma. It is a low-grade tumor associated with areas histologically typical of endometrioid adenocarcinoma in the majority of the cases. Due to deceptively benign microscopy, MDA may be overlooked leading to incorrect assessment of tumor extend and staging.

  8. Ovine intestinal adenocarcinomas: histologic and phenotypic comparison with human colon cancer.

    PubMed

    Munday, John S; Brennan, Moira M; Jaber, Azhar M; Kiupel, Matti

    2006-04-01

    Approximately 7% of old, unthrifty sheep (Ovis aries) in New Zealand have intestinal adenocarcinomas. To investigate whether these sheep might be used as a model of human colonic neoplasia, the biologic behavior and histologic appearance of ovine intestinal adenocarcinomas were compared with those reported for human colonic adenocarcinomas. We collected 50 intestinal tracts with grossly visible intestinal neoplasia from slaughtered sheep. Neoplasms were assessed using World Health Organization guidelines for assessment of human colonic adenocarcinomas. All ovine adenocarcinomas developed in the small intestine. In contrast, only 4% of human intestinal tumors develop at this location, whereas the majority develop in the colon. A visible polyp is present within 89% of human colonic adenocarcinomas, whereas polyps were present in only 46% of the ovine neoplasms. Intestinal wall infiltration by the neoplastic cells and rates of lymph node (84% in sheep; 61% in humans) and distant (52% in sheep; 17% in humans) metastases were comparable between ovine and human adenocarcinomas. However, ovine adenocarcinomas developed more peritoneal and fewer hepatic metastases than human adenocarcinomas. Histologic grading of ovine tumors revealed cell differentiation similar to that reported within human colonic adenocarcinomas. In conclusion, ovine intestinal adenocarcinomas, like human colonic adenocarcinomas, typically arise spontaneously and consistently develop widespread metastases. In addition, tumors appear histologically similar between these species. Therefore, sheep may provide a model of advanced human colonic cancer, possibly allowing evaluation of novel therapeutics and surgical procedures.

  9. TNF-alpha expression patterns as potential molecular biomarker for human skin cells exposed to vesicant chemical warfare agents: sulfur mustard (HD) and Lewisite (L).

    PubMed

    Arroyo, C M; Burman, D L; Kahler, D W; Nelson, M R; Corun, C M; Guzman, J J; Smith, M A; Purcell, E D; Hackley, B E; Soni, S-D; Broomfield, C A

    2004-11-01

    Studies were conducted to examine the effect of two vesicant chemical warfare agents (VCWA), one of them an arsenical, on cytokine gene expression in normal human epidermal keratinocyte (NHEK) cells. We tested 2,2'-dichlorethylsulfide (sulfur mustard, military designation HD) and 2,chlorovinyldichloroarsine (Lewisite, military designation L), which have significant differences in their chemical, physical, and toxicological properties. Human tumor necrosis factor-alpha (hTNF-alpha) cytokine was detected by using the enzyme-linked immunosorbent assay, a protein multiplex immunoassay, Luminex100, and reverse transcription-polymerase chain reaction (RT-PCR). The messenger RNA expression of hTNF-alpha was determined to provide a semi-quantitative analysis. HD-stimulated NHEK induced secretion of hTNF-alpha in a dose-dependent manner. Dose response effect of Lewisite decreased hTNF-alpha levels. Time-response data indicated that the maximum response for HD occurred at 24 h with an associated cytotoxic concentration of 10(-4) mol/L. NHEK cells stimulated with 10(-4) mol/L HD for 24 h at 37 degrees C increased detectable levels of hTNF-alpha from 5 to 28 ng/ml at an index of cell viability between 85 to 93% as detected by Luminex100. Our results indicated that the increased levels of hTNF-alpha by HD are dependent on the primary cultures, cell densities, and chemical properties of the stimulation. Lewisite under the same conditions as HD caused a reduction of hTNF-alpha from control levels of 1.5 ng/ml to 0.3 ng/ml after stimulation (10(-4) mol/L), with an index of cell viability of reverse similar 34%. We analyzed the transcriptional of hTNF-alpha gene and found that HD (10(-6) to 10(-4) mol/L) activates hTNF-alpha gene in cultured NHEK and that L at 10(-6) to 10(-4) mol/L markedly reduces hTNF-alpha gene. We conclude that the pro-inflammatory mediator, hTNF-alpha, could be a potential biomarker for differentiating between exposure of HD or L.

  10. Progression of Barrett’s esophagus toward esophageal adenocarcinoma: an overview

    PubMed Central

    Schoofs, Nele; Bisschops, Raf; Prenen, Hans

    2017-01-01

    In Barrett’s esophagus, normal squamous epithelium is replaced by a metaplastic columnar epithelium as a consequence of chronic gastroesophageal reflux disease. There is a strong association with esophageal adenocarcinoma. In view of the increasing incidence of esophageal adenocarcinoma in the western world, it is important that more attention be paid to the progression of Barrett’s esophagus toward esophageal adenocarcinoma. Recently, several molecular factors have been identified that contribute to the sequence towards adenocarcinoma. This might help identify patients at risk and detect new targets for the prevention and treatment of esophageal adenocarcinoma in the future. PMID:28042232

  11. Synchronous Adenocarcinoma of the Colon and Rectal Carcinoid

    PubMed Central

    Vootla, Vamshidhar; Ahmed, Rafeeq; Niazi, Masooma; Balar, Bhavna; Nayudu, Suresh

    2016-01-01

    Primary colonic adenocarcinoma and synchronous rectal carcinoids are rare tumors. Whenever a synchronous tumor with a nonmetastatic carcinoid component is encountered, its prognosis is determined by the associate malignancy. The discovery of an asymptomatic gastrointestinal carcinoid during the operative treatment of another malignancy will usually only require resection without additional treatment and will have little effect on the prognosis of the individual. This article reports a synchronous rectal carcinoid in a patient with hepatic flexure adenocarcinoma. We present a case of a 46-year-old Hispanic woman with a history of hypothyroidism, uterine fibroids and hypercholesterolemia presenting with a 2-week history of intermittent abdominal pain, mainly in the right upper quadrant. She had no family history of cancers. Physical examination was significant for pallor. Laboratory findings showed microcytic anemia with a hemoglobin of 6.6 g/dl. CT abdomen showed circumferential wall thickening in the ascending colon near the hepatic flexure and pulmonary nodules. Colonoscopy showed hepatic flexure mass and rectal nodule which were biopsied. Pathology showed a moderately differentiated invasive adenocarcinoma of the colon (hepatic flexure mass) and a low-grade neuroendocrine neoplasm (carcinoid of rectum). The patient underwent laparoscopic right hemicolectomy and chemotherapy. In patients diagnosed with adenocarcinoma of the colon and rectum, carcinoids could be missed due to their submucosal location, multicentricity and indolent growth pattern. Studies suggest a closer surveillance of the GI tract for noncarcinoid synchronous malignancy when a carcinoid tumor is detected and vice versa. PMID:27920648

  12. An unexpected digital papillary adenocarcinoma of the thumb *

    PubMed Central

    Nash, Mitchell; Burn, Juliet; Chan, Simon

    2016-01-01

    Abstract Digital papillary adenocarcinoma (DPAca) is an aggressive lesion with high metastatic potential, which is easily misdiagnosed. We present a 55-year-old male with a cystic lesion on his right thumb. Above all else, lesions of the digits should be sent for histopathology routinely, regardless of their history or appearance. PMID:27990456

  13. Polymorphous low-grade adenocarcinoma of the nasal fossa.

    PubMed

    González-Lagunas, Javier; Alasà-Caparrós, Cristian; Vendrell-Escofet, Gerard; Huguet-Redecilla, Pere; Raspall-Martin, Guillermo

    2005-01-01

    An unusual case of a T4N2CMx polymorphous low grade adenocarcinoma located in the nasal fossae and extending to the pterygoid area is presented. The primary tumor was excised through a Lefort I maxillotomy and the neck was managed with a supraomohyoid neck dissection. Adjuntive postoperative radiotherapy was also administered to the patient.

  14. Clinical implications of genetic heterogeneity in multifocal pulmonary adenocarcinomas

    PubMed Central

    Boyle, Theresa A.

    2016-01-01

    Multifocal pulmonary adenocarcinomas are increasingly encountered in clinical practice, in part due to the increased availability and improvement in the thoracic imaging. Recognized as a distinct entity in the upcoming 8th edition of American Joint Commission on Cancer (AJCC) staging system, multifocal adenocarcinomas exhibit several unique features such as the characteristic appearance of multiple ground glass opacities or nodules in computerized tomography (CT). Recent studies have suggested that the vast majority of these malignant lesions are genetically independent even when occurring synchronously in a single patient. For instance, the pattern of epidermal growth factor receptor (EGFR) mutations in multifocal pulmonary adenocarcinomas can vary from one lesion to another. This observation has several important clinical implications. These include the potential need to perform multiple molecular tests on multiple lesions, the possible role of molecular marker such as EGFR mutation in the staging of questionable multiple lung cancers, and the justification for empirical use EGFR inhibitors for multifocal adenocarcinomas among high-prevalence population when no known mutation has been detected. PMID:28149626

  15. Irreversible electroporation of locally advanced pancreatic neck/body adenocarcinoma

    PubMed Central

    2015-01-01

    Objective Irreversible electroporation (IRE) of locally advanced pancreatic adenocarcinoma of the neck has been used to palliate appropriate stage 3 pancreatic cancers without evidence of metastasis and who have undergone appropriate induction therapy. Currently there has not been a standardized reported technique for pancreatic mid-body tumors for patient selection and intra-operative technique. Patients Subjects are patients with locally advanced pancreatic adenocarcinoma of the body/neck who have undergone appropriate induction chemotherapy for a reasonable duration. Main outcome measures Technique of open IRE of locally advanced pancreatic adenocarcinoma of the neck/body is described, with the emphasis on intra-operative ultrasound and intra-operative electroporation management. Results The technique of open IRE of the pancreatic neck/body with bracketing of the celiac axis and superior mesenteric artery with continuous intraoperative ultrasound imaging and consideration of intraoperative navigational system is described. Conclusions IRE of locally advanced pancreatic adenocarcinoma of the body/neck is feasible for appropriate patients with locally advanced unresectable pancreatic cancer. PMID:26029461

  16. Metastasis to the appendix from adenocarcinoma of the ascending colon

    PubMed Central

    Li, Yingjie; Li, Mingshan; Li, Xiaoxia; Sang, Haiquan

    2017-01-01

    Abstract Rationale: Metastasis of cancer cells involves shedding from the primary tumor through various means to distant tissues and organs with continued growth and formation of new metastatic tumors of the same cancer type as the original tumor. The common sites for colon cancer metastases include the pelvis, retroperitoneal lymph nodes, liver, and lungs; Colon cancer metastases to the appendix are rare, as reported in this case. Patient concerns and diagnoses: A 45-year-old man was admitted to our department with a 24-hour history of abdominal distension and incomplete obstruction. Colonoscopy showed an elevated lesion in the ascending colon and the pathologic diagnosis was adenocarcinoma. Interventions and outcomes: This patient underwent a radical right hemi-colectomy. The post-operative pathologic examination revealed metastatic adenocarcinoma in all layers of the appendix, especially the muscularis mucosae. The diagnosis was adenocarcinoma of the ascending colon (pT4bN2bM0 stage IIIC) with metastatic adenocarcinoma of the appendix. Lessons: An absent right colic artery with lymph node fusion might increase the risk of appendiceal cancer metastasis. PMID:28296772

  17. Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy

    PubMed Central

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung

    2016-01-01

    Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008–2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC. PMID:27472385

  18. Novel Method for Differentiating Histological Types of Gastric Adenocarcinoma by Using Confocal Raman Microspectroscopy.

    PubMed

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chau, Lai-Kwan; Chen, Wenlung

    2016-01-01

    Gastric adenocarcinoma, a single heterogeneous disease with multiple epidemiological and histopathological characteristics, accounts for approximately 10% of cancers worldwide. It is categorized into four histological types: papillary adenocarcinoma (PAC), tubular adenocarcinoma (TAC), mucinous adenocarcinoma (MAC), and signet ring cell adenocarcinoma (SRC). Effective differentiation of the four types of adenocarcinoma will greatly improve the treatment of gastric adenocarcinoma to increase its five-year survival rate. We reported here the differentiation of the four histological types of gastric adenocarcinoma from the molecularly structural viewpoint of confocal Raman microspectroscopy. In total, 79 patients underwent laparoscopic or open radical gastrectomy during 2008-2011: 21 for signet ring cell carcinoma, 21 for tubular adenocarcinoma, 14 for papillary adenocarcinoma, 6 for mucinous carcinoma, and 17 for normal gastric mucosas obtained from patients underwent operation for other benign lesions. Clinical data were retrospectively reviewed from medical charts, and Raman data were processed and analyzed by using principal component analysis (PCA) and linear discriminant analysis (LDA). Two-dimensional plots of PCA and LDA clearly demonstrated that the four histological types of gastric adenocarcinoma could be differentiated, and confocal Raman microspectroscopy provides potentially a rapid and effective method for differentiating SRC and MAC from TAC or PAC.

  19. Do mesothelin/MUC16 interactions facilitate adenocarcinoma metastases to intracranial meningiomas?

    PubMed Central

    Johnson, Mahlon D.

    2016-01-01

    Background: Meningiomas have been shown to express mesothelin, a high affinity binding site for MUC16, a transmembrane protein on adenocarcinoma cells. The mechanisms underlying adenocarcinoma metastases to meningiomas may provide insight into tumor-to-tumor metastases and adenocarcinoma metastases to leptomeningeal cells. Methods: Two meningiomas containing metastases from adenocarcinomas were identified and evaluated immunohistochemically for the expression and localization of mesothelin and MUC16. Results: Both meningiomas show extensive mesothelin immunoreactivity, and the adenocarcinomas metastatic to the meningiomas show mesothelin and MUC16 immunoreactivity at the interface with meningioma. Conclusions: Interactions between MUC16 and/or mesothelin on the cell membrane of adenocarcinoma cells with mesothelin on meningioma cells may facilitate adenocarcinoma metastases to meningiomas and possibly the leptomeninges. PMID:28144481

  20. Adenocarcinoma of the paraurethral glands: a case report.

    PubMed

    Massari, Francesco; Ciccarese, Chiara; Modena, Alessandra; Maines, Francesca; Segala, Diego; Luchini, Claudio; Marcolini, Lisa; Cavicchioli, Francesca; Cavalleri, Stefano; Bria, Emilio; Brunelli, Matteo; Martignoni, Guido; Artibani, Walter; Tortora, Giampaolo

    2014-10-01

    Adenocarcinoma of the paraurethral glands represents a very rare neoplasm of the urinary tract. Due to the rarity of this disease, there is no standard therapeutic approach. We report a case of adenocarcinoma of the paraurethral glands in a 56-year-old woman, presenting with abnormal serous vaginal discharges. The radiologic examination revealed a 5-cm mass around the urethra, which underwent surgical resection. After surgical resection, the histology revealed a moderately differentiated adenocarcinoma, probably arising from the paraurethral glands. One month later, a pelvic recurrent mass was radiologically diagnosed; consequently, an anterior pelvic exenteration with lymph node dissection was performed. Histological examination revealed a moderately differentiated adenocarcinoma, with glandular and micropapillary architecture, with multiple lymph node metastases. The absence of modifications such as urethritis cystic glandularis on the urethral mucosa, as well as the lack of a lesion in situ, associated with the immunohistochemical expression of PAX8 and negativity for GATA3 and S100p, suggested that the adenocarcinoma originated from the paraurethral glands rather than from the urethral mucosa. Post-surgery CT scans revealed no evidence of metastatic disease. The patient received 6 courses of adjuvant chemotherapy with carboplatin and paclitaxel. One year after the pelvic exenteration, because of inguinal lymph node progression, an inguinal lymphadenectomy was performed. Four months later, a TC-PET revealed a multidistrectual lymph node and a lung micronodule disease progression. Invasive micropapillary carcinomas have been characterized as a rare distinctive variant of carcinomas in several anatomic sites and are distinguished by a marked tendency to lymphovascular invasion, justifying the association with high-stage disease and poor prognosis. In the present case, both the poor prognosis connected with micropapillary structure and the lymph node involvement

  1. Opium: an emerging risk factor for gastric adenocarcinoma.

    PubMed

    Shakeri, Ramin; Malekzadeh, Reza; Etemadi, Arash; Nasrollahzadeh, Dariush; Aghcheli, Karim; Sotoudeh, Masoud; Islami, Farhad; Pourshams, Akram; Pawlita, Michael; Boffetta, Paolo; Dawsey, Sanford M; Abnet, Christian C; Kamangar, Farin

    2013-07-15

    Opium use has been associated with higher risk of cancers of the esophagus, bladder, larynx, and lung; however, no previous study has examined its association with gastric cancer. There is also little information on the associations between hookah (water pipe) smoking or the chewing of tobacco products and the risk of gastric cancer. In a case-control study in Golestan Province of Iran, we enrolled 309 cases of gastric adenocarcinoma (118 noncardia, 161 cardia and 30 mixed-location adenocarcinomas) and 613 matched controls. Detailed information on long-term use of opium, tobacco products and other covariates were collected using structured and validated lifestyle and food frequency questionnaires. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were obtained using conditional logistic regression models. Opium use was associated with an increased risk of gastric adenocarcinoma, with an adjusted OR (95% CI) of 3.1 (1.9-5.1), and this increased risk was apparent for both anatomic subsites (cardia and noncardia). There was a dose-response effect, and individuals with the highest cumulative opium use had the strongest association (OR: 4.5; 95% CI: 2.3-8.5). We did not find a statistically significant association between the use of any of the tobacco products and risk of gastric adenocarcinoma, overall or by anatomic subsite. We showed, for the first time, an association between opium use and gastric adenocarcinoma. Given that opium use is a traditional practice in many parts of the world, these results are of public health significance.

  2. Influence of VEGFR and LHCGR on endometrial adenocarcinoma

    PubMed Central

    Kölbl, Alexandra C.; Birk, Amelie E.; Kuhn, Christina; Jeschke, Udo; Andergassen, Ulrich

    2016-01-01

    Endometrial adenocarcinoma is a common gynecological malignancy that is usually treated by surgical resection followed by radiation. However, the frequency of remote metastasis is high. The present study aimed to investigate whether patients with endometrial adenocarcinoma exhibited a positive response to treatment with a gonadotropin-releasing hormone analogue or inhibitors of neoangiogenesis, which are applied for the treatment of other malignancies. Immunohistochemical analyses were performed using 203 paraffin-embedded tissue samples of endometrial adenocarcinomas from patients who had undergone surgery at the Department of Obstetrics and Gynecology of the Ludwig Maximilians University of Munich, Germany. The tissues were incubated with antibodies against luteinizing hormone/choriogonadotropin receptor (LHCGR) and vascular endothelial growth factor receptor 2 (VEGFR2), and evaluated by bright field microscopy. The staining was categorized according to the Immune-Reactive-Score (IRS). The IRS scores were then statistically associated with various tumor traits, including tumor size, lymph node status, metastasis, grade, expression of steroid hormone receptors and patient survival. There was a significant association between VEGFR2 expression and tumor grading and estrogen receptor-α (ERα). For LHCGR, a correlation was observed with ERα and progesterone receptor (PR). No correlations were identified between VEGFR2 or LHCGR expression and the other examined tumor traits or patient survival. The associations between VEGFR2 and ERα, and between LHCGR and ERα or PR, may be explained by the interaction of these signal transduction molecules in the regulation of cellular growth and differentiation. These mechanisms also have an important role in the formation of remote metastases, which is the main cause for tumor-associated mortality. The results of the present study suggested that patients with endometrial adenocarcinoma may benefit from treatment with inhibitors

  3. Whole genome sequencing analysis of lung adenocarcinoma in Xuanwei, China

    PubMed Central

    Wang, Xiao; Li, Jing; Duan, Yong; Wu, Huifei; Xu, Qiuyue

    2017-01-01

    Background The lung cancer mortality rate in Xuanwei city is among the highest in China and adenocarcinoma is the major histological type. Lung cancer has been associated with exposure to indoor smoky coal emissions that contain high levels of polycyclic aromatic hydrocarbons; however, the pathogenesis of lung cancer has not yet been fully elucidated. Methods We performed whole genome sequencing with lung adenocarcinoma and corresponding non‐tumor tissue to explore the genomic features of Xuanwei lung cancer. We used the Molecule Annotation System to determine and plot alterations in genes and signaling pathways. Results A total of 3 428 060 and 3 416 989 single nucleotide variants were detected in tumor and normal genomes, respectively. After comparison of these two genomes, 977 high‐confidence somatic single nucleotide variants were identified. We observed a remarkably high proportion of C·G‐A·T transversions. HECTD4, RCBTB2, KLF15, and CACNA1C may be cancer‐related genes. Nine copy number variations increased in chromosome 5 and one in chromosome 7. The novel junctions were detected via clustered discordant paired ends and 1955 structural variants were discovered. Among these, we found 44 novel chromosome structural variations. In addition, EGFR and CACNA1C in the mitogen‐activated protein kinase signaling pathway were mutated or amplified in lung adenocarcinoma tumor tissue. Conclusion We obtained a comprehensive view of somatic alterations of Xuanwei lung adenocarcinoma. These findings provide insight into the genomic landscape in order to further learn about the progress and development of Xuanwei lung adenocarcinoma. PMID:28083984

  4. Histological subtypes of solitary pulmonary nodules of adenocarcinoma and their clinical relevance

    PubMed Central

    Hu, Hui-Di; Wan, Ming-Yue; Xu, Chun-Hua; Zhan, Ping; Zou, Jue; Zhang, Qian-Qian

    2013-01-01

    Objective To explore the histological subtypes of solitary pulmonary nodules (SPNs) of invasive adenocarcinoma and their clinical relevance. Methods A total of 188 patients with pathologically confirmed invasive adenocarcinoma in our hospital from January 2007 to December 2011 were enrolled in this study. In accordance with the new classification of lung adenocarcinoma, all the histological sections were reviewed and classified, and the clinical data were collected and analyzed. Results Of these 188 patients who had been initially diagnosed as SPNs of adenocarcinoma, there were 6 cases of lepidic predominant adenocarcinoma (LPA), 71 cases of acinar predominant adenocarcinoma (APA), 74 cases of papillary predominant adenocarcinoma (PPA), 15 cases of micorpapillary predominant adenocarcinoma (MPA), and 22 cases of solid predominant adenocarcinoma (SPA) with mucin production. The incidence of lymph node metastasis was 80.0% and 81.8% in MPA and SPA, respectively, which was significantly higher than those in LPA, APA, and PPA (all P<0.01). The incidence of LPA was 83.3% (5/6) in women, which was significantly higher than that in men (P=0.037). Conclusions According to the new classification, MPA and SPA have high incidence of lymph node metastasis. LPA is more likely to occur in women. Sub-typing of the lung adenocarcinoma based on the newest international classification criteria is helpful to identify the clinical features of this disease. PMID:24409363

  5. Pulmonary mucinous adenocarcinomas: architectural patterns in correlation with genetic changes, prognosis and survival.

    PubMed

    Geles, Abidin; Gruber-Moesenbacher, Ulrike; Quehenberger, Franz; Manzl, Claudia; Al Effah, Mohamed; Grygar, Elisabeth; Juettner-Smolle, Freyja; Popper, Helmut H

    2015-12-01

    Of pulmonary adenocarcinomas, about 25-30 % of cases is of a mucinous type. Mucinous adenocarcinomas are regarded as more aggressive compared to their non-mucinous counterparts. Invasive mucinous adenocarcinoma, colloid, and enteric adenocarcinomas are variants within adenocarcinomas. We investigated 76 invasive mucinous adenocarcinomas, including colloid variants, for predominant and secondary patterns, their different form of mucin storage and release, expression of cytokeratin 7 and 20, TTF1 and CDX2, MUC1, 2, and 5AC proteins, p14 and p16 proteins, possible rearrangements for EML4ALK and ROS1, as well as KRAS mutational status, and correlated this with survival. For comparison, 259 non-mucinous adenocarcinomas were selected. Overall survival for invasive mucinous adenocarcinomas corrected for T and N stage was not different from their non-mucinous counterpart. Most were of an acinar pattern. Neither pattern, nor type of mucin storage and release, such as luminal, extracellular, or goblet cell type had any influence on survival. Of adenocarcinomas expressing CK20, all but one expressed TTF1 either strongly or at least focally, and 8 co-expressed CDX2 focally. Most mucinous adenocarcinomas expressed either MUC1 or MUC5AC proteins, but rarely MUC2, while a few cases co-expressed both or all three. Loss of p16 expression correlated with worse outcome. KRAS mutation was found in 56 % of mucinous adenocarcinomas. Mutational status was neither correlated with architectural pattern nor survival. Codon 12 mutations were most frequent, and one case presented with KRAS mutations in codon 12 and 61. Goblet cell variants of mucinous adenocarcinomas presented predominantly with codon 12 mutations, while all colloid variants had KRAS mutation. Two cases had EML4 and ALK1 rearranged; ROS1 rearrangement was not found. Mucinous adenocarcinomas behave similar to non-mucinous variants. TNM stage is the most important factor followed by p16 loss predicting overall survival.

  6. Esophageal adenocarcinoma: treatment modalities in the era of targeted therapy.

    PubMed

    Mukherjee, Kaushik; Chakravarthy, A Bapsi; Goff, Laura W; El-Rifai, Wael

    2010-12-01

    Esophageal adenocarcinoma is an aggressive malignancy with a poor outcome, and its incidence continues to rise at an alarming rate. Current treatment strategies combining chemotherapy, radiation, and surgery are plagued with high rates of recurrence and metastasis. Multiple molecular pathways including the epidermal growth factor receptor, vascular endothelial growth factor, v-erb-b2 erythroblastic leukemia viral oncogene homolog (ERBB2), and Aurora kinase pathways are activated in many esophageal adenocarcinomas. In many cases, these pathways have critical roles in tumor progression. Research on the mechanisms by which these pathways contribute to disease progression has resulted in numerous biologic agents and small molecules with the potential to improve outcome. The promise of targeted therapy and personalized medicine in improving the clinical outcome is now closer than it has ever been.

  7. MAMMARY GLAND ADENOCARCINOMA IN A MALE BORNEAN ORANGUTAN (PONGO PYGMAEUS).

    PubMed

    Carpenter, Nancy A; Crook, Erika K

    2017-03-01

    An adult male Bornean orangutan ( Pongo pygmaeus ) was diagnosed with invasive, poorly differentiated grade 9/9 mammary gland adenocarcinoma from a subcutaneous mass that was surgically removed during a routine preventative health examination. The tumor was tested for estrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), and HER2 fluorescence in situ hybridization (HER2 FISH). Whole blood was tested for breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes. The orangutan was treated orally with two common human breast cancer drugs; tamoxifen and anastrozole. The orangutan lived for 4.5 yr postdetection, dying from an unrelated cause. This is the first reported case of mammary gland adenocarcinoma in a male great ape.

  8. ESOPHAGEAL ADENOCARCINOMA: TREATMENT MODALITIES IN THE ERA OF TARGETED THERAPY

    PubMed Central

    Mukherjee, Kaushik; Chakravarthy, A. Bapsi; Goff, Laura W.; El-Rifai, Wael

    2010-01-01

    Esophageal adenocarcinoma is an aggressive malignancy with a poor outcome, and its incidence continues to rise at alarming rates. Current treatment strategies combining chemotherapy, radiation, and surgery are plagued with high rates of recurrence and metastasis. Multiple molecular pathways including the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), v-erb-b2 erythroblastic leukemia viral oncogene homolog (ERBB2), and Aurora kinases’ (AURK) pathways are activated in many esophageal adenocarcinomas. In many cases, these pathways have critical roles in tumor progression. Research on the mechanisms by which these pathways contribute to disease progression has resulted in numerous biologic agents and small molecules with the potential to improve outcome. The promise of targeted therapy and personalized medicine in improving the clinical outcome is now closer than it has ever been. PMID:20300841

  9. Polymorphous low grade adenocarcinoma presenting an uncommon radiographic aspect.

    PubMed

    de Magalhães, M H C G; de Magalhães, R P; de Araújo, V C; de Sousa, S O M

    2006-05-01

    The aim of this study was to present clinical, histological and immunohistochemical aspects of a polymorphous low grade adenocarcinoma occurring in the mandible. A radiolucent tumour, located in the right mandible, was removed from a 40-year-old woman. Radiographic and CT exams revealed that the lesion expanded bucco-lingual cortical plates and presented an irregular scalloping of the bone. The surrounding lining mucosa was intact. The patient underwent total surgical removal of the lesion with an intraoperative biopsy. Histological diagnosis was polymorphous low-grade adenocarcinoma confirmed by immunohistochemical study. One-year follow up was uneventful. The accurate diagnosis of lesions presenting unusual clinical aspects, as the one presented here, is critical for correctly handling treatment.

  10. Operable gastro-oesophageal junctional adenocarcinoma: Where to next?

    PubMed Central

    Smyth, Elizabeth C; Cunningham, David

    2014-01-01

    Oesophageal junctional adenocarcinoma is a challenging and increasingly common disease. Optimisation of pre-operative staging and consolidation of surgery in large volume centres have improved outcomes, however the preferred adjunctive treatment approach remains a matter of debate. This review examines the benefits of neoadjuvant, peri-operative, and post-operative chemotherapy and chemoradiotherapy in this setting in an attempt to reach an evidence based conclusion. Recent findings relating to the molecular characterisation of oesophagogastric cancer and their impact on therapeutics are explored, in addition to the potential benefits of fluoro-deoxyglucose positron emission tomography (FDG-PET) directed therapy. Finally, efforts to decrease the incidence of junctional adenocarcinoma using early intervention in Barrett’s oesophagus are discussed, including the roles of screening, endoscopic mucosal resection, ablative therapies and chemoprevention. PMID:24936225

  11. 'Inflammatory breast cancer' due to metastatic adenocarcinoma of lung.

    PubMed

    Ninan, Jacob; Naik, Vinay; George, Gemy Maria

    2016-09-01

    A 67-year-old woman with a history of lung adenocarcinoma presented with 3 weeks of redness, pain, swelling and skin changes in her right breast. Her vital signs and physical examination were within physiological limits except for the right breast. She had extensive red streaks radiating from the right nipple with peau d'orange appearance of her overlying skin. Her breast was tender on examination and did not have any associated cervical or axillary lymphadenopathy. Her mammography revealed thickening of the skin, increased parenchymal markings and shrinkage the breast. Multiple skin biopsies demonstrated moderately differentiated lung adenocarcinoma with lymphovascular invasion. The patient made an informed decision to undergo radiotherapy following discussion with her oncologist and breast surgeon. She succumbed to her illness 2 months after the diagnosis of metastasis to her breast.

  12. Pulmonar collision tumor: metastatic adenoid cystic carcinoma and lung adenocarcinoma.

    PubMed

    Blanco, M; García-Fontán, E; Ríos, J; Rivo, J E; Fernández-Martín, R; Cañizares, M A

    2012-01-01

    We report an extraordinary case of collision tumor consisting of a lung adenocarcinoma and a metastatic adenoid cystic carcinoma in a 56 year-old man. He was diagnosed with a pulmonary nodule 11 years after treatment of an adenoid cystic carcinoma of the right maxillary sinus. A non-small cell carcinoma was observed when a transbronchial biopsy was performed. The other component of the nodule was only diagnosed with pathological examination of the resection specimen.

  13. The transcriptional landscape and mutational profile of lung adenocarcinoma

    PubMed Central

    Seo, Jeong-Sun; Ju, Young Seok; Lee, Won-Chul; Shin, Jong-Yeon; Lee, June Koo; Bleazard, Thomas; Lee, Junho; Jung, Yoo Jin; Kim, Jung-Oh; Shin, Jung-Young; Yu, Saet-Byeol; Kim, Jihye; Lee, Eung-Ryoung; Kang, Chang-Hyun; Park, In-Kyu; Rhee, Hwanseok; Lee, Se-Hoon; Kim, Jong-Il; Kang, Jin-Hyoung; Kim, Young Tae

    2012-01-01

    All cancers harbor molecular alterations in their genomes. The transcriptional consequences of these somatic mutations have not yet been comprehensively explored in lung cancer. Here we present the first large scale RNA sequencing study of lung adenocarcinoma, demonstrating its power to identify somatic point mutations as well as transcriptional variants such as gene fusions, alternative splicing events, and expression outliers. Our results reveal the genetic basis of 200 lung adenocarcinomas in Koreans including deep characterization of 87 surgical specimens by transcriptome sequencing. We identified driver somatic mutations in cancer genes including EGFR, KRAS, NRAS, BRAF, PIK3CA, MET, and CTNNB1. Candidates for novel driver mutations were also identified in genes newly implicated in lung adenocarcinoma such as LMTK2, ARID1A, NOTCH2, and SMARCA4. We found 45 fusion genes, eight of which were chimeric tyrosine kinases involving ALK, RET, ROS1, FGFR2, AXL, and PDGFRA. Among 17 recurrent alternative splicing events, we identified exon 14 skipping in the proto-oncogene MET as highly likely to be a cancer driver. The number of somatic mutations and expression outliers varied markedly between individual cancers and was strongly correlated with smoking history of patients. We identified genomic blocks within which gene expression levels were consistently increased or decreased that could be explained by copy number alterations in samples. We also found an association between lymph node metastasis and somatic mutations in TP53. These findings broaden our understanding of lung adenocarcinoma and may also lead to new diagnostic and therapeutic approaches. PMID:22975805

  14. Hydronephrosis as a complication of adenocarcinoma of the lung.

    PubMed

    Hiraki, Akio; Ueoka, Hiroshi; Gemba, Kenich; Kuyama, Syouich; Kishino, Daizo; Tabata, Masahiro; Kiura, Katsuyuki; Tanimoto, Mitsune; Harada, Mine

    2003-01-01

    We describe a patient with adenocarcinoma of the lung who developed hydronephrosis secondary to compression by right common iliac lymph node metastases. The most common primary sites of cancers causing ureteral obstruction are the cervix, prostate, bladder and colo-rectum. To date, few reports of ureteral obstruction attributable to lung cancer have been published. Although rare, physicians should be aware that hydronephrosis can complicate the course of patients with non-small cell lung cancer.

  15. Gastrointestinal Bleeding from Metastatic Prostate Adenocarcinoma to the Stomach

    PubMed Central

    Koop, Andree; Brauhmbhatt, Bhaumik; Lewis, Jason

    2017-01-01

    We present a rare case of gastrointestinal (GI) bleeding associated with metastatic prostate adenocarcinoma to the stomach. Prostate cancer, which is the most common noncutaneous malignancy among men, rarely spreads to the stomach, with only 7 cases reported in the English literature. Symptoms may include abdominal pain, nausea, vomiting, and GI bleeding. Our patient was treated with epinephrine injection and bipolar cautery, but GI bleeding recurred 7 months later when he had worsening of his thrombocytopenia while using ibuprofen. PMID:28377935

  16. Gastric Metastases from Lung Adenocarcinoma Causing Gastrointestinal Bleeding

    PubMed Central

    Abu Ghanimeh, Mouhanna; Albadarin, Sakher; Yousef, Osama

    2017-01-01

    Metastases to the stomach are rare. They are commonly asymptomatic, and the diagnosis is usually established during autopsy. We present a patient known to have stage IV lung adenocarcinoma who presented with melena and shock. Endoscopy revealed multiple gastric nodules, which were proved to be metastatic deposits from her lung cancer. The possibility of gastric metastases should be kept in mind in patients presenting with gastrointestinal bleeding. Endoscopy and biopsy remain the gold standard for diagnostic testing in such patients. PMID:28286791

  17. Increased risk of oesophageal adenocarcinoma among upstream petroleum workers

    PubMed Central

    Kirkeleit, Jorunn; Riise, Trond; Bjørge, Tone; Moen, Bente E; Bråtveit, Magne; Christiani, David C

    2013-01-01

    Objectives To investigate cancer risk, particularly oesophageal cancer, among male upstream petroleum workers offshore potentially exposed to various carcinogenic agents. Methods Using the Norwegian Registry of Employers and Employees, 24 765 male offshore workers registered from 1981 to 2003 was compared with 283 002 male referents from the general working population matched by age and community of residence. The historical cohort was linked to the Cancer Registry of Norway and the Norwegian Cause of Death Registry. Results Male offshore workers had excess risk of oesophageal cancer (RR 2.6, 95% CI 1.4 to 4.8) compared with the reference population. Only the adenocarcinoma type had a significantly increased risk (RR 2.7, 95% CI 1.0 to 7.0), mainly because of an increased risk among upstream operators (RR 4.3, 95% CI 1.3 to 14.5). Upstream operators did not have significant excess of respiratory system or colon cancer or mortality from any other lifestyle-related diseases investigated. Conclusion We found a fourfold excess risk of oesophageal adenocarcinoma among male workers assumed to have had the most extensive contact with crude oil. Due to the small number of cases, and a lack of detailed data on occupational exposure and lifestyle factors associated with oesophageal adenocarcinoma, the results must be interpreted with caution. Nevertheless, given the low risk of lifestyle-related cancers and causes of death in this working group, the results add to the observations in other low-powered studies on oesophageal cancer, further suggesting that factors related to the petroleum stream or carcinogenic agents used in the production process might be associated with risk of oesophageal adenocarcinoma. PMID:19858535

  18. Citrobacter koseri Pneumonia As Initial Presentation of Underlying Pulmonary Adenocarcinoma.

    PubMed

    Pennington, Kelly; Van Zyl, Martin; Escalante, Patricio

    2016-01-01

    Citrobacter koseri is a motile, gram-negative rod traditionally known to cause infection in individuals with significant comorbidities and immunocompromised status. While most cases represent nosocomial infections, rarely community-acquired infections have been reported. We present a previously healthy man in his 60s with C. koseri pneumonia who was subsequently found to have underlying pulmonary adenocarcinoma, illustrating the need for further investigation for immunodeficiency and/or intrapulmonary pathology.

  19. Citrobacter koseri Pneumonia As Initial Presentation of Underlying Pulmonary Adenocarcinoma

    PubMed Central

    Pennington, Kelly; Van Zyl, Martin; Escalante, Patricio

    2016-01-01

    Citrobacter koseri is a motile, gram-negative rod traditionally known to cause infection in individuals with significant comorbidities and immunocompromised status. While most cases represent nosocomial infections, rarely community-acquired infections have been reported. We present a previously healthy man in his 60s with C. koseri pneumonia who was subsequently found to have underlying pulmonary adenocarcinoma, illustrating the need for further investigation for immunodeficiency and/or intrapulmonary pathology. PMID:27746678

  20. Signet cell adenocarcinoma of the rectum metastatic to the orbit.

    PubMed

    Charles, Norman C; Ng, Diana D; Zoumalan, Christopher I

    2012-01-01

    A 24-year-old man developed abdominal carcinomatosis from signet cell carcinoma of the rectum. His only distal metastasis involved the superior orbit. Orbital pathology showed signet cells with a characteristic immunopathologic pattern. No hereditary syndrome was found. The authors identified only 5 cases in the literature describing colorectal adenocarcinoma metastatic to the orbit, with 2 showing histopathology. The authors believe that this rare case represents the first illustrating bona fide signet cell colorectal cancer involving the orbit.

  1. Immunotherapy for pancreatic ductal adenocarcinoma: an overview of clinical trials

    PubMed Central

    Paniccia, Alessandro; Merkow, Justin; Edil, Barish H.

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death and current therapeutic strategies are often unsatisfactory. Identification and development of more efficacious therapies is urgently needed. Immunotherapy offered encouraging results in preclinical models during the last decades, and several clinical trials have explored its therapeutic application in PDAC. The aim of this review is to summarize the results of clinical trials conducted to evaluate the future perspective of immunotherapy in the treatment of PDAC. PMID:26361407

  2. [Chicken pox recurrence revealing a renal adenocarcinoma in an adult].

    PubMed

    Thieulent, N; Grezard, P; Wolf, F; Barrut, D; Perrot, H

    2000-09-01

    A new episode of chicken pox in adults who had a well documented infection previously is usually observed in immunocompromised individuals. The principal immunodeficiency factors are hematology diseases, acquired immunodeficiency disease and old age. We report here the case of a young woman who after a contaminating contact presented a recurrence of typical chicken pox. Morphological investigations evidenced a right kidney tumor which pathology revealed to be a renal adenocarcinoma. We discuss this pathological association and review cases reported in the literature.

  3. Metastatic adenocarcinoma to the brain: MR with pathologic correlation

    SciTech Connect

    Carrier, D.A. ); Mawad, M.E.; Kirkpatrick, J.B.; Schmid, M.F. )

    1994-01-01

    To describe the appearance on T2-weighted scans of metastatic adenocarcinoma to the brain and to show that the hypointensity frequently associated with these lesions is not related to the presence of mucin, blood products, iron, or calcium. The MR scans of 14 patients with metastatic adenocarcinoma to the brain were reviewed retrospectively. The signal intensity on T2-weighted scans of the solid enhancing portion of the tumors was compared with white matter. Histologic examination of the surgical specimens included special stains to search for calcium, mucin, and iron. Eight of nine surgical and all six nonsurgical lesions were either iso- or hypointense to white matter on T2-weighted scans. There was no correlation with tumor histology or the presence of mucin, blood products, iron, or calcium. The presence of a hypointense intraaxial mass on T2-weighted scans strongly suggests the possibility of metastatic adenocarcinoma. The MR appearance is not explained by the presence of mucin, blood products, iron, or calcium. This phenomenon most likely reflects the relaxation parameters of the tissue from which the metastasis arose. 21 refs., 3 figs., 1 tab.

  4. Small bowel adenocarcinoma in Lynch syndrome: A case report

    PubMed Central

    Sun, Ke-Kang; Liu, Gang; Shen, Xiaojun; Wu, Xiaoyang

    2016-01-01

    Small bowel adenocarcinoma is part of the tumor spectrum of Lynch syndrome, which is caused by germline mutations in the mismatch repair genes. The present study describes the case of a 51-year-old man fulfilling the Amsterdam II criteria for Lynch syndrome, who had a 15-mm early-stage colorectal cancer resected endoscopically from the ascending colon. Due to upper abdominal discomfort after eating and consequent anorexia, a computed tomography scan performed 1 month later showed a tumoral mass of the upper jejunum with local lymphadenopathy. The laparotomy revealed a completely obstructing mass. Intraoperative frozen section showed a small bowel adenocarcinoma. Subsequent genetic testing confirmed the germline mutation of mutL homolog 1. The patient received 6 cycles of an adjuvant folinic acid, fluorouracil and ocaliplatin chemotherapy regimen. The latest CT scan, 16 months after the chemotherapy, did not show any recurrence. This case highlights the importance of considering the possibility of small bowel adenocarcinoma in patients with upper bowel obstruction, particularly for patients with Lynch syndrome. PMID:27446478

  5. IL-17 induces EMT via Stat3 in lung adenocarcinoma

    PubMed Central

    Huang, Qi; Han, Jieli; Fan, Jinshuo; Duan, Limin; Guo, Mengfei; Lv, Zhilei; Hu, Guorong; Chen, Lian; Wu, Feng; Tao, Xiaonan; Xu, Juanjuan; Jin, Yang

    2016-01-01

    Epithelial-mesenchymal transition (EMT) plays a vital role in lung inflammatory diseases, including lung cancer. However, the role and mechanism of action of the proinflammatory cytokine IL-17 in EMT in lung adenocarcinoma remain unresolved. In our study, we discovered that the expression of N-cadherin, Vimentin, Snail1, Snail2, and Twist1 was positively correlated with IL-17 expression, while E-cadherin expression was negatively correlated with IL-17 expression in human lung adenocarcinoma tissues. Moreover, we confirmed that IL-17 promoted EMT in A549 and Lewis lung carcinoma (LLC) cells in vitro by upregulating N-cadherin, Vimentin, Snail1, Snail2, and Twist1 expression and downregulating E-cadherin expression. Stat3 was activated in IL-17-treated A549 and LLC cells, and Stat3 inhibition or siRNA knockdown notably reduced IL-17-induced EMT in A549 and LLC cells. Thus, IL-17 promotes EMT in lung adenocarcinoma via Stat3 signaling; these observations suggest that targeting IL-17 and EMT are potential novel therapeutic strategies for lung cancer. PMID:27186414

  6. Combined adenocarcinoma-carcinoid tumor of transverse colon.

    PubMed

    Bhattacharjee, Prosanta Kumar; Halder, Shyamal

    2013-01-01

    A 65-year-old male presented with painless hematochezia associated with episodic cramps in upper abdomen, watery diarrhea, and a slowly growing mass in upper abdomen. Examination revealed a firm 6 x 5 cm, intra-abdominal, epigastric mass. Colonoscopy up to 90 cm showed a stenosing, ulcero-proliferative lesion in the transverse colon. No synchronous lesion was detected. Biopsy revealed mucin secreting adenocarcinoma. Exploration showed the growth involving the transverse colon proximal to the splenic flexure with a part of ileum, approximately three feet proximal to ileo-caecal junction, adherent to it. No significant mesenteric lymph node enlargement was evident. The patient underwent resection of the growth along with the segment of adherent ileum. Continuity was re-established by a colo-colic and ileo-ileal anastomosis respectively. Patient received adjuvant chemotherapy. Post-operative histopathology demonstrated a composite histological pattern with an admixture of carcinoid tumor and adenocarcinoma, invasion of ileal serosa and adenocarcinomatous deposits in mesocolic lymph nodes, the tumor staging being (T4, N0, M0/Stage II) for carcinoid and (T4, N1, M0/Stage III) for adenocarcinoma. Patient was followed-up for a year and was doing well without any evidence of recurrence.

  7. Targeting adhesion signaling in KRAS, LKB1 mutant lung adenocarcinoma.

    PubMed

    Gilbert-Ross, Melissa; Konen, Jessica; Koo, Junghui; Shupe, John; Robinson, Brian S; Wiles, Walter Guy; Huang, Chunzi; Martin, W David; Behera, Madhusmita; Smith, Geoffrey H; Hill, Charles E; Rossi, Michael R; Sica, Gabriel L; Rupji, Manali; Chen, Zhengjia; Kowalski, Jeanne; Kasinski, Andrea L; Ramalingam, Suresh S; Fu, Haian; Khuri, Fadlo R; Zhou, Wei; Marcus, Adam I

    2017-03-09

    Loss of LKB1 activity is prevalent in KRAS mutant lung adenocarcinoma and promotes aggressive and treatment-resistant tumors. Previous studies have shown that LKB1 is a negative regulator of the focal adhesion kinase (FAK), but in vivo studies testing the efficacy of FAK inhibition in LKB1 mutant cancers are lacking. Here, we took a pharmacologic approach to show that FAK inhibition is an effective early-treatment strategy for this high-risk molecular subtype. We established a lenti-Cre-induced Kras and Lkb1 mutant genetically engineered mouse model (KLLenti) that develops 100% lung adenocarcinoma and showed that high spatiotemporal FAK activation occurs in collective invasive cells that are surrounded by high levels of collagen. Modeling invasion in 3D, loss of Lkb1, but not p53, was sufficient to drive collective invasion and collagen alignment that was highly sensitive to FAK inhibition. Treatment of early, stage-matched KLLenti tumors with FAK inhibitor monotherapy resulted in a striking effect on tumor progression, invasion, and tumor-associated collagen. Chronic treatment extended survival and impeded local lymph node spread. Lastly, we identified focally upregulated FAK and collagen-associated collective invasion in KRAS and LKB1 comutated human lung adenocarcinoma patients. Our results suggest that patients with LKB1 mutant tumors should be stratified for early treatment with FAK inhibitors.

  8. Spontaneous Rupture of Hepatic Metastasis from Pancreatic Adenocarcinoma

    PubMed Central

    Robin, Fernandes; Adarsh, Hiremath

    2016-01-01

    A 58-year-old man with advanced-stage pancreatic adenocarcinoma presented with fatigue and dyspnea. Examination revealed tachycardia (102 b/min) with mild tenderness in right upper quadrant. His hemoglobin (Hb) was 7.9 g/dL (10 days prior to presentation 12.2 g/dL), International normalized ratio (INR), platelet count was normal, and the stool guaiac test was negative. On admission, abdominal computed tomography (CT) scan showed hepatic metastatic lesion with a rupture and hemoperitoneum communicating to the subdiaphragmatic space. This rapid progression of anemia along with presenting symptoms and CT imaging were attributed to diagnosis of spontaneous rupture of liver metastasis from pancreatic adenocarcinoma. Patient received blood transfusion and hemoglobin was monitored in successive intervals. His general condition and anemia improved with conservative management and he was discharged in 3 days. Repeated CT after 4 months showed resolving hemoperitoneum and stable hemoglobin levels. The patient deceased 9 months after being diagnosed. A literature search revealed limited data regarding the incidence and management of spontaneous rupture of metastatic lesion secondary to pancreatic adenocarcinoma which has been managed conservatively and thus we are reporting our experience. PMID:27597912

  9. Endoscopic assessment and management of early esophageal adenocarcinoma

    PubMed Central

    Hammoud, Ghassan M; Hammad, Hazem; Ibdah, Jamal A

    2014-01-01

    Esophageal carcinoma affects more than 450000 people worldwide and the incidence is rapidly increasing. In the United States and Europe, esophageal adenocarcinoma has superseded esophageal squamous cell carcinoma in its incidence. Esophageal cancer has a high mortality rates secondary to the late presentation of most patients at advanced stages. Endoscopic screening is recommended for patients with multiple risk factors for cancer in Barrett’s esophagus. These risk factors include chronic gastroesophageal reflux disease, hiatal hernia, advanced age, male sex, white race, cigarette smoking, and obesity. The annual risk of esophageal cancer is approximately 0.25% for patients without dysplasia and 6% for patients with high-grade dysplasia. Twenty percent of all esophageal adenocarcinoma in the United States is early stage with disease confined to the mucosa or submucosa. The significant morbidity and mortality of esophagectomy make endoscopic treatment an attractive option. The American Gastroenterological Association recommends endoscopic eradication therapy for patients with high-grade dysplasia. Endoscopic modalities for treatment of early esophageal adenocarcinoma include endoscopic resection techniques and endoscopic ablative techniques such as radiofrequency ablation, photodynamic therapy and cryoablation. Endoscopic therapy should be precluded to patients with no evidence of lymphovascular invasion. Local tumor recurrence is low after endoscopic therapy and is predicted by poor differentiation of tumor, positive lymph node and submucosal invasion. Surgical resection should be offered to patients with deep submucosal invasion. PMID:25132925

  10. Targeting adhesion signaling in KRAS, LKB1 mutant lung adenocarcinoma

    PubMed Central

    Konen, Jessica; Koo, Junghui; Robinson, Brian S.; Wiles, Walter Guy; Huang, Chunzi; Martin, W. David; Behera, Madhusmita; Smith, Geoffrey H.; Hill, Charles E.; Rossi, Michael R.; Sica, Gabriel L.; Rupji, Manali; Chen, Zhengjia; Kowalski, Jeanne; Kasinski, Andrea L.; Ramalingam, Suresh S.; Khuri, Fadlo R.; Marcus, Adam I.

    2017-01-01

    Loss of LKB1 activity is prevalent in KRAS mutant lung adenocarcinoma and promotes aggressive and treatment-resistant tumors. Previous studies have shown that LKB1 is a negative regulator of the focal adhesion kinase (FAK), but in vivo studies testing the efficacy of FAK inhibition in LKB1 mutant cancers are lacking. Here, we took a pharmacologic approach to show that FAK inhibition is an effective early-treatment strategy for this high-risk molecular subtype. We established a lenti-Cre–induced Kras and Lkb1 mutant genetically engineered mouse model (KLLenti) that develops 100% lung adenocarcinoma and showed that high spatiotemporal FAK activation occurs in collective invasive cells that are surrounded by high levels of collagen. Modeling invasion in 3D, loss of Lkb1, but not p53, was sufficient to drive collective invasion and collagen alignment that was highly sensitive to FAK inhibition. Treatment of early, stage-matched KLLenti tumors with FAK inhibitor monotherapy resulted in a striking effect on tumor progression, invasion, and tumor-associated collagen. Chronic treatment extended survival and impeded local lymph node spread. Lastly, we identified focally upregulated FAK and collagen-associated collective invasion in KRAS and LKB1 comutated human lung adenocarcinoma patients. Our results suggest that patients with LKB1 mutant tumors should be stratified for early treatment with FAK inhibitors. PMID:28289710

  11. Distinction between endometrial and endocervical adenocarcinoma: an immunohistochemical study.

    PubMed

    Castrillon, Diego H; Lee, Kenneth R; Nucci, Marisa R

    2002-01-01

    We investigated the possibility of distinguishing between primary endometrial and endocervical adenocarcinomas by using a panel of immunohistochemical stains, which included vimentin (VIM), carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), and cytokeratins 7 and 20 (CK7 and CK20). Twenty-nine endocervical adenocarcinomas (CCAs) and 30 endometrial adenocarcinomas (EMCAs) including cases with overlapping histologic features (CCAs with endometrioid differentiation [15/29] and EMCAs with mucinous differentiation [16/30]) were evaluated. Most EMCAs (29/30, 97%) were VIM positive, whereas only 2/29 (7%) CCAs were VIM positive. The great majority of EMCAs (28/30) and all 29 CCAs were CK7 positive, whereas all 30 EMCAs and 27/29 CCAs were negative for CK20. CEA positivity was more common in CCAs (18/29, 62%) than in EMCAs (8/30, 27%). EMA positivity was present in all 30 EMCAs and in 26 of 29 (90%) CCAs. We conclude that VIM and CEA are useful immunohistochemical markers in distinguishing EMCAs and CCAs, but CK7, CK20, and EMA are not useful in this distinction.

  12. Adenocarcinoma in Caroli's Disease Treated by Liver Transplantation

    PubMed Central

    Margarit, C.; Murio, E.; Lazaro, J. L.; Charco, R.; Vidal, M. T.; Bonnin, J.

    1993-01-01

    Caroli's disease is characterized by congenital cystic dilatation of the intrahepatic bile ducts. In 7% of casea a malignant tumor develops complicating the course of the disease. We report the case of a 25 year-old woman in whom Caroli's disease was diagnosed at the age of 11. From that time on, she had several episodes of cholangitis. In 1989, the abdominal ultrasound and CT scan showed dilatation of the intrahepatic bile ducts, intracystic lithiasis and a solid mass. FNA cytology showed a papillary adenocarcinoma. At laparotomy a tumor was found occupying both hepatic lobes, and intraoperative US showed another two nodules in the left lobe. The tumor was considered unresectable. Examination of the hilar lymph nodes was tumor-negative. Two weeks later, the patient underwent an ortothopic liver transplantation (OLT). The pathological examination confirmed Caroli's disease with adenocarcinoma. Two years after OLT, the patient is alive with normal liver function and no evidence of disease. To our knowledge this is the first case report of adenocarcinoma in Caroli's disease treated by OLT. PMID:8260439

  13. Well-differentiated adenocarcinoma associated with ulcerative colitis

    PubMed Central

    Yamamoto, Tomoko; Hiroi, Atsuko; Itagaki, Hiroko; Kato, Yoichiro; Iizuka, Bunei; Itabashi, Michio; Shibata, Noriyuki; Nagashima, Yoji

    2017-01-01

    Objectives: Adenocarcinoma is known to be associated with ulcerative colitis, but the diagnosis is sometimes challenging, both clinically and pathologically. Methods and Results: We present a case of extremely well-differentiated adenocarcinoma associated with ulcerative colitis, in which preoperative diagnosis was not possible. Glands in biopsy specimens showed a serrated appearance that looked like low-grade dysplasia or regenerative mucosa. After an operation due to severe symptoms of stenosis, carcinoma was diagnosed. Tumor cells, especially in invasive glands, tended to show stronger immunoreactivity against anti-CK7, TNF-α and Aurora B antibodies compared to cells of mucosal lesion. Interestingly, CD44v6, one of the adhesion molecules, was less expressed in invasive glands, while those glands exhibited stronger expression of a disintegrin and metalloproteinase 17 (ADAM 17), one of the sheddases that cleaves an extracellular domain of CD44. Conclusions: These observations appear interesting to consider the pathogenesis and to diagnose extremely well-differentiated adenocarcinoma in ulcerative colitis, although further investigation is needed. PMID:28255443

  14. Case Report: Bazex Syndrome Associated With Pulmonary Adenocarcinoma

    PubMed Central

    Zhao, Jing; Zhang, Xilin; Chen, Zhuo; Wu, Jian-hua

    2016-01-01

    Abstract Bazex syndrome, a rare paraneoplastic syndrome characterized by psoriasiform eruptions, palmoplantar keratosis, and symmetric onychodystrophy, is most prevalent with squamous cell carcinomas of the upper aerodigestive tract. Here, we reported an uncommon case of Bazex syndrome about an 83-year-old man with pulmonary adenocarcinoma and osseous metastasis, Physical examination found psoriasiform eruptions on the nose, cheeks, ears, knees, and the dorsa of interphalangeal joints, along with plantar keratosis and symmetric onychodystrophy involving hands and feet. Imaging analyses pulmonary adenocarcinoma with both local metastatic nodules and osseous metastasis. Symptomatic treatment with topical corticosteroids and oral retinoids showed no improvement. A 4-month follow-up showed that Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, successfully reduced primary tumor size and alleviated cutaneous lesions. Our report here highlighted a potential correlation between pulmonary adenocarcinoma and Bazex syndrome, which is characterized by hallmark nail destruction and preferential involvement of body extremities. Moreover, etiological therapy against underlying malignancy is essential for treating paraneoplastic Bazex syndrome. PMID:26765420

  15. Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour (GIST) of the Stomach: A Case Report

    PubMed Central

    Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna

    2016-01-01

    Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols. PMID:27042477

  16. Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour (GIST) of the Stomach: A Case Report.

    PubMed

    Telugu, Ramesh Babu; Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna

    2016-02-01

    Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols.

  17. Barrett’s oesophagus and oesophageal adenocarcinoma: time for a new synthesis

    PubMed Central

    Reid, Brian J.; Li, Xiaohong; Galipeau, Patricia C.; Vaughan, Thomas

    2010-01-01

    The public health importance of Barrett’s oesophagus lies in its association with oesophageal adenocarcinoma. The incidence of oesophageal adenocarcinoma has risen at an alarming rate over the past four decades in many regions of the Western world and there are indications that the incidence of this disease is on the rise in Asian populations where it has been rare. Much has been learned of host and environmental risk factors that affect the incidence of oesophageal adenocarcinoma and data indicate that patients with Barrett’s oesophagus rarely develop oesophageal adenocarcinoma. Given that 95% of oesophageal adenocarcinoma arise in individuals without a prior diagnosis of Barrett’s oesophagus, what strategies can be used to reduce late diagnosis of oesophageal adenocarcinoma? PMID:20094044

  18. Primary enteric-type mucinous adenocarcinoma of the urethra in a patient with ulcerative colitis.

    PubMed

    Dimitroulis, Dimitrios; Patsouras, Dimitrios; Katsargyris, Athanasios; Charalampoudis, Petros; Anastasiou, Ioannis; Kouraklis, Gregory

    2014-01-01

    Primary carcinoma of the male urethra accounts for less than 1% of malignancies in men. Mucinous adenocarcinoma of the urethra is extremely rare, and its biologic behavior is poorly understood. We present herein a rare case of mucinous urethral adenocarcinoma in a male patient with longstanding ulcerative colitis and multiple sclerosis. The patient presented with a voluminous pelvic mass; core biopsy of the lesion demonstrated a mucus-producing adenocarcinoma. Given the patient's history of subtotal colectomy, preoperative diagnosis was oriented towards a rectal stump adenocarcinoma. The patient underwent a pelvic exenteration: surprisingly, histology marked the prostatic urethra as the primary lesion site.

  19. CHKA mediates the poor prognosis of lung adenocarcinoma and acts as a prognostic indicator

    PubMed Central

    Zhang, Li; Chen, Ping; Yang, Shen; Li, Guodong; Bao, Wentao; Wu, Peng; Jiang, Shujuan

    2016-01-01

    Choline kinase α (CHKA), the enzyme that converts choline to phosphocholine, has been studied in human carcinogenesis widely. However, the expression and underlying clinicopathological characteristics of CHKA in lung adenocarcinoma remains elusive. In the present study, a tissue microarray of 119 pairs of lung adenocarcinoma samples and corresponding adjacent normal mucosae was used to analysis CHKA expression by immunohistochemistry, and CHKA was observed to exhibit enhanced expression in lung adenocarcinoma tissues. Elevated CHKA expression in lung adenocarcinoma tissues at the gene and protein level was observed. The levels of CHKA expression were closely associated with the poor prognosis status of lung adenocarcinoma patients. Furthermore, certain clinicopathological characteristics such as tumor diameter and differentiation were observed to be significant in those lung adenocarcinoma patients who displayed enhanced CHKA expression. The analysis of CHKA expression could provide a more precise way to predict the prognosis of lung adenocarcinoma patients. Collectively, the present study revealed a novel biomarker in lung adenocarcinoma, and indicated that CHKA may be a promising prognostic marker and therapeutic target for lung adenocarcinoma. PMID:27588131

  20. [Role of postoperative chemoradiotherapy in the therapeutic management of adenocarcinomas of the stomach and oesogastric junction].

    PubMed

    Ben Salah, H; Bahri, M; Dhouib, F; Daoud, J

    2016-12-01

    The available data in the literature show that for gastric adenocarcinoma or gastroesophageal junction adenocarcinoma, postoperative chemoradiotherapy improves disease-free survival after surgery with D0 or D1 lymph node dissection (and perhaps D2) as well as in case of positive node or R1 resection. With the publications of perioperative chemotherapy trials, the role of postoperative radiotherapy in the therapeutic arsenal of gastric adenocarcinoma or gastroesophageal junction adenocarcinoma becomes difficult to define. Postoperative radiotherapy is indicated in case of R1 resection.

  1. Aurora Kinase A Is a Prognostic Marker in Colorectal Adenocarcinoma

    PubMed Central

    Koh, Hyun Min; Jang, Bo Geun; Hyun, Chang Lim; Kim, Young Sill; Hyun, Jin Won; Chang, Weon Young; Maeng, Young Hee

    2017-01-01

    Background Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea. Methods AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological characteristics and AURKA expression. In addition, the prognostic significance of various clinicopathological data for progression-free survival (PFS) was assessed. Also we evaluated copy number variations by array comparative genomic hybridization and AURKA gene amplification using fluorescence in situ hybridization in colorectal carcinoma tissues. Results AURKA gene amplification was found more frequently in the 20q13.2–13.33 gain-positive group than the group with no significant gain on the AURKA-containing locus. AURKA protein expression was detected in 45% of the cases (68/151). Positive staining for AURKA was observed more often in male patients (p = .035) and distally located tumors (p = .021). PFS was shorter in patients with AURKA expression compared to those with low-level AURKA expression (p < .001). Univariate analysis revealed that AURKA expression (p = .001), age (p = .034), lymphatic invasion (p = .001), perineural invasion (p = .002), and TNM stage (p = .013) significantly affected PFS. In a multivariate analysis of PFS, a Cox proportional hazard model confirmed that AURKA expression was an independent and significant prognostic factor in colorectal adenocarcinoma (hazard ratio, 3.944; p < .001). Conclusions AURKA could serve as an independent factor to predict a poor prognosis in Korean colorectal adenocarcinoma patients. PMID:28013532

  2. EGFR mutation and lobar location of lung adenocarcinoma.

    PubMed

    Tseng, Chien-Hua; Chen, Kun-Chieh; Hsu, Kuo-Hsuan; Tseng, Jeng-Sen; Ho, Chao-Chi; Hsia, Te-Chun; Su, Kang-Yi; Wu, Ming-Fang; Chiu, Kuo-Liang; Liu, Chien-Ming; Wu, Tzu-Chin; Chen, Hung-Jen; Chen, Hsuan-Yu; Chang, Chi-Sheng; Hsu, Chung-Ping; Hsia, Jiun-Yi; Chuang, Cheng-Yen; Lin, Chin-Hung; Chen, Jeremy J W; Chen, Kuan-Yu; Liao, Wei-Yu; Shih, Jin-Yuan; Yu, Sung-Liang; Yu, Chong-Jen; Yang, Pan-Chyr; Yang, Tsung-Ying; Chang, Gee-Chen

    2016-02-01

    The objective of this study was to investigate the associations among lung cancer location, and epidermal growth factor receptor (EGFR) mutation status. Treatment-naive, pathologically confirmed lung adenocarcinomas with tumor specimens available for genetic analysis were included from 2011 through 2014. Overall, 1771 patients with lung adenocarcinoma were included for analysis, after excluding those with carcinoma not otherwise specified, or synchronous multiple primary lung cancers. The median age was 64 years, and the female:male and never smoker:ever smoker ratios were 930:855 (52:48%) and 1167:604 (65:35%), respectively. The EGFR mutation rate was 56%. Among patients, 1093 (62%) had primary tumors in the upper lobes. Compared with the characteristics of the EGFR wild-type, tumors with EGFR activating mutations were more common in women (P < 0.001), never smokers (P < 0.001), and in the upper lobes (P = 0.004). Among EGFR activating mutations, compared with the EGFR exon 19 deletion, L858R mutation were more common in women (P = 0.002), never smokers (P = 0.038), and the upper lobes P < 0.0005). The present study is the first to address that different pulmonary lobar locations might harbor different EGFR mutation subtypes. We demonstrated that adenocarcinomas with L858R mutation, rather than exon 19 deletion or wild-type EGFR gene, prefer to locate over the upper lungs. This phenomenon was more significant in females and never-smokers, implying the result of complex interactions between genetic susceptibility and environmental factors. Therefore, EGFR L858R mutation and exon 19 deletion may not be identical disease entity from the point of carcinogenesis.

  3. 184AA3: A Xenograft Model of ER+ Breast Adenocarcinoma

    PubMed Central

    Hines, William C.; Kuhn, Irene; Thi, Kate; Chu, Berbie; Stanford-Moore, Gaelen; Sampayo, Rocío; Garbe, James C.; Stampfer, Martha; Borowsky, Alexander D.; Bissell, Mina

    2015-01-01

    Purpose Despite the prevalence and significant morbidity resulting from estrogen receptor positive (ER+) breast adenocarcinomas, there are only a few models of this cancer subtype available for drug development, and arguably none for studying etiology. Those models that do exist have questionable clinical relevance. Methods Given our goal of developing luminal models, we focused on six cell lines derived by minimal mutagenesis from normal human breast cells, and asked if any could generate clinically relevant xenografts, which we then extensively characterized. Results Xenografts of one cell line, 184AA3, consistently formed ER+ adenocarcinomas that had a high proliferative rate and other features consistent with “luminal B” intrinsic subtype. Squamous and spindle cell/mesenchymal differentiation was absent, in stark contrast to other cell lines that we examined or others have reported. We explored intratumoral heterogeneity produced by 184AA3 by immunophenotyping xenograft tumors and cultured cells, and characterized marker expression by immunofluorescence and flow cytometry. A CD44High subpopulation was discovered, yet their tumor forming ability was far less than CD44Low cells. Single cell cloning revealed the phenotypic plasticity of 184AA3, consistent with the intratumoral heterogeneity observed in xenografts. Characterization of ER expression in cultures revealed ER protein and signaling is intact, yet when estrogen was depleted in culture, and in vivo, it did not impact cell or tumor growth, analogous to therapeutically resistant ER+ cancers. Conclusions This model is appropriate for studies of the etiology of ovarian hormone independent adenocarcinomas, for identification of therapeutic targets, predictive testing and drug development. PMID:26661596

  4. Immunohistochemical detection of P-glycoprotein in endometrial adenocarcinoma.

    PubMed Central

    Axiotis, C. A.; Monteagudo, C.; Merino, M. J.; LaPorte, N.; Neumann, R. D.

    1991-01-01

    P-glycoprotein (Pgp) has emerged as the central mediator in classic multidrug resistance in model systems in vitro. High levels of Pgp also have been detected in many normal human tissues and tumors; and its role in clinical drug resistance is currently under investigation. Recently significant levels of Pgp were localized to gravid and secretory endometrium; and it was demonstrated that the combination of estrogen and progesterone is sufficient to induce high levels of both Pgp mRNA and Pgp in uterine secretory epithelium. These findings suggest that increased Pgp expression also may be present in hormone-responsive malignancies such as endometrial adenocarcinoma. To determine whether Pgp is expressed in endometrial adenocarcinoma, 36 endometrial adenocarcinomas (grade I [n = 17]; grade II [n = 6]; grade III [n = 13]) were investigated retrospectively by the avidin-biotin-complex immunohistochemical procedure using three murine monoclonal antibodies (MAb) MAb C219, MAb C494, and MAb JSB-1, which recognize spatially distinct cytoplasmic epitopes of Pgp. Seventy-two percent of the tumors showed positive immunostaining with at least one MAb; 67% showed immunostaining with MAb C219, 50% with MAb C494, and 62% with MAb JSB-1. Forty-six percent of tumors were immunoreactive to two and 29% to all three antibodies. Membranous and Golgi/paranuclear type staining patterns were observed. Overall the intensity of immunostaining varied from one sample to another for a given tumor type, and considerable heterogeneity of expression was commonly seen within a given tumor. Strong to moderate immunoreactivity was seen in diffusely infiltrating, adenosquamous, and serous papillary carcinomas. In general, immunoreactivity to MAb C494 was weaker than MAb C219 or MAb JSB-1. Adenomatous and non-neoplastic endometrium adjacent to the tumors displayed strong membranous immunostaining with MAb JSB-1. Endometrial capillaries showed weak-to-moderate immunostaining to all three antibodies. It

  5. Unresectable pancreatic adenocarcinoma with complete clinical response following chemoradiotherapy

    PubMed Central

    Aksoy, Erol; Ulaş, Murat; Çolakoğlu, Muhammet Kadri; Özer, İlter; Bostancı, Erdal Birol; Akoğlu, Musa

    2015-01-01

    Locally advanced or metastatic disease is present in 2/3s of patients with pancreatic cancer. Pancreatic cancer patients are assessed as resectable, potentially resectable (borderline) and unresectable according to pre-operative examinations. The chance for operability may be enhanced by using adjuvant-neoadjuvant systemic chemotherapy, radiotherapy or both. The rates of R0 resection may be increased by means of treatment delivered this way. This case report presents a pancreatic adenocarcinoma case that was assessed to be resectable but was identified to be unresectable during surgical exploration, thus received adjuvant chemoradiotherapy. The patient was then re-evaluated, identified as resectable and received pancreaticoduodenectomy. PMID:25931951

  6. Adjuvant, neoadjuvant, and experimental regimens in overcoming pancreatic ductal adenocarcinoma

    PubMed Central

    Wysocka, Olga; Kulbacka, Julita; Saczko, Jolanta

    2016-01-01

    Pancreatic cancer is one of the most aggressive and deadly malignancies. Despite better understanding of its biology and pathogenesis, contemporary treatment regimens are still insufficient. Along with the introduction of new treatment agents and combination therapy, the response rates are increasing, but these scores do not go with overall survival, and results are frequently conflicting. Therefore, contemporary medicine faces the challenge of expanding the knowledge base and practice on all grounds – pathology, factor risk, diagnosis, and finally surgical and palliative treatment of this disease. This paper provides a review of current adjuvant and neoadjuvant regimens and the role of experimental therapies in pancreatic ductal adenocarcinoma. PMID:27713776

  7. Variation of tumoral marker after radiofrequency ablation of pancreatic adenocarcinoma

    PubMed Central

    Barbi, Emilio; Girelli, Roberto; Tinazzi Martini, Paolo; De Robertis, Riccardo; Ciaravino, Valentina; Salvia, Roberto; Butturini, Giovanni; Frigerio, Isabella; Milazzo, Teresa; Crosara, Stefano; Paiella, Salvatore; Pederzoli, Paolo; Bassi, Claudio

    2016-01-01

    Background To evaluate the correlation between variations of CA 19.9 blood levels and the entity of necrosis at CT after radiofrequency ablation (RFA) of unresectable pancreatic adenocarcinoma. Methods In this study, from June 2010 to February 2014, patients with diagnosis of unresectable and not metastatic pancreatic ductal adenocarcinoma, expressing tumor marker CA 19.9, treated with RFA procedure were included. All these patients underwent RFA. CT study was performed 1 week after RFA. The dosage of CA 19.9 levels was performed 1 month after RFA. Features of necrosis at CT, as mean entity, density and necrosis percentages compared to the original lesion, were evaluated and compared by using t-test with CA 19.9 blood levels variations after RFA procedure. Results In this study were included 51 patients with diagnosis of unresectable and not metastatic pancreatic ductal adenocarcinoma, expressing tumor marker CA 19.9, treated with RFA procedure and with CT study and CA 19.9 available for analysis. After the procedure, CA 19.9 blood levels reduced in 24/51 (47%), remained stable in 10/51 (20%) and increased in 17/51 (33%). In patients with CA 19.9 levels reduced, the tumor marker were reduced less than 20% in 4/24 (17%) and more than 20% in 20/24 (83%); instead the tumor marker were reduced less than 30% in 8/24 (33%) and more than 30% in 16/24 (67%). At CT scan necrotic area density difference was not statistically significant. Also there was no statistically significant difference among the mean area, the mean volume and the mean ablation volume in percentage related to the treated tumor among the three different groups of patients divided depending on the CA 19.9 blood levels. But a tendency to a statistically significant difference was found in comparing the mean percentage of ablation volume between two subgroups of patients with a decrease of CA 19.9 levels with less or more than 20% reduction of tumor markers and between two subgroups with less or more than

  8. Molecular Analysis of Motility in Metastatic Mammary Adenocarcinoma Cells

    DTIC Science & Technology

    1996-09-01

    Culture MTLn3 cells were clonally derived from a lung metastasis of the 13762NF rat mammary adenocarcinoma ( Neri et al., 1982) (kindly provided by Dr...MTLn3 cells were plated on collagen I coated MATTEK tissue culture dishes for 24 hours. Cells were plated at a density of 5000 cells/sq cm and...mM KOH; 4 mM MgC12 ; 10 mM EGTA pH 6.5 with 20 mM KOH; 5 1M phallacidin; 0.025 % saponin) was added to the culture well. After 15 seconds of extraction

  9. Metachronous metastasis to the penis from a rectal adenocarcinoma.

    PubMed

    Ketata, Sabeur; Boulaire, Jean Loup; Soulimane, Benamar; Bargain, Alain

    2007-09-01

    Penile metastases arise most frequently from genitourinary cancers, but can also arise from tumors of the large bowel; other primary sites are extremely uncommon. We report the case of a 59-year-old patient with 2 penile metastases from a rectal adenocarcinoma, which was discovered 26 years after abdominoperineal resection. Penile biopsy was carried out and established the metastatic nature. The patient underwent palliative chemotherapy treatment with cetuximab/irinotecan. All previously reported cases of penile metastasis from the rectum are reviewed. Regardless of the treatment options, the prognosis of such metastasis remains poor.

  10. Cecal adenocarcinoma presenting as colonic intussusception in adulthood.

    PubMed

    Gonzalez-Hernandez, Jessica; Garcia, Fernando

    2015-04-01

    Intussusception occurs when a proximal segment of intestine invaginates into a distal segment. It is a common cause of intestinal obstruction in children but is infrequent in adults. A 77-year-old woman presented with a 1-month history of intermittent abdominal pain associated with nausea and distended abdomen. Imaging showed a complex elongated sausage-shaped mass in the transverse colon with no obstructive pattern or free air. Surgery confirmed colonic intussusception in addition to a palpable cecal mass requiring a right hemicolectomy. Histologic study demonstrated adenocarcinoma in situ within a tubulovillous adenoma. Surgical excision of the affected intestine is the recommended treatment of choice.

  11. Endometrioid adenocarcinoma arising from endometriosis of the rectosigmoid.

    PubMed

    Kobayashi, Shigeru; Sasaki, Morio; Goto, Tatsuya; Asakage, Naoki; Sekine, Masayuki; Suzuki, Takahisa; Tsukada, Kenji; Yamasaki, Shigetaka; Ukawa, Shiro

    2010-01-01

    A case of endometrioid adenocarcinoma supposedly arising from endometriosis of the rectum is reported. Malignant transformation is uncommon but a well-known complication of endometriosis. In the present case, it was proved by histopathological findings and immunophenotype such as cytokeratin7+/cytokeratin20-/estrogen receptor+. The cause of rectal endometriosis in this case might have been related with previously received hormone replacement therapy for ovarian endometriosis. Following surgical removal of the lesion, this patient underwent adjuvant chemotherapy with paclitaxel and carboplatin, although this kind of therapy is still controversial as to its effectiveness.

  12. "Big IGF-II"-induced hypoglycemia secondary to gastric adenocarcinoma.

    PubMed

    Morbois-Trabut, L; Maillot, F; De Widerspach-Thor, A; Lamisse, F; Couet, C

    2004-06-01

    Non-islet cell tumor-related hypoglycemia is a rare phenomenon. We report the case of a 63 Year-old man admitted for hemiparesia and a capillary blood glucose of 20 mg/dL. The presence of an immature form of IGF-II that can mimic the effect of insulin, namely "big IGF-II", explained this patient's hypoglycaemia. A moderately differentiated adenocarcinoma of the cardia with metastatic extension to the stomach and the liver was demonstrated. Octreotide failed to control the hypoglycaemia, therefore prednisolone (2 mg/kg per day) and enteral feeding prevented new episodes of severe hypoglycaemia.

  13. Metastatic anaplastic adenocarcinoma suspected to be of mammary origin in an intact male rabbit (Oryctolagus cuniculus)

    PubMed Central

    Summa, Noémie M.; Eshar, David; Snyman, Heindrich N.; Lillie, Brandon N.

    2014-01-01

    A 7-year-old, intact male, pet dwarf rabbit (Oryctolagus cuniculus) was presented for a ventral abdominal subcutaneous mass. Histolopathology of the resected mass was suggestive of a mammary adenocarcinoma. Six months later, the rabbit died from severe dyspnea. Necropsy showed recurrence of the original mass with hepatic and pulmonary metastasis of the anaplastic adenocarcinoma, suspected to be of mammary origin. PMID:24790235

  14. Primary Seminal Vesicle Adenocarcinoma Presenting With Bilateral Orbital Metastasis: A Case Report

    PubMed Central

    Sterling, Matthew E.; Kovell, Robert C.; Jaffe, William I.

    2016-01-01

    Seminal vesicle (SV) adenocarcinoma is a rare and poorly understood malignancy. Symptoms are non-specific and prognosis is extremely poor. Herein we present a case report of a primary SV clear cell adenocarcinoma with bilateral orbital metastases at the time of initial presentation treated with multimodal therapy including radiotherapy and multi-drug chemotherapy. PMID:27175340

  15. Review of the investigation and surgical management of resectable ampullary adenocarcinoma

    PubMed Central

    Askew, James; Connor, Saxon

    2013-01-01

    Background Ampullary adenocarcinoma is considered to have a better prognosis than either pancreatic or bile duct adenocarcinoma. Pancreaticoduodenectomy is associated with significant mortality and morbidity. Some recent publications have advocated the use of endoscopic papillectomy for the treatment of early ampullary adenocarcinoma. This article reviews investigations and surgical treatment options of ampullary tumours. Methods A systematic review of English-language articles was carried out using an electronic search of the Ovid MEDLINE (from 1996 onwards), PubMed and Cochrane Database of Systematic Reviews databases to identify studies related to the investigation and management of ampullary tumours. Results Distinguishing between ampullary adenoma and adenocarcinoma is challenging given the inaccuracy of endoscopic biopsy, for which high false negative rates of 25–50% have been reported. Endoscopic ultrasound is the most accurate method for local staging of ampullary lesions, but distinguishing between T1 and T2 adenocarcinomas is difficult. Lymph node metastasis occurs early in the disease process; it is lowest for T1 tumours, but the risk is still high at 8–45%. Case reports of successful endoscopic resection and transduodenal ampullectomy of T1 adenocarcinomas have been published, but their duration of follow-up is limited. Conclusions Optimal staging should be used to distinguish between ampullary adenoma and adenocarcinoma. Pancreaticoduodenectomy remains the treatment of choice for all ampullary adenocarcinomas. PMID:23458317

  16. Frequent mutations of KRAS in addition to BRAF in colorectal serrated adenocarcinoma

    PubMed Central

    Stefanius, Karoliina; Ylitalo, Laura; Tuomisto, Anne; Kuivila, Rami; Kantola, Tiina; Sirniö, Päivi; Karttunen, Tuomo J; Mäkinen, Markus J

    2011-01-01

    Aims To define the occurrence of KRAS and BRAF mutations, microsatellite instability (MSI), and MGMT and hMLH1 methylation and expression in colorectal serrated adenocarcinoma. Methods and results KRAS codon 12/13 and 59/61 and BRAF V600E mutations, MSI, and MGMT and hMLH1 methylation and expression in 42 serrated adenocarcinomas and 17 serrated adenomas were compared with those in 59 non-serrated colorectal carcinomas (CRCs) and nine adenomas. KRAS and BRAF mutations were observed in 45% and 33% of serrated adenocarcinomas and in 27% and 0% of non-serrated CRCs (P < 0.001). The KRAS c12G→A transition was the predominant type of mutation in serrated adenocarcinomas. Forty-two per cent of BRAF-mutated serrated adenocarcinomas showed high-level MSI (MSI-H) (P = 0.075), 100% showed hMLH1 methylation (P = 0.001) and 90.9% showed MGMT methylation (P = 0.019). Fifty-six per cent of serrated adenocarcinomas with microsatellite stability/low-level microsatellite instability harboured KRAS mutations. In non-serrated cancers, KRAS mutations were not associated with MSI status. Conclusions A high combined mutation rate (79–82%) of KRAS and BRAF in serrated adenomas and adenocarcinomas indicates that mitogen-activated protein kinase activation is a crucial part of the serrated pathway. BRAF mutations are specific for serrated adenocarcinoma and identify a subset of serrated adenocarcinomas with gene methylation and a tendency for MSI-H. A high frequency of KRAS mutations in serrated adenocarcinomas suggests that a significant proportion of KRAS-mutated CRCs originate from serrated precursors, thus challenging the traditional model of Vogelstein. PMID:21457162

  17. Introducing crucial protein panel of gastric adenocarcinoma disease

    PubMed Central

    Rezaei-Tavirani, Mostafa; Rezaei-Tavirani, Majid; Mansouri, Vahid; Mahdavi, Seyed Mohammad; Valizadeh, Reza; Rostami-Nejad, Mohammad; Zali, Mohammad Reza

    2017-01-01

    Aim: Since interactome analysis of diseases can provide candidate biomarker panel related to the diseases, in this research, protein-protein interaction (PPI) network analysis is used to introduce the involved crucial proteins in Gastric adenocarcinoma (GA). Background: Gastric adenocarcinoma (GA) is the most common type of stomach cancer. There is no efficient diagnostic molecular method for GA. Method: Applying Cytoscape software 3.4.0 and String Database, the PPI network was constructed for 200 genes. Based on centrality parameters, the critical nodes were screened. Gene ontology of the key proteins for pathway analysis and molecular function processing were done and the highlighted pathways and activities were discussed. Results: Among 200 initial genes, 141 genes were included in a main connected network. Seven crucial proteins, including tumor protein p53, epidermal growth factor receptor, albumin, v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian), v-akt murine thymoma viral oncogene homolog 1, v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) and catenin (cadherin-associated protein), beta 1, 88kDa, and Myogenic differentiation 1, were introduced as key nodes of the network. These identified proteins are mostly involved in pathways and activities related to cancer. Conclusion: In conclusion, the finding is corresponding to the significant roles of these introduced proteins in GA disease. This protein panel may be a useful probe in the management of GA. PMID:28331560

  18. Her2+ and b-HCG Producing Undifferentiated Gastric Adenocarcinoma.

    PubMed

    Eivaz-Mohammadi, Sahar; Gonzalez-Ibarra, Fernando; Abdul, Waheed; Tarar, Omer; Malik, Khurram; Syed, Amer K

    2014-01-01

    A 25-year-old Hispanic female with a history of anemia, schizoaffective disorder, and psychosis was admitted for anemia associated with fatigue, weakness, shortness of breath, night sweats, weight loss, and abdominal and lower back pain for the past two months. On routine management, she was found to have a positive serum b-HCG of 80.4 (0-5 mIU/mL) but the patient denied any sexual activity in her life. During her admission, U/S of the pelvis was noncontributory. CT angiogram of the chest was significant for prominent mediastinal and hilar lymph nodes, diffusely thickened stomach suggesting gastric malignancy with multiple hypoenhancing lesions in the liver and diffuse lytic lesions in the spine and sacrum suspicious for metastatic disease. The MRI of the abdomen confirmed the CT angiogram findings. After these findings, EGD was performed which showed lesions in the antrum, body of the stomach, fundus, and cardia on the lesser curvature of the stomach body correlating with carcinoma. The biopsy was positive for Her2, b-HCG producing poorly differentiated gastric adenocarcinoma. Patient underwent one successful round of chemotherapy with Taxotene, Cisplatin, and 5-FU for Stage IV gastric adenocarcinoma.

  19. Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma.

    PubMed

    Rodić, Nemanja; Steranka, Jared P; Makohon-Moore, Alvin; Moyer, Allison; Shen, Peilin; Sharma, Reema; Kohutek, Zachary A; Huang, Cheng Ran; Ahn, Daniel; Mita, Paolo; Taylor, Martin S; Barker, Norman J; Hruban, Ralph H; Iacobuzio-Donahue, Christine A; Boeke, Jef D; Burns, Kathleen H

    2015-09-01

    Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed after the disease has metastasized; it is among the most lethal forms of cancer. We recently described aberrant expression of an open reading frame 1 protein, ORF1p, encoded by long interspersed element-1 (LINE-1; L1) retrotransposon, in PDAC. To test whether LINE-1 expression leads to somatic insertions of this mobile DNA, we used a targeted method to sequence LINE-1 insertion sites in matched PDAC and normal samples. We found evidence of 465 somatic LINE-1 insertions in 20 PDAC genomes, which were absent from corresponding normal samples. In cases in which matched normal tissue, primary PDAC and metastatic disease sites were available, insertions were found in primary and metastatic tissues in differing proportions. Two adenocarcinomas secondarily involving the pancreas, but originating in the stomach and duodenum, acquired insertions with a similar discordance between primary and metastatic sites. Together, our findings show that LINE-1 contributes to the genetic evolution of PDAC and suggest that somatic insertions are acquired discontinuously in gastrointestinal neoplasms.

  20. Polymorphous low grade adenocarcinoma: review and case report.

    PubMed

    Pintor, María Fernanda; Figueroa, Liberto; Martínez, Benjamín

    2007-12-01

    Polymorphous Low-Grade Adenocarcinoma is a rare, malignant salivary gland tumor, which is found almost exclusively in minor salivary glands. It is more frequent in the age range from 30 to 70, with a clear female predilection in a 2:1 ratio. It is usually located in the hard or soft palate, although it may be found in the rest of the oral cavity too. It is rare in major salivary glands. In general it has good prognosis, with recurrence rates in the range of 17% - 24%. Although rare, metastasis to regional lymph nodes may occur in 9% of the cases. This report describes the case of a patient that consulted at the Military Odontological Center (Central Odontológica del Ejército) due to an esthetic alteration of her dental prosthesis, which had been made 8 years before. The patient was sent to the Maxillofacial Surgery Service, where the intraoral examination showed a big mass compromising the hard palate and the alveolar ridge. During examination, a dent in her prosthesis was found to correspond to the tumor mass; it was therefore concluded that the tumor had at least an eight-year-old evolution. An incisional biopsy was carried out, and once the polymorphous low-grade adenocarcinoma diagnosis had been stated, the patient was sent to the Head and Neck Surgery Service of the Military Hospital, where the lesion was treated by wide surgical excision followed by radiation therapy.

  1. Endoscopic therapy in early adenocarcinomas (Barrett's cancer) of the esophagus.

    PubMed

    Knabe, Mate; May, Andrea; Ell, Christian

    2015-07-01

    The incidence of early esophageal adenocarcinoma has been increasing significantly in recent decades. Prognosis depends greatly on the choice of treatment. Early cancers can be treated by endoscopic resection, whereas advanced carcinomas have to be sent for surgery. Esophageal resection is associated with high perioperative mortality (1-5%) even in specialized centers. Early diagnosis enables curative endoscopic treatment option. Patients with gastrointestinal symptoms and a familial risk for esophageal cancer should undergo upper gastrointestinal endoscopy. High-definition endoscopes have been developed with technical add-on that helps endoscopists to find fine irregularities in the esophageal mucosa, but interpreting the findings remains challenging. In this review we discussed novel and old diagnostic procedures and their values, as well as our own recommendations and those of the authors discussed for the diagnosis and treatment of early Barrett's carcinoma. Endoscopic resection is the therapy of choice in early esophageal adenocarcinoma. It is mandatory to perform a subsequent ablation of all residual Barrett's mucosa to avoid metachronous lesions.

  2. Ocular manifestations of a metastatic adenocarcinoma in a horse.

    PubMed

    Matheis, Franziska L; Birkmann, Katharina; Ruetten, Maja; Pot, Simon A; Spiess, Bernhard M

    2013-05-01

    A 10-year-old German Warmblood gelding was referred to the Equine Department of the Vetsuisse Faculty, University of Zurich, Switzerland, for an iris mass OD, lethargy, intermittent fever, and coughing. Ophthalmic examination revealed a 7 × 9 mm raised, fleshy, whitish to pinkish, vascularized iris mass at the 2 o`clock position OD. Fundic examination showed multifocal round, brown to black, slightly raised lesions with indistinct margins and a surrounding hyperreflective zone OU. Physical examination revealed a temperature of 39.2 °C, sinus tachycardia, preputial and ventral edema, and an enlarged right mandibular lymph node. Results of a complete blood count and plasma biochemical profile showed mild anemia, leukocytosis, and thrombocytopenia. Severe splenopathy, moderate splenomegaly, and severe pulmonary pathology with nodules and large areas of consolidated lung parenchyma were observed on abdominal ultrasound and thoracic radiographs, respectively. Fine needle aspirates of the enlarged mandibular lymph node showed malignant epithelial neoplastic cells. The horse was euthanized because of the poor prognosis and subsequently underwent postmortem examination. Macroscopic necropsy and histopathology revealed an adenocarcinoma of suspected pulmonary origin with involvement of eyes, heart, liver, kidneys, spleen, diaphragm, skeletal muscles, mandibular, pulmonary, and internal iliac lymph nodes. Metastatic adenocarcinoma should be considered as a differential diagnosis in horses with iris masses, multifocal chorioretinal infiltrates, and clinical signs that conform to a paraneoplastic syndrome.

  3. Decreased Dp71 expression is associated with gastric adenocarcinoma prognosis

    PubMed Central

    Tan, Sipin; Tan, Jin; Tan, Sichuang; Zhao, Shuai; Cao, Xiaoxia; Chen, Zhikang; Weng, Qiaocheng; Zhang, Huali; Wang, Kang kai; Zhou, Jiang; Xiao, Xianzhong

    2016-01-01

    For the first time, dramatically decreased Dp71 protein and mRNA was found in 34 pairs of resected primary gastric adenocarcinoma. Immunohistochemistry identified Dp71 expression suppressed in 72.2% of 104 gastric cancer patients. The decreased Dp71 expression was significantly correlated with cancer differentiation (P=0.001) and lymph vascular invasion (p=0.041). Decreased Dp71 expression was associated with a poor gastric adenocarcinoma prognosis (P=0.001). Significantly less Dp71 mRNA and protein were found in BGC823, SGC7901, AGS compared with GES-1. Via increasing lamin B1 mRNA and protein, enforced Dp71d and Dp71f expression resulted in SGC7901 proliferation inhibition. Co-IP proved interaction of Dp71 with lamin B1 in GES-1 cells. Further expression characterization showed reduced lamin B1 in gastric cancer tissue and cancer cells. Increasing lamin B1 expression results in the growth inhibition of SGC7901, which suggests that Dp71-lamin B1 protein complex plays an important role for the newly identified tumor suppressive function of Dp71. PMID:27449096

  4. Isolation, cultivation and identification of human lung adenocarcinoma stem cells

    PubMed Central

    ZHANG, DE-GENG; JIANG, AI-GUI; LU, HUI-YU; ZHANG, LI-XIN; GAO, XIAO-YAN

    2015-01-01

    Recently, an increasing number of studies have demonstrated that lung cancer is a stem cell disease. However, ideal cell surface markers for isolating stem cells in lung cancer are yet to be identified. In the present study, a cell population with a cluster of differentiation (CD)133+ phenotype was successfully isolated from a single cell suspension of lung adenocarcinoma tissue using magnetic-activated cell sorting (MACS) and enriched in a serum-free culture. In comparison to CD133− cells, the CD133+ cells exhibited an enhanced capacity for self-renewal and differentiation, and a greater potential for in vivo tumor formation, in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. Tumors could be induced in NOD/SCID mice by the transplantation of 102 stem-like cells per mouse. The results of the present study demonstrated that CD133 may serve as a specific cell surface marker for lung adenocarcinoma stem cells, and that MACS combined with serum-free culture is an effective method for isolating and enriching lung cancer stem cells. PMID:25435932

  5. Adenocarcinoma of the ileum: A rare and challenging entity

    PubMed Central

    Nabais, Celso; Salústio, Raquel; Sousa, Francisco V.; Porto, Eusébio; Cardoso, Carlos; Fradique, Caldeira

    2015-01-01

    Introduction Primary small bowel malignancy is unusual and accounts for 1–3% of all gastrointestinal tract neoplasms. Adenocarcinoma is one of the most common histologic types, but its frequency decreases with more distal locations. Its clinical presentation is nonspecific and is usually associated with advanced disease, which contributes to delayed diagnosis. Presentation of case A 66-year-old woman was admitted to the hospital with a 6-day history of progressively worsening abdominal pain localized in the right lower quadrant, nausea, and vomiting. Investigation revealed an inflammatory appendiceal tumor. The patient underwent surgery and an unexpected tumor involving the distal ileal segment and ileocecal appendix was found. Right radical hemicolectomy with en bloc resection of the distal ileum was performed. Histopathological examination revealed adenocarcinoma of the ileum. Discussion This rare entity is associated with a nonspecific clinical presentation that contributes to delayed diagnosis and treatment, and consequently to a worse prognosis. Approximately half of the cases are only diagnosed at surgery. Primary treatment consists of wide resection with locoregional lymphadenectomy. The role of adjuvant chemotherapy has yet to be determined. Conclusion This case demonstrates an unusual condition characterized by late and challenging diagnosis. We highlight the importance of an earlier diagnosis and optimal treatment for improved patient outcomes. PMID:25973190

  6. Distant metastasis of rectal adenocarcinoma in a temporary tracheostoma

    PubMed Central

    Sifrer, Robert; Strojan, Primoz; Zidar, Nina; Zargi, Miha; Groselj, Ales; Krajinovic, Milena

    2014-01-01

    Background The temporary tracheostoma’s metastases of head and neck cancer had already been reported in the literature. So far, they had been considered as regional dissemination of the malignant disease. We report a case of temporary tracheostoma’s metastasis of carcinoma from non-head-and-neck primary site, what has not been reported in the literature, yet. Therefore, it is the first reported case of the systemic dissemination of malignant tumour into temporary tracheostoma. Case report. Fifty-four-year-old female patient, previously treated for a rectal adenocarcinoma, reported in our office with exophytic pink tissue masses around the temporary tracheostoma. The biopsy and immunohistochemistry findings were consistent with temporary tracheostoma’s metastasis of the rectal adenocarcinoma. The patient received palliative radiotherapy and died of systemic progression of the disease. Conclusions The patients with history of primary cancer of any origin and exophytic proliferating changes around the tracheostoma require an appropriate diagnostic work-up including a biopsy. The type of treatment depends on the extent of the disease, previous therapy and general condition of the patient. PMID:25435853

  7. Epidemiology of Barrett’s Esophagus and Esophageal Adenocarcinoma

    PubMed Central

    Runge, Thomas M.; Abrams, Julian A.; Shaheen, Nicholas J.

    2015-01-01

    Barrett’s esophagus (BE) is a common condition, and is the precursor to esophageal adenocarcinoma, a disease with increasing burden in the western world, especially in Caucasian males. The incidence of BE increased dramatically during the late-20th century and incidence estimates continue to increase, with a prominent male:female ratio. The prevalence is between 0.5 – 2.0 percent. A number of anthropomorphic and behavioral risk factors exist for BE including obesity and tobacco smoking, but GERD is the strongest risk factor, and the risk is more pronounced with long-standing GERD. Esophageal adenocarcinoma (EAC) is the most common form of esophageal cancer in the U.S. Risk factors include GERD, tobacco smoking, and obesity, while NSAIDs and statins may be protective. A major factor predicting progression from non-dysplastic BE to EAC is the presence of dysplastic changes seen on esophageal histology, although a number of issues limit the utility of dysplasia as a marker for disease. Length of the involved BE segment is another risk for progression to high-grade dysplasia and cancer. Biomarkers have shown promise, but none are approved for clinical use. PMID:26021191

  8. Raman Spectroscopy Study of Prostatic Adenocarcinoma Bulk Tissues

    NASA Astrophysics Data System (ADS)

    Devpura, S.; Dai, H.; Thakur, J. S.; Naik, R.; Cao, A.; Pandya, A.; Auner, G. W.; Sarkar, F.; Sakr, W.; Naik, V.

    2009-03-01

    Prostate cancer is one of the most common types of cancer among men. The mortality rate for this disease can be dramatically reduced if it can be diagnosed in its early stages. Raman spectroscopy is one of the optical techniques which can provide fingerprints of a disease in terms of its molecular composition which changes due to the onset of disease. The aim of this project is to investigate the differences in the Raman spectra to identify benign epithelium (BE), prostatic intraepithelial neoplasia (PIN) and adenocarcinoma of various Gleason grades in archived bulk tissues embedded in paraffin wax. For each tissue, two adjacent tissue sections were cut and dewaxed, where one of the sections was stained using haematoxylin and eosin for histological examination and the other unstained adjacent section was used for Raman spectroscopic studies. We have collected Raman spectra from 10 prostatic adenocarcinoma dewaxed tissue sections using Raman microscope (785 nm excitation laser). The data were analyzed using statistical methods of principal component analysis and discriminant function analysis to classify the tissue regions. The results indicate that Raman Spectroscopy can differentiate between BE, PIN and Cancer regions.

  9. Genomic similarity between gastroesophageal junction and esophageal Barrett's adenocarcinomas

    PubMed Central

    Kuick, Rork; Thomas, Dafydd G.; Nadal, Ernest; Lin, Jules; Chang, Andrew C.; Reddy, Rishindra M.; Orringer, Mark B.; Taylor, Jeremy M. G.; Wang, Thomas D.; Beer, David G.

    2016-01-01

    The current high mortality rate of esophageal adenocarcinoma (EAC) reflects frequent presentation at an advanced stage. Recent efforts utilizing fluorescent peptides have identified overexpressed cell surface targets for endoscopic detection of early stage Barrett's-derived EAC. Unfortunately, 30% of EAC patients present with gastroesophageal junction adenocarcinomas (GEJAC) and lack premalignant Barrett's metaplasia, limiting this early detection strategy. We compared mRNA profiles from 52 EACs (tubular EAC; tEAC) collected above the gastroesophageal junction with 70 GEJACs, 8 normal esophageal and 5 normal gastric mucosa samples. We also analyzed our previously published whole-exome sequencing data in a large cohort of these tumors. Principal component analysis, hierarchical clustering and survival-based analyses demonstrated that GEJAC and tEAC were highly similar, with only modest differences in expression and mutation profiles. The combined expression cohort allowed identification of 49 genes coding cell surface targets overexpressed in both GEJAC and tEAC. We confirmed that three of these candidates (CDH11, ICAM1 and CLDN3) were overexpressed in tumors when compared to normal esophagus, normal gastric and non-dysplastic Barrett's, and localized to the surface of tumor cells. Molecular profiling of tEAC and GEJAC tumors indicated extensive similarity and related molecular processes. Identified genes that encode cell surface proteins overexpressed in both Barrett's-derived EAC and those that arise without Barrett's metaplasia will allow simultaneous detection strategies. PMID:27363029

  10. Urinary microRNA-30a-5p is a potential biomarker for ovarian serous adenocarcinoma.

    PubMed

    Zhou, Jun; Gong, Guanghui; Tan, Hong; Dai, Furong; Zhu, Xin; Chen, Yile; Wang, Junpu; Liu, Ying; Chen, Puxiang; Wu, Xiaoying; Wen, Jifang

    2015-06-01

    MicroRNAs (miRNAs) can serve as biomarkers in human cancer. To determine the clinical value of urinary miRNAs for ovarian serous adenocarcinoma, we collected urine samples from 39 ovarian serous adenocarcinoma patients, 26 patients with benign gynecological disease and 30 healthy controls. The miRNA microarray data showed that only miR-30a-5p was upregulated and 37 miRNAs were downregulated in the urine samples of ovarian serous adenocarcinoma patients, when compared to healthy controls, which was confirmed after conducting quantitative PCR. The upregulation of urinary miR-30a-5p was closely associated with early stage of ovarian serous adenocarcinoma as well as lymphatic metastasis. Receiver operator characteristic (ROC) analysis demonstrated the potential use of urinary miR-30a-5p as a diagnostic marker for ovarian serous adenocarcinoma. Furthermore, a lower urine level of miR-30a-5p was found in 20 gastric cancer and 20 colon carcinoma patients when compared to ovarian serous adenocarcinoma, suggesting that the upregulation of urinary miR-30a-5p may be specific for ovarian serous adenocarcinoma. miR-30a-5p was also upregulated in ovarian serous adenocarcinoma tissues and cell lines, while urinary miR-30a-5p from ovarian cancer patients was notably reduced following the surgical removal of ovarian serous adenocarcinoma, suggesting that urinary miR-30a-5p was derived from the ovarian serous adenocarcinoma tissue. Notably, miR-30a-5p was concentrated with exosomes from the ovarian cancer cell supernatant or urine from ovarian serous adenocarcinoma patients, supporting a pathway for excretion into the urine. The results also showed that the knockdown of miR-30a-5p significantly inhibited the proliferation and migration of ovarian cancer cells. In summary, to the best of our knowledge, the present study provided the first evidence of increased miR-30a-5p in the urine of ovarian serous adeno-carcinoma patients, while the inhibition of miR-30a-5p suppressed the

  11. P16-positive continuous minimal deviation adenocarcinoma and gastric type adenocarcinoma in a patient with Peutz-Jeghers syndrome.

    PubMed

    Peng, Wei-Xia; Kure, Shoko; Ishino, Kousuke; Kurose, Keisuke; Yoneyama, Koichi; Wada, Ryuichi; Naito, Zenya

    2015-01-01

    We report a case of Peutz-Jeghers syndrome (PJS) in a 33-year-old female patient with synchronous uterine cervical minimal deviation adenocarcinoma (MDA) and gastric type adenocarcinoma (GTA). The patient was diagnosed with PJS at the age of 10. At the time of consultation, she complained of watery discharge. Magnetic resonance imaging of the pelvis showed a poorly circumscribed mass in the uterine cervix. Histologically, both MDA and GTA components, as well as their transitional area, were observed. Both components were diffusely positive for MUC6, CK7 and, robustly, for p16. Moreover, the components were negative for ER, PgR and CEA, while HIK1083 and CK20 positive cells were found focally. Ki-67 labeling index in the MDA component was 5% while that in the GTA component was 50%. This case of GTA accompanied by MDA in a patient with PJS is distinct from the single previously-reported comparable case of which we are aware, with respect to the overexpression of p16 protein, an event considered rare in these tumors, and the continuity between the MDA and GTA components. This continuity favors the hypothesis that GTA arises from the dedifferentiation of MDA.

  12. Canine pulmonary adenocarcinoma tyrosine kinase receptor expression and phosphorylation

    PubMed Central

    2014-01-01

    Background This study evaluated tyrosine kinase receptor (TKR) expression and activation in canine pulmonary adenocarcinoma (cpAC) biospecimens. As histological similarities exist between human and cpAC, we hypothesized that cpACs will have increased TKR mRNA and protein expression as well as TKR phosphorylation. The molecular profile of cpAC has not been well characterized making the selection of therapeutic targets that would potentially have relevant biological activity impossible. Therefore, the objectives of this study were to define TKR expression and their phosphorylation state in cpAC as well as to evaluate the tumors for the presence of potential epidermal growth factor receptor (EGFR) tyrosine kinase activating mutations in exons 18–21. Immunohistochemistry (IHC) for TKR expression was performed using a tissue microarray (TMA) constructed from twelve canine tumors and companion normal lung samples. Staining intensities of the IHC were quantified by a veterinary pathologist as well as by two different digitalized algorithm image analyses software programs. An antibody array was used to evaluate TKR phosphorylation of the tumor relative to the TKR phosphorylation of normal tissues with the resulting spot intensities quantified using array analysis software. Each EGFR exon PCR product from all of the tumors and non-affected lung tissues were sequenced using sequencing chemistry and the sequencing reactions were run on automated sequencer. Sequence alignments were made to the National Center for Biotechnology Information canine EGFR reference sequence. Results The pro-angiogenic growth factor receptor, PDGFRα, had increased cpAC tumor mRNA, protein expression and phosphorylation when compared to the normal lung tissue biospecimens. Similar to human pulmonary adenocarcinoma, significant increases in cpAC tumor mRNA expression and receptor phosphorylation of the anaplastic lymphoma kinase (ALK) tyrosine receptor were present when compared to the

  13. A retrospective study of ampullary adenocarcinomas: overall survival and responsiveness to fluoropyrimidine-based chemotherapy†

    PubMed Central

    Jiang, Z.-Q.; Varadhachary, G.; Wang, X.; Kopetz, S.; Lee, J. E.; Wang, H.; Shroff, R.; Katz, M.; Wolff, R. A.; Fleming, J.; Overman, M. J.

    2013-01-01

    Background Whether carcinomas of the ampulla of Vater should be classified with biliary tract tumors and treated in a similar manner remains unknown. We sought to compare the outcomes of similarly staged periampullary adenocarcinomas (AAs) and analyze the chemotherapy responsiveness of AAs. Patients and methods A total of 905 patients with resected periampullary adenocarcinomas were identified from a prospective surgical registry from 1988 to 2010. A second cohort of 64 metastatic AA patients from 1992 to 2009 who received either front-line fluoropyrimidine-based or gemcitabine-based chemotherapy was also identified. Results Overall survival (OS) for AAs was similar to survival with duodenal adenocarcinomas, but was significantly different from both extrahepatic biliary and pancreatic adenocarcinomas (P < 0.001 for each comparison). In multivariate analysis, AAs had a significantly improved OS in comparison with extrahepatic biliary adenocarcinomas (HR = 1.97, P = 0.006). Fluoropyrimidine-based as opposed to gemcitabine-based chemotherapy for metastatic AAs resulted in a significant improvement in time to progression (P = 0.001) but only a trend toward benefit for OS (P = 0.07) in multivariate analysis. Conclusions Differences in the natural history of ampullary and extrahepatic biliary adenocarcinomas exist. Analyses of metastatic ampullary adenocarcinomas suggest that fluoropyrimidine-based chemotherapy may represent a more appropriate front-line chemotherapy approach. PMID:23704197

  14. Adenocarcinoma arising from an anal gland—Report of a case

    PubMed Central

    Sakamoto, Takashi; Konishi, Fumio; Yoshida, Takayoshi; Yoshinaga, Yasuo; Izumo, Toshiyuki; Lefor, Alan

    2014-01-01

    INTRODUCTION Adenocarcinoma arising from an anal gland is extremely rare. Most anal canal cancers are squamous cell carcinoma, and adenocarcinoma is infrequently diagnosed. Diagnostic criteria and the standard treatment for adenocarcinoma of the anal canal have not been clearly defined, in part because of the rarity of this lesion. PRESENTATION OF CASE An 84-year-old man who presented with a piece of tissue prolapsing from the anus. An incisional biopsy showed adenocarcinoma, and an abdomino-perineal resection was then performed. Cytokeratin 7 (CK7), cytokeratin 19 (CK19) stained positive in the specimen, suggesting that the tumor developed from an anal gland. The patient was discharged after surgery without any complications. DISCUSSION Exact diagnostic criteria for adenocarcinoma of the anal canal have not been previously described. In the present case, CK7 and CK19 were stained, and the tumor showed positivity for both of these markers, which is compatible with the staining patterns of anal gland origin cancer. Radical resection is recommended rather than local resection, because of the tumor's high recurrence rate. Some authors recommend combined modality treatment with preoperative or postoperative chemoradiotherapy because of the high rate of distant recurrence. CONCLUSION The preoperative diagnosis of adenocarcinoma arising from an anal gland is not easily established. However, it may be possible to suspect an anal glandular adenocarcinoma based on a meticulous physical examination, appropriate diagnostic studies and pathological findings on biopsy. PMID:24705191

  15. Cholecystokinin A and B receptors are differentially expressed in normal pancreas and pancreatic adenocarcinoma.

    PubMed Central

    Weinberg, D S; Ruggeri, B; Barber, M T; Biswas, S; Miknyocki, S; Waldman, S A

    1997-01-01

    Cholecystokinin (CCK) plays an important role in pancreatic carcinogenesis. While human CCK-A and -B receptors have been fully characterized, their relative roles in human pancreatic adenocarcinoma remain unclear. Thus, expression of CCK-A and -B receptors in normal human pancreas, pancreatic adenocarcinomas, and other human extrapancreatic tissues and malignancies was examined, using reverse transcription followed by the polymerase chain reaction (RT-PCR). mRNA isolated from 15 normal pancreas specimens, 22 pancreatic adenocarcinomas, and 58 extrapancreatic tissues and tumors was subjected to RT-PCR using primers specific for human CCK-A and -B receptors. Expression of CCK-B receptors was detected in all tissues arising from pancreas and in most extrapancreatic tissues and tumors. In contrast, CCK-A receptors exhibited a more selective pattern of expression in gall bladder, intestine, brain, ovary, spleen, and thymus. Of significance, CCK-A receptors were expressed selectively in all pancreatic adenocarcinomas, but not in any normal pancreas specimens. In situ hybridization, using receptor-specific riboprobes, localized CCK-A receptor expression to ductal cells, the presumed origin of most human pancreatic adenocarcinomas. Southern blot analysis revealed no evidence of CCK-A receptor gene amplification or rearrangement in pancreatic adenocarcinomas. Because of its selective expression, the CCK-A receptor may serve as selective biomarker for pancreatic adenocarcinoma. PMID:9239407

  16. Esophageal adenocarcinoma arising in cervical inlet patch with synchronous Barrett's esophagus-related dysplasia.

    PubMed

    Tanaka, Mariko; Ushiku, Tetsuo; Ikemura, Masako; Shibahara, Junji; Seto, Yasuyuki; Fukayama, Masashi

    2014-08-01

    Esophageal adenocarcinomas usually develop in Barrett's esophagus, typically through the metaplasia-dysplasia-carcinoma sequence, but adenocarcinomas can occur from heterotopic gastric mucosa in cervical esophagus (inlet patch). This report describes the first case of synchronous presentation of adenocarcinoma arising from cervical inlet patch and Barrett's esophagus-related dysplasia in a 76-year-old man. Surveillance CT detected a 3-cm polypoid mass in the cervical esophagus. Endoscopic biopsies confirmed a diagnosis of adenocarcinoma of the cervical esophagus. Barrett's esophagus was present also in the lower esophagus. Histologic examination of the surgically resected specimen revealed the polypoid mass as composed of tubular adenocarcinoma, and was associated with non-neoplastic columnar mucosa representing pre-existing inlet patch. Another isolated cervical inlet patch with intestinal metaplasia was also recognized. In the lower esophagus, high-grade dysplasia was noted within the Barrett's esophagus. Immunohistochemically, the adenocarcinoma associated with inlet patch had intestinal immunophenotype (CDX2-, CD10- and MUC2-positive), whereas the Barrett's esophagus-related high-grade dysplasia showed mixed immunophenotype (MUC5AC- and MUC6-positive, with scattered MUC2-positive goblet cells). Previous studies and our findings suggest that intestinal metaplasia might predispose to the development of adenocarcinoma in the inlet patch. Therefore, endoscopists and pathologists should be aware of rare malignant transformation of inlet patches, especially those with intestinal metaplasia.

  17. Yes associated protein is a poor prognostic factor in well-differentiated lung adenocarcinoma.

    PubMed

    Kim, Mi Hyun; Kim, Young Keum; Shin, Dong Hoon; Lee, Hyun Jeong; Shin, Nari; Kim, Arong; Lee, Jung Hee; Choi, Kyung Un; Kim, Jee Yeon; Lee, Chang Hun; Sol, Mee Young

    2015-01-01

    The Hippo pathway is a highly conserved potent regulator of cell growth and apoptosis including large tumor suppressor (LATS) and Yes-associated protein (YAP). LATS has been regarded as a tumor suppressor gene and YAP as either of a tumor suppressor gene or an oncogene. We investigated their expression in lung adenocarcinoma. YAP and LATS protein expression was assessed in 167 surgically resected lung adenocarcinomas and compared with clinicopathologic factors. Disease free survival and overall survival were also evaluated. YAP expression was noted in cytoplasm (48 cases; 28.7%), nuclear (34; 20.4%) and both locations (4; 2.4%). The nuclear expression was typically observed in well differentiated adenocarcinoma. LATS was expressed in cytoplasm when its signal is weak. Perinuclear expression of LATS was observed when it is strongly expressed. While cytoplasmic and nuclear YAP expressions were inversely related. In well differentiated adenocarcinoma patients, YAP nuclear expression was related with more frequent relapse. Both of nuclear YAP and LATS expression were more frequently observed in well differentiated adenocarcinoma. Furthermore, YAP expression exhibited more frequent relapse in well differentiated adenocarcinoma group. We suggest that YAP may act as an oncogene and predict poorer prognosis in well differentiated lung adenocarcinoma.

  18. NFAT5 promotes proliferation and migration of lung adenocarcinoma cells in part through regulating AQP5 expression

    SciTech Connect

    Guo, Kai; Jin, Faguang

    2015-09-25

    The osmoregulated transcription factor nuclear factor of activated T-cells 5(NFAT5), has been found to play important roles in the development of many kinds of human cancers, including breast cancer, colon carcinoma, renal cell carcinoma and melanoma. The aim of the present study was to determine whether NFAT5 is involved in the proliferation and migration of lung adenocarcinoma cells. We found that NFAT5 was upregulated in lung adenocarcinoma cells and knockdown of NFAT5 decreased proliferation and migration of the cells, accompanied by a significant reduction in the expression of AQP5. AQP5 was upregulated in lung adenocarcinoma cells and knockdown of AQP5 also inhibited proliferation and migration of the cells as knockdown of NFAT5 did. Moreover, overexpression of NFAT5 promoted proliferation and migration of lung adenocarcinoma cells, accompanied by a significant increase in the expression of AQP5. These results indicate that NFAT5 plays important roles in proliferation and migration of human lung adenocarcinoma cells through regulating AQP5 expression, providing a new therapeutic option for lung adenocarcinoma therapy. - Highlights: • NFAT5 expression is higher in lung adenocarcinoma cells compared with normal cells. • NFAT5 knockdown decreases proliferation and migration of lung adenocarcinoma cells. • Knockdown of NFAT5 reduces AQP5 expression in human lung adenocarcinoma cells. • Overexpression of NFAT5 promotes proliferation and migration of lung adenocarcinoma cells. • Overexpression of NFAT5 increases AQP5 expression in human lung adenocarcinoma cells.

  19. microRNA expression profiling of endometrial endometrioid adenocarcinomas and serous adenocarcinomas reveals profiles containing shared, unique and differentiating groups of microRNAs.

    PubMed

    Devor, Eric J; Hovey, Adriann M; Goodheart, Michael J; Ramachandran, Shyam; Leslie, Kimberly K

    2011-10-01

    microRNAs (miRNAs) control a multitude of pathways in human cancers. Differential expression of miRNAs among different histological types of tumors within the same type of tissue offers insight into the mechanism of pathogenesis and may help to direct treatment to improve prognosis. We assessed expression of 667 miRNAs in endometrial endometrioid and serous adenocarcinomas using RNA extracted from benign endometrium as well as from primary endometrial tumors. Quantitative miRNA profiling of endometrial adenocarcinomas revealed four overlapping groups of significantly overexpressed and underexpressed miRNAs. The first group was composed of 20 miRNAs significantly dysregulated in both adenocarcinoma types compared with benign endometrium, two groups were composed of miRNAs significantly dysregulated in either endometrioid adenocarcinomas or in serous adenocarcinomas compared with benign endometrium, and the fourth group was composed of 17 miRNAs that significantly distinguished between endometrioid adenocarcinomas and serous adenocarcinomas themselves. Validation of the expression levels of the selected miRNAs was carried out in a second panel composed of ten endometrioid and five serous tumors. Experimentally validated mRNA targets of these dysregulated miRNAs were identified using published sources, whereas TargetScan was used to predict targets of miRNAs in the first and fourth profile groups. These validated and potential miRNA target lists were filtered using published lists of genes displaying significant overexpression or underexpression in endometrial cancers compared to benign endometrium. Our results revealed a number of dysregulated miRNAs that are commonly found in endometrial (and other) cancers as well as several dysregulated miRNAs not previously identified in endometrial cancers. Understanding these differences may permit the development of both prognostic and diagnostic biomarkers.

  20. Spontaneous Rupture of Adenocarcinoma of Meckel’s Diverticulum- A Rare Entity

    PubMed Central

    2015-01-01

    Meckel’s diverticulum is a true diverticulum from remnant of vitelline duct. It is most common congenital anomaly of intestine. It is associated with intestinal atresia and anorectal anomalies. It contains heterotrophic epithelium. Most common heterotrophic mucosa is gastric followed by pancreatic tissue. Adenocarcinoma arising from Meckel’s diverticulum is very rare. Spontaneous perforation of adenocarcinoma rarely reported. Most of perforation reported in Meckel’s diverticulum diagnosed during intraoperative period. This is a case report of spontaneous rupture of adenocarcinoma of Meckel’s diverticulum, which was managed with primary resection and ileostomy. PMID:26672729

  1. A case of signet ring cell adenocarcinoma of the bladder with spontaneous urinary extravasation

    PubMed Central

    Shringarpure, Sanish S.; Thachil, Joseph V.; Raja, T. `; Mani, Rama

    2011-01-01

    Primary signet ring cell adenocarcinoma (PSRCC) of the bladder is a relatively rare variant of adenocarcinoma of the bladder with poor prognosis. Also PSRCC of the bladder presenting with spontaneous urinary extravasation is very rare. We present the case of a 48-year male who presented with spontaneous urinary extravasation and was diagnosed to have PSRCC of the urinary bladder on evaluation. He was treated with radical cystectomy and adjuvant chemotherapy. This report emphasizes the need to rule out other primary sites of adenocarcinoma in the body, which may metastasize to the urinary bladder. PMID:22022068

  2. Subglottic Metastatic Rectal Adenocarcinoma: A Specialist Multidisciplinary Airway Team Approach for Optimized Voice and Airway Outcome

    PubMed Central

    Balakumar, Ramkishan; Ramdoo, Krishan; Tatla, Taran

    2017-01-01

    A 56-year-old female with a background of metastatic rectal adenocarcinoma presented with a subglottic mass causing biphasic stridor. Transoral laser microsurgery and the use of fibrin glue prevented the need for tracheostomy. Six months postoperatively there was no evidence of recurrence. Laryngeal metastasis of colorectal adenocarcinoma, although remarkably rare, is perhaps more prevalent than commonly perceived and the presence of laryngeal symptoms in a patient with colorectal adenocarcinoma should raise concern. This case is presented to aid physicians should they encounter a similar presentation of metastasis to the subglottis. PMID:28154767

  3. Metastasis of lung adenocarcinoma to the mandible: Report of a case

    PubMed Central

    Misir, Ahmet Ferhat; Mercan, Uğur; Günhan, Ömer

    2013-01-01

    Adenocarcinoma of the lung that metastasizes to the mandible is uncommon. There are only a few cases described in the English-language literature regarding metastasis to mandible from adenocarcinoma of the lung. This article shows a metastasis from adenocarcinoma of the lung affecting the mandible of a 55-year-old male patient where the metastatic lesion was detected before primary tumor. This article emphasizes the importance of detailed dentoalveolar examination and early diagnosis for finding the primary focus of metastatic lesions. PMID:24250088

  4. Primary mucinous adenocarcinoma of the larynx in female patient: a rare entity.

    PubMed

    Ebru, Tastekin; Omer, Yalcin; Fulya, Oz Puyan; Ufuk, Usta; Kemal, Kutlu

    2012-10-01

    Laryngeal malignant tumors are mainly composed of squamous cell carcinomas. Glandular carcinomas of the larynx are rare tumors that constitute less than 1% of all laryngeal malignancies where "adenocarcinoma not otherwise specified" is the most common histologic subtype. Here we report a case of a 70-year-old female patient with primary laryngeal mucinous adenocarcinoma. The rarity of the tumor type and the differential diagnosis of this tumor before reporting it as a primary adenocarcinoma of the larynx are discussed here with literature findings.

  5. Radiotherapy in the adjuvant management of pancreatic adenocarcinoma: is it helpful?

    PubMed

    Abrams, Ross A

    2012-04-01

    Curative-intent management for pancreatic adenocarcinoma requires gross total resection. Only 15-20% of patients are eligible for resection and of these only approximately 20% are long-term survivors. Adjuvant and neoadjuvant approaches have been, and are being, sought to improve upon surgical results. Radiotherapy has a role in the adjuvant management of many gastrointestinal malignancies and historically has also had a role in the adjuvant management of pancreatic adenocarcinoma. However, the role of radiotherapy in the management of pancreatic adenocarcinoma has been called into question. This review examines this controversy and the underlying issues and considers current efforts towards resolving them, as well as some likely future developments.

  6. Synchronous primary oesophageal malignant melanoma and sigmoid adenocarcinoma

    PubMed Central

    Malik, Ahsan; Bansil, Sandeep; Junglee, Naushad; Sutton, Jonathon; Gasem, Jaber; Ahmed, Waqar

    2011-01-01

    The authors present a case of a gentleman in his 70s who was referred to the gastroenterology outpatient clinic with dysphagia. An oesophagogastroduodenoscopy was performed which showed a polypoidal black coloured mass in the oesophagus. Endoscopic biopsies confirmed malignant melanoma. Further staging investigations were organised to assess suitability for surgery which revealed a mass in the sigmoid colon. Subsequent colonoscopy and biopsy confirmed adenocarcinoma. As this was an unusual case to associate these two malignancies at the same time, there was no ideal or recognised management plan available. Different treatment options were considered and a consensus was developed regarding best surgical approach but due to the lapse in time a repeat staging CT scan was organised which unfortunately now demonstrated lymph node metastasis. Patient was managed conservatively from this point onwards and he died 12 months later. PMID:22689833

  7. Does St. John's Wort cause regression in gastrointestinal system adenocarcinomas?

    PubMed

    Karaarslan, Serap; Cokmert, Suna; Cokmez, Atilla

    2015-11-15

    St. John's Wort (SJW) is an old herb which has long been consumed widely for its anti-inflammatory, antiviral, and anti-depressive properties. Here we present a detailed clinical evaluation of three cases (two colon and one duodenal adenocarcinoma) with remarkable and intensive lymphoplasmocytic host reaction, at the basal part of tumor, intensive fibrosis, giant cells, plasma cell increase in lymph nodes and few giant cells in germinal centers in resection specimens. The observation of similar host reaction in those tumors having otherwise usual appearance was interesting. None of the cases received neoadjuvant chemoradiotherapy or additional treatment before surgery but only SJW. These cases are presented to increase the awareness about such cases. Further research is needed to reveal the possible effect of SJW, which has long been consumed for different treatment purposes, on human tumors.

  8. [Detection of T-antigen in colorectal adenocarcinoma and polyps].

    PubMed

    Xu, S; Lu, Y; Wang, Q

    1995-10-01

    Galactose oxidase method was employed to detect the beta-D-Gal (1-->3) -D-Gal NAc residue of T-antigen present in the large intestinal mucus of 156 subjects. The positive rates of the test were 84.4%, 29.1%, and 7.2% in the mucus samples obtained from 32 patients with colorectal adenocarcinomas, 55 with polyps and 69 controls respectively. Chi-square test demonstrated that there were significant differences between the group of carcinoma and control (P < 0.001) as well as between also polyp and control (P < 0.01). The test had a high sensitivity (84.4%) and specificity (92.8%) in the diagnosis of colorectal cancer and may be used as a practical mass screening test for colorectal neoplasms.

  9. Afatinib-Induced Acute Fatal Pneumonitis in Metastatic Lung Adenocarcinoma

    PubMed Central

    Yoo, Sang Hoon; Ryu, Jin Ah; Kim, Seo Ree; Oh, Su Yun; Jung, Gu Sung; Lee, Dong Jae; Kwak, Bong Gyu; Nam, Yu Hyun; Kim, Kyung Hyun

    2016-01-01

    Afatinib is an oral tyrosine kinase inhibitor (TKI) that inhibit Endothelial Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4. The common side effects of EGFR TKI are rash, acne, diarrhea, stomatitis, pruritus, nausea, and loss of appetite. Drug induced pneumonitis is the less common adverse effects of EGFR TKI. Afatinib, 2nd generation EGFR TKI is anticipated to overcome drug resistance from 1st generation EGFR TKI according to preclinical study, and several studies are being conducted to compare clinical efficacy between 1st and 2nd EGFR TKI. Several cases of rug induced acute fatal pneumonitis were reported after use of erlotinib or gefitinib. However, a case of acute fatal pneumonitis associated with afatinib was note reported except drug induced pneumonitis in other clinical study. Here, we present a cases of acute severe pneumonitis related with afatinib in metastatic lung adenocarcinoma with literature review. PMID:27900074

  10. Adenocarcinoma of the lung in Down syndrome: first clinical report.

    PubMed

    Satgé, Daniel; Salmeron, Sergio; Homsi, Toufik; Réthoré, Marie-Odile; Tredaniel, Jean

    2013-01-01

    Lung cancer is rare in persons with Down syndrome, and the clinical presentation of the disease has not been described in adults with intellectual disability. We report the first detailed clinical observation of a 33-year-old man with Down syndrome who developed an adenocarcinoma of the lung 30 years after an acute lymphoblastic leukemia in infancy. Despite advanced disease at initial presentation and extensive tumor spreading during the course of the disease, he presented with unusually mild symptoms. The scarcity of lung cancer in people with intellectual disability, and particularly those with Down syndrome, is due, in part, to reduced tobacco use. However, cytogenetic and molecular studies suggest that genes mapping to chromosome 21 may protect against lung cancer. Numerous reports also suggest that, in persons with Down syndrome and other intellectual disability, cancers are often discovered late, leading to loss of the chance of cure and recovery.

  11. Endometrial adenocarcinoma in a 13-year-old girl

    PubMed Central

    Kim, Sung Mee; Shin, So Jin; Bae, Jin Gon; Kwon, Kun Young

    2016-01-01

    Endometrial cancer is the third most common gynecologic cancer in the Korea and occurs mainly in menopausal women. Although it can develop in young premenopausal women cancer as well, an attack in the adolescent girl is very rare. A 13-year-old girl visited gynecology department with the complaint of abnormal uterine bleeding. An endometrial biopsy revealed FIGO (International Federation of Gynecology and Obstetrics) grade II endometrial adenocarcinoma. In the treatment of endometrial cancer, conservative management should be considered if the patient is nulliparous or wants the fertility preservation. Therefore, we decided to perform a hormonal therapy and a follow-up endometrial biopsy after progestin administration for eight months revealed no residual tumor. We report a case of endometrial cancer occurred in a 13-year-old girl with a brief review of the literature. PMID:27004208

  12. IMP2 expression distinguishes endometrioid from serous endometrial adenocarcinomas.

    PubMed

    Zhang, Liping; Liu, Yuxin; Hao, Suyang; Woda, Bruce A; Lu, Di

    2011-06-01

    Among various endometrial adenocarcinomas, endometrioid carcinoma can be very difficult to separate from serous carcinomas. Various biomarkers have been studied with proven value, including p53, Ki-67, and p16. In this study, we present data on another biomarker, IMP2, which we believe is sensitive and specific. Using 320 endometrial biopsy cases, we demonstrate that IMP2 is normally expressed in all proliferative and inactive endometrial glandular cells. The pattern of such expression is unchanged in serous carcinomas. IMP2 expression is, however, lost in all cases of endometrioid carcinomas by at least 25% to >95% of tumor cell populations. Therefore, loss of IMP2 expression can differentiate endometrioid from serous carcinomas. Such finding of IMP2 expression remained the same in mixed endometrioid and serous carcinomas; IMP2 expression is lost in all endometrioid components by at least 25% of tumor cell population, whereas it remained diffuse and strong in all serous components of carcinomas.

  13. Factors that may influence polymorphous low-grade adenocarcinoma growth.

    PubMed

    Soares, Andresa Borges; Martinez, Elizabeth Ferreira; Ribeiro, Patricia Fernandes Avila; Barreto, Icleia Siqueira; Aguiar, Maria Cássia; Furuse, Cristiane; Sperandio, Marcelo; Montalli, Victor Angelo; de Araújo, Ney Soares; de Araújo, Vera Cavalcanti

    2017-04-01

    There is mounting evidence on the importance of some biological processes in tumor growth, such as vascular supply, apoptosis, autophagy, and senescence. We have investigated these processes in polymorphous low-grade adenocarcinoma (PLGA), in an attempt to identify those that are relevant for this particular lesion. We analyzed 31 cases of PLGA using immunohistochemistry to antibodies against CD34 and CD105 to detect blood vessels; against D2-40 to detect lymphatic vessels; against Bax, Bcl-2, and survivin to explore cell apoptosis; and against Beclin and LCB3 to investigate autophagy and against p21 and p16 to assess senescence. Our results showed that PLGA growth does not depend on newly formed vessels but only on preexisting vasculature. Furthermore, PLGA is promoted by autophagy, sustained by both anti-apoptotic and anti-senescence signals, and stimulated by Bcl-2 and survivin.

  14. Role of Radiotherapy in Aggressive Digital Papillary Adenocarcinoma.

    PubMed

    Feldmeyer, Laurence; Prieto, Victor G; Ivan, Doina; Nagarajan, Priyadharsini; Tetzlaff, Michael T; Curry, Jonathan L; Bell, Diana; Moon, Bryan S; Torres-Cabala, Carlos A; Aung, Phyu P

    2016-01-01

    Aggressive digital papillary adenocarcinoma (ADPA) is a rare and often misdiagnosed malignant tumor of the sweat glands, most commonly encountered on the extremities. Due to the relatively high metastatic potential of the tumor, aggressive surgical treatment, including amputation, is generally recommended. We present a case of a 36-year-old male with an over 10-year history of a skin lesion on the right hand in the web space between the index and the middle finger. Histologically, the lesion revealed a malignant epithelioid neoplasm with features consistent with ADPA. The lesion was treated with 5-weeks preoperative radiation (total 5000 cGy) followed by surgical resection. There was no evidence of residual disease confirmed by pathological study of re-excision specimen as well as imaging studies. This is, to the best of knowledge, the first report of complete regression of an ADPA after radiotherapy.

  15. Pancreatic Ductal Adenocarcinoma: A Review of Immunologic Aspects

    PubMed Central

    Wachsmann, Megan B.; Pop, Laurentiu M.; Vitetta, Ellen S.

    2012-01-01

    With the continued failures of both early diagnosis and treatment options for pancreatic cancer, it is now time to comprehensively evaluate the role of the immune system on the development and progression of pancreatic cancer. It is important to develop strategies that harness the molecules and cells of the immune system to treat pancreatic cancer. This review will focus primarily on the role of immune cells in the development and progression of pancreatic ductal adenocarcinoma (PDAC). We will evaluate what is known about the interaction of immune cells with the tumor microenvironment and their role in tumor growth and metastasis. We will conclude with a brief discussion of therapy for pancreatic cancer and the potential role for immunotherapy. We hypothesize that the role of the immune system in tumor development and progression is tissue specific. Our hope is that better understanding of this process will lead to better treatments for this devastating disease. PMID:22406516

  16. [Perineal cutaneous metastases from adenocarcinoma after surgery for colorectal cancer].

    PubMed

    Placer, Carlos; Elósegui, José Luis; Irureta, Idoia; Mujika, José Andrés; Goena, Ignacio; Enríquez Navascués, José M

    2007-07-01

    The development of cutaneous metastases in the context of colorectal cancer is exceptional, especially in the absence of visceral lesions. We present the case of a 50-year-old woman who underwent surgery for a T3N0M0 tumor in the sigmoid colon, with resection of ovarian metastases at 12 months. Reoperation was performed 14 months later for local anastomotic recurrence. Four months after surgery, a nodular ulcerated lesion was observed in the perineum due to metastases from adenocarcinoma. Aggressive local surgery was performed and the patient has presented no recurrences after a 5-year follow-up. We discuss the need for correct management of the rectal or anal stump (through the use of iodine povidone wash solution) during instrumental anastomoses.

  17. DDX59 promotes DNA replication in lung adenocarcinoma

    PubMed Central

    You, Jin; Wang, Xingshun; Wang, Jiuling; Yuan, Baolei; Zhang, Yandong

    2017-01-01

    DEAD box proteins are multifunctional proteins involved in every aspect in RNA metabolism and have essential roles in many cellular activities. Despite their importance, many DEAD box proteins remain uncharacterized. In this report, we found DDX59 overexpressed in lung adenocarcinoma. DDX59 knockdown reduced cell proliferation, anchorage-independent cell growth, and caused reduction of tumor formation in immunocompromised mice. In multiple lung cancer cells, we found that DDX59 knockdown inhibits DNA synthesis; wild-type DDX59 but not helicase-defective mutant of DDX59 enhances DNA synthesis. DDX59 knockdown caused reduction of MCM protein levels, decreased the loading of MCM ring protein onto chromatin, and therefore inhibited DNA replication. Our study reveals for the first time that DDX59 has an important role in lung cancer development through promoting DNA replication. PMID:28090355

  18. Targeting mTOR in Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Iriana, Sentia; Ahmed, Shahzad; Gong, Jun; Annamalai, Alagappan Anand; Tuli, Richard; Hendifar, Andrew Eugene

    2016-01-01

    Treatment options for advanced pancreatic ductal adenocarcinoma (PDAC) are limited; however, new therapies targeting specific tumor-related molecular characteristics may help certain patient cohorts. Emerging preclinical data have shown that inhibition of mammalian target of rapamycin (mTOR) in specific KRAS-dependent PDAC subtypes leads to inhibition of tumorigenesis in vitro and in vivo. Early phase II studies of mono-mTOR inhibition have not shown promise. However, studies have shown that combined inhibition of multiple steps along the mTOR signaling pathway may lead to sustained responses by targeting mechanisms of tumor resistance. Coordinated inhibition of mTOR along with specific KRAS-dependent mutations in molecularly defined PDAC subpopulations may offer a viable alternative for treatment in the future. PMID:27200288

  19. Review: Experimental models for Barrett's esophagus and esophageal adenocarcinoma

    PubMed Central

    Orlando, Roy C.; Chen, Xiaoxin

    2012-01-01

    Several different cell culture systems and laboratory animal models have been used over the years to study Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). Most of the existing models have key differences with the human esophagus and complex pathogenesis of disease. None of the models offers an ideal system for the complex study of environmental exposure, genetic risk, and prevention strategies. In fact, different model systems may be required to answer different specific research questions about the pathogenesis of BE and EAC. Given the high mortality associated with EAC and the fact that current screening strategies miss most cases of EAC, advances in basic and translational science related to esophageal injury, repair, and carcinogenesis are clearly needed. This review describes several of the existing and potential model systems for BE and EAC with their benefits and disadvantages. PMID:22421618

  20. Two cases of pancreatic ductal adenocarcinoma with intrapancreatic metastasis

    PubMed Central

    Fujita, Yusuke; Kitago, Minoru; Masugi, Yohei; Itano, Osamu; Shinoda, Masahiro; Abe, Yuta; Hibi, Taizo; Yagi, Hiroshi; Fujii-Nishimura, Yoko; Sakamoto, Michiie; Kitagawa, Yuko

    2016-01-01

    There are no standardized diagnostic criteria for intrapancreatic metastasis of pancreatic ductal adenocarcinoma (PDAC). Here, we report two cases of patients with PDAC who were pathologically diagnosed as harboring intrapancreatic metastasis. In both cases, the main lesions were located in the pancreatic body, and no other lesion was detected preoperatively. The patients were diagnosed with pancreatic body cancers and distal pancreatectomy was performed. Pathological findings revealed microscopic cancer nests, which had connections to neither the main lesion nor the premalignant lesion in the pancreatic tail parenchyma. In both cases, the histological type of the daughter lesion was quite similar to that of the main lesion. Hence, we diagnosed the daughter lesions as metastatic foci in the pancreas. Although intrapancreatic metastasis of PDAC has been regarded as a poor prognostic factor, few reports of intrapancreatic metastasis are available. This article reports two such cases and provides a review of the literature. PMID:27895409

  1. Coexistence of xanthogranulomatous cholecystitis and gallbladder adenocarcinoma: a fortuitous association?

    PubMed

    Limaiem, F; Chelly, B; Hassan, F; Haddad, I; Ben Slama, S; Lahmar, A; Bouraoui, S; Mzabi-Regaya, S

    2013-08-01

    Xanthogranulomatous cholecystitis is a relatively uncommon variant of chronic cholecystitis, characterized by marked thickening of the gallbladder wall and dense local adhesions. Not only does xanthogranulomatous cholecystitis mimic malignancy, it can also be infrequently associated with gallbladder carcinoma in 0.2% to 35.4% of cases. Herein, the authors report a new case of xanthogranulomatous cholecystitis concomitant with gallbladder adenocarcinoma in a 65-year-old female patient. Because of its overlapping clinical, radiological and macroscopic findings with gallbladder cancer, definitive diagnosis of xanthogranulomatous cholecystitis relies on extensive sampling and thorough microscopic examination of the surgical specimen to exclude the possibility of coexisting tumour. It is still a matter of debate whether xanthogranulomatous cholecystitis is truly a precursor of gallbladder carcinoma or if it is just an incidental finding. This aspect needs to be explored in the future with further studies.

  2. Adenocarcinoma of lung masquerading as systemic auto-immune disease.

    PubMed

    Naha, Kushal; Thakare, Sayali; Vivek, G; Prabhu, Mukhyaprana

    2012-06-14

    A 40-year-old previously healthy male presented with acute onset painless dimness of vision in both eyes since the past week and low-grade fever, anorexia and weight loss for the past 1 month. He had been evaluated at a local hospital and diagnosed to have a posterior cerebral artery territory infarct on the left side on the strength of cranial CT. Shortly after receiving antiplatelets and warfarin he had developed severe coagulopathy as evidenced by haematemesis, epistaxis and haematuria. Preliminary investigation revealed prolonged clotting parameters, renal failure and anaemia. Cerebral MRI showed multiple areas of cortical haemorrhage. In the course of his hospital stay, he developed further stigmata of auto-immunity including Coomb's positive haemolytic anaemia, recurrent venous thromboses and a palpable purpuric truncal rash. He was eventually diagnosed to have an adenocarcinoma of the lung, and was subsequently referred to an oncologist for further therapy.

  3. Tracking the genomic evolution of esophageal adenocarcinoma through neoadjuvant chemotherapy

    PubMed Central

    Kumar, Sacheen; Abbassi-Ghadi, Nima; Salm, Max; Mitter, Richard; Horswell, Stuart; Rowan, Andrew; Phillimore, Benjamin; Biggs, Jennifer; Begum, Sharmin; Matthews, Nik; Hochhauser, Daniel; Hanna, George B; Swanton, Charles

    2015-01-01

    Esophageal adenocarcinomas (EACs) are associated with dismal prognosis. Deciphering the evolutionary histories of this disease may shed light on therapeutically tractable targets and reveal dynamic mutational processes during the disease course and following neoadjuvant chemotherapy (NAC). We exome sequenced 40 tumor regions from 8 patients with operable EACs, before and after platinum-containing NAC. This revealed the evolutionary genomic landscape of EACs with the presence of heterogeneous driver mutations, parallel evolution, early genome doubling events and an association between high intratumor heterogeneity and poor response to NAC. Multi-region sequencing demonstrated a significant reduction in T>G mutations within a CTT context when comparing early and late mutational processes and the presence of a platinum signature with enrichment of C>A mutations within a CpC context following NAC. EACs are characterized by early chromosomal instability leading to amplifications containing targetable oncogenes persisting through chemotherapy, providing a rationale for future therapeutic approaches. PMID:26003801

  4. A salivary gland adenocarcinoma mimicking a microcystic adnexal carcinoma.

    PubMed

    Basile, John R; Lin, Yi-Ling

    2010-04-01

    The microcystic adnexal carcinoma (MAC) is a rare, slow-growing but locally aggressive neoplasm arising in the midface and lips of middle-aged adults. The MAC is histologically characterized by deeply infiltrating nests and islands of basaloid or squamous cells forming cysts and ductal structures, proliferating in a dense sclerotic stroma and occasionally exhibiting perineural invasion. We describe a salivary gland adenocarcinoma arising in the lower lip, characterized by ductal structures and cords, 3-5 cell layers in thickness, set in a dense fibrous stroma and also invading nerves, thus mimicking a MAC in both its clinical and its histopathologic appearance. The diagnostic dilemma presented by this lesion is discussed, along with a differential diagnosis and brief review of the literature.

  5. Immunohistochemical profile of ductal adenocarcinoma of the prostate.

    PubMed

    Seipel, Amanda H; Samaratunga, Hemamali; Delahunt, Brett; Wiklund, Fredrik; Wiklund, Peter; Lindberg, Johan; Grönberg, Henrik; Egevad, Lars

    2014-11-01

    Ductal adenocarcinoma of the prostate (DAC) is considered to be an aggressive subtype of prostate cancer with greater risk of progression than acinar adenocarcinoma (AC). It has been debated whether DAC is a distinct subtype or a morphological variant of AC. Our aim was to examine the protein expression of DAC and to compare the results with AC. A tissue microarray was constructed from 60 DAC and 46 AC matched by Gleason score. The slides were stained for 28 immunomarkers (estrogen, progesterone and androgen receptor, prolactin, PSA, prostein, PSMA, PSAP, CDX2, lysozyme, villin, monoclonal CEA, CK7, CK20, HMWCK, p63, p504s, c-myc, EGFR, Ki-67, p16, p21, p27, p53, PTEN, ERG, PAX-2, and PAX-8). HMWCK was positive in 8.5 % of DAC, but negative in all cases of AC (p = 0.045). p16 was positive in 53.3 % of DAC and in 26.1 % of AC (p = 0.005). p53 was positive in 42.4 % of DAC and 26.7 % of AC (p = 0.031). A distinct patchy positivity of CK20 was seen in 23.7 % of DAC, and this pattern was also seen in 9.1 % of AC (p = 0.047). Villin was positive in 3.4 % of DAC while expression was negative in AC. Ki-67 labeling index was significantly higher in DAC than in AC (mean 9.2 % [95 % CI 6.4-12.0] and 2.6 % [1.9-3.4], p < 0.001). While there is some overlap in the immunohistochemical expression of DAC and AC, the differences between these two morphotypes of prostatic carcinoma are consistent with DAC having a more aggressive phenotype than AC.

  6. Incidental adenocarcinoma in patients undergoing surgery for stricturing Crohn's disease

    PubMed Central

    Kristo, Ivan; Riss, Stefan; Argeny, Stanislaus; Maschke, Svenja; Chitsabesan, Praminthra; Stift, Anton

    2017-01-01

    AIM To evaluate frequency and clinical course of incidental adenocarcinoma in patients with stricturing Crohn's disease (CD). METHODS In this study, consecutive patients, who were operated on for stricturing CD between 1997-2012, were included at an academic tertiary referral center. Demographic data and clinical course were obtained by an institutional database and individual chart review. Besides baseline characteristics, intraoperative findings and CD related history were also recorded. Colorectal cancer was classified and staged according to the Union for International Cancer Control (UICC). RESULTS During the study period 484 patients underwent resections due to stricturing CD. Incidental adenocarcinoma was histologically confirmed in 6 (1.2%) patients (4 males, 2 females). Patients diagnosed with colorectal cancer had a median age of 43 (27-66) years and a median history of CD of 16 (7-36) years. Malignant lesions were found in the rectum (n = 4, 66.7%), descending colon (n = 1, 16.7%) and ileocolon (n = 1, 16.7%). According to the UICC classification two patients were stages as I (33.3%), whereas the other patients were classified as stage IIA (16.7%), stage IIIB (16.7%), stage IIIC (16.7%) and stage IV (16.7%), respectively. After a median follow-up of 2 (0.03-8) years only 1 patient is still alive. CONCLUSION The frequency of incidental colorectal cancer in patients, who undergo surgery for stenotic CD, is low but associated with poor prognosis. However, surgeons need to be aware about the possibility of malignancy in stricturing CD, especially if localized in the rectum. PMID:28210083

  7. Microbiome and Potential Targets for Chemoprevention of Esophageal Adenocarcinoma

    PubMed Central

    Neto, Antonio Galvao; Whitaker, April; Pei, Zhiheng

    2015-01-01

    Esophageal cancer is one of the deadliest cancers, with a dismal prognosis. It is increasingly recognized that esophageal cancer is a heterogeneous disease. It can be subdivided into two distinct groups: squamous cell carcinoma and adenocarcinoma, based on histological appearance. In the Western world, the incidence of squamous cell carcinoma was considerably higher than esophageal adenocarcinoma (EA) until the 1990s when, due to a dramatic increase, the incidence of EA surpassed that of squamous cell carcinoma. EA typically follows a well-established stepwise evolution from chronic inflammation due to reflux esophagitis (RE) that progresses to metaplasia (Barrett’s esophagus- BE) to dysplasia, which often culminates in EA. The pathophysiology of EA is complex and involves diverse factors, including gastroesophageal reflux, gastric acid secretion, dysfunction of the antireflux barrier, gastric emptying disturbances, and abnormalities in esophageal defense mechanisms. The current understanding of the etiology of EA is mainly derived from epidemiological studies of risk factors such as cigarette smoking, obesity, gastroesophageal reflux disorders (GERD), and low fruit and vegetable consumption. Numerous studies have been done but the factors that drive the dynamic increase in the incidence of EA remain elusive. The advent of widespread antibiotic use occurred in the 1950s, preceding the surge of EA. Based on this temporal sequence, it has been hypothesized that antibiotics alter the microbiome to which the esophagus is exposed in patients who have GERD and that chronic exposure to this abnormal microbiome (i.e., changes in species diversity or abundance) accounts for the increase in EA. If changes in the proposed factors alter the stepwise progression (RE-BE-dysplasia- EA), they may represent potential targets for chemoprevention. New discoveries will help improve our understanding of the biology and pathogenesis of these cancers, and aid in finding novel

  8. Transcriptomic profiles differentiate normal rectal epithelium and adenocarcinoma.

    PubMed

    Hogan, J; Dejulius, K; Liu, X; Coffey, J C; Kalady, M F

    2015-05-01

    Adenocarcinoma is a histologic diagnosis based on subjective findings. Transcriptional profiles have been used to differentiate normal tissue from disease and could provide a means of identifying malignancy. The goal of this study was to generate and test transcriptomic profiles that differentiate normal from adenocarcinomatous rectum. Comparisons were made between cDNA microarrays derived from normal epithelium and rectal adenocarcinoma. Results were filtered according to standard deviation to retain only highly dysregulated genes. Genes differentially expressed between cancer and normal tissue on two-groups t test (P < 0.05, Bonferroni P value adjustment) were further analyzed. Genes were rank ordered in terms of descending fold change. For each comparison (tumor versus normal epithelium), those 5 genes with the greatest positive fold change were grouped in a classifier. Five separate tests were applied to evaluate the discriminatory capacity of each classifier. Genetic classifiers derived comparing normal epithelium with malignant rectal epithelium from pooled stages had a mean sensitivity and specificity of 99.6% and 98.2%, respectively. The classifiers derived from comparing normal and stage I cancer had comparable mean sensitivities and specificities (97% and 98%, respectively). Areas under the summary receiver-operator characteristic curves for each classifier were 0.981 and 0.972, respectively. One gene was common to both classifiers. Classifiers were tested in an independent Gene Expression Omnibus-derived dataset. Both classifiers retained their predictive properties. Transcriptomic profiles comprising as few as 5 genes are highly accurate in differentiating normal from adenocarcinomatous rectal epithelium, including early-stage disease.

  9. Sulphamoylated 2-Methoxyestradiol Analogues Induce Apoptosis in Adenocarcinoma Cell Lines

    PubMed Central

    Visagie, Michelle; Theron, Anne; Mqoco, Thandi; Vieira, Warren; Prudent, Renaud; Martinez, Anne; Lafanechère, Laurence; Joubert, Annie

    2013-01-01

    2-Methoxyestradiol (2ME2) is a naturally occurring estradiol metabolite which possesses antiproliferative, antiangiogenic and antitumor properties. However, due to its limited biological accessibility, synthetic analogues have been synthesized and tested in attempt to develop drugs with improved oral bioavailability and efficacy. The aim of this study was to evaluate the antiproliferative effects of three novel in silico-designed sulphamoylated 2ME2 analogues on the HeLa cervical adenocarcinoma cell line and estrogen receptor-negative breast adenocarcinoma MDA-MB-231 cells. A dose-dependent study (0.1–25 μM) was conducted with an exposure time of 24 hours. Results obtained from crystal violet staining indicated that 0.5 μM of all 3 compounds reduced the number of cells to 50%. Lactate dehydrogenase assay was used to assess cytotoxicity, while the mitotracker mitochondrial assay and caspase-6 and -8 activity assays were used to investigate the possible occurrence of apoptosis. Tubulin polymerization assays were conducted to evaluate the influence of these sulphamoylated 2ME2 analogues on tubulin dynamics. Double immunofluorescence microscopy using labeled antibodies specific to tyrosinate and detyrosinated tubulin was conducted to assess the effect of the 2ME2 analogues on tubulin dynamics. An insignificant increase in the level of lactate dehydrogenase release was observed in the compounds-treated cells. These sulphamoylated compounds caused a reduction in mitochondrial membrane potential, cytochrome c release and caspase 3 activation indicating apoptosis induction by means of the intrinsic pathway in HeLa and MDA-MB-231 cells. Microtubule depolymerization was observed after exposure to these three sulphamoylated analogues. PMID:24039728

  10. EGFR gene deregulation mechanisms in lung adenocarcinoma: A molecular review.

    PubMed

    Tsiambas, Evangelos; Lefas, Alicia Y; Georgiannos, Stavros N; Ragos, Vasileios; Fotiades, Panagiotis P; Grapsa, Dimitra; Stamatelopoulos, Athanasios; Kavantzas, Nikolaos; Patsouris, Efstratios; Syrigos, Konstantinos

    2016-08-01

    For the last two decades, evolution in molecular biology has expanded our knowledge in decoding a broad spectrum of genomic imbalances that progressively lead normal cells to a neoplastic state and finally to complete malignant transformation. Concerning oncogenes and signaling transduction pathways mediated by them, identification of specific gene alterations remains a critical process for handling patients by applying targeted therapeutic regimens. The epidermal growth factor receptor (EGFR) signaling pathway plays a crucial role in regulating cell proliferation, differentiation and apoptosis in normal cells. EGFR mutations and amplification represent the gene's main deregulation mechanisms in cancers of different histo-genetic origin. Furthermore, intra-cancer molecular heterogeneity due to clonal rise and expansion mainly explains the variable resistance to novel anti-EGFR monoclonal antibody (mAb), and also tyrosine kinase inhibitors (TKIs). According to recently published 2015 WHO new classification, lung cancer is the leading cause of death related to cancer and its incidence is still on the increase worldwide. The majority of patients suffering from lung cancer are diagnosed with epithelial tumors (adenocarcinoma predominantly and squamous cell carcinoma represent ∼85% of all pathologically defined lung cancer cases). In those patients, EGFR-activating somatic mutations in exons 18/19/20/21 modify patients' sensitivity (i.e. exon 21 L858R, exon 19 LREA deletion) or resistance (ie exon 20 T790M and/or insertion) to TKI mediated targeted therapeutic strategies. Additionally, the role of specific micro-RNAs that affect EGFR regulation is under investigation. In the current review, we focused on EGFR gene/protein structural and functional aspects and the corresponding alterations that occur mainly in lung adenocarcinoma to critically modify its molecular landscape.

  11. [Genomics of lung adenocarcinoma: pathogenetic significance and clinical applications.

    PubMed

    Palmirotta, Raffaele; Acquafredda, Silvana; Argentiero, Antonella; Carella, Claudia; Lanotte, Laura; Pappagallo, Nicla; Quaresmini, Davide; Silvestris, Franco

    2016-12-01

    Diagnostic and therapeutic approaches to non small cell lung cancer (NSCLC), especially adenocarcinoma, have recently undergone dramatic evolution according to the tremendous amount of molecular data collected on this cancer. In fact, the application of oncogenomics has identified novel molecular subtypes of NSCLC and led the way to diagnostic criteria based on the expression of specific genetic alterations that can provide prognostic and specific indications to the molecular targeted therapies. In NSCLC, several genes show "driver" molecular alterations that confer oncogenic potential to progenitor cells through the enrollment of metabolic pathways critical for cell proliferation and tumor development. On the other hand, clinical management of NSCLC with small molecules has undoubtedly provided optimistic results with both a significant increase in overall survival and reduction in therapy-related toxicity including relative complications. Thus, pharmacogenomics, as the newest tool for using the targeted therapy represents the most innovative approach for treatment of this cancer once the molecular aberrations are identified. In particular, the relative mutational status of several driver genes including EGFR, ALK, ROS1 and others, is directly correlated to a better response to thyrosin-kinase inhibitors. Furthermore, other therapeutic strategies with inhibitors of angiogenic receptors, PARP, histone-deacetylase, PI3K and HSP90, are intensively studied in pre-clinical models as well as in clinical trials for a potential adoption in clinical practice. The introduction of more advanced techniques for molecular profiling also allows to identify pathogenic variants of many other genes involved in the progression of lung adenocarcinoma with the aim to develop novel molecular targets for pharmacological research. In this review, we will revisit the current applications of oncogenomics in the diagnosis and treatment of this tumor.

  12. Cytokines as Biomarkers of Pancreatic Ductal Adenocarcinoma: A Systematic Review

    PubMed Central

    Yako, Yandiswa Yolanda; Kruger, Deirdré; Smith, Martin; Brand, Martin

    2016-01-01

    Objectives A systematic review of the role of cytokines in clinical medicine as diagnostic, prognostic, or predictive biomarkers in pancreatic ductal adenocarcinoma was undertaken. Materials and Methods A systematic review was conducted according to the 2009 PRISMA guidelines. PubMed database was searched for all original articles on the topic of interest published until June 2015, and this was supplemented with references cited in relevant articles. Studies were evaluated for risk of bias using the Quality in Prognosis Studies tools. Results Forty one cytokines were investigated with relation to pancreatic ductal adenocarcinoma (PDAC) in 65 studies, ten of which were analyzed by more than three studies. Six cytokines (interleukin[IL]-1β, -6, -8, -10, vascular endothelial growth factor, and transforming growth factor) were consistently reported to be increased in PDAC by more than four studies; irrespective of sample type; method of measurement; or statistical analysis model used. When evaluated as part of distinct panels that included CA19-9, IL-1β, -6 and -8 improved the performance of CA19-9 alone in differentiating PDAC from healthy controls. For example, a panel comprising IL-1β, IL-8, and CA 19–9 had a sensitivity of 94.1% vs 85.9%, specificity of 100% vs 96.3%, and area under the curve of 0.984 vs 0.925. The above-mentioned cytokines were associated with the severity of PDAC. IL-2, -6, -10, VEGF, and TGF levels were reported to be altered after patients received therapy or surgery. However, studies did not show any evidence of their ability to predict treatment response. Conclusion Our review demonstrates that there is insufficient evidence to support the role of individual cytokines as diagnostic, predictive or prognostic biomarkers for PDAC. However, emerging evidence indicates that a panel of cytokines may be a better tool for discriminating PDAC from other non-malignant pancreatic diseases or healthy individuals. PMID:27170998

  13. Lung adenocarcinoma with giant cyst formation showing a variety of histologic patterns: a case report

    PubMed Central

    2010-01-01

    Introduction Lung cancer with large cyst formation is relatively rare. This is a case report of a patient with lung cystic adenocarcinoma with multiple histologic patterns. This type of lung adenocarcinoma is believed to be the first reported case in English language medical literature. Case presentation A 60-year-old Japanese woman was admitted to hospital complaining of dyspnea and died of respiratory failure. She had been suffering from lung cancer with pleural effusion for five years. Autopsy analysis revealed lung adenocarcinoma with large cyst formation showing a variety of histologic patterns. Conclusions Autopsy analysis of this atypical case of lung cancer may provide insight and lead to a better understanding of the heterogeneity and clonal expansion of lung adenocarcinoma. PMID:21108775

  14. Concurrent small bowel adenocarcinoma and carcinoid tumor in Crohn's disease--case report and literature review.

    PubMed

    Boltin, Doron; Levi, Zohar; Halpern, Marisa; Fraser, Gerald M

    2011-10-01

    Adenocarcinomas of the large and small bowel, as well as intestinal carcinoid tumors have been reported at increased rates in Crohn's disease. We herein report a rare case of concurrent adenocarcinoma and carcinoid tumor of the small bowel presenting as intestinal obstruction and found incidentally at laparotomy in a 55 year old male with longstanding ileal Crohn's disease. We performed a Medline Pubmed search for cases of synchronous or composite adenocarcinoma and carcinoid tumor in the setting of Crohn's disease and identified four similar cases. Concurrent adenocarcinoma and carcinoid tumor occurred both in newly diagnosed and longstanding Crohn's disease, most commonly involved the terminal ileum and presented with symptoms mimicking Crohn's disease. Diagnosis was made incidentally at laparotomy in all cases. Lymph node involvement was variable. Clinicians should be aware of this rare entity for expeditious surgical intervention.

  15. Meltzer 3-marker panel with clinical features for Esophageal Adenocarcinoma — EDRN Public Portal

    Cancer.gov

    Barrett's esophagus predisposes to esophageal adenocarcinoma. This biomarker is part of a three-tiered risk stratification strategy, based on systematically selected epigenetic and clinical parameters, to improve Barrett's esophagus surveillance efficiency.

  16. Prostatic intraepithelial neoplasia-like ductal prostatic adenocarcinoma: A case suitable for active surveillance?

    PubMed Central

    Rais-Bahrami, Soroush; Dillard, Melissa R.; Zhu, Grace G.; Gordetsky, Jennifer B.

    2017-01-01

    In contrast to typical prostatic ductal adenocarcinoma, prostatic intraepithelial neoplasia (PIN)-like ductal adenocarcinoma is a rare variant of prostate cancer with low-grade clinical behavior. We report a case of a 66-year-old African-American male with an elevated serum prostate-specific antigen who underwent multiparametric prostate magnetic resonance imaging (MRI) and MRI/ultrasound fusion-guided biopsies. Pathology demonstrated low-volume Gleason score 3 + 3 = 6 (Grade Group 1), acinar adenocarcinoma involving one core and PIN-like ductal adenocarcinoma on a separate core. Herein, we discuss the potential role of active surveillance for patients with this rare variant of prostate cancer found in the era of advanced imaging with multiparametric MRI for prostate cancer. PMID:28216939

  17. Metachronous Primary Adenocarcinoma of Distal and Proximal Ureter within Two Years

    PubMed Central

    Abt, Dominik; Müllhaupt, Gautier; Mordasini, Livio; Diener, Pierre André; Schmid, Hans-Peter

    2014-01-01

    Primary adenocarcinoma of the upper urinary tract, particularly of the ureter, is an extremely rare entity. We are reporting on the first case of metachronous appearance in one patient. The 71-year-old man underwent partial ureterectomy (R0 resection) for primary adenocarcinoma of the left distal ureter. 3 years later, nephroureterectomy had to be performed because of metachronous primary adenocarcinoma of the left proximal ureter. Extensive examinations revealed no evidence for further malignancies at both times. Primary adenocarcinoma of the upper urinary tract is rare but should be kept in mind, especially in patients with chronic inflammation and urinary tract obstruction. Due to the low incidence, there is a lack of data regarding its pathogenesis, diagnosis, and optimal treatment. PMID:24982812

  18. High-Throughput Functional Validation of Progression Drivers in Lung Adenocarcinoma

    DTIC Science & Technology

    2014-11-01

    injected cells, tumors and metastases positively select driver genes and lose those with no role in tumor growth or metastasis (i.e., passengers... Drivers in Lung Adenocarcinoma PRINCIPAL INVESTIGATOR: Don L. Gibbons, M.D., Ph.D. CONTRACTING ORGANIZATION: The University of Texas...Progression Drivers in Lung Adenocarcinoma 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0294 5c. PROGRAM ELEMENT NUMBER

  19. IASLC/ATS/ERS International Multidisciplinary Classification of Lung Adenocarcinoma: novel concepts and radiologic implications.

    PubMed

    Lee, Hyun-Ju; Lee, Chang Hun; Jeong, Yeon Joo; Chung, Doo Hyun; Goo, Jin Mo; Park, Chang Min; Austin, John H M

    2012-11-01

    In 2011, the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society proposed a new classification for lung adenocarcinoma that included a number of changes to previous classifications. This classification now considers resection specimens, small biopsies, and cytology specimens. Two former histopathologic terms, bronchioloalveolar carcinoma and mixed subtype adenocarcinoma, are no longer to be used. For resection specimens, the new terms of adenocarcinoma in situ and minimally invasive adenocarcinoma are introduced for small adenocarcinomas showing pure lepidic growth and predominantly lepidic growth, with invasion ≤5 mm, respectively. Invasive adenocarcinomas are now classified by their predominant pattern as lepidic, acinar, papillary, and solid; a micropapillary pattern is newly added. This classification also provides guidance for small biopsies and cytology specimens. For adenocarcinomas that include both an invasive and a lepidic component, it is suggested that for T staging the size of the T-factor may be best measured on the basis of the size of the invasive component rather than on the total size of tumors including lepidic components, both on pathologic and computed tomography assessment. This suggestion awaits confirmation in clinical-radiologic trials. An implication for M staging is that comprehensive histologic subtyping along with other histologic and molecular features can be very helpful in determining whether multiple pulmonary nodules are separate primaries or intrapulmonary metastases. In this review article, we provide an illustrated overview of the proposed new classification for lung adenocarcinoma with an emphasis upon what the radiologist needs to know in order to successfully contribute to the multidisciplinary strategic management of patients with this common histologic subtype of lung cancer.

  20. Gynecologic Cancer InterGroup (GCIG) consensus review for cervical adenocarcinoma.

    PubMed

    Fujiwara, Hiroyuki; Yokota, Harushige; Monk, Bradley; Treilleux, Isabelle; Devouassoux-Shisheboran, Mojgan; Davis, Alison; Kim, Jae-Weon; Mahner, Sven; Stany, Michael; Pignata, Sandro; Ray-Coquard, Isabelle; Fujiwara, Keiichi

    2014-11-01

    Cervical adenocarcinoma is known to be less common than squamous cell carcinoma of the cervix comprising approximately 25% of all cervical carcinomas. Differences in associated human papillomavirus types, patterns of spread, and prognosis call for treatments that are not always like those for squamous cancers. In this review, we report a consensus developed by the Gynecologic Cancer InterGroup surrounding cervical adenocarcinoma for epidemiology, pathology, treatment, and unanswered questions. Prospective clinical trials are needed to help develop treatment guidelines.

  1. Endoscopic Ultrasound Does Not Accurately Stage Early Adenocarcinoma or High-Grade Dysplasia of the Esophagus

    DTIC Science & Technology

    2010-01-01

    MeSH search terms: " endoscopic ultrasound," "Barrett’s esophagus ," "adeno· carcinoma," "Barrett’s esophagus and high grade dyspla.c;ia...adenocarcinoma of the esophagus ; EMR, endoscopic mucosal resection; EUS, endoscopic ul- trasound; HGD, high-grade dysplasia. <D 2010 by the AGA Institute... esophagus and early adenocarcinoma found EUS examination to have perfecr accuracy for differentiating Tl CLINICAL GASTROENTEROLOGY AND HEPATOLOGY Vol

  2. A case of esophageal adenocarcinoma arising from the ectopic gastric mucosa in the thoracic esophagus

    PubMed Central

    Komori, Shuji; Osada, Shinji; Tanaka, Yoshihiro; Takahashi, Takao; Nagao, Narutoshi; Yamaguchi, Kazuya; Asano, Nami; Yoshida, Kazuhiro

    2010-01-01

    A 75-year old man was detected with a pediculate tumor in the upper esophagus. A biopsy determined that it was an adenocarcinoma. A subtotal esophagectomy with dissection of three-fields of lymph nodes was selected. The pathological study revealed it to be an esophageal adenocarcinoma arising from ectopic gastric mucosa of the fundus of the stomach. His post-operative course was uneventful and without sign of recurrence for 3.5 years. PMID:21139950

  3. Perianal Paget's Disease Co-Associated with Anorectal Adenocarcinoma: Primary or Secondary Disease?

    PubMed Central

    Liao, Xiujun; Mao, Weiming; Lin, A'Li

    2014-01-01

    Perianal Paget's disease (PPD) represents a skin neoplasm which can be either primary or secondary to carcinoma from an adjacent internal organ. PPD with underlying colorectal adenocarcinoma is usually looked upon as a secondary disease. We report a rare case of co-associated PPD and anorectal adenocarcinoma. The PPD was found to be located near the anorectal adenocarcinoma with normal tissues between them. Immunohistochemical stains demonstrated that the Paget's cells were CK7+/GCDFP-15–/CK20–/MUC2–/CDX2–, whereas the anorectal adenocarcinoma was shown to be CK7+/GCDFP-15–/CK20+/MUC2+/CDX2+. This immunological phenotypic profile supported the notion that PPD and anorectal adenocarcinoma were of different origins, but could not define the exact origins of PPD. In our determination, this case was a primary PPD with anorectal adenocarcinoma. PPD remains a heterogeneous and complex pathology, and additional studies are required to differentiate between the various possible origins. PMID:24932167

  4. Overexpression of a novel regulator of p120 catenin, NLBP, promotes lung adenocarcinoma proliferation

    PubMed Central

    Kim, Chang Hee; Nam, Hae-Seong; Lee, Eun Hee; Han, Seung Hun; Cho, Hyun Jung; Chung, Hee Jin; Lee, Nam Soo; Choi, Suk Jin; Kim, Hojoong; Ryu, Jeong Seon; Kwon, Junhye; Kim, Hongtae

    2013-01-01

    NLBP (novel LZAP-binding protein) was recently shown to function as a tumor suppressor capable of inhibiting the NFκB signaling pathway. NLBP is also known as a negative regulator of cell invasion, and its expression is reduced in several cancer cell lines that have little invasive activity. Although these phenomena suggest that NLBP may be a potential tumor suppressor, its role as a tumor suppressor in human lung cancer is not well established. In contrast to our expectation, NLBP was highly expressed in the early stage of lung adenocarcinoma tissues, and overexpression of NLBP promoted proliferation of H1299 lung adenocarcinoma cells. We also found that p120 catenin (p120ctn) was a novel binding partner of NLBP, and that NLBP binds to the regulatory domain of p120ctn, and p120ctn associates with N-terminal region of NLBP, respectively. This binding leads to p120ctn stability to inhibit proteasomal degradation of p120ctn by inhibiting its ubiqutination. In addition, we also found that overexpression of NLBP and p120ctn in human lung cancer are closely related with adenocarcinoma compared with squamous cell carcinoma. Taken together, our findings reveal that NLBP is highly overexpressed in human lung adenocarcinoma, and that overexpression of NLBP promotes the cell proliferation of lung adenocarcinoma through interacting with p120ctn and suggest that NLBP may function as an oncogene in early stage carcinogenesis of lung adenocarcinoma. PMID:23839039

  5. Differentiating gastrointestinal stromal tumors from gastric adenocarcinomas and normal mucosae using confocal Raman microspectroscopy

    NASA Astrophysics Data System (ADS)

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chen, Wenlung

    2016-07-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and gastric adenocarcinomas are a common cancer worldwide. To differentiate GISTs from adenocarcinomas is important because the surgical processes for both are different; the former excises the tumor with negative margins, while the latter requires radical gastrectomy with lymph node dissection. Endoscopy with biopsy is used to distinguish GISTs from adenocarcinomas; however, it may cause tumor bleeding in GISTs. We reported here the confocal Raman microspectroscopy as an effective tool to differentiate GISTs, adenocarcinomas, and normal mucosae. Of 119 patients enrolled in this study, 102 patients underwent gastrectomy (40 GISTs and 62 adenocarcinomas), and 17 patients with benign lesions were obtained as normal mucosae. Raman signals were integrated for 100 s for each spot on the specimen, and 5 to 10 spots, depending on the sample size, were chosen for each specimen. There were significant differences among those tissues as evidenced by different Raman signal responding to phospholipids and protein structures. The spectral data were further processed and analyzed by using principal component analysis. A two-dimensional plot demonstrated that GISTs, adenocarcinomas, and normal gastric mucosae could be effectively differentiated from each other.

  6. Hypoxia induced CCL28 promotes angiogenesis in lung adenocarcinoma by targeting CCR3 on endothelial cells.

    PubMed

    Huang, Guichun; Tao, Leilei; Shen, Sunan; Chen, Longbang

    2016-06-02

    Tumor hypoxia is one of the important features of lung adenocarcinoma. Chemokines might mediate the effects caused by tumor hypoxia. As confirmed in tumor tissue and serum of patients, CC chemokine 28 (CCL28) was the only hypoxia induced chemokine in lung adenocarcinoma cells. CCL28 could promote tube formation, migration and proliferation of endothelial cells. In addition, angiogenesis was promoted by CCL28 in the chick chorioallantoic membrane and matrigel implanted in dorsal back of athymic nude mice (CByJ.Cg-Foxn1(nu)/J). Tumors formed by lung adenocarcinoma cells with high expression of CCL28 grew faster and had a higher vascular density, whereas tumor formation rate of lung adenocarcinoma cells with CCL28 expression knockdown was quite low and had a lower vascular density. CCR3, receptor of CCL28, was highly expressed in vascular endothelial cells in lung adenocarcinoma when examining by immunohistochemistry. Further signaling pathways in endothelial cells, modulated by CCL28, were analyzed by Phosphorylation Antibody Array. CCL28/CCR3 signaling pathway could bypass that of VEGF/VEGFR on the levels of PI3K-Akt, p38 MAPK and PLC gamma. The effects could be neutralized by antibody against CCR3. In conclusion, CCL28, as a chemokine induced by tumor hypoxia, could promote angiogenesis in lung adenocarcinoma through targeting CCR3 on microvascular endothelial cells.

  7. Possible involvement of leptin and leptin receptor in developing gastric adenocarcinoma

    PubMed Central

    Zhao, Liang; Shen, Zhi-Xiang; Luo, He-Sheng; Shen, Lei

    2005-01-01

    AIM: To investigate the expression of leptin and leptin receptor (ob-R) in intestinal-type gastric cancer and precancerous lesions, and to explore the possible mechanism and role of the leptin system in developing intestinal-type gastric adenocarcinoma. METHODS: Immunohistochemistry was performed to examine the expression of leptin and leptin receptor in archival samples of gastric adenocarcinoma and preneoplastic lesions, including intestinal metaplasia and mild to severe gastric epithelial dysplasia. Positive staining was identified and percentage of positive staining was graded. RESULTS: Dual expression of leptin and leptin receptor were detected in 80% (16/20) intestinal metaplasia, 86.3% (25/30) mild gastric epithelial dysplasia, 86.7% (26/30) moderate gastric epithelial dysplasia, 93.3% (28/30) severe gastric epithelial dysplasia, 91.3% (55/60) intestinal-type gastric adenocarcinoma and 30.0% (9/30) diffuse-type gastric carcinoma. The percentage of dual expression of leptin and leptin receptor in intestinal-type gastric adenocarcinoma was significantly higher than that in diffuse-type gastric adenocarcinoma (χ2 = 37.022, P<0.01). CONCLUSION: Our results indicate the presence of an autocrine loop of leptin system in the development of intestinal-type gastric adenocarcinoma. PMID:16437696

  8. Identification of ubiquinol cytochrome c reductase hinge (UQCRH) as a potential diagnostic biomarker for lung adenocarcinoma

    PubMed Central

    Gao, Feng; Liu, Qicai; Li, Guoping; Dong, Feng; Qiu, Minglian; Lv, Xiaoting; Zhang, Sheng; Guo, Zheng

    2016-01-01

    Ubiquinol cytochrome c reductase hinge (UQCRH) is a novel protein that localizes in the mitochondrial membrane and induces mitochondrial reactive oxygen species (ROS) generation. It had a high expression rate of 87.10% (108/124) in lung adenocarcinoma. Moreover, serum UQCRH level in patients with lung adenocarcinoma was significantly increased compared with that of pneumonia patients (p < 0.0001) and normal control subjects (p < 0.0001). Receiver operating characteristic curve analysis using an optimal cut-off value of 162.65 pg ml−1 revealed sensitivity and specificity for the diagnosis of lung adenocarcinoma of 88.7% and 85.7%, respectively, with an area under the curve of 0.927 (95% CI: 0.892 to 0.962, p < 0.0001). Serum UQCRH discriminates lung adenocarcinoma patients from the population without cancer with considerable sensitivity and specificity, but it does not distinguish between heavy smokers and lung adenocarcinoma patients. Serum UQCRH could be a potential diagnostic biomarker for lung adenocarcinoma. PMID:27358292

  9. Validation of a protocol to compare the effectiveness of experimental decontaminants with both components of the M258A1 kit against percutaneous application of undiluted vesicant chemical surety material to the laboratory albino rabbit. Final report, 1 March 1985-24 July 1987

    SciTech Connect

    Joiner, R.L.

    1987-07-24

    A rabbit model was developed and validated for screening noninvasive candidate decontamination systems for their efficacies against topical exposure to the vesicant chemical surety material sulfur mustard (HD). Rabbits were dosed with HD on their shaved dorsa and then decontaminated at varying times with either both components of the M258A1 field kit or twice with distilled water. Lesion lengths were estimated and compared contralaterally. Results revealed statistically shorter lesions for M258A1 decontamination relative to the respective lesions decontaminated with distilled water.

  10. Association of adenocarcinomas of the distal esophagus, "gastroesophageal junction," and "gastric cardia" with gastric pathology.

    PubMed

    Wijetunge, Sulochana; Ma, Yanling; DeMeester, Steve; Hagen, Jeffrey; DeMeester, Tom; Chandrasoma, Parakrama

    2010-10-01

    Controversy exists as to whether adenocarcinomas occurring in the gastroesophageal junctional region and gastric cardia originate in the esophagus or the stomach. Esophageal adenocarcinoma is known to be strongly associated with gastroesophageal reflux disease; gastric adenocarcinoma with Helicobacter pylori gastritis, and gastric intestinal metaplasia. This study evaluates the association of these tumors with pathologic findings in the biopsies of the gastric body and the antrum. It is hypothesized that if these malignancies are esophageal, they should have little or no significant association with gastric pathology; if they are gastric, these patients should have a high prevalence of gastric pathology. Between 2004 and 2008, 234 patients were diagnosed with high-grade dysplasia (HGD) and/or adenocarcinoma; 107 were distal esophageal, 79 straddled the distal end of the tubular esophagus, and 48 were in the "gastric cardia." Simultaneous biopsies of the distal body and antrum were present in 185 patients; 49 had biopsy of either antrum or body. Gastric biopsies were assessed for inflammation, H. pylori infection, and intestinal metaplasia. During this period, 2146 patients had nonmalignant columnar epithelia in the esophagus with similar assessment of the stomach; these acted as a control group. The gastric biopsy was normal in 201/234 (85.9%) patients and showed significant inflammation, H. pylori infection, and/or gastric intestinal metaplasia in 33/234 (14.1%) patients. There was no gastritis, H. pylori infection, or intestinal metaplasia in 88/107 (82.2%) of the patients with distal esophageal HGD and/or adenocarcinoma, 70/79 (88.6%) with junctional HGD and/or adenocarcinoma, and 43/48 (85.9%) with "gastric cardiac" HGD and/or adenocarcinoma. The incidence of gastritis was significantly higher in the patients with HGD and/or adenocarcinoma (33/234 or 14.1%) than in the control population (146/2146 or 9.0%; P=0.01). This difference was largely the result of a

  11. Genetic alterations in lung adenocarcinoma with a micropapillary component

    PubMed Central

    FURUKAWA, MASASHI; TOYOOKA, SHINICHI; ICHIMURA, KOUICHI; YAMAMOTO, HIROMASA; SOH, JUNICHI; HASHIDA, SHINSUKE; OUCHIDA, MAMORU; SHIEN, KAZUHIKO; ASANO, HIROAKI; TSUKUDA, KAZUNORI; MIYOSHI, SHINICHIRO

    2016-01-01

    Pulmonary adenocarcinoma (PA) with a micropapillary component (PA-MPC) is known as an aggressive subtype of PA. The molecular profiles of PA-MPC have not been well characterized. the pathological reports of patients who underwent surgical resection for lung cancer between April, 2004 and May, 2012 were reviewed. Of the 674 patients diagnosed with PA, 28 were found to have MPC. A total of 138 resected PAs without MPC were selected in the same period to serve as age-, gender- and smoking status-matched controls to the PA-MPC group. Mutational status was determined by the following two methods: SNaPshot assay based on multiplex polymerase chain reaction (PCR), primer extension and capillary electrophoresis that was designed to assess 38 somatic mutations in 8 genes [AKT1, BRAF, endothelial growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), mitogen-activated protein kinase kinase 1, neuroblastoma RAS viral oncogene homolog, phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit α (PIK3CA) and phosphatase and tensin homolog]; and a PCR-based sizing assay that assesses EGFR exon 19 (deletions), EGFR exon 20 (insertions) and human epidermal growth factor receptor 2 exon 20 (insertions). echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene (EML4-ALK) was screened by ALK immunohistochemistry and confirmed using the reverse transcription PCR assay and the break-apart fluorescence in situ hybridization assay. Regarding genetic alterations, 13 (46.4%) of the 28 PA-MPCs harbored mutually exclusive mutations: 9 (32.1%) EGFR mutations, 1 (3.6%) KRAS mutation and 3 (10.7%) EML4-ALK fusion genes. PAs without MPC harbored 42 (30.4%) EGFR mutations, 17 (12.3%) KRAS mutations, 3 (2.2%) EML4-ALK fusion genes and 1 (0.7%) PIK3CA mutation. EML4-ALK fusion genes appeared to occur significantly more frequently in PA-MPCs compared with PAs without MPC (P=0.027). Although the sample size was small, our study

  12. Pancreas Adenocarcinoma: Ascites, Clinical Manifestations, and Management Implications

    PubMed Central

    Hicks, Angel Mier; Chou, Joanne; Capanu, Marinela; Lowery, Maeve A.; Yu, Kenneth H.; O’Reilly, Eileen M.

    2016-01-01

    This was a cohort analysis evaluating patients with pancreatic adenocarcinoma who presented with or developed ascites. Among the 180 patients analyzed, the use of serial paracenteses and indwelling catheters is a common practice to effect symptom palliation. The complication rate was higher in patients with indwelling catheters. Analyzing ascitic fluid and calculating the serum ascites albumin gradient can help attribute the etiology of the ascites and potentially identify which patients may benefit from diuretics or other intervention. Background Ascites develops in a subset of patients with pancreatic adenocarcinoma (PAC) at presentation or as the disease advances. Limited data exist on the prognostic importance of malignant ascites in PAC. Our hypothesis is that this information will provide an understanding of the natural history and facilitate management decisions. Methods We conducted a retrospective analysis of 180 patients treated at Memorial Sloan Kettering Cancer Center diagnosed between January 1, 2009 and December 31, 2014, with PAC and with ascites either at presentation or that developed during the disease course. Results For the 180 patients, the overall survival was 15 months. The time from diagnosis to ascites presentation was 11 months, and the survival time after ascites development was 1.8 months (range, 1.6–2.3 months; 95% confidence interval). Of 62 patients (34%) who had ascitic fluid analyzed, 36 (58%) had positive cytology. Fifty-one (82%) patients had a serum ascites albumin gradient ≥ 1, and 11 (18%) had serum ascites albumin gradient < 1. Sixty-four (36%) patients had their ascites managed solely by serial paracenteses. A total of 116 patients required a catheter; of these, 108 (93%) had a Tenckhoff catheter, 4 (3%) a Pleurx catheter, 4 (3%) a pigtail catheter, and 1 (1%) a Denver catheter. Eight (7%) patients required 2 catheters to be placed, and in 6 (5%), Tenckhoff catheters had to be removed. The main observed complications were

  13. Intramural adenocarcinoma of the uterus, arisen from adenomyosis uteri, showing unique histologic appearances. Report of two cases.

    PubMed

    Kuwashima, Y; Uehara, T; Kishi, K; Tajima, H; Shiromizu, K; Matsuzawa, M; Takayama, S

    1994-01-01

    Two cases of uterine adenocarcinoma which grew mainly in myometrium and showed unique histologic appearances are reported. Both cases were considered to have arisen from adenomyosis uteri because transitional figures were observed between carcinoma cells and adenmyotic glands in one case, and carcinomatous glands were scattered in myometrium and were associated with endometrial stroma which mimicked benign adenomyosis in another. The former case was poorly differentiated adenocarcinoma and the latter was well-differentiated adenocarcinoma. Interestingly, in the latter case, the carcinoma cells were transformed into papillary adenocarcinoma such as has been observed in the thyroid gland, and formed well-demarcated nodular mass. These findings indicate that adenocarcinoma which arise from adenomyosis uteri could show various histologic appearances, in addition to usual endometrioid adenocarcinoma.

  14. Well-differentiated mucinous uterine adenocarcinoma predominantly diagnosed as adenoma malignum: a case report with an immunohistochemical analysis.

    PubMed

    Semczuk, Andrzej; Tomaszewski, Jacek; Gogacz, Marek; Obrzut, Bogdan; Rigau, Marina; Lewkowicz, Dorota; Semczuk-Sikora, Anna

    2015-01-01

    Adenoma malignum (AM), also referred to as "minimal deviation adenocarcinoma", is an extremely uncommon variant of highly-differentiated adenocarcinoma of the uterine cervix. The study presented herein describes a case of uterine AM found out after hysteroscopy. An early-stage, well-differentiated mucinous uterine adenocarcinoma was diagnosed post-operatively. A subsequent immunohistochemical assessment of a panel of antibodies was applied, in order to distinguish between female genital tract malignancies.

  15. Synchronous and metachronous gastric gist with pancreatic adenocarcinoma: report of 2 cases and a review of literature.

    PubMed

    Fiore, Marco; de Stefano, Giorgio; Coppola, Nicola; Giorgio, Antonio

    2015-01-01

    We report two cases of a Gastrointestinal Stromal Tumor (GIST) synchronous and metachronous, respectively, with pancreatic adenocarcinoma. To our knowledge, this is the first report of a GIST involved 3 years after a ductal pancreatic adenocarcinoma. Data from the literature and our cases seem to suggest that incidental GIST may occur synchronously and metachronously with other cancers more frequently than expected. Thus, the patients with a diagnosis of pancreatic adenocarcinoma may have undergone a strict follow up for GIST.

  16. Histologic characteristics of thymic adenocarcinomas: Clinicopathologic study of a nine-case series and a review of the literature.

    PubMed

    Kwon, Ah-Young; Han, Joungho; Chu, Jinah; Choi, Yong Soo; Jeong, Byeong-Ho; Ahn, Myung-Ju; Ahn, Yong Chan

    2017-02-01

    Primary thymic adenocarcinoma is an extraordinarily rare malignancy; only 49 cases have been reported in the medical literature to date. Because of its rarity, clinical and pathologic characteristics of thymic adenocarcinoma are unclear. We present nine cases of primary thymic adenocarcinoma and discuss clinicopathologic findings in the context of the existing literature. Two-hundred twenty-six thymic carcinoma cases were diagnosed at Samsung Medical Center in Korea, from January, 2001 to July, 2016. Nine of these 226 cases were primary thymic adenocarcinomas. The mean age of primary thymic adenocarcinoma patients was 53.6 years, slightly younger than the mean age of patients with thymic squamous cell carcinomas. The male to female ratio was 2:1. Symptoms, if present, were usually due to compression by the tumor. Tumors showed an extra- or intra-cellular mucin and tubular growth pattern, with CK20- and CDX2-immunoreactivity, similar to adenocarcinomas of the lower intestinal tract. Twenty-five previously reported cases, classified as mucinous adenocarcinoma and adenocarcinoma, not otherwise specified, also had similar characteristics to enteric-type adenocarcinoma and generally expressed CK20, CDX2, CEA, and/or MUC2. Some of these cases had a thymic cyst. These characteristics are different from those of papillary thymic carcinomas, which are morphologically similar to papillary thyroid carcinomas, express CK7 but not CK20, and are often associated with thymoma. The prognosis of thymic adenocarcinoma, enteric type appeared to be worse than the prognosis of papillary thymic carcinoma or carcinoma with adenoid cystic carcinoma-like features. In summary, we demonstrated that common primary thymic adenocarcinomas show enteric-type differentiation with mucin. This tumor type has distinct clinical, pathological, immunohistochemical and prognostic characteristics and is different from other subtypes of thymic adenocarcinoma, papillary thymic carcinoma, and carcinoma with

  17. Prognostic significance of WNT signaling in pancreatic ductal adenocarcinoma.

    PubMed

    Nakamoto, Mitsuhiro; Matsuyama, Atsuji; Shiba, Eisuke; Shibuya, Ryo; Kasai, Takahiko; Yamaguchi, Koji; Hisaoka, Masanori

    2014-10-01

    Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies and is associated with a variety of molecular abnormalities. Although WNT signaling through its canonical/non-canonical pathways is one of the major factors involved in oncogenesis or progression of PDA, the prognostic significance of WNT signaling still remains poorly investigated. In this study, the status of the WNT signaling pathways was immunohistochemically analyzed in 101 PDAs, and its potential association with patient postoperative survival was assessed. Nuclear expression of beta-catenin, a hallmark of the activated canonical pathway, was identified in 59 cases, and was associated with reduced survival compared to the patients lacking nuclear beta-catenin expression (P = 0.002). In contrast, activation of the non-canonical pathway (25 cases), as indicated by co-expression of WNT2/5a and nuclear NFATc1, was not correlated with reduced survival (P = 0.268). Co-activation of both pathways (16 cases) was associated with worse prognosis in comparison with cases with an activated non-canonical pathway (P = 0.034). In addition, nuclear beta-catenin expression was an independent unfavorable prognostic factor (P = 0.006). Our data indicate that activated WNT signaling through its canonical pathway has a significantly negative effect on the clinical course of PDA, and the canonical WNT pathway should be considered as a future therapeutic target for PDA.

  18. [Central diabetes insipidus as a first manifestation of lung adenocarcinoma].

    PubMed

    Granata, A; Figura, M; Gulisano, S; Romeo, G; Sicurezza, E; Failla, A; Scuderi, R

    2007-01-01

    The pituitary gland and infundibulum can be involved in a variety of medical conditions, including infiltrative diseases, fungal infections, tuberculosis, primary and metastatic tumors. Metastases to the pituitary gland are absolutely rare, and they are generally secondary to pulmonary carcinoma in men and breast carcinoma in women. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The posterior lobe involvement may explain why patients with pituitary metastases frequently present with diabetes insipidus. We are presenting a case report of a 48-year-old male patient with sudden onset of polyuria and persistent thirst. Laboratory results revealed central diabetes insipidus. Computed tomography (CT) scan of the brain showed a mass located in the sella turcica and suprasellar region. CT scan of the chest showed a mass in the right superior lobe with mediastinal lymphadenopathy. Bronchoscopy and biopsy demonstrated a pulmonary adenocarcinoma. Thus, we made a diagnosis of lung cancer with local and pituitary metastases. The patient received radiotherapy on the pituitary gland and adjuvant chemotherapy. As a result the intrasellar and suprasellar mass decreased in size and urinary output accordingly decreased. In conclusion, in patients presenting with sudden onset of diabetes insipidus pituitary metastases should be taken in account in differential diagnosis.

  19. Clinical outcomes in pancreatic adenocarcinoma associated with BRCA-2 mutation.

    PubMed

    Vyas, Ojas; Leung, Keith; Ledbetter, Leslie; Kaley, Kristin; Rodriguez, Teresa; Garcon, Marie C; Saif, Muhammad W

    2015-02-01

    Patients with BRCA-1 and BRCA-2 germ line mutations are at an increased risk of developing pancreatic adenocarcinoma (PAC). In particular, the BRCA-2 mutation has been associated with a relative risk of developing PAC of 3.51. The BRCA-2 protein is involved in repair of double-stranded DNA breaks. Recent reports have suggested that in the setting of impaired DNA repair, chemotherapeutic agents that induce DNA damage, such as platinum-based antineoplastic drugs (platins) and poly(ADP-ribose) polymerase inhibitors (PARP inhibitors), have improved efficacy. However, because of the relative rarity of BRCA-related PAC, studies evaluating such agents in this setting are scarce. Patients with a known BRCA-2 mutation and PAC were retrospectively reviewed. Ten patients with PAC and BRCA-2 mutation were identified. Four patients (40%) were of Ashkenazi Jewish descent. Seven patients (70%) received platinum agents, two (20%) received mitomycin-C, one (10%) received a PARP inhibitor, and seven (70%) received a topoisomerase-I inhibitor. Overall, chemotherapy was well tolerated with expected side effects. Patients with a BRCA-2 mutation and PAC represent a group with a unique biology underlying their cancer. Chemotherapies such as platinum derivatives, mitomycin-C, topoisomerase-I inhibitors, and PARP inhibitors targeting DNA require further investigation in this population. Genetic testing may guide therapy in the future.

  20. Whole-genome sequencing of nine esophageal adenocarcinoma cell lines

    PubMed Central

    Contino, Gianmarco; Eldridge, Matthew D.; Secrier, Maria; Bower, Lawrence; Fels Elliott, Rachael; Weaver, Jamie; Lynch, Andy G.; Edwards, Paul A.W.; Fitzgerald, Rebecca C.

    2016-01-01

    Esophageal adenocarcinoma (EAC) is highly mutated and molecularly heterogeneous. The number of cell lines available for study is limited and their genome has been only partially characterized. The availability of an accurate annotation of their mutational landscape is crucial for accurate experimental design and correct interpretation of genotype-phenotype findings. We performed high coverage, paired end whole genome sequencing on eight EAC cell lines—ESO26, ESO51, FLO-1, JH-EsoAd1, OACM5.1 C, OACP4 C, OE33, SK-GT-4—all verified against original patient material, and one esophageal high grade dysplasia cell line, CP-D. We have made available the aligned sequence data and report single nucleotide variants (SNVs), small insertions and deletions (indels), and copy number alterations, identified by comparison with the human reference genome and known single nucleotide polymorphisms (SNPs). We compare these putative mutations to mutations found in primary tissue EAC samples, to inform the use of these cell lines as a model of EAC. PMID:27594985

  1. Cell death in cancer therapy of lung adenocarcinoma.

    PubMed

    Zagryazhskaya, Anna; Gyuraszova, Katarina; Zhivotovsky, Boris

    2015-01-01

    Lung cancer is the main cause of all cancer-related deaths in the world, with lung adenocarcinoma (ADC) being the most common subtype of this fatal disease. Lung ADC is often diagnosed at advanced stages involving disseminated metastatic tumors. This is particularly important for the successful development of new cancer therapy approaches. The high resistance of lung ADC to conventional radio- and chemotherapies represents a major challenge to treatment effectiveness. Here we discuss recent progress in understanding the mechanisms of ADC's broad resistance to treatment and its possible therapeutic implications. A number of driving oncogenic alterations were identified in a subset of lung ADCs, making them suitable for targeted therapies directed towards specific cancer-associated molecular changes. In addition, we discuss the molecular aberrations common in lung ADC that are currently being exploited or are potentially important for targeted cancer therapy, as well as limitations of this type of therapy. Furthermore, we highlight possible treatment modalities that hold promise for overcoming resistance to targeted therapies as well as alternative treatment options such as immunotherapies that are potentially promising for improving the clinical outcome of lung ADC patients.

  2. 25-Hydroxycholesterol promotes migration and invasion of lung adenocarcinoma cells.

    PubMed

    Chen, Li; Zhang, Lishan; Xian, Guozhe; Lv, Yinping; Lin, Yanliang; Wang, Yibing

    2017-03-18

    25-hydroxycholesterol (25-HC) is enzymatically produced by cholesterol 25-hydorxylase in various organs and is involved in many processes, including lipid metabolism, inflammation and the immune response. However, the role of 25-HC in the migration and invasion of lung adenocarcinoma (ADC) cells remains largely unknown. In this study, we demonstrated that 0.1 μM 25-HC promoted ADC cell migration and invasion without affecting cell proliferation, especially after coculture with THP1-derived macrophages. Further investigation showed that 0.1 μM 25-HC significantly stimulated interleukin-1β (IL-1β) secretion in a coculture system and increased the expression of LXR and Snail. IL-1β also mimicked the effect of 25-HC. LXR knockdown notably blocked the 25-HC-induced Snail expression, migration and invasion in both the monoculture system and the coculture system, but it did not impact the effect of IL-1β, which suggested that IL-1β functioned in an LXR-independent manner. These results suggested that 25-HC promoted ADC cell migration and invasion in an LXR-dependent manner in the monoculture system but that in the coculture system, the 25-HC-induced IL-1β secretion enhanced the effect of 25-HC in an LXR-independent manner.

  3. Visualization of early prostatic adenocarcinoma as a stem cell disease

    PubMed Central

    Jiang, Maggie Y.; Lee, Tammy L.; Hao, Su-Shin; Mahooti, Sepi; Baird, Stephen M.; Donoghue, Daniel J.; Haas, Martin

    2016-01-01

    Prostate Cancer represents the second leading cause of cancer death among men in the United States, and the third leading cause of cancer death among men in Europe. We have previously shown that cells possessing Cancer Stem Cell (CSC) characteristics can be grown from human PrCa tissue harvested at the time of prostatectomy. However, the cellular origin of these CSCs was not previously known. In most cases, simple hematoxylin and eosin (H&E) stained sections are sufficient to make a definitive diagnosis of prostatic adenocarcinoma (PrCa) in needle biopsy samples. We utilized six different antibodies specific for stem cell antigens to examine paraffin sections of PrCa taken at the time of needle-biopsy diagnosis. These antisera were specific for CD44, CD133, ALDH7A1, LGR-5, Oct-4 and NANOG. We demonstrate specific staining of tumor cells with all six antisera specific for stem cell antigens. Some of these antibodies also react with cells of hyperplastic glands, but the patterns of reactivity differ from those of malignant glands. These findings demonstrate that at the time of diagnosis, PrCa consists of cells exhibiting properties of CSCs and consistent with the possibility that PrCa is a stem cell disease. PMID:27764770

  4. Genetic determinants and potential therapeutic targets for pancreatic adenocarcinoma

    PubMed Central

    Reznik, Robert; Hendifar, Andrew E.; Tuli, Richard

    2014-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer deaths in both men and women in the United States, carrying a 5-year survival rate of approximately 5%, which is the poorest prognosis of any solid tumor type. Given the dismal prognosis associated with PDAC, a more thorough understanding of risk factors and genetic predisposition has important implications not only for cancer prevention, but also for screening techniques and the development of personalized therapies. While screening of the general population is not recommended or practicable with current diagnostic methods, studies are ongoing to evaluate its usefulness in people with at least 5- to 10-fold increased risk of PDAC. In order to help identify high-risk populations who would be most likely to benefit from early detection screening tests for pancreatic cancer, discovery of additional pancreatic cancer susceptibility genes is crucial. Thus, specific gene-based, gene-product, and marker-based testing for the early detection of pancreatic cancer are currently being developed, with the potential for these to be useful as potential therapeutic targets as well. The goal of this review is to provide an overview of the genetic basis for PDAC with a focus on germline and familial determinants. A discussion of potential therapeutic targets and future directions in screening and treatment is also provided. PMID:24624093

  5. Exploiting the neoantigen landscape for immunotherapy of pancreatic ductal adenocarcinoma

    PubMed Central

    Bailey, Peter; Chang, David K.; Forget, Marie-Andrée; Lucas, Francis A. San; Alvarez, Hector A.; Haymaker, Cara; Chattopadhyay, Chandrani; Kim, Sun-Hee; Ekmekcioglu, Suhendan; Grimm, Elizabeth A.; Biankin, Andrew V.; Hwu, Patrick; Maitra, Anirban; Roszik, Jason

    2016-01-01

    Immunotherapy approaches for pancreatic ductal adenocarcinoma (PDAC) have met with limited success. It has been postulated that a low mutation load may lead to a paucity of T cells within the tumor microenvironment (TME). However, it is also possible that while neoantigens are present, an effective immune response cannot be generated due to an immune suppressive TME. To discern whether targetable neoantigens exist in PDAC, we performed a comprehensive study using genomic profiles of 221 PDAC cases extracted from public databases. Our findings reveal that: (a) nearly all PDAC samples harbor potentially targetable neoantigens; (b) T cells are present but generally show a reduced activation signature; and (c) markers of efficient antigen presentation are associated with a reduced signature of markers characterizing cytotoxic T cells. These findings suggest that despite the presence of tumor specific neoepitopes, T cell activation is actively suppressed in PDAC. Further, we identify iNOS as a potential mediator of immune suppression that might be actionable using pharmacological avenues. PMID:27762323

  6. Polystyrene nanoparticles internalization in human gastric adenocarcinoma cells.

    PubMed

    Forte, Maurizio; Iachetta, Giuseppina; Tussellino, Margherita; Carotenuto, Rosa; Prisco, Marina; De Falco, Maria; Laforgia, Vincenza; Valiante, Salvatore

    2016-03-01

    The increase in the use of nanoparticles, as a promising tool for drug delivery or as a food additive, raises questions about their interaction with biological systems, especially in terms of evoked responses. In this work, we evaluated the kinetics of uptake of 44 nm (NP44) and 100 nm (NP100) unmodified polystyrene nanoparticles (PS-NPs) in gastric adenocarcinoma (AGS) cells, as well as the endocytic mechanism involved, and the effect on cell viability and gene expression of genes involved in cell cycle regulation and inflammation processes. We showed that NP44 accumulate rapidly and more efficiently in the cytoplasm of AGS compared to NP100; both PS-NPs showed an energy dependent mechanism of internalization and a clathrin-mediated endocytosis pathway. Dose response treatments revealed a non-linear curve. PS-NPs also affected cell viability, inflammatory gene expression and cell morphology. NP44 strongly induced an up-regulation of IL-6 and IL-8 genes, two of the most important cytokines involved in gastric pathologies. Our study suggests that parameters such as time, size and concentration of NPs must be taken carefully into consideration during the development of drug delivery systems based on NPs and for the management of nanoparticles associated risk factors.

  7. Malignant priapism: Penile metastasis originating on a primary prostate adenocarcinoma

    PubMed Central

    da Silva Gaspar, Sandro Roberto; Nunes, Alvaro; Dias, Jose Santos; Lopes, Tome

    2015-01-01

    Malignant priapism is a definition invented in 1938 by Peacock, defined as a persistent erection, not related with sexual activity, caused by cavernous sinus and associated venous systems invasion with malignant cells. Penile secondary lesions are rare entities. Primary locations are usually the pelvic cavity organs, namely the prostate and the bladder as the most common ones. Priapism as a first manifestation of these kinds of lesions is even rarer. The aim was to present a 52-year-old patient harboring a penile metastasis that originated in the primary prostate adenocarcinoma, manifesting itself as a “common” priapism. The patient referred to the emergency room presenting with a priapism and nodules at the coronal sulcus, without previous similar episodes. His evolution until properly diagnosed was catastrophic with multiple lymph nodes, bone and organ involvement, and with his demise soon after from serious bleeding and congestive heart failure, almost 2 months after he first came to the emergency room. We review the literature concerning malignant priapism, diagnosis, and current treatment and survival perspectives. PMID:26229335

  8. A global assessment of the male predominance in esophageal adenocarcinoma

    PubMed Central

    Xie, Shao-Hua; Lagergren, Jesper

    2016-01-01

    Background Esophageal adenocarcinoma (EAC) is characterized by a male predominance. However, variations in the sex difference across populations and over time have not previously been thoroughly investigated. Results The male-to-female ratio in EAC incidence varied greatly across continents, ranging from 1.03 in Africa to 7.64 in Northern America during 2003– 2007. The ratio was high in Europe (6.04) and Oceania (6.24), and lower in Asia (4.37) and Latin America and the Caribbean (3.94). The sex ratio remained relatively stable over time in most populations. In absolute terms, the sex difference in EAC incidence increased over time in populations of higher incidence, while it remained stable or slightly decreased in low-incidence populations. Materials and Methods We used data from the Cancer Incidence in Five Continents series to compute sex-specific age-standardized rates of EAC by population. The sex difference in incidence was evaluated on both absolute and relative scales, measured by the absolute difference and ratio between sexes, respectively. Conclusions This first global assessment of the sex ratio in EAC shows that the male predominance is particularly strong in developed countries. The underlying reasons remain to be identified, but the emerging EAC burden in men merits consideration for targeted prevention and early detection. PMID:27145283

  9. Recognition of Intrabiliary Hepatic Metastases From Colorectal Adenocarcinoma

    PubMed Central

    Povoski, Stephen P.; Klimstra, David S.; Brown, Karen T.; Schwartz, Lawrence H.; Kurtz, Robert C.; Jarnagin, William R.; Fong, Yuman

    2000-01-01

    Intrinsic involvement of bile ducts, by metastatic colorectal adenocarcinoma growing from within or invading the lumen of bile ducts, is not a well recognized pattern of tumor growth. Clinical, radiographic, operative, and histopathologic aspects of 15 patients with intrabiliary colorectal metastases were described. Fourteen patients were explored for possible hepatic resection. Two had jaundice, two radiographic evidence of an intrabiliary filling defect, 10 intraoperative evidence of intrabiliary tumor, and six microscopic evidence of intrabiliariy tumor. Eleven patients underwent hepatic resection. Five of the resected patients developed hepatic recurrence. Four patients were explored for possible repeat resection. One had jaundice, one radiographic evidence of an intrabiliary filling defect, all had intraoperative evidence of intrabiliary tumor, and three microscopic evidence of intrabiliary tumor. Three patients underwent repeat hepatic resection. All patients with preoperative jaundice and radiographic evidence of an intrabiliary filling defect were unresectable. Overall, actuarial five-year survival is 33% for those patients resected versus 0% for those not resected. Intraoperative recognition of intrabiliary tumor at exploration for hepatic resection was more common than clinical, radiographic, or histopathologic recognition. More diligent examination of resected liver tissue by the surgeon and pathologist may increase identification of bile duct involvement and aid in achieving adequate tumor clearance. PMID:10977117

  10. Ileal adenocarcinoma in a mild phenotype of abetalipoproteinemia.

    PubMed

    Al-Shali, K; Wang, J; Rosen, F; Hegele, R A

    2003-02-01

    Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder that is characterized by defective assembly and secretion of plasma apolipoprotein (apo) B-containing lipoproteins. This disorder results from mutations in the MTP gene encoding the microsomal triglyceride transfer protein. We report a 58-year-old male homozygote for a missense mutation, S590I, in MTP. The patient had a lifelong history of fat malabsorption, but was only diagnosed with ABL at age 52, based upon such classic features as absence of apo B-containing lipoproteins, acanthocytosis, atypical retinitis pigmentosa and markedly depressed serum beta-carotene concentration. However, his presentation was notable not only by survival to the sixth decade of life without specific treatment, but also by the absence of neurological involvement and by normal serum vitamin E concentration. He subsequently developed adenocarcinoma of the ileum, which required ileal resection. Therefore, this missense mutation appears to be associated with a late-presenting and relatively mild ABL phenotype that lacks some classical features, particularly neuropathy, but appears to be associated with other atypical features, specifically small intestinal cancer.

  11. Retrobulbar adenocarcinoma in an Amazon parrot (Amazona autumnalis).

    PubMed

    Watson, Victoria E; Murdock, Jessica H; Cazzini, Paola; Schnellbacher, Rodney; Divers, Stephen J; Sakamoto, Kaori

    2013-03-01

    Retrobulbar neoplasms are not common in mammals and are even more infrequently seen in nonmammalian species. The current report describes a retrobulbar mass creating exophthalmia and neurologic signs in a red-lored Amazon parrot (Amazona autumnalis). A 27-year-old female parrot presented for a 3-day history of anorexia and a 2-week history of periocular soft tissue swelling and exophthalmia of the right eye. Physical examination revealed 9% dehydration and right eye exophthalmia with inability to retropulse the globe. A fine-needle aspirate was performed, and cytologic evaluation revealed necrotic debris with scattered clusters of epithelial cells, moderate numbers of macrophages, and few heterophils. Given the possibility of neoplasia and paucity of treatment options, the owners elected euthanasia and submitted the body for necropsy. A large, fluctuant, friable, red, retrobulbar mass with multiple areas of hemorrhage, on cut surface, was noted at necropsy. Histologically, the mass was composed of neoplastic, cuboidal to columnar epithelial cells, forming rosette-like glandular structures, admixed with abundant necrotic debris. The neoplastic cells were strongly positive for cytokeratin (AE1/AE3) by immunohistochemistry. Based on histopathology and immunohistochemistry, the mass was diagnosed as an adenocarcinoma.

  12. Co-expressed miRNAs in gastric adenocarcinoma.

    PubMed

    Yepes, Sally; López, Rocío; Andrade, Rafael E; Rodriguez-Urrego, Paula A; López-Kleine, Liliana; Torres, Maria Mercedes

    2016-08-01

    Co-expression networks may provide insights into the patterns of molecular interactions that underlie cellular processes. To obtain a better understanding of miRNA expression patterns in gastric adenocarcinoma and to provide markers that can be associated with histopathological findings, we performed weighted gene correlation network analysis (WGCNA) and compare it with a supervised analysis. Integrative analysis of target predictions and miRNA expression profiles in gastric cancer samples was also performed. WGCNA identified a module of co-expressed miRNAs that were associated with histological traits and tumor condition. Hub genes were identified based on statistical analysis and network centrality. The miRNAs 100, let-7c, 125b and 99a stood out for their association with the diffuse histological subtype. The 181 miRNA family and miRNA 21 highlighted for their association with the tumoral phenotype. The integrated analysis of miRNA and gene expression profiles showed the let-7 miRNA family playing a central role in the regulatory relationships.

  13. Cytotoxicity of selected magnetic fluids on human adenocarcinoma cells

    NASA Astrophysics Data System (ADS)

    Hilger, Ingrid; Frühauf, Sylvia; Linß, Werner; Hiergeist, Robert; Andrä, Wilfried; Hergt, Rudolf; Kaiser, Werner A.

    2003-04-01

    Based on the knowledge that the magnetite particles seem to be well tolerated by the human body, the cytotoxic potential of coated particles was investigated, which had been selected for potential applications regarding the minimal-invasive elimination of breast tumors by magnetic thermoablation. Human adenocarcinoma cells (BT-20) were exposed (24, 48 and 72 h) to different magnetite particles with diverging total size (8, 10 and 220 nm) and coating (cationic and anionic). One sample contained only non-coated magnetite particles. The magnetite concentration ranged between 0.2 and 20 ng/cell. Cytotoxicity was estimated by measuring the succinate dehydrogenase activity. The morphologic features resulting from the interaction of magnetic fluids with BT-20 cells was determined by transmission electron microscopy. As opposed to the non-coated magnetic particles, cationic particles induced the strongest decrease in cell survival rates depending on time and concentration. Morphologically, the cationic particle samples exerted a strong binding to cellular membranes. Changes in the subcellular structure were found in relation to the coated magnetic particles. In conclusion, our results show that the coated prototype magnetic particles, particularly those with a cationic surfactant, are cytotoxic to BT-20 cells. The cytotoxicity is attributed to electrostatic bindings with cellular membranes, influences of chemical components or non-physiologic pH. Considering the in vivo applications, adverse systemic effects are conceivable and more biocompatible coatings for the selected magnetic particles should be elaborated.

  14. Clinical outcomes among women with mucinous adenocarcinoma of the ovary

    PubMed Central

    Massad, L. Stewart; Gao, Feng; Hagemann, Ian; Powell, Mathew

    2016-01-01

    Background/Aims Patterns of metastasis and clinical behavior of mucinous ovarian cancers are poorly understood because of their rarity. Methods A retrospective review of records of women identified with pure mucinous invasive ovarian/tubal/peritoneal cancer 1992–2012 at one institution. Survival differences were compared using Kaplan-Meier methods with log-rank tests. Results Among 42 women with mucinous adenocarcinomas the median age was 55 years (range 33–83 years). Most cancers were well differentiated (n = 26, 68%) and stage I/II (n = 31, 74%). One of 27 women with sampled nodes had nodal metastasis; one additional woman recurred in a pelvic node. Most had no visible residual tumor after initial surgery, but of 10 women with stage III/IV cancer and documented residual, 8 had >2cm residual. Except for one woman alive with disease at last follow-up, all who recurred died of disease. Five-year survival was 83% for stage I/II cases but 29% among stage III/IV cases. Stage was a strong predictor of survival (hazard ratio of death among women with stage III/IV cancer 7.73, 95% C.I. 2.33–25.66, P<0.001 vs women with stage I/II cancer). Conclusion Mucinous ovarian cancers have a distinct biology, such that lymphadenectomy for staging is unnecessary and metastatic cancers have poor prognosis. PMID:26583769

  15. Oviduct adenocarcinoma in some species of captive snakes.

    PubMed

    Pereira, M E; Viner, T C

    2008-09-01

    This article reports 5 cases of oviduct adenocarcinoma in adult captive snakes from Smithsonian's National Zoological Park. This neoplasm was found in 1 of each of the following species: emerald tree boa (Corallus caninus), Amazonian tree boa (Corallus enydris enydris), Burmese rock python (Python molurus bivittatus), Northern pine snake (Pituophis melanoleucus melanoleucus), and corn snake (Elaphe guttata). Grossly, tan to red firm masses were found within oviducts in 3 cases. In an additional 2 cases, the primary tumor was detected only histologically. Microscopically, neoplasms were papillary, and often extended transmurally. The neoplastic cells were polygonal and organized in acini or cords, with often abundant fibrovascular stroma. Hemorrhages and necrosis were present in all cases. Inflammation, myxomatous material, desmoplasia, and bacteria were often observed. Histologic evidence of metastasis was present in all cases. Solid metastases were seen in all animals except the Northern pine snake and involved several organs including the liver, lung, and heart. Emboli of neoplastic cells were observed in all animals but the Burmese rock python and corn snake.

  16. Circulating Tumor Cells in the Adenocarcinoma of the Esophagus

    PubMed Central

    Gallerani, Giulia; Fabbri, Francesco

    2016-01-01

    Circulating tumor cells (CTCs) are elements of indisputable significance as they seem to be responsible for the onset of metastasis. Despite this, research into CTCs and their clinical application have been hindered by their rarity and heterogeneity at the molecular and cellular level, and also by a lack of technical standardization. Esophageal adenocarcinoma (EAC) is a highly aggressive cancer that is often diagnosed at an advanced stage. Its incidence has increased so much in recent years that new diagnostic, prognostic and predictive biomarkers are urgently needed. Preliminary findings suggest that CTCs could represent an effective, non-invasive, real-time assessable biomarker in all stages of EAC. This review provides an overview of EAC and CTC characteristics and reports the main research results obtained on CTCs in this setting. The need to carry out further basic and translational research in this area to confirm the clinical usefulness of CTCs and to provide oncologists with a tool to improve therapeutic strategies for EAC patients was herein highlighted. PMID:27527155

  17. The HSP90 Inhibitor Ganetespib Radiosensitizes Human Lung Adenocarcinoma Cells

    PubMed Central

    Gomez-Casal, Roberto; Bhattacharya, Chitralekha; Epperly, Michael W.; Basse, Per H.; Wang, Hong; Wang, Xinhui; Proia, David A.; Greenberger, Joel S.; Socinski, Mark A.; Levina, Vera

    2015-01-01

    The molecular chaperone HSP90 is involved in stabilization and function of multiple client proteins, many of which represent important oncogenic drivers in NSCLC. Utilization of HSP90 inhibitors as radiosensitizing agents is a promising approach. The antitumor activity of ganetespib, HSP90 inhibitor, was evaluated in human lung adenocarcinoma (AC) cells for its ability to potentiate the effects of IR treatment in both in vitro and in vivo. The cytotoxic effects of ganetespib included; G2/M cell cycle arrest, inhibition of DNA repair, apoptosis induction, and promotion of senescence. All of these antitumor effects were both concentration- and time-dependent. Both pretreatment and post-radiation treatment with ganetespib at low nanomolar concentrations induced radiosensitization in lung AC cells in vitro. Ganetespib may impart radiosensitization through multiple mechanisms: such as down regulation of the PI3K/Akt pathway; diminished DNA repair capacity and promotion of cellular senescence. In vivo, ganetespib reduced growth of T2821 tumor xenografts in mice and sensitized tumors to IR. Tumor irradiation led to dramatic upregulation of β-catenin expression in tumor tissues, an effect that was mitigated in T2821 xenografts when ganetespib was combined with IR treatments. These data highlight the promise of combining ganetespib with IR therapies in the treatment of AC lung tumors. PMID:26010604

  18. Effect of gyromagnetic fields on human prostatic adenocarcinoma cells

    PubMed Central

    Lei, Hongen; Xu, Yongde; Guan, Ruili; Li, Meng; Hui, Yu; Gao, Zhezhu; Yang, Bicheng; Xin, Zhongcheng

    2015-01-01

    Purpose To investigate the biological effect of gyromagnetic fields (GMFs) on cell proliferation and apoptosis of human prostatic adenocarcinoma cells and explore the underlying mechanisms. Methods PC-3 cells were grouped into normal control (NC) and GMF treatment groups. Cell proliferation was analyzed with kit-8 and Ki67 immunofluorescence staining, while cell apoptosis was analyzed with flow cytometry double staining of Annexin V-PE/7-AAD. The Akt and p38 MAPK/Caspase signaling pathways were analyzed by western blotting and immunofluorescence staining, and cell polarization was analyzed with PARD3. Results Cell proliferation and activity of the Akt pathway were significantly decreased by the GMF, while cell apoptosis, activity of p38 MAPK, and PARD3-positive cell number were significantly increased in the GMF group compared to the NC group. Conclusion GMFs inhibit cell proliferation, induce apoptosis, and regulate tumor cell polarity conditions, potentially through down-regulating Akt, activating the p38 MAPK/Caspase pathway, and promoting PARD3 expression in PC-3 cells. PMID:26648740

  19. 5-Fluorouracil-radiation interactions in human colon adenocarcinoma cells

    SciTech Connect

    Buchholz, D.J.; Lepek, K.J.; Rich, T.A.

    1995-07-15

    The purpose of this investigation was to determine the effect of cellular proliferation and cell cycle stage on the ability of postirradiation 5-fluorouracil (5-FU) to radiosensitize cultured human colon adenocarcinoma Clone A cells. Cell survival curves were generated for irradiated: (a) log- and plateau-phase Clone A cells; and (b) Clone A cells separated by centrifugal elutriation into the various phases of the cell cycle; with and without postirradiation treatment with 100 {mu}g/ml 5-FU. Postirradiation treatment with 5-FU sensitized proliferating cells to a greater degree than it sensitized cells growing in plateau phase. The {beta} component of cell kill in log-phase cells was increased by a factor of 1.5 with a sensitizer enhancement ratio of 1.21 at the 0.01 survival level. Plateau-phase cells showed less radiosensitization (sensitizer enhancement ratio of 1.13 at the 0.01 survival level); however, there was a mild increase in both {alpha} and {beta} kill in plateau-phase cells. Elutriated G{sub 1} cells were the most radiosensitive, independent of treatment with 5-FU. The phase of the cell cycle had little effect on the ability of fluorouracil to radiosensitize Clone A cells. Proliferating cells are more susceptible to radiosensitization with 5-FU than plateau-phase cells are, but this effect appears to be independent of the phase of the cell cycle. 18 refs., 4 figs., 3 tabs.

  20. Genetic progression of Barrett's oesophagus to oesophageal adenocarcinoma.

    PubMed

    Gregson, Eleanor M; Bornschein, Jan; Fitzgerald, Rebecca C

    2016-08-09

    Barrett's oesophagus (BE) is the premalignant condition associated with the development of oesophageal adenocarcinoma (OAC). Diagnostically, p53 immunohistochemistry remains the only biomarker recommended clinically to aid histopathological diagnosis. The emerging mutational profile of BE is one of highly heterogeneous lesions at the genomic level with many mutations already occurring in non-dysplastic tissue. As well as point mutations, larger scale copy-number changes appear to have a key role in the progression to OAC and clinically applicable assays for the reliable detection of aneuploidy will be important to incorporate into future clinical management of patients. For some patients, the transition to malignancy may occur rapidly through a genome-doubling event or chromosomal catastrophe, termed chromothripsis, and detecting these patients may prove especially difficult. Given the heterogeneous nature of this disease, sampling methods to overcome inherent bias from endoscopic biopsies coupled with the development of more objective biomarkers than the current reliance on histopathology will be required for risk stratification. The aim of this approach will be to spare low-risk patients unnecessary procedures, as well as to provide endoscopic therapy to the patients at highest risk, thereby avoiding the burden of incurable metastatic disease.

  1. Visualization of early prostatic adenocarcinoma as a stem cell disease.

    PubMed

    Jiang, Maggie Y; Lee, Tammy L; Hao, Su-Shin; Mahooti, Sepi; Baird, Stephen M; Donoghue, Daniel J; Haas, Martin

    2016-11-15

    Prostate Cancer represents the second leading cause of cancer death among men in the United States, and the third leading cause of cancer death among men in Europe. We have previously shown that cells possessing Cancer Stem Cell (CSC) characteristics can be grown from human PrCa tissue harvested at the time of prostatectomy. However, the cellular origin of these CSCs was not previously known. In most cases, simple hematoxylin and eosin (H&E) stained sections are sufficient to make a definitive diagnosis of prostatic adenocarcinoma (PrCa) in needle biopsy samples. We utilized six different antibodies specific for stem cell antigens to examine paraffin sections of PrCa taken at the time of needle-biopsy diagnosis. These antisera were specific for CD44, CD133, ALDH7A1, LGR-5, Oct-4 and NANOG. We demonstrate specific staining of tumor cells with all six antisera specific for stem cell antigens. Some of these antibodies also react with cells of hyperplastic glands, but the patterns of reactivity differ from those of malignant glands. These findings demonstrate that at the time of diagnosis, PrCa consists of cells exhibiting properties of CSCs and consistent with the possibility that PrCa is a stem cell disease.

  2. Prostatic adenocarcinoma with mandibular metastatic lesion: case report.

    PubMed

    Reyes Court, Daniel; Encina, Susana; Levy, Irene

    2007-10-01

    Metastatic lesions of primary tumors, which originate in different parts of the body, comprise almost 1 % of different types of oral cancers. These lesions can affect either bones or soft tissues in the maxillofacial region. Whenever the maxillofacial area is affected, the most common location is in the molar region of the mandible. The clinical presentation of mandibular metastasis follows a clinical pattern characterized by irradiated dental pain in the third molar region. The most frequent sign is parethesia of the area innervated by the mandibular alveolar dental nerve. Differential diagnosis and treatment of these patients can be extremely difficult because there a number of pathologic conditions with similar symptoms and because diagnostic examination can be highly confusing. The aim of this article is to present a case of prostatic adenocarcinoma where the only metastasis was found in the jaw. A literature review will be presented, hoping to contribute to the scarce information regarding this lesion, due to its low frequency and atypical expression of this type of metastasis in terms of etiology, biological behavior and treatment.

  3. Study of aggressiveness prediction of mammary adenocarcinoma by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Andrade Bitar, Renata; da Silva Martinho, Herculano; Zambelli Ramalho, Leandra Náira; dos Santos Junior, Arnaldo Rodrigues; Silva Ramalho, Fernando; Raniero, Leandro; Martin, Airton A.

    2012-01-01

    Although there are many articles focused on in vivo or ex vivo Raman analysis for cancer diagnosis, to the best of our knowledge its potential to predict the aggressiveness of tumor has not been fully explored yet. In this work Raman spectra in the finger print region of ex vivo breast tissues of both healthy mice (normal) and mice with induced mammary gland tumors (abnormal) were measured and associated to matrix metalloproteinase-19 (MMP-19) immunohistochemical exam. It was possible to verify that normal breast, benign lesions, and adenocarcinomas spectra, including the subtypes (cribriform, papillary and solid) could have their aggressiveness diagnosed by vibrational Raman bands. By using MMP- 19 exam it was possible to classify the samples by malignant graduation in accordance to the classification results of Principal Component Analysis (PCA). The spectra NM /MH were classified correctly in 100% of cases; CA/CPA group had 60 % of spectra correctly classified and for PA/AS 54% of the spectra were correctly classified.

  4. Stem cells as the root of pancreatic ductal adenocarcinoma

    SciTech Connect

    Balic, Anamaria; Dorado, Jorge; Alonso-Gomez, Mercedes; Heeschen, Christopher

    2012-04-01

    Emerging evidence suggests that stem cells play a crucial role not only in the generation and maintenance of different tissues, but also in the development and progression of malignancies. For the many solid cancers, it has now been shown that they harbor a distinct subpopulation of cancer cells that bear stem cell features and therefore, these cells are termed cancer stem cells (CSC) or tumor-propagating cells. CSC are exclusively tumorigenic and essential drivers for tumor progression and metastasis. Moreover, it has been shown that pancreatic ductal adenocarcinoma does not only contain one homogeneous population of CSC rather than diverse subpopulations that may have evolved during tumor progression. One of these populations is called migrating CSC and can be characterized by CXCR4 co-expression. Only these cells are capable of evading the primary tumor and traveling to distant sites such as the liver as the preferred site of metastatic spread. Clinically even more important, however, is the observation that CSC are highly resistant to chemo- and radiotherapy resulting in their relative enrichment during treatment and rapid relapse of disease. Many laboratories are now working on the further in-depth characterization of these cells, which may eventually allow for the identification of their Achilles heal and lead to novel treatment modalities for fighting this deadly disease.

  5. Role of Nampt and Visceral Adiposity in Esophagogastric Junction Adenocarcinoma

    PubMed Central

    Li, Haijun; Bai, E.; Zhang, Yong; Jia, Zhuoqi

    2017-01-01

    Nampt including eNampt and iNampt may contribute to mediating obesity-associated cancers. This study investigated the role of Nampt in esophagogastric junction adenocarcinoma (EGA), a cancer strongly correlated with obesity. Visceral adiposity was defined by waist circumference or VFA. eNampt in sera were measured by enzyme-linked immunosorbent assay. iNampt expression in EGA was determined by PCR, western blot, and immunohistochemistry. Sera eNampt were significantly elevated in these overweight and obese patients, especially for viscerally obese patients, and positively correlated with BMI, waist circumference, VFA, and also primary tumor, regional lymph nodes, and TNM stage (P < 0.05). iNampt expression in both the mRNA and protein levels was upregulated in EGAs (P < 0.05). iNampt staining was found primarily in the cytoplasm and nuclei and significantly associated with tumor, lymph nodes, and TNM stage and also correlated positively with serum eNampt, BMI, total fat area, VFA, superficial fat area, and waist circumference (P < 0.05). iNampt, eNampt, tumor, lymph nodes, and TNM stage correlated to the survival of EGAs, and iNampt expression and TNM stage affected the prognosis independently (P < 0.05). This study highlighted the association of eNampt/iNampt with visceral obesity and a potential impact on the biology of EGA. PMID:28168205

  6. Adenosine deaminase complexing protein (ADCP) immunoreactivity in colorectal adenocarcinoma.

    PubMed

    ten Kate, J; van den Ingh, H F; Khan, P M; Bosman, F T

    1986-04-15

    Immunoreactive adenosine deaminase complexing protein (ADCP) was studied in 91 human colorectal adenocarcinomas. The expression of ADCP was correlated with that of secretory component (SC) and carcinoembryonic antigen (CEA), with the histological grade and the Dukes' stage of the carcinomas. The histological grade was scored semi-quantitatively according to 5 structural and 4 cytological variables. ADCP expression was observed in 3 different staining patterns, namely: (1) diffuse cytoplasmic (77% of the carcinomas); (2) granular cytoplasmic (13%); and (3) membrane-associated (66%). These patterns were observed alone or in combination. Eleven percent of the carcinomas exhibited no ADCP immunoreactivity. Linear regression analysis showed that the expression of ADCP correlates with that of SC and CEA. However, no significant correlation emerged between the histological parameters or the Dukes' stage and any of the immunohistological parameters. Comparison of the histological characteristics of carcinomas exhibiting little or no ADCP immunoreactivity with those showing extensive immunoreactivity, showed that membranous ADCP immunoreactivity occurs more frequently in well-differentiated carcinomas. Structural parameters showed a better correlation with membranous ADCP expression than the cytological variables. It is concluded that membranous expression of ADCP and CEA are indicators of a high level of differentiation as reflected primarily in the structural characteristics of the tumor.

  7. Quantitative changes in adenosine deaminase isoenzymes in human colorectal adenocarcinomas.

    PubMed

    ten Kate, J; Wijnen, J T; van der Goes, R G; Quadt, R; Griffioen, G; Bosman, F T; Khan, P M

    1984-10-01

    Several reports have suggested that a decrease or absence of adenosine deaminase complexing protein (ADCP) is consistently associated with cancer. However, in other studies, decreased as well as increased ADCP levels were found. In the present study, we investigated ADCP levels in 37 colorectal adenocarcinomas and correlated the results with clinicopathological characteristics in individual carcinomas. The levels of adenosine deaminase (EC 3.5.4.4) and soluble ADCP were determined in tissue samples by, respectively, a spectrophotometric assay and an ADCP specific radioimmunoassay. The values in the individual tumors were compared with their histological characteristics, such as degree of differentiation, nuclear grading, and the preoperative plasma carcinoembryonic antigen levels in the patients. It was found that ADCP was decreased in about a third of the tumors but unaltered or even increased in others. However, there was an overall 40% increase of the adenosine deaminase activity in the tumors compared to normal tissue. There seems to be no simple correlation between any of the clinicopathological parameters and the ADCP or adenosine deaminase levels. Methods detecting ADCP at single cell level might be helpful in exploring its potential use as a cancer-associated marker.

  8. Alterations of Membrane Glycopeptides in Human Colonic Adenocarcinoma

    PubMed Central

    Kim, Young S.; Isaacs, Richard; Perdomo, Jose M.

    1974-01-01

    Membrane glycopeptides were examined in human colonic adenocarcinoma and normal colonic mucosa. The carbohydrates of membrane glycopeptides were found to be markedly reduced in tumor tissue and the relative proportions of the various sugars were altered. Although all of the sugars were lower in tumor tissue when compared to the adjacent normal mucosa, galactosamine, fucose, and sialic acid were more significantly reduced. Examination of the blood group activity and lectin-binding properties of membrane glycopeptides revealed that specific carbohydrate structures had changed in the tumor tissue. Most striking of these changes was the disappearance of glycoprotein-associated blood group A activity. Assay of the enzyme responsible for synthesis of the blood group A determinant showed that this glycosyltransferase activity was greatly diminished in tumor tissue. A galactosyltransferase and a fucosyltransferase were also significantly lower in the tumor tissue whereas the levels of another galactosyltransferase and a sialyltransferase were unaltered. Glycosidase activities in the normal and tumor tissues were similar. The results show that an alteration in glycoprotein biosynthesis occurred during tumorigenesis that resulted in a modified membrane glycoprotein composition and that these changes are probably a reflection of reduced levels of the enzymes responsible for glycoprotein synthesis. PMID:4140512

  9. Subcellular localization of the human papillomavirus 16 E7 oncoprotein in CaSki cells and its detection in cervical adenocarcinoma and adenocarcinoma in situ.

    PubMed

    Dreier, Kerstin; Scheiden, René; Lener, Barbara; Ehehalt, Daniela; Pircher, Haymo; Müller-Holzner, Elisabeth; Rostek, Ursula; Kaiser, Andreas; Fiedler, Marc; Ressler, Sigrun; Lechner, Stefan; Widschwendter, Andreas; Even, Jos; Capesius, Catherine; Jansen-Dürr, Pidder; Zwerschke, Werner

    2011-01-05

    E7 is the major oncoprotein of high-risk human papillomaviruses (HPV) which causes cervical cancer. To date E7 oncoproteins have not been investigated in cervical adenocarcinoma. In this study we generated a rabbit monoclonal anti-HPV-16 E7 antibody, RabMab42-3, which recognizes a conformational epitope in the E7 carboxy-terminal zinc-finger resulting in a strong increase in the sensitivity for the detection of cell-associated HPV-16 E7 protein relative to conventional polyclonal anti-HPV-16 E7 antibodies. Using RabMab42-3, we show that the subcellular localization of endogenous HPV-16 E7 oncoprotein varies during the cell cycle in cervical cancer cells. Moreover, we demonstrate for the first time that the HPV-16 E7 oncoprotein is abundantly expressed in cervical adenocarcinoma in situ and adenocarcinoma, suggesting an important role of HPV-16 E7 for the development of these tumors. Our findings suggest that the HPV-16 E7 oncoprotein could be a useful marker for the detection of cervical adenocarcinoma and their precursors.

  10. Adenocarcinoma arising from vaginal stump: unusual vaginal carcinogenesis 7 years after hysterectomy due to cervical intraepithelial neoplasia.

    PubMed

    Shibata, Takashi; Ikura, Yoshihiro; Iwai, Yasuhiro; Tokuda, Hisato; Cho, Yuka; Morimoto, Noriyuki; Nakago, Satoshi; Oishi, Tetsuya

    2013-11-01

    Primary vaginal adenocarcinomas are one of the rarest malignant neoplasms, which develop in the female genital tract. Because of the extremely low incidence, their clinical and pathologic characteristics are still obscure. Recently, we experienced a case of vaginal adenocarcinoma that appeared 7 yr after hysterectomy because of cervical intraepithelial neoplasia. The patient, a 65-yr-old obese woman, was diagnosed as having adenocarcinoma in the vaginal stump and was treated by simple tumor excision and radiation. Immunohistochemical and molecular biologic examinations indicated a potential association with human papilloma virus infection in the development of the vaginal adenocarcinoma. There has been no evidence of recurrence for 3 yr after the operation.

  11. Survival after attempted surgical resection and intraoperative radiation therapy for pancreatic and periampullary adenocarcinoma

    SciTech Connect

    O'Connor, John K.; Sause, William T. . E-mail: ldwsause@ihc.com; Hazard, Lisa J.; Noyes, R. Dirk

    2005-11-15

    Purpose: To evaluate a single institution's experience with intraoperative radiation therapy (IORT) in combination with attempted surgical resection for pancreatic and periampullary adenocarcinoma. Methods and Materials: From May 1986 until June 2001, 77 patients at LDS Hospital underwent attempted surgical resection and IORT for pancreatic or periampullary adenocarcinoma. A potentially curative resection was defined as surgery with negative or microscopic positive margins. No patients had metastatic disease at the time of surgery and IORT. Forty-four patients with tumors located in the pancreas and 9 patients with periampullary tumors underwent potentially curative surgical resection and IORT. Twenty-four patients had pancreatic tumors deemed unresectable and underwent surgical bypass and IORT. Actuarial survival was calculated from the date of IORT until last follow-up or death by use of the Kaplan-Meier method. Results: Patients undergoing a potentially curative resection and IORT for periampullary adenocarcinoma had a median survival of 167 months and a 56% 5-year actuarial survival, compared with a median survival of 16 months and a 19% 5-year actuarial survival for patients undergoing the same treatment for pancreatic adenocarcinoma (p = 0.03). Patients with unresectable disease who underwent bypass and IORT had a median survival of 11 months and a 0% 3-year survival, significantly worse than patients able to undergo surgical resection and IORT (p = 0.0002). The operative mortality for all patients undergoing potentially curative resection and IORT was 3.7%. Conclusions: Intraoperative radiation therapy is well tolerated and does not increase the morbidity or mortality of potentially curative surgical resection for pancreatic or periampullary adenocarcinoma. Patients with periampullary adenocarcinoma have a better prognosis than those with pancreatic adenocarcinoma, and patients with unresectable pancreatic disease fared worse.

  12. Stratified epithelium in prostatic adenocarcinoma: a mimic of high-grade prostatic intraepithelial neoplasia.

    PubMed

    Hameed, Omar; Humphrey, Peter A

    2006-07-01

    Typically glands of prostatic adenocarcinoma have a single cell lining, although stratification can be seen in invasive carcinomas with a cribriform architecture, including ductal carcinoma. The presence and diagnostic significance of stratified cells within non-cribriform carcinomatous prostatic glands has not been well addressed. The histomorphological features and immunohistochemical profile of cases of non-cribriform prostatic adenocarcinoma with stratified malignant glandular epithelium were analyzed. These cases were identified from needle biopsy cases from the consultation files of one of the authors and from a review of 150 consecutive in-house needle biopsy cases of prostatic adenocarcinoma. Immunohistochemistry was performed utilizing antibodies reactive against high molecular weight cytokeratin (34betaE12), p63 and alpha-methylacyl-coenzyme-A racemase (AMACR). A total of 8 cases were identified, including 2 from the 150 consecutive in-house cases (1.3%). In 4 cases, the focus with glands having stratified epithelium was the sole carcinomatous component in the biopsy, while such a component represented 5-30% of the invasive carcinoma seen elsewhere in the remaining cases. The main attribute in all these foci was the presence of glandular profiles lined by several layers of epithelial cells with cytological and architectural features resembling flat or tufted high-grade prostatic intraepithelial neoplasia, but lacking basal cells as confirmed by negative 34betaE12 and/or p63 immunostains in all cases. The AMACR staining profile of the stratified foci was variable, with 4 foci showing positivity, and 3 foci being negative, including two cases that displayed AMACR positivity in adjacent non-stratified prostatic adenocarcinoma. Prostatic adenocarcinoma with stratified malignant glandular epithelium can be identified in prostate needle biopsy samples harboring non-cribriform prostatic adenocarcinoma and resembles glands with high-grade prostatic

  13. The incidence of EGFR-activating mutations in bone metastases of lung adenocarcinoma.

    PubMed

    Krawczyk, Paweł; Nicoś, Marcin; Ramlau, Rodryg; Powrózek, Tomasz; Wojas-Krawczyk, Kamila; Sura, Sylwia; Jarosz, Bożena; Szumiło, Justyna; Warda, Edward; Mazurkiewicz, Tomasz; Sawicki, Marek; Milanowski, Janusz

    2014-01-01

    Poor prognosis of lung adenocarcinoma is associated with early occurrence of distant metastases. This type of non-small-cell lung carcinoma more frequently involves EGFR gene abnormalities, which determine the efficacy of EGFR tyrosine kinase inhibitor therapies (EGFR TKIs). It is probable that genetic abnormalities present in primary tumor will also be present in metastases. Unfortunately little is known about the incidence of these mutations in the metastases and about the effectiveness of molecularly targeted therapy in such patients. Formalin-fixed, paraffin-embedded tumor tissue was prepared from 431 samples of primary adenocarcinoma, 61 of adenocarcinoma central nervous system (CNS) metastases and 8 of adenocarcinoma bone metastases. The presence of exon 19 deletions was examined using the PCR technique and amplified PCR product fragment length analysis. The ASP-PCR technique was used to evaluate the L858R substitutions in exon 21, and the results were analyzed using ALF Express II sequencer. In the adenocarcinoma metastases to bone obtained from 8 patients, deletions in exon 19 of the EGFR gene were revealed in 3 smoking men and one non-smoking woman, while L858R substitution in exon 21 was found in one smoking woman and one man of unknown smoking status. The incidence of EGFR gene mutations in the bone metastases was 75%, in the primary adenocarcinoma--12.8%, and in the adenocarcinoma metastases to CNS--14.75%. Five patients with EGFR gene mutation revealed in bone metastases were treated with EGFR TKIs; the majority of them had a satisfactory response to therapy.

  14. Semiquantitative Computed Tomographic Characteristics for Lung Adenocarcinoma and Their Association with Lung Cancer Survival

    PubMed Central

    Wang, Hua; Schabath, Matthew B.; Liu, Ying; Berglund, Anders E.; Bloom, Gregory C.; Kim, Jongphil; Stringfield, Olya; Eikman, Edward A.; Klippenstein, Donald L.; Heine, John J.; Eschrich, Steven A.; Ye, Zhaoxiang; Gillies, Robert J.

    2015-01-01

    Background Computed tomographic (CT) characteristics derived from noninvasive images that represent the entire tumor may have diagnostic and prognostic value. The purpose of this study was to assess the association of a standardized set of semiquantitative CT characteristics of lung adenocarcinoma with overall survival. Patients and Methods An initial set of CT descriptors was developed to semiquantitatively assess lung adenocarcinoma in patients (n=117) who underwent resection. Survival analyses were used to determine the association between each characteristic and overall survival. Principle component analysis (PCA) was used to determine characteristics that may differentiate histological subtypes. Results Characteristics significantly associated with overall survival included pleural attachment (p < 0.001), air bronchogram (p = 0.03), and lymphadenopathy (p = 0.02). Multivariate analyses revealed pleural attachment was significantly associated with an increased risk of death overall (hazard ratio [HR] = 3.21; 95% confidence interval [CI] 1.53 – 6.70) and among patients with lepidic predominant adenocarcinomas (HR = 5.85; 95% CI 1.75 – 19.59), while lymphadenopathy was significantly associated with an increased risk of death among patients with adenocarcinomas without a predominant lepidic component (HR = 3.07; 95% CI 1.09 – 8.70). A PCA model showed that texture (ground-glass opacity component) was most important for separating the two subtypes. Conclusion A subset of the semiquantitative characteristics described herein has prognostic importance and ability to distinguish between different histological subtypes of lung adenocarcinoma. PMID:26077095

  15. The role of the obestatin/GPR39 system in human gastric adenocarcinomas.

    PubMed

    Alén, Begoña O; Leal-López, Saúl; Alén, María Otero; Viaño, Patricia; García-Castro, Victoria; Mosteiro, Carlos S; Beiras, Andrés; Casanueva, Felipe F; Gallego, Rosalía; García-Caballero, Tomás; Camiña, Jesús P; Pazos, Yolanda

    2016-02-02

    Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer.

  16. Lymphatic vessel densities of lymph node-negative prostate adenocarcinoma in Korea.

    PubMed

    Kim, Hyun-Soo; Sung, Wooseok; Lee, Sun; Chang, Sung-Goo; Park, Yong-Koo

    2009-01-01

    Although lymphatic vessel density (LVD) is associated with regional lymph node (LN) metastasis in prostate adenocarcinoma, no study is available that examines whether the LVD is correlated with prognostic factors other than LN metastasis in LN-negative prostate adenocarcinoma. The aim of our study was to analyze intratumoral (IT), peritumoral (PT), and nontumoral (NT) LVDs, and to determine if there is a correlation between the LVD and the clinicopathological parameters in the Korean LN-negative prostate adenocarcinoma patients. Lymphatics were detected by immunohistochemical staining using D2-40 antibody on 39 radical prostatectomy specimens. Mean LVDs of IT, PT, and NT compartments were 5.39+/-4.22, 10.71+/-4.61, and 2.04+/-1.34 per 200 x field, respectively. The difference in LVD among the compartments was significant (P<0.001). The IT-LVD was significantly lower in patients with larger tumor volume (P=0.029) and higher preoperative prostate-specific antigen level (P=0.008). The PT-LVD showed no significant correlation with the clinicopathological parameters. Our results suggest that IT- and PT-LVDs may increase in LN-negative prostate adenocarcinoma as a result of lymphangiogenesis, but IT lymphatics may decrease due to mechanical compression and destruction caused by proliferating tumor cells. In addition, IT-LVD may be used as a prognostic factor in LN-negative prostate adenocarcinoma.

  17. Apocrine Adenocarcinoma of the Vulva: A Case Report and Review of the Literature

    PubMed Central

    Aoyama, Kohei; Sawada, Morio; Mori, Taisuke; Yasukawa, Satoru

    2016-01-01

    Primary vulvar adenocarcinomas are very rare. We describe the rare case of primary vulvar apocrine adenocarcinoma, a histologically rare subtype of vulvar adenocarcinoma. A 57-year-old Japanese woman presented with an enlarging vulvar mass. A dark-red, hemorrhagic, ulcerated tumor was on the right side of the anterior labial commissure measuring approximately 3.5 × 3.5 cm. Preoperative biopsy showed poorly differentiated carcinoma with partial differentiation to adenocarcinoma. Systemic examination revealed lymph node metastases in both inguinal regions and no other primary source. We performed radical vulvectomy and bilateral inguinal and pelvic lymphadenectomy. Histopathologic diagnosis was apocrine adenocarcinoma of the vulva with inguinal lymph node metastases, pT1bN2bM0. Surgical margins were negative. The patient received no adjuvant chemotherapy or radiation. Inguinal lymph node recurrence occurred after six months. Reresection and adjuvant tomotherapy were performed. After a further 12 months of observation, no rerecurrence was observed. The patient is now on follow-up. PMID:27668109

  18. Comparison of EGFR mutation rates in lung adenocarcinoma tissue and pleural effusion samples.

    PubMed

    Guan, Y; Wang, Z J; Wang, L Q; Hua, D F; Liu, J

    2016-04-04

    The goal of the current study was to investigate the differences in epidermal growth factor receptor (EGFR) mutation rates in tumor tissue and pleural effusion specimens from patients with lung adenocarcinoma. PCR amplification and gene sequencing were used to detect EGFR mutations in exons 18, 19, 20, and 21 in tumor tissue and pleural effusion samples from 50 patients with advanced lung adenocarcinoma. The EGFR mutation rate was 34.0% in tissue samples from patients with advanced lung adenocarcinoma. There were 11 cases with exon 19 mutations and 6 cases with exon 21 mutations. The EGFR mutation rate was 30.0% in pleural effusion specimens, including 10 cases with exon 19 mutation and 5 cases with exon 21 mutations. Although the tissue samples had a slightly higher mutation rate compared to the pleural effusion samples, the difference was not statistically significant. These results indicate that the EGFR mutation rate detected in pleural effusion specimens from patients with advanced lung adenocarcinoma is similar to that detected in tumor tissue samples. Therefore, pleural effusion specimens can potentially be used for EGFR mutation detection in advanced lung adenocarcinoma.

  19. ALK gene rearranged lung adenocarcinomas: molecular genetics and morphology in cohort of patients from North India.

    PubMed

    Bal, Amanjit; Singh, Navneet; Agarwal, Parimal; Das, Ashim; Behera, Digambar

    2016-10-01

    ALK gene rearrangement in the lung adenocarcinomas is the second most common (1.6-11.7% of NSCLC) targetable genomic change after EGFR mutations. However, the prevalence and clinicopathological features of ALK-rearranged lung adenocarcinomas from North India are lacking. A total of 240 cases of lung adenocarcinoma were screened for EGFR mutations and for ALK expression. Smoking status, TNM stage, and treatment response were recorded in all cases. Out of 240 cases screened, 37 cases were positive for EGFR mutations and 17 cases (7.08%) showed ALK positivity with immunohistochemistry and break-apart FISH. On excluding 37 EGFR mutation-positive cases, the incidence of ALK-positive adenocarcinoma appears to be higher (17/203 cases, 8.03%). Eight were men and nine were women with mean age of 51.7 years. Majority (62.5%) were non-smokers and had unresectable disease (70.6% stage IV, 17.6% IIIB). The morphological patterns noted were solid (12 cases), papillary (four cases), and micropapillary (one case). Signet ring (two cases) and clear cell change (one cases) were noted. Out of five patients who received crizotinib, three had partial response and two had stable disease. ALK-rearranged lung adenocarcinomas account for a minor proportion of NSCLC with prevalence similar to that reported in literature. However, as contrast to published data in our series, patients were in older age group and had solid and papillary pattern on morphology with an aggressive course.

  20. First reports of esophageal adenocarcinoma with white globe appearance in Japanese and Caucasian patients

    PubMed Central

    Tonai, Yusuke; Ishihara, Ryu; Yamasaki, Yasushi; Kanesaka, Takashi; Yamamoto, Sachiko; Akasaka, Tomofumi; Hanaoka, Noboru; Takeuchi, Yoji; Higashino, Koji; Uedo, Noriya; Tomita, Yasuhiko; Iishi, Hiroyasu

    2016-01-01

    Background and study aims: Better endoscopic diagnosis in case of Barrett’s esophagus is still needed. White globe appearance (WGA) is a novel endoscopic marker for gastric adenocarcinoma, with high sensitivity for differentiating between gastric cancer/high-grade dysplasia and other lesions. We report 2 cases of esophageal adenocarcinoma with WGA. In Case 1, esophagogastroduodenoscopy (EGD) revealed a 10-mm esophageal adenocarcinoma in a 48-year-old Japanese woman with short-segment Barrett’s esophagus. A small (< 1 mm) white globular lesion, typical of WGA, was observed under the epithelium by magnifying narrow-band imaging. A dilated neoplastic gland with eosinophilic material and necrotic epithelial fragments was identified at the site of the WGA by histologic examination. In Case 2, EGD revealed a 5-mm esophageal adenocarcinoma in a 60-year-old Caucasian man with long-segment Barrett’s esophagus. A typical WGA was observed by magnifying narrow-band imaging and similar histologic findings were identified at the site of the WGA. WGA could be a reliable endoscopic finding for target biopsy in esophageal adenocarcinoma, if its specificity is as high as in gastric cancer. The clinical implications of WGA in patients with Barrett’s esophagus should be investigated further. PMID:27747281

  1. Nasopharyngeal non-intestinal-type adenocarcinoma: a case report and updated review of the literature

    PubMed Central

    Jain, C.; Caulley, L.; Macdonald, K.I.; Purgina, B.; Lai, C.K.; Esche, B.; Johnson-Obaseki, S.

    2017-01-01

    Background Non-intestinal-type adenocarcinoma is a malignancy traditionally found in the sinonasal cavity. To our knowledge, this case is the first reported of this rare condition originating in the nasopharynx. Case Presentation A 67-year-old woman with nasopharyngeal non-intestinal-type adenocarcinoma, with an accompanying parapharyngeal mass received primary radiation treatment for both lesions. Her tumour subsequently persisted, with a concomitant conversion in pathology from a low- to a high-grade malignancy. Results Non-intestinal-type and intestinal-type adenocarcinomas of the nasopharynx are extremely rare tumours and do not appear in the World Health Organization classification system. We review the pathophysiologic features of these malignancies and propose modifications to the current classification system. Conclusions Non-intestinal-type adenocarcinoma should be included in the differential diagnosis of nasopharyngeal masses. In our experience, this tumour in this location showed a partial response to primary radiation but later converted from a low- to a high-grade adenocarcinoma. PMID:28270733

  2. Rb and p53 gene deletions in lung adenocarcinomas from irradiated and control mice

    SciTech Connect

    Zhang, Y.; Woloschak, G.E.

    1997-08-01

    This study was conducted on mouse lung adenocarcinoma tissues that were formalin-treated and paraffin-embedded 25 years ago to investigate the large gene deletions of mRb and p53 in B6CF{sub 1} male mice. A total of 80 lung tissue samples from irradiated mice and 40 lung samples from nonirradiated controls were randomly selected and examined in the mRb portion of this study. The results showed a significant (P < 0.05) higher percentage of mRb deletions in lung adenocarcinomas from mice exposed to 60 once-weekly {gamma}-ray doses than those from mice receiving 24 once-weekly {gamma}-ray doses at low doses and low dose rates; however, the percentage was not significantly different (P > 0.05) from that for spontaneous lung adenocarcinomas or lung adenocarcinomas from mice exposed to single-dose {gamma} irradiation at a similar total dose. mRb fragments 3 (71%) and 5 (67%), the parts of the gene that encoded the pocket binding region of Rb protein to adenovirus E1A and SV40 T-antigen, were the most frequently deleted fragments. p53 gene deletion analysis was carried out on normal lungs and lung adenocarcinomas that were initially found to bear mRb deletions. Exons 1,4,5,6, and 9 were chosen to be analyzed.

  3. An unusual variant of prostatic adenocarcinoma with metastasis to testis. A case report.

    PubMed

    Anila, K R; Somanathan, T; Mathews, A; Jayasree, K

    2012-07-01

    Ductal adenocarcinoma of the prostate is considered to be a rare variant of prostatic adenocarcinoma when compared to the more common acinar adenocarcinoma. We report here a case of ductal adenocarcinoma of the prostate in a 68-year old man who presented with complaints of abdominal pain, retention of urine and hematuria of one month duration. Clinical examination showed prostatomegaly. The serum Prostate Specific Antigen (PSA) value was raised to 79ng/mL. Histopathological and immunohistochemical evaluation of resected specimen of prostate revealed ductal adenocarcinoma of the prostate. The patient was lost to follow up and presented four years after the initial diagnosis with metastasis to the bone and testis. Though prostatic cancers have the ability for wide spread dissemination, metastasis to testis is rare. Immunohistochemical staining with PSA and Prostatic Acid Phosphatase (PAP) can help in establishing prostatic nature of the neoplasm. We are reporting this case because of the rarity of metastasis of prostatic carcinoma to testis and for stressing the need for keeping in mind the possibility of metastatic carcinoma also while dealing with testicular tumors.

  4. The role of the obestatin/GPR39 system in human gastric adenocarcinomas

    PubMed Central

    Alén, Begoña O.; Leal-López, Saúl; Alén, María Otero; Viaño, Patricia; García-Castro, Victoria; Mosteiro, Carlos S.; Beiras, Andrés; Casanueva, Felipe F.; Gallego, Rosalía; García-Caballero, Tomás; Camiña, Jesús P.; Pazos, Yolanda

    2016-01-01

    Obestatin, a 23-amino acid peptide encoded by the ghrelin gene, and the GPR39 receptor were reported to be involved in the control of mitogenesis of gastric cancer cell lines; however, the relationship between the obestatin/GPR39 system and gastric cancer progression remains unknown. In the present study, we determined the expression levels of the obestatin/GPR39 system in human gastric adenocarcinomas and explored their potential functional roles. Twenty-eight patients with gastric adenocarcinomas were retrospectively studied, and clinical data were obtained. The role of obestatin/GPR39 in gastric cancer progression was studied in vitro using the human gastric adenocarcinoma AGS cell line. Obestatin exogenous administration in these GPR39-bearing cells deregulated the expression of several hallmarks of the epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, obestatin signaling promoted phenotypic changes via GPR39, increasingly impacting on the cell morphology, proliferation, migration and invasion of these cells. In healthy human stomachs, obestatin expression was observed in the neuroendocrine cells and GPR39 expression was localized mainly in the chief cells of the oxyntic glands. In human gastric adenocarcinomas, no obestatin expression was found; however, an aberrant pattern of GPR39 expression was discovered, correlating to the dedifferentiation of the tumor. Altogether, our data strongly suggest the involvement of the obestatin/GPR39 system in the pathogenesis and/or clinical outcome of human gastric adenocarcinomas and highlight the potential usefulness of GPR39 as a prognostic marker in gastric cancer. PMID:26716511

  5. Ex vivo characterization of normal and adenocarcinoma colon samples by Mueller matrix polarimetry

    NASA Astrophysics Data System (ADS)

    Ahmad, Iftikhar; Ahmad, Manzoor; Khan, Karim; Ashraf, Sumara; Ahmad, Shakil; Ikram, Masroor

    2015-05-01

    Mueller matrix polarimetry along with polar decomposition algorithm was employed for the characterization of ex vivo normal and adenocarcinoma human colon tissues by polarized light in the visible spectral range (425-725 nm). Six derived polarization metrics [total diattenuation (DT), retardance (RT), depolarization (ΔT), linear diattenuation (DL), retardance (δ), and depolarization (ΔL)] were compared for normal and adenocarcinoma colon tissue samples. The results show that all six polarimetric properties for adenocarcinoma samples were significantly higher as compared to the normal samples for all wavelengths. The Wilcoxon rank sum test illustrated that total retardance is a good candidate for the discrimination of normal and adenocarcinoma colon samples. Support vector machine classification for normal and adenocarcinoma based on the four polarization properties spectra (ΔT, ΔL, RT,and δ) yielded 100% accuracy, sensitivity, and specificity, while both DT and D showed 66.6%, 33.3%, and 83.3% accuracy, sensitivity, and specificity, respectively. The combination of polarization analysis and given classification methods provides a framework to distinguish the normal and cancerous tissues.

  6. The different functions and clinical significances of caveolin-1 in human adenocarcinoma and squamous cell carcinoma

    PubMed Central

    Fu, Pin; Chen, Fuchun; Pan, Qi; Zhao, Xianda; Zhao, Chen; Cho, William Chi-Shing; Chen, Honglei

    2017-01-01

    Caveolin-1 (Cav-1), a major structural protein of caveolae, is an integral membrane protein which plays an important role in the progression of carcinoma. However, whether Cav-1 acts as a tumor promoter or a tumor suppressor still remains controversial. For example, the tumor-promoting function of Cav-1 has been found in renal cancer, prostate cancer, tongue squamous cell carcinoma (SCC), lung SCC and bladder SCC. In contrast, Cav-1 also plays an inhibitory role in esophagus adenocarcinoma, lung adenocarcinoma and cutaneous SCC. The role of Cav-1 is still controversial in thyroid cancer, hepatocellular carcinoma, gastric adenocarcinoma, colon adenocarcinoma, breast cancer, pancreas cancer, oral SCC, laryngeal SCC, head and neck SCC, esophageal SCC and cervical SCC. Besides, it has been reported that the loss of stromal Cav-1 might predict poor prognosis in breast cancer, gastric cancer, pancreas cancer, prostate cancer, oral SCC and esophageal SCC. However, the accumulation of stromal Cav-1 has been found to be promoted by the progression of tongue SCC. Taken together, Cav-1 seems playing a different role in different cancer subtypes even of the same organ, as well as acting differently in the same cancer subtype of different organs. Thus, we hereby explore the functions of Cav-1 in human adenocarcinoma and SCC from the perspective of clinical significances and pathogenesis. We envision that novel targets may come with the further investigation of Cav-1 in carcinogenesis. PMID:28243118

  7. Incidence of adenocarcinoma of the esophagus among white Americans by sex, stage, and age.

    PubMed

    Brown, Linda Morris; Devesa, Susan S; Chow, Wong-Ho

    2008-08-20

    Rapid increases in the incidence of adenocarcinoma of the esophagus have been reported among white men. We further explored the temporal patterns of this disease among white individuals by sex, stage, and age by use of data from the Surveillance, Epidemiology, and End Results program. We identified 22,759 patients from January 1, 1975, through December 31, 2004, with esophageal cancer, of whom 9526 were diagnosed with adenocarcinoma of the esophagus. Among white men, increases in the incidence of esophageal cancer were largely attributed to a 463% increase in the incidence of adenocarcinoma over this time period, from 1.01 per 100,000 person-years (95% confidence interval [CI] = 0.90 to 1.13) in 1975-1979 to 5.69 per 100,000 person-years (95% CI = 5.47 to 5.91) in 2000-2004. A similar rapid increase was also apparent among white women, among whom the adenocarcinoma rate increased 335%, from 0.17 (95% CI = 0.13 to 0.21) to 0.74 per 100,000 person-years (95% CI = 0.67 to 0.81), over the same time period. Adenocarcinoma rates rose among white men and women in all stage and age groups, indicating that these increases are real and not an artifact of surveillance.

  8. Membrane bile acid receptor TGR5 predicts good prognosis in ampullary adenocarcinoma patients with hyperbilirubinemia

    PubMed Central

    Chen, Min-Chan; Chen, Yi-Ling; Wang, Tzu-Wen; Hsu, Hui-Ping; Lai, Ming-Derg

    2016-01-01

    Bile acids are potential carcinogens in gastrointestinal cancer, and interact with nuclear and membrane receptors to initiate downstream signaling. The effect of TGR5 [also known as G protein-coupled bile acid receptor 1 (GPBAR1)] on cancer progression is dependent on the tissue where it is activated. In this report, the function of TGR5 expression in cancer was studied using a bioinformatic approach. TGR5 expression in ampullary adenocarcinoma and normal duodenum was compared by western blotting, reverse transcription polymerase chain reaction, and immunohistochemistry (IHC). High GPBAR1 gene expression was found to be an indicator of worse prognosis in gastric and breast cancer patients, and an indication of better prognosis in ovarian cancer patients. The level of GPBAR1 gene expression was higher in bile-acid exposed cancer than in other types of cancer, and was increased in well-differentiated ampullary adenocarcinoma. Negative, weak or mild expression of TGR5 was correlated with younger age, higher plasma level of total/direct bilirubin, higher plasma concentration of CA-125, advanced tumor stage and advanced AJCC TNM stage. The disease-specific survival rate was highest in ampullary adenocarcinoma patients with high TGR5 expression and high total bilirubin level. In summary, TGR5 functions as a tumor-suppressor in patients with ampullary adenocarcinoma and preoperative hyperbilirubinemia. Further study of the suppressive mechanism may provide a new therapeutic option for patients with ampullary adenocarcinoma. PMID:27510297

  9. Synchronous multiple colonic adenocarcinomas arising in patient with neurofibromatosis type 1

    PubMed Central

    Kim, Ik Yong; Cho, Mee Yon

    2014-01-01

    We report a case of synchronous multiple colon adenocarcinomas in a patient with neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant inherited disorder and patients with NF1 have high risk for both benign and malignant tumors. However, adenocarcinomas involving the colon have rarely been reported in patients with NF1. A 61-year-old man was referred for generalized peritonitis due to descending colon perforation. Left hemicolectomy was performed and pathologic examination showed four adenocarcinomas. Peritoneal nodules were confirmed as metastatic adenocarcinoma (pT4N1M1). The patient also had clinical features compatible with NF1 such as café au lait macules, axillary freckles, neurofibromas across the body, and Lisch nodules. Upon review of the literature, colon adenocarcinoma in patients with NF1 tends to occur in males and relatively young age groups, and is associated with advanced tumor stages and multiple colon cancers. To improve treatment outcome, early colonoscopic surveillance should be considered in patients with NF1. PMID:25247170

  10. Novel Diagnostic and Predictive Biomarkers in Pancreatic Adenocarcinoma

    PubMed Central

    Chang, John C.; Kundranda, Madappa

    2017-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease for a multitude of reasons including very late diagnosis. This in part is due to the lack of understanding of the biological behavior of PDAC and the ineffective screening for this disease. Significant efforts have been dedicated to finding the appropriate serum and imaging biomarkers to help early detection and predict response to treatment of PDAC. Carbohydrate antigen 19-9 (CA 19-9) has been the most validated serum marker and has the highest positive predictive value as a stand-alone marker. When combined with carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA 125), CA 19-9 can help predict the outcome of patients to surgery and chemotherapy. A slew of novel serum markers including multimarker panels as well as genetic and epigenetic materials have potential for early detection of pancreatic cancer, although these remain to be validated in larger trials. Imaging studies may not correlate with elevated serum markers. Critical features for determining PDAC include the presence of a mass, dilated pancreatic duct, and a duct cut-off sign. Features that are indicative of early metastasis includes neurovascular bundle involvement, duodenal invasion, and greater post contrast enhancement. 18-F-fluorodeoxyglucose (18-FDG) radiotracer uptake and changes following treatment may predict patient overall survival following treatment. Similarly, pretreatment apparent diffusion coefficient (ADC) values may predict prognosis with lower ADC lesions having worse outcome. Although these markers have provided significant improvement in the care of pancreatic cancer patients, further advancements can be made with perhaps better combination of markers or discovery of unique marker(s) to pancreatic cancer. PMID:28335509

  11. Identification and validation of candidate epigenetic biomarkers in lung adenocarcinoma

    PubMed Central

    Daugaard, Iben; Dominguez, Diana; Kjeldsen, Tina E.; Kristensen, Lasse S.; Hager, Henrik; Wojdacz, Tomasz K.; Hansen, Lise Lotte

    2016-01-01

    Lung cancer is the number one cause of cancer-related deaths worldwide. DNA methylation is an epigenetic mechanism that regulates gene expression, and disease-specific methylation changes can be targeted as biomarkers. We have compared the genome-wide methylation pattern in tumor and tumor-adjacent normal lung tissue from four lung adenocarcinoma (LAC) patients using DNA methylation microarrays and identified 74 differentially methylated regions (DMRs). Eighteen DMRs were selected for validation in a cohort comprising primary tumors from 52 LAC patients and tumor-adjacent normal lung tissue from 32 patients by methylation-sensitive high resolution melting (MS-HRM) analysis. Significant increases in methylation were confirmed for 15 DMRs associated with the genes and genomic regions: OSR1, SIM1, GHSR, OTX2, LOC648987, HIST1H3E, HIST1H3G/HIST1H2BI, HIST1H2AJ/HIST1H2BM, HOXD10, HOXD3, HOXB3/HOXB4, HOXA3, HOXA5, Chr1(q21.1).A, and Chr6(p22.1). In particular the OSR1, SIM1 and HOXB3/HOXB4 regions demonstrated high potential as biomarkers in LAC. For OSR1, hypermethylation was detected in 47/48 LAC cases compared to 1/31 tumor-adjacent normal lung samples. Similarly, 45/49 and 36/48 LAC cases compared to 3/31 and 0/31 tumor-adjacent normal lung samples showed hypermethylation of the SIM1 and HOXB3/HOXB4 regions, respectively. In conclusion, this study has identified and validated 15 DMRs that can be targeted as biomarkers in LAC. PMID:27782156

  12. Can endobronchial or endotracheal metastases appear from rectal adenocarcinoma?

    PubMed Central

    Serbanescu, GL; Anghel, RM

    2017-01-01

    Background: Endobronchial and endotracheal metastases from extra-pulmonary solid tumors are rare. Patients and methods: We reported the case of a patient diagnosed with endobronchial and endotracheal metastases from rectal adenocarcinoma. Case report: Patient P.G., 62 years old, was diagnosed with a rectal tumor in 2011, for which, a surgical intervention was performed (pT3 pN2a M0, stage IIIB). Afterwards, she underwent adjuvant chemotherapy and concomitant radiochemotherapy. In September 2013, the chest CT showed 2 nodules for which, an incomplete surgical resection was done and which were histopathologically diagnosed as metastases from rectal cancer. The patient continued the treatment with chemotherapy associated with Bevacizumab and after 6 months only Bevacizumab for maintenance. In June 2015, the chest CT pointed out a nodule in the right upper lobe and the bronchoscopy highlighted a 4-5 mm lesion at the level of the right primary bronchus, whose biopsy proved the rectal origin. Afterwards, another surgical intervention was performed. Unfortunately, the postoperative chest CT revealed an intratracheal tissue mass (11/ 7mm) and multiple metastases in the right lung. The bronchoscopy showed 2 endotracheal lesions, out of which one was biopsied (histopathological result of metastasis from rectal cancer). Despite the fact that chemotherapy was continued, other endobronchial lesions appeared. All of them were removed and the patient started radiotherapy on the tracheal area. Afterwards, she refused to continue chemotherapy. The last bronchoscopy highlighted one endobronchial and two endotracheal secondary malignant lesions. Conclusion: Endobronchial and endotracheal metastases must be taken into consideration in all the patients with a history of extra-pulmonary cancer. Abbreviations: CT = computed tomography, MRI = magnetic resonance imaging, IMRT = intensity-modulated radiotherapy, ESMO = European Society for Medical Oncology, NCCN = National Comprehensive

  13. Response of adenocarcinoma of the uterine cervix to chemoradiotherapy

    PubMed Central

    KAIDAR-PERSON, ORIT; YOSEFIA, SAWSAN; ABDAH-BORTNYAK, ROXOLYANA

    2015-01-01

    The aim of the current retrospective study was to investigate the response of advanced cervical adenocarcinoma (AC) to definitive chemoradiotherapy. Uterine cervical cancer is one of the most common cancer types among females, with squamous cell carcinoma (SQCC) being the most prevalent histological type. The incidence of cervical AC and its variants has markedly increased in recent decades. The current understanding with regard to the treatment of cervical cancer has been established through studies in which the majority of the patients suffered from SQCC, while only a limited number of studies have focused on the treatment of AC. Therefore, the optimal treatment for uterine cervical AC remains unclear. In the present study, data were collected from the medical files of patients who were diagnosed with advanced uterine cervical AC and treated with chemoradiotherapy between 1998 and 2013. Data were also collected from a group of patients with SQCC for comparison with AC patients in terms of response and survival. A total of 68 uterine cervical cancer cases were included, including 29 AC patients and 39 SQCC patients. Compared with the SQCC subgroup, a higher number of AC patients required surgery following chemoradiotherapy due to a lack of response to the initial treatment (5% vs. 31%, respectively; P=0.0065). After a median follow-up period of 10 years, patients with AC exhibited shorter overall survival (7.4 years vs. 11 years for AC and SQCC groups, respectively; P=0.01). Differences in recurrence (40.7% vs. 34.4%; P=0.79) and disease-free interval (1.2 years vs. 2 years; P=0.11) were not statistically significant. The results indicated that cervical AC is less responsive to chemoradiotherapy compared with SQCC. PMID:26137148

  14. Proton Pump Inhibitors Display Antitumor Effects in Barrett's Adenocarcinoma Cells

    PubMed Central

    Chueca, Eduardo; Apostolova, Nadezda; Esplugues, Juan V.; García-González, María A.; Lanas, Ángel; Piazuelo, Elena

    2016-01-01

    Recent evidence has reported that proton pump inhibitors (PPIs) can exert antineoplastic effects through the disruption of pH homeostasis by inhibiting vacuolar ATPase (H+-VATPase), a proton pump overexpressed in several tumor cells, but this aspect has not been deeply investigated in EAC yet. In the present study, the expression of H+-VATPase was assessed through the metaplasia-dysplasia-adenocarcinoma sequence in Barrett's esophagus (BE) and the antineoplastic effects of PPIs and cellular mechanisms involved were evaluated in vitro. H+-VATPase expression was assessed by immunohistochemistry in paraffined-embedded samples or by immunofluorescence in cultured BE and EAC cell lines. Cells were treated with different concentrations of PPIs and parameters of citotoxicity, oxidative stress, and autophagy were evaluated. H+-VATPase expression was found in all biopsies and cell lines evaluated, showing differences in the location of the pump between the cell lines. Esomeprazole inhibited proliferation and cell invasion and induced apoptosis of EAC cells. Production of reactive oxygen species (ROS) seemed to be involved in the cytotoxic effects observed since the addition of N-acetylcysteine significantly reduced esomeprazole-induced apoptosis in EAC cells. Esomeprazole also reduced intracellular pH of tumor cells, whereas only disturbed the mitochondrial membrane potential in OE33 cells. Esomeprazole induced autophagy in both EAC cells, but also triggered a blockade in autophagic flux in the metastatic cell line. These data provide in vitro evidence supporting the potential use of PPIs as novel antineoplastic drugs for EAC and also shed some light on the mechanisms that trigger PPIs cytotoxic effects, which differ upon the cell line evaluated. PMID:27932981

  15. Clinical implications of chromosomal abnormalities in gastric adenocarcinomas

    SciTech Connect

    Wu, Chew-Wun; Chen, Gen-Der; Fann, Cathy S.-J.; Lee, Anna F.-Y.; Chi, Chin-Wen; Liu, Jacqueline M.; Weier, Ulli; Chen, Jeou-Yuan

    2003-06-23

    Gastric carcinoma (GC) is one of the most common malignancies worldwide and has a very poor prognosis. Genetic imbalances in 62 primary gastric adenocarcinomas of various histopathologic types and pathologic stages and six gastric cancer-derived cell lines were analyzed by comparative genomic hybridization, and the relationship of genomic abnormalities to clinical features in primary GC was evaluated at a genome-wide level. Eighty-four percent of the tumors and all six cell lines showed DNA copy number changes. The recurrent chromosomal abnormalities including gains at 15 regions and losses at 8 regions were identified. Statistical analyses revealed that gains at 17q24-qter (53 percent), 20q13-qter (48 percent), 1p32-p36 (42 percent), 22q12-qter (27 percent), 17p13-pter (24 percent), 16p13-pter (21 percent), 6p21-pter (19 percent), 20p12-pter (19 percent), 7p21-pter (18 percent), 3q28-qter (8 percent), and 13q13-q14 (8 percent), and losses at 18q12-qter (11 percent), 3p12 (8 percent), 3p25-pter (8 percent), 5q14-q23 (8 percent), and 9p21-p23 (5 percent), are associated with unique patient or tumor-related features. GCs of differing histopathologic features were shown to be associated with distinct patterns of genetic alterations, supporting the notion that they evolve through distinct genetic pathways. Metastatic tumors were also associated with specific genetic changes. These regions may harbor candidate genes involved in the pathogenesis of this malignancy.

  16. Globally increased ultraconserved noncoding RNA expression in pancreatic adenocarcinoma

    PubMed Central

    Lee, Eun Joo; Gusev, Yuriy; Allard, David; Sutaria, Dhruvitkumar S.; Badawi, Mohamed; Elgamal, Ola A.; Lerner, Megan R.; Brackett, Daniel J.; Calin, George A.; Schmittgen, Thomas D.

    2016-01-01

    Transcribed ultraconserved regions (T-UCRs) are a class of non-coding RNAs with 100% sequence conservation among human, rat and mouse genomes. T-UCRs are differentially expressed in several cancers, however their expression in pancreatic adenocarcinoma (PDAC) has not been studied. We used a qPCR array to profile all 481 T-UCRs in pancreatic cancer specimens, pancreatic cancer cell lines, during experimental pancreatic desmoplasia and in the pancreases of P48Cre/wt; KrasLSL-G12D/wt mice. Fourteen, 57 and 29% of the detectable T-UCRs were differentially expressed in the cell lines, human tumors and transgenic mouse pancreases, respectively. The vast majority of the differentially expressed T-UCRs had increased expression in the cancer. T-UCRs were monitored using an in vitro model of the desmoplastic reaction. Twenty-five % of the expressed T-UCRs were increased in the HPDE cells cultured on PANC-1 cellular matrix. UC.190, UC.233 and UC.270 were increased in all three human data sets. siRNA knockdown of each of these three T-UCRs reduced the proliferation of MIA PaCa-2 cells up to 60%. The expression pattern among many T-UCRs in the human and mouse pancreases closely correlated with one another, suggesting that groups of T-UCRs are co-activated in PDAC. Successful knockout of the transcription factor EGR1 in PANC-1 cells caused a reduction in the expression of a subset of T-UCRs suggesting that EGR1 may control T-UCR expression in PDAC. We report a global increase in expression of T-UCRs in both human and mouse PDAC. Commonalties in their expression pattern suggest a similar mechanism of transcriptional upregulation for T-UCRs in PDAC. PMID:27363020

  17. Dynamics of regulatory networks in gastrin-treated adenocarcinoma cells.

    PubMed

    Doni Jayavelu, Naresh; Bar, Nadav

    2014-01-01

    Understanding gene transcription regulatory networks is critical to deciphering the molecular mechanisms of different cellular states. Most studies focus on static transcriptional networks. In the current study, we used the gastrin-regulated system as a model to understand the dynamics of transcriptional networks composed of transcription factors (TFs) and target genes (TGs). The hormone gastrin activates and stimulates signaling pathways leading to various cellular states through transcriptional programs. Dysregulation of gastrin can result in cancerous tumors, for example. However, the regulatory networks involving gastrin are highly complex, and the roles of most of the components of these networks are unknown. We used time series microarray data of AR42J adenocarcinoma cells treated with gastrin combined with static TF-TG relationships integrated from different sources, and we reconstructed the dynamic activities of TFs using network component analysis (NCA). Based on the peak expression of TGs and activity of TFs, we created active sub-networks at four time ranges after gastrin treatment, namely immediate-early (IE), mid-early (ME), mid-late (ML) and very late (VL). Network analysis revealed that the active sub-networks were topologically different at the early and late time ranges. Gene ontology analysis unveiled that each active sub-network was highly enriched in a particular biological process. Interestingly, network motif patterns were also distinct between the sub-networks. This analysis can be applied to other time series microarray datasets, focusing on smaller sub-networks that are activated in a cascade, allowing better overview of the mechanisms involved at each time range.

  18. Biomarkers of metastatic potential in cultured adenocarcinoma clones.

    PubMed

    Dabbous, Mustafa Kh; Jefferson, M Margaret; Haney, Lena; Thomas, Edwin L

    2011-02-01

    Two-dimensional isoelectric focusing and gel electrophoresis followed by mass spectrometry were used to detect, measure, and identify changes in protein expression correlated with differences in the metastatic potential of cultured rat mammary adenocarcinoma cells. MTC is a non-metastatic cell clone derived from a primary tumor. MTLn2 and MTLn3 are low and high metastatic potential cell clones derived from lung metastases of the primary tumor. A total of 1,500 proteins was detected. The patterns of protein expression of MTLn2 and MTLn3 cells were similar. Only five spots had a threefold or greater statistically significant difference in staining intensity between MTLn2 and MTLn3 cells, whereas 70 spots differed between MTC and MTLn3 cells. Twenty spots were selected for further study, ten that had a positive correlation of staining intensity with metastatic potential and ten that had a negative (inverse) correlation. Of the 17 unique proteins that were identified, five have often been cited as tumor biomarkers. These included the positive biomarkers nucleophosmin (NPM) and 14-3-3 protein sigma and the negative biomarkers raf kinase inhibitor protein (RKIP), peroxiredoxin-2, and galectin-1. The only identified protein that was markedly higher in MTLn3 cells than in the less-metastatic MTLn2 cells was 14-3-3 protein sigma. The results indicate that increased metastatic potential is associated with positive and negative changes in expression of particular proteins. Proteins that are positively correlated with metastatic potential may prove more useful as clinical biomarkers, but those with negative correlations may still provide useful information about underlying mechanisms of metastatic spread.

  19. Modulation of prostaglandin biosynthesis in murine mammary adenocarcinoma tumor cells

    SciTech Connect

    Shalinsky, D.R.

    1988-01-01

    In efforts to exploit the differential oxygen levels within the subcompartments of solid neoplasms, this project has focused on modulating prostaglandin (PG) biosynthesis under aerobic and hypoxic conditions. Mammary adenocarcinoma tumor cells (Line 4526), either intact or sonicated, were incubated with either 2.0 uM {sup 14}C-arachidonic acid (AA) or 20.0 uM {sup 14}C-PGH{sub 2}, respectively. Following metabolism, products were extracted, separated by thin layer chromatography and analyzed by radiochromatographic scan. PGE{sub 2} was predominantly formed with minimal amounts of PGF{sub 2a} or PGD{sub 2}. Indomethacin and ibuprofen inhibited the PGE{sub 2} formation from AA with an IC{sub 50} value of 6.3 {times} 10{sup {minus}8} and 9.6 {times} 10{sup {minus}5}M, respectively. Suspended cells in glass vials were made hypoxic by flushing with N{sub 2} for varying time intervals to study AA metabolism. A time-dependent inhibition of PG biosynthesis was observed under hypoxia, and by 30 min, the PGE{sub 2} synthesis was reduced by 50% which was further inhibited by indomethacin. Misonidazole, a 2-nitroimidazole analogue, partially reversed the inhibition of PGE{sub 2} synthesis under hypoxia by 49% at 100 uM. However, misonidazole did not affect PG biosynthesis under aerobic conditions. The stimulation of PGE{sub 2} biosynthesis by misonidazole under hypoxia was blocked by indomethacin, suggesting that misonidazole can not act independently of the cyclooxygenase.

  20. Cell-surface markers for colon adenoma and adenocarcinoma.

    PubMed

    Sewda, Kamini; Coppola, Domenico; Enkemann, Steven; Yue, Binglin; Kim, Jongphil; Lopez, Alexis S; Wojtkowiak, Jonathan W; Stark, Valerie E; Morse, Brian; Shibata, David; Vignesh, Shivakumar; Morse, David L

    2016-04-05

    Early detection of colorectal cancer (CRC) is crucial for effective treatment. Among CRC screening techniques, optical colonoscopy is widely considered the gold standard. However, it is a costly and invasive procedure with a low rate of compliance. Our long-term goal is to develop molecular imaging agents for the non-invasive detection of CRC by molecular imaging-based colonoscopy using CT, MRI or fluorescence. To achieve this, cell surface targets must be identified and validated. Here, we report the discovery of cell-surface markers that distinguish CRC from surrounding tissues that could be used as molecular imaging targets. Profiling of mRNA expression microarray data from patient tissues including adenoma, adenocarcinoma, and normal gastrointestinal tissues was used to identify potential CRC specific cell-surface markers. Of the identified markers, six were selected for further validation (CLDN1, GPR56, GRM8, LY6G6D/F, SLCO1B3 and TLR4). Protein expression was confirmed by immunohistochemistry of patient tissues. Except for SLCO1B3, diffuse and low expression was observed for each marker in normal colon tissues. The three markers with the greatest protein overexpression were CLDN1, LY6G6D/F and TLR4, where at least one of these markers was overexpressed in 97% of the CRC samples. GPR56, LY6G6D/F and SLCO1B3 protein expression was significantly correlated with the proximal tumor location and with expression of mismatch repair genes. Marker expression was further validated in CRC cell lines. Hence, three cell-surface markers were discovered that distinguish CRC from surrounding normal tissues. These markers can be used to develop imaging or therapeutic agents targeted to the luminal surface of CRC.

  1. Sarcomatoid carcinoma of the prostate: ductal adenocarcinoma and stromal sarcoma-like appearance: a rare association.

    PubMed

    Parada, David; Peña, Karla B; Riu, Francesc

    2011-01-01

    Sarcomatoid carcinoma (SC) of prostate gland is a rare biphasic tumour. In about half of cases, initial diagnosis is acinar adenocarcinoma, followed by nonsurgical therapy, with a subsequent diagnosis of SC. The survival rate is lower. We report a case of an 59-years-old man with unusual histopathologic finding of prostate sarcomatoid carcinoma, showing characteristics of ductal prostatic adenocarcinoma and prostatic stromal sarcoma-like appearance. Ductal adenocarcinoma was characterized by tall columnar cells with abundant amphophilic to eosinophil cytoplasm. Pleomorphic sarcoma was characterized to have overall glandular growth pattern, simulating a malignant phyllodes tumour. Estrogen and progesterone receptors showed nuclear immunostaining in mesenchymal multinucleated giant cells. In conclusion, SC of the prostate is an exceedingly rare tumour. Retrospective analyses render prostate SC as one of the most aggressive prostate malignancies. The prognosis is dismal regardless of other histologic or clinical findings.

  2. Preclinical trial on the use of doxycycline for the treatment of adenocarcinoma of the duodenum

    PubMed Central

    Galván-Salazar, Hector R.; Soriano-Hernández, Alejandro D.; Montes-Galindo, Daniel A.; Espíritu, Gabriel Ceja; Guzman-Esquivel, José; Rodríguez-Sánchez, Iram P.; Newton-Sánchez, Oscar A.; Martinez-Fierro, Margarita L.; Gómez, Xóchitl G. Briseño; Rojas-Martínez, Augusto; Delgado-Enciso, Iván

    2016-01-01

    Adenocarcinoma of the duodenum comprises 50–70% of duodenal tumors. There is an increase in extracellular matrix metalloproteinases in this disease and it has been suggested that they play an important role in the development and pathology. Therefore, new therapeutic recommendations based on inhibitors of these enzymes, such as doxycycline, are under investigation. The cytotoxic effect of doxycycline was evaluated in the HuTu-80 duodenal adenocarcinoma cell line and its antitumor effect was determined in an immunodeficient murine model. A 10-µM (4.4 µg/ml) concentration of doxycycline was capable of causing apoptosis in 90% of the culture cells. Doxycycline was also responsible for a decrease in tumor growth and an increase in the survival of the mice with HuTu-80-cell tumors. These results suggest that doxycycline is a potential cytotoxic and antitumor agent effective in the treatment of adenocarcinoma of the duodenum. PMID:27900107

  3. Advanced pancreatic adenocarcinoma: a review of current treatment strategies and developing therapies

    PubMed Central

    Teague, Andrea; Lim, Kian-Huat

    2015-01-01

    Pancreatic adenocarcinoma is one of the deadliest solid malignancies. A large proportion of patients are diagnosed with locally advanced or metastatic disease at the time of presentation and, unfortunately, this severely limits the number of patients who can undergo surgical resection, which offers the only chance for cure. Recent therapeutic advances for patients with advanced pancreatic cancer have extended overall survival, but prognosis still remains grim. Given that traditional chemotherapy is ineffective in curing advanced pancreatic adenocarcinoma, current research is taking a multidirectional approach in the hopes of developing more effective treatments. This article reviews the major clinical trial data that is the basis for the current chemotherapy regimens used as first- and second-line treatments for advanced pancreatic adenocarcinoma. We also review the current ongoing clinical trials, which include the use of agents targeting the oncogenic network signaling of K-Ras, agents targeting the extracellular matrix, and immune therapies. PMID:25755680

  4. Immunohistochemical characterization of endometrial carcinomas: endometrioid, serous and clear cell adenocarcinomas in association with genetic analysis.

    PubMed

    Yasuda, Masanori

    2014-12-01

    Developments in immunohistochemistry, which are closely linked with the advances in the analyses of genetic abnormalities and their associated molecular disorders as early and late histogenetic events, have contributed greatly to the improvement of pathological diagnostic confirmation and validation. Immunohistochemistry has also generated great benefit to the innovation of therapeutic strategies for various kinds of cancers. In this article, the three representative histological types of corpus cancer, namely, endometrioid adenocarcinoma, serous adenocarcinoma and clear cell adenocarcinoma, will be histologically approached in association with their immunohistochemical profiles as well as genetic disorders. First, the focus will be on 'Conventional/prototypic features,' followed by 'Controversy over conventional histological subclassification,' and subsequently 'Tumorigenesis and re-subclassification'.

  5. Rectal adenocarcinoma infiltrating the bulbar urethra and metastasising to the penis.

    PubMed

    James, Mathews; Amaranathan, Anandhi; Nelamangala Ramakrishnaiah, Vishnu Prasad; Toi, Pampa Chakrabarty

    2016-06-16

    Secondary penile tumours from rectal carcinoma is a known clinical entity but can be missed unless carefully evaluated. We report a case of rectal adenocarcinoma with synchronous painless penile nodules. A patient presented with constipation and rectal bleeding. He had an anorectal growth as well as palpable nodules on his penis. Rectal biopsy yielded adenocarcinoma. Imaging revealed direct infiltration of tumour into the bulb of the penis as well as distal shaft lesions. Fine-needle aspiration cytology of the penile nodule showed metastatic adenocarcinoma. Diversion colostomy was performed and the patient referred for chemoradiation. Since he did not have any urinary symptoms, the penile lesions were left unaltered. Repeat imaging after concurrent chemoradiotherapy showed no response. The prognosis was explained and the patient was given palliative clinic care.

  6. Adenocarcinoma of the ampulla of Vater metastasising into the right ventricle.

    PubMed

    Moser, Magdalena; Wiedemann, Dominik; Kitzwögerer, Melitta; Frank, Herbert

    2016-04-08

    A 43-year-old woman, after resected adenocarcinoma of the ampulla of Vater, presented dyspnoea and beginning signs of right heart failure. Echocardiography revealed a mass within the right ventricle (RV) suspicious for a metastasis of the known adenocarcinoma. The decision for surgical resection was made by cardiovascular MR, which was able to delineate the infiltrative growth of a metastasis. An extensive resection had to be performed. Parts of the intraventricular septum as well as the tricuspid valve had to be resected. After six cycles of adjuvant systemic chemotherapy with gemcitabine and nab-paclitaxel, the patient had no macroscopic tumour recurrence. To our knowledge, this is the first report of a pancreatobiliary tumour metastasising exclusively to the RV of the heart. We conclude that in this special case aggressive surgical management following chemotherapy was very effective in controlling the disseminated adenocarcinoma of the ampulla of Vater.

  7. Development of a panel of DNA Aptamers with High Affinity for Pancreatic Ductal Adenocarcinoma

    NASA Astrophysics Data System (ADS)

    Champanhac, Carole; Teng, I.-Ting; Cansiz, Sena; Zhang, Liqin; Wu, Xiaoqiu; Zhoa, Zilong; Fu, Ting; Tan, Weihong

    2015-11-01

    Pancreatic cancer costs nearly 40,000 lives in the U.S. each year and has one of the lowest survival rates among cancers. Effective treatment of pancreatic ductal adenocarcinoma is hindered by lack of a reliable biomarker. To address this challenge, aptamers were selected by cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) targeting human pancreatic ductal adenocarcinoma (PL45). Five promising aptamers presenting low Kd values and good specificity were generated. Among these five aptamers, one was tailored into a nanostructure carrying a high drug payload for specific drug delivery. The results show a viability of almost 80% for negative cells while only 50% of the target cells remained alive after 48 h incubation. These results lead to the conclusion that further research could reveal protein biomarkers specific to pancreatic adenocarcinoma, with probes available for early detection.

  8. Invasive mucinous adenocarcinoma mimicking organizing pneumonia associated with Mycobacterium fortuitum infection.

    PubMed

    Morichika, Daisuke; Miyahara, Nobuaki; Hotta, Katsuyuki; Okamoto, Yoshiko; Minami, Daisuke; Irie, Masahiro; Tanimoto, Yasushi; Kanehiro, Arihiko; Tanimoto, Mitsune; Kiura, Katsuyuki

    2014-01-01

    We herein report the case of a 68-year-old man diagnosed with invasive mucinous adenocarcinoma of the lungs. Chest computed tomography showed subpleural ground-glass opacity and small nodules with cavitation. A culture of the bronchoalveolar lavage fluid resulted in the detection of Mycobacterium fortuitum. The patient's lung consolidation rapidly progressed; however, repeated bronchoscopy showed no atypical cells, thus suggesting a diagnosis of organizing pneumonia associated with M. fortuitum infection. However, the surgical biopsy specimen was diagnostic for adenocarcinoma, with no mycobacterial infection. Invasive mucinous adenocarcinoma should not be excluded in the differential diagnosis of patients with clinical features of organizing pneumonia and nontuberculous mycobacterium infection, even if a transbronchial biopsy confirms the absence of malignancy.

  9. Synchronous Malignant Peripheral Nerve Sheath Tumor and Adenocarcinoma of the Prostate: Case Report and Literature Review

    PubMed Central

    Bouropoulos, Konstantinos; Farmakis, Antonios

    2016-01-01

    Malignant Peripheral Nerve Sheath Tumors (MPNSTs) of the prostate are extremely rare. A very unusual case of simultaneous adenocarcinoma and MPNST of the prostate is reported. A 60-year-old Caucasian male presented for annual urologic examination. Digital rectal examination revealed a painless, toughish, and asymmetrically enlarged prostate. Serum prostate-specific antigen was 1 ng/mL. Radiologic examinations demonstrated a large mass, which was arising from the left peripheral lobe of the prostate. The patient underwent transrectal ultrasound-guided biopsy of the prostate which revealed a smooth muscle tumor of uncertain malignant potential. Radical retropubic prostatectomy with en bloc removal of the mass and the seminal vesicles was performed and histology demonstrated low-grade MPNST and adenocarcinoma of the prostate. To the best of our knowledge, this is the first report of simultaneous prostatic adenocarcinoma and MPNST in the English literature. PMID:27872787

  10. Detected EGFR mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis

    PubMed Central

    Chunhua, Ma; Yuan, Lv; Ning, Mu; Jinduo, Li; Bin, Wang; Liwei, Sun

    2016-01-01

    Abstract Objective To discuss the application of ARMS method to detect EGFR gene mutation in cerebrospinal fluid of lung adenocarcinoma patients with meningeal metastasis. Methods 5 cases of lung adenocarcinoma were identified with meningeal metastasis that were cleared EGFR gene mutation by gene sequencing method. From each patient 5ml cerebrospinal fluid was obtained by lumbar puncture. ARMS method was used to detect EGFR mutations in cerebrospinal fluid. Results 5 samples of cerebrospinal fluid were successfully detected by ARMS method, 3 samples found that EGFR gene mutations, the mutations in line with direct sequencing method. Conclusion ARMS method can be used to detect EGFR gene mutations of cerebrospinal fluid samples in lung adenocarcinoma with meningeal metastasis. But cerebrospinal fluid specimens from histological specimens, blood samples need to be confirmed by further comparative study whether there is advantage.

  11. Stage IB adenocarcinoma of the cervix: metastatic potential and patterns of dissemination

    SciTech Connect

    Kjorstad, K.E.; Bond, B.

    1984-10-01

    The metastatic potential patterns of dissemination have been investigated in 150 patients with Stage 1B adenocarcinoma of the cervix treated during a 20-year period from 1956 to 1977. All cases with the exception of one were treated with a combination of intracavitary radium implants followed by a radical surgical procedure with pelvic lymph node dissection. It was found that the incidence of pelvic metastases and distant recurrences and the survival rates were the same as in previously published reports for squamous cell carcinomas treated in the same manner. In one respect adenocarcinomas showed a significant difference when compared with squamous cell cancers: The incidence of residual tumor in the hysterectomy specimens after intracavitary treatment was much higher (30% versus 11%). This is considered a strong argument for surgical treatment of patients with early stages of adenocarcinoma of the cervix.

  12. Comparison of absorption spectra of adenocarcinoma and squamous cell carcinoma cervical tissue

    NASA Astrophysics Data System (ADS)

    Peresunko, O. P.; Zelinska, N. V.; Prydij, O. G.; Zymnyakov, D. A.; Ushakova, O. V.

    2013-12-01

    We studied a methods of assessment of a connective tissue of cervix in terms of specific volume of fibrous component and an optical density of staining of connective tissue fibers in the stroma of squamous cancer and cervix adenocarcinoma. An absorption spectra of blood plasma of the patients suffering from squamous cancer and cervix adenocarcinoma both before the surgery and in postsurgical periods were obtained. Linear dichroism measurements transmittance in polarized light at different orientations of the polarization plane relative to the direction of the dominant orientation in the structure of the sample of biotissues of stroma of squamous cancer and cervix adenocarcinoma were carried. Results of the investigation of the tumor tissues showed that the magnitude of the linear dichroism Δ is insignificant in the researched spectral range λ=280-840 nm and specific regularities in its change observed short-wave ranges.

  13. Association between human papillomavirus and EGFR mutations in advanced lung adenocarcinoma

    PubMed Central

    Li, Ming; Deng, Fang; Qian, Li-Ting; Meng, Shui-Ping; Zhang, Yang; Shan, Wu-Lin; Zhang, Xiao-Lei; Wang, Bao-Long

    2016-01-01

    Previous studies have demonstrated an association between human papillomavirus (HPV) and mutations in the epidermal growth factor receptor (EGFR) gene in lung cancer patients; however, few studies have investigated this association in advanced lung adenocarcinoma patients undergoing gefitinib treatment. The present study investigated the association between HPV and EGFR mutations in advanced lung adenocarcinoma patients. A total of 95 advanced lung adenocarcinoma patients were enrolled in the study. The HPV infection status and presence of EGFR mutations in tumor tissue was evaluated. Patient clinical characteristics were also determined and compared with HPV infection and EGFR mutation status to analyze their impact on progression-free survival. HPV DNA was identified in 27/95 (28.4%) lung adenocarcinoma tumors and was most common in patients with lymph node metastasis (P=0.016). A total of 44/95 (46.3%) cases exhibited EGFR mutations, which were predominantly observed in female patients and non-smokers. The presence of HPV DNA was significantly associated with EGFR mutations (P=0.012) and multivariate analysis also revealed that HPV DNA was significantly associated with EGFR mutations (odds ratio=3.971) in advanced lung adenocarcinoma. Patients with both HPV infections and EGFR mutations exhibit a marked decrease in the risk of lung cancer progression when compared with those without HPV infection or EGFR mutations (adjusted HR=0.640; 95% confidence interval: 0.488–0.840; P=0.001). HPV infection was significantly associated with EGFR mutations in advanced lung adenocarcinoma patients. Furthermore, patients with HPV infections exhibited the longest progression-free survival times, which may be due to good response to tyrosine kinase inhibitor- or platinum-based-adjuvant therapy in these patients. Patients with EGFR mutations exhibited a better prognosis when compared with those exhibiting wild-type EGFR, regardless of HPV status. PMID:27602120

  14. High expression of cellular retinol binding protein-1 in lung adenocarcinoma is associated with poor prognosis

    PubMed Central

    Doldo, Elena; Costanza, Gaetana; Ferlosio, Amedeo; Pompeo, Eugenio; Agostinelli, Sara; Bellezza, Guido; Mazzaglia, Donatella; Giunta, Alessandro; Sidoni, Angelo; Orlandi, Augusto

    2015-01-01

    Purpose Adenocarcinoma, the most common non-small cell lung cancer is a leading cause of death worldwide, with a low overall survival (OS) despite increasing attempts to achieve an early diagnosis and accomplish surgical and multimodality treatment strategies. Cellular retinol binding protein-1 (CRBP-1) regulates retinol bioavailability and cell differentiation, but its role in lung cancerogenesis remains uncertain. Experimental design CRBP-1 expression, clinical outcome and other prognostic factors were investigated in 167 lung adenocarcinoma patients. CRBP-1 expression was evaluated by immunohistochemistry of tissue microarray sections, gene copy number analysis and tumor methylation specific PCR. Effects of CRBP-1 expression on proliferation/apoptosis gene array, protein and transcripts were investigated in transfected A549 lung adenocarcinoma cells. Results CRBP-1High expression was observed in 62.3% of adenocarcinomas and correlated with increased tumor grade and reduced OS as an independent prognostic factor. CRBP-1 gene copy gain also associated with tumor CRBP-1High status and dedifferentiation. CRBP-1-transfected (CRBP-1+) A549 grew more than CRBP-1− A549 cells. At >1μM concentrations, all trans-retinoic acid and retinol reduced viability more in CRBP-1+ than in CRBP-1− A549 cells. CRBP-1+ A549 cells showed up-regulated RARα/ RXRα and proliferative and transcriptional genes including pAkt, pEGFR, pErk1/2, creb1 and c-jun, whereas RARβ and p53 were strongly down-regulated; pAkt/pErk/ pEGFR inhibitors counteracted proliferative advantage and increased RARα/RXRα, c-jun and CD44 expression in CRBP-1+ A549 cells. Conclusion CRBP-1High expression in lung adenocarcinoma correlated with increased tumor grade and reduced OS, likely through increased Akt/Erk/EGFR-mediated cell proliferation and differentiation. CRBP-1High expression can be considered an additional marker of poor prognosis in lung adenocarcinoma patients. PMID:26807202

  15. Inflammation and focal atrophy in prostate needle biopsy cores and association to prostatic adenocarcinoma.

    PubMed

    Benedetti, Ines; Bettin, Alfonso; Reyes, Niradiz

    2016-10-01

    The possible origin of proliferative inflammatory atrophy in the regenerative proliferation of prostate epithelial cells in response to injury caused by inflammation, and their relation to prostate adenocarcinoma have not been defined. Inflammation and focal atrophy are common pathological findings in prostate biopsies, currently not routinely included in surgical pathology reports. The objective of the study was to determine the correlation between inflammation and focal atrophy with prostate adenocarcinoma. Prostate needle biopsies from 203 patients with clinical parameters suspicious for malignancy were evaluated for the presence and extent of chronic inflammation, type and grade of focal atrophy, high-grade intraepithelial neoplasia, and adenocarcinoma. Relations among them and with age were also analyzed. χ(2) tests and binary logistic regression were used to estimate associations. Chronic inflammation was observed in 77.3% of the biopsies, significantly associated to adenocarcinoma (P = .031). Moderate/severe inflammation in at least 1 biopsy core increased the risk of prostate adenocarcinoma (odds ratio, 2.94; 95% confidence interval, 1.27-6.8), whereas glandular localization of inflammation decreased the risk. Focal atrophy was present in 72.9% of the biopsies, proliferative inflammatory atrophy was the most common type, and its grade was significantly associated to inflammation (P < .0001) and inflammation intensity (P = .003). An association between prostate adenocarcinoma and inflammation was found, with higher odds in presence of moderate/severe inflammation in at least 1 biopsy core. Increasing grades of proliferative inflammatory atrophy were associated to high levels of inflammation, supporting its previously proposed inflammatory nature.

  16. Immunohistochemical Typing of Adenocarcinomas of the Pancreatobiliary System Improves Diagnosis and Prognostic Stratification

    PubMed Central

    Fernandez-Woodbridge, Alejandro; Alistair D'souza, Melroy; Zhang, Qianni; Bozoky, Benedek; Kandaswamy, Senthil Vasan; Catalano, Piera; Heuchel, Rainer; Shtembari, Sonia; Del Chiaro, Marco; Danielsson, Olof; Björnstedt, Mikael; Löhr, J. Matthias; Isaksson, Bengt; Verbeke, Caroline; Bozóky, Béla

    2016-01-01

    Background & Aims Adenocarcinomas of the pancreatobiliary system are currently classified by their primary anatomical location. In particular, the pathological diagnosis of intrahepatic cholangiocarcinoma is still considered as a diagnosis of exclusion of metastatic adenocarcinoma. Periampullary cancers have been previously classified according to the histological type of differentiation (pancreatobiliary, intestinal), but overlapping morphological features hinder their differential diagnosis. We performed an integrative immunohistochemical analysis of pancreato-biliary tumors to improve their diagnosis and prediction of outcome. Methods This was a retrospective observational cohort study on patients with adenocarcinoma of the pancreatobiliary system who underwent diagnostic core needle biopsy or surgical resection at a tertiary referral center. 409 tumor samples were analyzed with up to 27 conventional antibodies used in diagnostic pathology. Immunohistochemical scoring system was the percentage of stained tumor cells. Bioinformatic analysis, internal validation, and survival analysis were performed. Results Hierarchical clustering and differential expression analysis identified three immunohistochemical tumor types (extrahepatic pancreatobiliary, intestinal, and intrahepatic cholangiocarcinoma) and the discriminant markers between them. Among patients who underwent surgical resection of their primary tumor with curative intent, the intestinal type showed an adjusted hazard ratio of 0.19 for overall survival (95% confidence interval 0.05–0.72; p value = 0.014) compared to the extrahepatic pancreatobiliary type. Conclusions Integrative immunohistochemical classification of adenocarcinomas of the pancreatobiliary system results in a characteristic immunohistochemical profile for intrahepatic cholangiocarcinoma and intestinal type adenocarcinoma, which helps in distinguishing them from metastatic and pancreatobiliary type adenocarcinoma, respectively. A diagnostic

  17. Prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma

    PubMed Central

    Che, Keying; Zhao, Yang; Qu, Xiao; Pang, Zhaofei; Ni, Yang; Zhang, Tiehong; Du, Jiajun; Shen, Hongchang

    2017-01-01

    Purpose Gastric carcinoma (GC) is a highly aggressive cancer and one of the leading causes of cancer-related deaths worldwide. Histopathological evaluation pertaining to invasiveness is likely to provide additional information in relation to patient outcome. In this study, we aimed to evaluate the prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma. Materials and methods Hematoxylin and eosin-stained slides generated from 296 gastric adenocarcinoma patients with full clinical and pathological and follow-up information were systematically reviewed. The patients were grouped on the basis of tumor budding, single cell invasion, large cell invasion, mitotic count, and fibrosis. The association between histopathological parameters, different classification systems, and overall survival (OS) was statistically analyzed. Results Among the 296 cases that were analyzed, high-grade tumor budding was observed in 49.0% (145) of them. Single cell invasion and large cell invasion were observed in 62.8% (186) and 16.9% (50) of the cases, respectively. Following univariate analysis, patients with high-grade tumor budding had shorter OS than those with low-grade tumor budding (hazard ratio [HR]: 2.260, P<0.001). Similarly, the OS of patients with single cell invasion and large cell invasion was reduced (single cell invasion, HR: 3.553, P<0.001; large cell invasion, HR: 2.466, P<0.001). Following multivariate analysis, tumor budding and single cell invasion were observed to be independent risk factors for gastric adenocarcinoma (P<0.05). According to the Lauren classification, patients with intestinal-type adenocarcinoma had better outcomes than those with diffuse-type adenocarcinoma (HR: 2.563, P<0.001). Conclusion Tumor budding and single cell invasion in gastric adenocarcinoma are associated with an unfavorable prognosis. PMID:28255247

  18. Nanovectors for anti-cancer drug delivery in the treatment of advanced pancreatic adenocarcinoma

    PubMed Central

    Hsueh, Chung-Tzu; Selim, Julie H; Tsai, James Y; Hsueh, Chung-Tsen

    2016-01-01

    Liposome, albumin and polymer polyethylene glycol are nanovector formulations successfully developed for anti-cancer drug delivery. There are significant differences in pharmacokinetics, efficacy and toxicity between pre- and post-nanovector modification. The alteration in clinical pharmacology is instrumental for the future development of nanovector-based anticancer therapeutics. We have reviewed the results of clinical studies and translational research in nanovector-based anti-cancer therapeutics in advanced pancreatic adenocarcinoma, including nanoparticle albumin-bound paclitaxel and nanoliposomal irinotecan. Furthermore, we have appraised the ongoing studies incorporating novel agents with nanomedicines in the treatment of pancreatic adenocarcinoma. PMID:27610018

  19. [Mucinous adenocarcinoma of the renal pelvis associated with renal calculi of the inflammatory type].

    PubMed

    Kalafatis, P; Zarifis, I; Sotrillis, T; Stefis, A

    1999-03-01

    A rare case of mucinous adenocarcinoma of the renal pelvis associated with renal staghorn calculosis in a 60-years-old male patient with pyuria and mucin content of the urine is presented. History was significant for recurrent calculosis of the left kidney. A non functioning hydronephrotic left kidney with staghorn calculosis was diagnosed. Laboratory tests were remarkable only for Carcinoembrionic Antigen (CEA). Pathology of the surgical specimen followed by its immunoreactivity revealed an intestinal type metaplasia and papillary, tubular and mucinous adenocarcinoma of the renal pelvis. Pathogenesis of the intestinal metaplasia and the role of chronic irritation of the urothelium are mentioned.

  20. Potential Role of the Microbiome in Barrett's Esophagus and Esophageal Adenocarcinoma.

    PubMed

    Snider, Erik J; Freedberg, Daniel E; Abrams, Julian A

    2016-08-01

    Esophageal adenocarcinoma and its precursor Barrett's esophagus have been rapidly increasing in incidence for half a century, for reasons not adequately explained by currently identified risk factors such as gastroesophageal reflux disease and obesity. The upper gastrointestinal microbiome may represent another potential cofactor. The distal esophagus has a distinct microbiome of predominantly oral-derived flora, which is altered in Barrett's esophagus and reflux esophagitis. Chronic low-grade inflammation or direct carcinogenesis from this altered microbiome may combine with known risk factors to promote Barrett's metaplasia and progression to adenocarcinoma.

  1. Exfoliative erythroderma as a paraneoplastic presentation of adenocarcinoma of the gallbladder

    PubMed Central

    Eltawansy, Sherif Ali; Modi, Anar; Hassanien, Samaa; Zhang, Bin; Pei, Zhengtong; Ghali, Wael

    2015-01-01

    We report a case of a 71-year-old Caucasian male presenting with an exfoliative skin rash all over his body. The patient was also found to have a huge gall bladder mass extending into the liver that turned out to be adenocarcinoma of the gall bladder on biopsy. Gall bladder cancer usually presents with abdominal pain, swelling or jaundice. We report only the second case in literature of a gall bladder adenocarcinoma presenting with exfoliative erythroderma as its paraneoplastic presentation. PMID:25830047

  2. SMALL INTESTINAL ADENOCARCINOMA WITH CARCINOMATOSIS IN A SWIFT FOX (VULPES VELOX).

    PubMed

    Choudhary, Shambhunath; Andrews, Gordon A; Carpenter, James W

    2015-09-01

    A 7-yr-old, intact, female swift fox (Vulpes velox) presented to the Veterinary Health Center at Kansas State University with a history of chronic weight loss, lethargy, inappetence, and myiasis. On physical examination, a firm mass was palpated in the mid- to cranial abdomen. The fox was euthanatized as a result of the grave prognosis. Gross necropsy and histologic findings included a small intestinal adenocarcinoma with diffuse transperitoneal spread throughout the abdominal cavity (carcinomatosis). To the authors' knowledge, this is the first report of intestinal adenocarcinoma with carcinomatosis in a swift fox.

  3. Invasive Squamous Carcinoma and Adenocarcinoma of an Unreconstructed Exstrophic Bladder with HPV Infection

    PubMed Central

    Altan, Mesut; Çıtamak, Burak; Haberal, Hakan Bahadır; Söğütdelen, Emrullah; Bozaci, Ali Cansu; Baydar, Dilek Ertoy; Doğan, Hasan Serkan; Tekgül, Serdar

    2016-01-01

    Bladder exstrophy is a complex abnormality and is traditionally treated within the early years of life. It is associated with an increased risk of bladder cancer, with 95% of the arising tumors being adenocarcinomas and 3 to 5% being squamous cell carcinomas. HPV infections are also associated with an increased risk of bladder cancer. This case represents a patient with bladder exstrophy that gave rise to coinciding squamous cell carcinoma and adenocarcinoma. Final pathology results showed an infection with HPV. We presented the management of the case and discussed the diagnosis and treatment methods for this patient. PMID:27390585

  4. HIGH PREVALENCE OF INTESTINAL ADENOCARCINOMA IN A CAPTIVE POPULATION OF AMAZON MILK FROG (TRACHYCEPHALUS RESINIFICTRIX).

    PubMed

    López, Javier; Barbón, Alberto R; Smithyman, Juliet; Goetz, Matt; Marschang, Rachel E; Dastjerdi, Akbar; Stidworthy, Mark F

    2016-12-01

    :  A series of eight cases of intestinal adenocarcinoma in Amazon milk frog (Trachycephalus resinifictrix) is described. All cases presented with signs of inappetence and weight loss, and evidence of large intestinal distention on gross postmortem, with six of the eight cases showing a grossly visible large intestinal mass. Histologic examination identified the mass as an intestinal adenocarcinoma in all cases. No specific etiologic agent could be identified. This is the first report of neoplasia in the Amazon milk frog, and the first reported series of amphibian gastrointestinal neoplasia.

  5. Hepatoid Adenocarcinoma of the Extrahepatic Bile Duct in a Patient with Polysplenia Syndrome

    PubMed Central

    Yorita, Kenji; Sasaki, Shiori; Kawada, Ai; Okazaki, Michiyo; Yamai, Hiromichi; Uchita, Kunihisa; Iwamura, Shinichi; Nakatani, Kimiko; Ito, Satoshi; Kuroda, Naoto

    2017-01-01

    Hepatoid adenocarcinoma (HAC) is a rare subtype of extrahepatic adenocarcinoma that is characterized by its morphological and functional similarities to hepatocellular carcinoma. We herein present a novel case of HAC arising from the extrahepatic bile duct in a 75-year-old Japanese woman with polysplenia syndrome. This is the second reported case of HAC arising from this site. The tumor induced jaundice and hemobilia. A total of four isolated intraductal polypoid masses of HAC were found. No recurrence was seen five months after surgery. Further reports of similar cases will be needed to clarify the clinical characteristics and the prognosis of this malignancy. PMID:28202861

  6. Clear cell adenocarcinoma of the renal pelvis: an extremely rare neoplasm of the upper urinary tract.

    PubMed

    Liu, K-W; Lin, V C-H; Chang, I-W

    2013-12-01

    Clear cell adenocarcinoma (CCA) in the urinary tract is a rare neoplasm morphologically identical to the Müllerian counterpart. Clear cell adenocarcinoma is extremely rare in the upper urinary tract. We present a case with CCA of the renal pelvis. Microscopically, the tumor exhibited exophytic growth with predominantly tubulocystic structures, as well as solid and papillary patterns. The neoplastic cells were cuboidal with clear to pale eosinophilic cytoplasm and abundant intracellular and extracellular eosinophilic hyaline globules. By immunohistochemically, the tumor was labeled by cytokeratins and hepatocyte nuclear factor-1β. The patient was still alive without evidence of recurrence in the follow-up period of nineteen months after diagnosis.

  7. Prostate adenocarcinoma presenting with supraclavicular node enlargement: report of a case.

    PubMed

    Platania, Marco; Bajetta, Emilio; Guadalupi, Valentina; Buzzoni, Roberto; Colecchia, Maurizio

    2008-01-01

    This report describes a case of prostate adenocarcinoma presenting with supraclavicular adenopathy and deep venous thrombosis in the ipsilateral arm. Biopsy revealed the enlarged node to be an undifferentiated adenocarcinoma of unknown origin, while CT scan evidenced widespread adenopathies. Because of the increase in serum PSA, the immunohistochemical staining of the biopsy specimen was reviewed and strong positivity for PSA suggested a prostatic origin. We emphasize the importance of PSA immunohistochemistry and serum PSA level monitoring in men presenting with carcinoma of undetermined origin and generalized lymphadenopathies.

  8. Correlation in histological subtypes with high resolution computed tomography signatures of early stage lung adenocarcinoma

    PubMed Central

    Miao, Yingying; Zhang, Jianya; Zou, Jiawei; Zhu, Qingqing

    2017-01-01

    Background Uncertainty remains on the association between image characteristics of the nodules in computed tomography (CT) scans and lung adenocarcinoma histopathologic subtypes. We aimed to estimate the correlation between preoperative high resolution computed tomography (HRCT) scan and postoperative histopathology of stage IA lung adenocarcinoma in East Asian Chinese population. Methods We retrospectively reviewed the clinical records and HRCT images of 190 patients (106 female and 84 male) with resected, preoperatively untreated stage IA adenocarcinomas. The relationship between image characteristics of nodules at preoperative HRCT and their histological subtypes after resection were analyzed. The one-way ANOVA, chi-square test and logistic regression were used for analysis. Results In 190 patients with stage IA lung adenocarcinoma, median tumor diameter was significantly lower in lepidic predominant invasive adenocarcinoma (LPA) (15.96±6.95 mm). Univariate analysis revealed that ground-glass opacity (GGO) proportion (P<0.001), margin (P<0.001), border definition (P=0.015), pleural retraction (P<0.001) and enhancement (P<0.001) had statistically significant differences in four histological subtypes. The multivariate analysis referenced for lepidic group which indicated that GGO proportion and pleural retraction were independent associated with acinar group (RR=4.221, 95% CI: 1.770–10.066, P=0.001; RR=0.380, 95% CI: 0.158–0.916, P=0.031, respectively). Male and whose nodule margin with spiculation or lobulation were prone to papillary predominant invasive adenocarcinoma (PPA) (RR=0.288, 95% CI: 0.090–0.920, P=0.036; RR=0.250, 95% CI: 0.070–0.887, P=0.032, respectively). GGO proportion and nodule margin were independent related factors in solid predominant invasive adenocarcinoma (SPA) (RR=13.338, 95% CI: 2.974–59.811, P=0.001; RR=0.097, 95% CI: 0.016–0.606, P=0.013, respectively). Conclusions Nodules with spiculation or lobulation and less GGO

  9. Choroidal metastasis secondary to prostatic adenocarcinoma: case report and review of literature.

    PubMed

    Albadainah, Faisal; Khader, Jamal; Salah, Samer; Salem, Ahmed

    2015-03-01

    Choroidal metastasis from prostate adenocarcinoma is exceedingly rare. Furthermore, data addressing the optimal therapeutic strategy is limited. A 62-year-old male patient with metastatic prostate cancer was found to have a choroidal metastasis after complaining of decreased vision in his left eye. Following treatment with external beam radiotherapy, complete response in the choroidal metastasis was demonstrated. A literature search was undertaken to highlight the therapeutic options for this rare presentation. Choroidal metastasis secondary to adenocarcinoma of the prostate is exceedingly rare, as only eight cases have been reported so far. External beam radiotherapy is an effective therapeutic modality.

  10. Helical tomotherapy for duodenal adenocarcinoma in an elderly patient: A case report

    PubMed Central

    Lancellotta, Valentina; Russo, Giuseppe; Lupattelli, Marco; Iacco, Martina; Perrucci, Elisabetta; Zucchetti, Claudio; Falcinelli, Lorenzo; Aristei, Cynthia

    2017-01-01

    To evaluate the efficacy and feasibility of external beam radiotherapy (EBRT) for duodenal adenocarcinoma in an 84-year-old female who underwent EBRT (2.2 Gy/d for a total dose of 46.2 Gy) using helical tomotherapy (HT). Toxicity was evaluated on the National Cancer Institute’s common toxicity criteria (CTCAE 3.0). The patient completed the treatment without G3-G4 toxicity. After 22-mo follow-up, she is alive and well, in complete remission with no late side effects. HT seems to be feasible and effective for duodenal adenocarcinoma in old to very old patients. PMID:28255431

  11. Lymph node dissection for Siewert II esophagogastric junction adenocarcinoma

    PubMed Central

    Duan, Xiao-Feng; Yue, Jie; Tang, Peng; Shang, Xiao-Bin; Jiang, Hong-Jing; Yu, Zhen-Tao

    2017-01-01

    Abstract The present study was aimed to investigate the application of right thansthoracic Ivor–Lewis (IL), left transthoracic (LTT), and left thoracoabdominal (LTA) approach in Siewert type II adenocarcinoma of esophagogastric junction (AEG). The data of 196 patients with Siewert type II AEG received surgical resection in our cancer center between January 2014 and April 2016 was retrospectively analyzed. Finally, 136 patients met the inclusion criteria were enrolled in the study and divided into the IL (47 cases), LTT (51 cases), and LTA group (38 cases). Clinical and short-term treatment effects were compared among the 3 groups. The patients with weight loss, diabetes, and heart disease increased in the LTT group (P = 0.054, P = 0.075, and P = 0.063, respectively). Operation time was significantly longest in the IL group (P < 0.001), but the amount of bleeding and tumor size did not significantly differ among the 3 groups (P = 0.176 and P = 0.228, respectively). The IL group had the significantly longest proximal surgical margin (P < 0.001) and most number of total (P < 0.001) and thoracic lymph nodes (P < 0.001) dissected. Both the IL and LTA groups had more abdominal lymph nodes dissected than the LTT group (P < 0.001). In general, the IL and LTT groups had the highest dissection rates of every station of thoracic (P < 0.05) and lower mediastinal lymph nodes (P < 0.05), respectively. The dissection rate of the paracardial, left gastric artery, and gastric lesser curvature lymph nodes did not differ significantly among the 3 groups (P > 0.05), but the dissection rate of the hepatic artery, splenic artery, and celiac trunk lymph nodes was significantly highest in the IL group (P < 0.05). Postoperative hospital stay, perioperative complications, and mortality did not differ significantly among the 3 groups (P > 0.05). Compared with the traditional left transthoracic approach, the Ivor–Lewis approach

  12. Outcomes of robotic surgery for pancreatic ductal adenocarcinoma

    PubMed Central

    Zhan, Qian; Deng, Xiaxing; Weng, Yuanchi; Jin, Jiabin; Wu, Zhichong; Li, Hongwei; Shen, Baiyong

    2015-01-01

    Background To explore the effectiveness, safety, and efficacy of the robot-assisted surgery in the radical resection of pancreatic ductal adenocarcinoma (PDAC). Methods The clinical data of 72 patients with PDAC who underwent radical resection using the da Vinci Surgical System from April 2010 to December 2014 were retrospectively analyzed. Results Among these 72 patients, three were converted to conventional laparotomy due to the vascular invasion or due to the difficulties in tissue isolation from the surrounding organs. Among 39 patients who underwent the pancreatoduodenectomy, the average operative time was 395.3±118.8 min, and the mean intra-operative blood loss was 447.3±269.9 mL. Among 31 patients who underwent the distal pancreatectomy (DP), the average operative time was 185.5±74.1 min, and the mean intra-operative blood loss was 267.1±305.3 mL. In two patients who received the middle pancreatectomy (MP), the average operative time was 225 min and mean intra-operative blood loss was 100 mL. Among all the 72 patients, an average of 4.2±2.6 lymph nodes were dissected, with an average hospital stay of 22.6±10.7 days. Complications were observed in 18 patients, which included pancreatic fistula (n=11), bile leak (n=5), anastomotic bleeding (n=2), pancreatic fistula complicated with portal vein thrombosis (n=1), and anastomotic bleeding complicated with acute renal failure (n=1). Except that one patient died due to post-operative bleeding and acute renal failure, all the other patients were cured after conservative treatment. These 72 patients were followed for 1-45 (15.6±5.8) months, during which 10 patients died. Eleven patients suffered from recurrence or metastasis, among which 6 had local recurrence, 4 had liver metastasis, and 1 had ascites accompnaied with incision site tumor metastasis. Conclusions Radical resection of PDAC by robotic surgical system is safe and feasible. It has less surgical trauma and enables faster post-operative recovery, and

  13. A rapid in vivo screen for pancreatic ductal adenocarcinoma therapeutics.

    PubMed

    Ocal, Ozhan; Pashkov, Victor; Kollipara, Rahul K; Zolghadri, Yalda; Cruz, Victoria H; Hale, Michael A; Heath, Blake R; Artyukhin, Alex B; Christie, Alana L; Tsoulfas, Pantelis; Lorens, James B; Swift, Galvin H; Brekken, Rolf A; Wilkie, Thomas M

    2015-10-01

    Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related deaths in the United States, and is projected to be second by 2025. It has the worst survival rate among all major cancers. Two pressing needs for extending life expectancy of affected individuals are the development of new approaches to identify improved therapeutics, addressed herein, and the identification of early markers. PDA advances through a complex series of intercellular and physiological interactions that drive cancer progression in response to organ stress, organ failure, malnutrition, and infiltrating immune and stromal cells. Candidate drugs identified in organ culture or cell-based screens must be validated in preclinical models such as KIC (p48(Cre);LSL-Kras(G12D);Cdkn2a(f/f)) mice, a genetically engineered model of PDA in which large aggressive tumors develop by 4 weeks of age. We report a rapid, systematic and robust in vivo screen for effective drug combinations to treat Kras-dependent PDA. Kras mutations occur early in tumor progression in over 90% of human PDA cases. Protein kinase and G-protein coupled receptor (GPCR) signaling activates Kras. Regulators of G-protein signaling (RGS) proteins are coincidence detectors that can be induced by multiple inputs to feedback-regulate GPCR signaling. We crossed Rgs16::GFP bacterial artificial chromosome (BAC) transgenic mice with KIC mice and show that the Rgs16::GFP transgene is a Kras(G12D)-dependent marker of all stages of PDA, and increases proportionally to tumor burden in KIC mice. RNA sequencing (RNA-Seq) analysis of cultured primary PDA cells reveals characteristics of embryonic progenitors of pancreatic ducts and endocrine cells, and extraordinarily high expression of the receptor tyrosine kinase Axl, an emerging cancer drug target. In proof-of-principle drug screens, we find that weanling KIC mice with PDA treated for 2 weeks with gemcitabine (with or without Abraxane) plus inhibitors of Axl signaling

  14. Regulation of cholesterol synthesis in four colonic adenocarcinoma cell lines.

    PubMed

    Cerda, S R; Wilkinson, J; Broitman, S A

    1995-12-01

    Colon tumor cells, unlike normal human fibroblasts, exhibited an uncoupling of low density lipoprotein (LDL)-derived cholesterol from cellular growth, when endogenous cholesterol synthesis was inhibited by mevinolin, a hydroxymethylglutaryl-CoA reductase (HMG-CoAR) competitive inhibitor [Fabricant, M., and Broitman, S.A. (1990) Cancer Res. 50, 632-636]. Further evaluation of cholesterol metabolism was conducted in two undifferentiated (SW480, SW1417) and two differentiated (HT29, CACO2) colonic adenocarcinoma (adeno-CA) cell lines and an untransformed human fibroblast, AG1519A. Cells grown in monolayer culture to near subconfluency were used to assess endogenous cholesterol synthesis by 14C-acetate incorporation, in response to the following treatments in lipoprotein-deficient serum (LPDS)-supplemented minimum essential medium (MEM): LPDS alone, LDL, mevinolin, mevinolin with LDL, and 25-hydroxy-cholesterol (25-OH-CH). Complete fetal bovine serum (FBS)-supplemented MEM was used as control. All colon tumor lines exhibited similarly high endogenous cholesterol synthesis in both FBS and LPDS relative to the fibroblasts which demonstrated low basal levels in FBS and maximal synthesis in LPDS. LDL treatment did not inhibit cholesterol synthesis in colon tumor cells, but suppressed that in the fibroblast by 70%. Sterol repression of cholesterol synthesis mediated by 25-OH-CH occurred in all cells. Mevinolin caused a reduction in cholesterol synthesis in the colonic cancer cell lines, which was not further decreased by concurrent addition of LDL. In contrast, in mevinolin-treated fibroblasts, LDL further inhibited cholesterol synthesis. When the effect of cell density on cholesterol synthesis regulation was evaluated under conditions of sparse density in SW480 and SW147, results indicated that (i) basal rates of cholesterol synthesis were higher, (ii) LDL inhibited cholesterol synthesis more effectively, and (iii) mevinolin or 25-OH-CH had a more pronounced effect than in

  15. Small bowel adenocarcinoma phenotyping, a clinicobiological prognostic study

    PubMed Central

    Aparicio, T; Svrcek, M; Zaanan, A; Beohou, E; Laforest, A; Afchain, P; Mitry, Emmanuel; Taieb, J; Di Fiore, F; Gornet, J-M; Thirot-Bidault, A; Sobhani, I; Malka, D; Lecomte, T; Locher, C; Bonnetain, F; Laurent-Puig, P

    2013-01-01

    Background: Small bowel adenocarcinoma (SBA) is a rare tumour with a poor prognosis. Molecular biology data on SBA carcinogenesis are lacking. Methods: Expression of HER2, β-catenin, p53 and mismatch repair (MMR) protein was assessed by immunohistochemistry. KRAS, V600E BRAF mutations and microsatellite instability were investigated. Results: We obtained samples from 63 SBA patients (tumour stages: I–II: 30% III: 35% IV: 32% locally advanced: 3%). HER2 overexpression (3+) was observed in 2 out of 62 patients, overexpression of p53 in 26 out of 62, abnormal expression of β-catenin in 12 out of 61, KRAS mutation in 21 out of 49, BRAF V600E mutation in 1 out of 40 patients, MMR deficiency (dMMR) in 14 out of 61 and was consistent with Lynch syndrome in 9 out of 14 patients. All of the dMMR tumours were in the duodenum or jejunum and only one was stage IV. Median overall survival (OS) was 36.6 months (95% CI, 26.9–72.2). For all patients, in univariate analysis, stages I–II (P<0.001), WHO PS 0–1 (P=0.01) and dMMR phenotype (P=0.02) were significantly associated with longer OS. In multivariate analysis, disease stage (P=0.01) and WHO PS 0–1 (P=0.001) independently predicted longer OS. For stage IV patients, median OS was 20.5 months (95% CI: 14.6; 36.6 months). In multivariate analysis, WHO PS 0–1 (P=0.0001) and mutated KRAS status (P=0.02) independently predicted longer OS. Conclusion: This large study suggests that molecular alterations in SBA are closer to those in colorectal cancer (CRC) than those in gastric cancer, with low levels of HER 2 overexpression and high frequencies of KRAS mutations. The seemingly higher frequency of dMMR than in CRC may be explained by the higher frequency of Lynch syndrome in SBA patients. A dMMR phenotype was significantly associated with a non-metastatic tumour (P=0.02). A trend for a good prognosis and a duodenum or jejunum primary site was associated with dMMR. PMID:24196786

  16. LncRNA expression profiles of EGFR exon 19 deletions in lung adenocarcinoma ascertained by using microarray analysis.

    PubMed

    Wang, Yumin; Chen, Wei; Chen, Jie; Pan, Qinshi; Pan, Jingye

    2014-09-01

    Studies showed that long chain non-coding RNAs (lncRNAs) involved in the development and progression of lung cancer. However, the mechanisms of EGFR exon 19 deletion in lung adenocarcinoma were unclear. Lung adenocarcinoma was divided into EGFR exon 19 deletion group and EGFR wild-type group. We studied the differential expression profiles of lncRNAs in EGFR exon 19 deletion in lung adenocarcinoma by high-throughput microarray. Using abundant and varied probes, we were able to assess 30,586 lncRNAs and 26,109 mRNAs in our microarray. Compared with the wild-type EGFR, we found that 1,533 lncRNAs and 1,406 mRNAs were differentially expressed (≥ twofold change) in EGFR exon 19 deletion in lung adenocarcinoma, indicating that many lncRNAs were significantly upregulated or downregulated in EGFR exon 19 deletion in lung adenocarcinoma. The 10 lncRNAs were aberrantly expressed in EGFR exon 19 deletion in lung adenocarcinoma compared with wild-type EGFR group validated by real-time RT-PCR. Among these, RP11-325I22.2 and LOC440905 were the most aberrantly expressed in 20 cases of EGFR exon 19 deletion in lung adenocarcinoma samples by real-time RT-PCR. Our study showed lncRNAs expression pattern in EGFR exon 19 deletion in lung adenocarcinoma by microarray. RP11-325I22.2 and LOC440905 might play an important role in the mechanism of EGFR exon 19 deletion in lung adenocarcinoma. The study may provide a new mechanism of EGFR exon 19 deletion in lung adenocarcinoma.

  17. Primary Vaginal Adenocarcinoma Arising in Vaginal Adenosis After CO2 Laser Vaporization and 5-Fluorouracil Therapy

    PubMed Central

    Paczos, Tamera A.; Ackers, Stacey; Odunsi, Kunle; Lele, Shashikant; Mhawech-Fauceglia, Paulette

    2016-01-01

    Summary We present a case of a 45-year-old woman with a long-standing history of persistent cervical dysplasia that resulted in a hysterectomy. Subsequent vaginal smears revealed high-grade vaginal intraepithelial neoplasia (VAIN III) on Pap smear with positive human papilloma virus (HPV) testing. Over the course of 2 years, the patient underwent 2 CO2 laser vaporization procedures of the upper vagina and intermittent 5-fluorouracil therapy. A biopsy performed at the time of the second laser procedure revealed endocervical-type well-differentiated adenocarcinoma, associated with VAIN III. HPV in situ hybridization for HPV types 16 and 18 was positive in both the glandular and squamous mucosa. The patient has no known history of intrauterine diethylstilbestrol exposure or mullerian developmental abnormalities. Subsequently, the patient underwent a radical upper vaginetcomy with bilateral pelvic lymph nodes dissection and bilateral salpingo-oophorectomy. The vaginectomy specimen showed residual adenocarcinoma associated with VAIN-III and extensive vaginal adenosis with free resection margins. This is the second reported case in the literature of adenocarcinoma arising in vaginal adenosis after 5-fluorouracil. Herein, we highlight these important findings and shed some light on the pathogenesis of vaginal adenosis and the subsequent development of vaginal adenocarcinoma. PMID:20173507

  18. Improved survival with neoadjuvant therapy and resection for adenocarcinoma of the esophagus.

    PubMed Central

    Stewart, J R; Hoff, S J; Johnson, D H; Murray, M J; Butler, D R; Elkins, C C; Sharp, K W; Merrill, W H; Sawyers, J L

    1993-01-01

    OBJECTIVE: This study sought to determine the impact of preoperative chemotherapy and radiation therapy (neoadjuvant therapy) followed by resection in patients with adenocarcinoma of the esophagus. SUMMARY BACKGROUND DATA: Long-term survival in patients with carcinoma of the esophagus has been poor. An increase in the incidence of adenocarcinoma of the esophagus has been reported recently. METHODS: Fifty-eight patients with biopsy-proven adenocarcinoma of the esophagus treated at this institution from January 1951 through February 1993 were studied. Since 1989, 24 patients were entered prospectively into a multimodality treatment protocol consisting of preoperative cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without etoposide, and concomitant mediastinal radiation (30 Gy). Patients were re-evaluated and offered resection. RESULTS: There were no deaths related to neoadjuvant therapy and toxicity was minimal. Before multimodality therapy was used, the operative mortality rate was 19% (3 of 16 patients). With multimodality therapy, there have been no operative deaths (0 of 23 patients). The median survival time in patients treated before multimodality therapy was 8 months and has yet to be reached for those treated with the neoadjuvant regimen (> 26 months, p < 0.0001). The actuarial survival rate at 24 months was 15% before multimodality therapy and 76% with multimodality therapy. No difference in survival was noted in neoadjuvant protocols with or without etoposide (p = 0.827). CONCLUSIONS: Multimodality therapy with preoperative chemotherapy and radiation therapy followed by resection appears to offer a survival advantage to patients with adenocarcinoma of the esophagus. PMID:8215648

  19. Nuclear distribution of claudin-2 increases cell proliferation in human lung adenocarcinoma cells.

    PubMed

    Ikari, Akira; Watanabe, Ryo; Sato, Tomonari; Taga, Saeko; Shimobaba, Shun; Yamaguchi, Masahiko; Yamazaki, Yasuhiro; Endo, Satoshi; Matsunaga, Toshiyuki; Sugatani, Junko

    2014-09-01

    Claudin-2 is expressed in human lung adenocarcinoma tissue and cell lines, although it is absent in normal lung tissue. However, the role of claudin-2 in cell proliferation and the regulatory mechanism of intracellular distribution remain undefined. Proliferation of human adenocarcinoma A549 cells was decreased by claudin-2 knockdown together with a decrease in the percentage of S phase cells. This knockdown decreased the expression levels of ZONAB and cell cycle regulators. Claudin-2 was distributed in the nucleus in human adenocarcinoma tissues and proliferating A549 cells. The nuclear distribution of ZONAB and percentage of S phase cells were higher in cells exogenously expressing claudin-2 with a nuclear localization signal than in cells expressing claudin-2 with a nuclear export signal. Nuclear claudin-2 formed a complex with ZO-1, ZONAB, and cyclin D1. Nuclear distribution of S208A mutant, a dephosphorylated form of claudin-2, was higher than that of wild type. We suggest that nuclear distribution of claudin-2 is up-regulated by dephosphorylation and claudin-2 serves to retain ZONAB and cyclin D1 in the nucleus, resulting in the enhancement of cell proliferation in lung adenocarcinoma cells.

  20. Laminin 5 expression protects against anoikis at aerogenous spread and lepidic growth of human lung adenocarcinoma.

    PubMed

    Kodama, Keiji; Ishii, Gen'ichiro; Miyamoto, Shin'ichi; Goya, Masato; Zhang, Shi-Chuan; Sangai, Takafumi; Yoshikawa, Takeshi; Hasebe, Takahiro; Hitomi, Yoshiaki; Izumi, Keisuke; Ochiai, Atsushi

    2005-10-10

    Adenocarcinoma of the lung is characterized by frequent aerogenous spread (AE) and advancement along the alveolar wall (BAC growth). To elucidate the mechanism of AE metastasis and BAC growth in human lung adenocarcinoma, we established an in vivo orthotopic animal model and an in vitro culture. Investigation of expression levels of integrins, laminins and Type IV collagens, which are the major regulating molecules for cell attachment and anoikis was carried out and a clear correlation between the expression level of laminin 5 (LN5) and the BAC growth was observed using an orthotopic animal model. Introduction of LN5 cDNA to A549 cells increased anoikis resistance in an expression dependent manner. Cells with LN5 overexpression resisted with anoikis after treatment with PI3K-Akt and ERK inhibitors. The amount of phosphorylated focal adhesion kinase (FAK) was also higher in LN5 overexpressing cells. Major tyrosine residues of the EGF receptor at 1068, 1086 and 1173, except at 1148, remained phosphorylated only in the LN5 overexpressing cells even without EGF stimulation, that indicates the ligand independent activation of EGF receptor. BAC growth ratio and AE was confirmed to be significantly correlated with LN5 expression in surgically resected human lung adenocarcinomas by immunohistochemistry. Our results indicate that the activation of the EGF receptor by overexpressing LN5-integrin-FAK signaling pathway may play a crucial role in BAC growth and AE metastasis in human lung adenocarcinoma.

  1. [Thumb acrometastasis revealing lung adenocarcinoma: a case report with review of literature].

    PubMed

    Akjouj, S; El Kettani, N; Semlali, S; Chaguar, B; Chaouir, S; Hanine, A; Benameur, M

    2006-06-01

    Bone metastases in the hand and foot bone (acrometastases) are rarely observed. The authors report a case of a 57-years-old man diagnosed as hand tumour, revealing a bronchic adenocarcinoma. Radiography showed destruction of the phalanx, and histology study confirmed a metastasis of the lung cancer.

  2. Microsatellite instability in adenocarcinomas of the upper gastrointestinal tract. Relation to clinicopathological data and family history.

    PubMed Central

    Keller, G.; Rotter, M.; Vogelsang, H.; Bischoff, P.; Becker, K. F.; Mueller, J.; Brauch, H.; Siewert, J. R.; Höfler, H.

    1995-01-01

    We analyzed 66 adenocarcinomas arising in the upper gastrointestinal tract for microsatellite instability at eight microsatellite loci to investigate the role of these genetic alterations in the etiology of these tumors. We identified alterations in at least one locus in 11/46 adenocarcinomas of the stomach, in 2/15 adenocarcinomas arising in Barrett's esophagus, and in 1/5 adenocarcinomas of the duodenum and jejunum. Microsatellite instability in gastric tumors was found in 5/22 of intestinal, 1/3 of mixed, and 5/21 of diffuse type tumors. No relationship to the tumor stage (TNM), age, and survival time of the patients was observed. One patient had two synchronous gastric tumors both exhibiting microsatellite instability at multiple loci. His family history revealed four individuals in the maternal line afflicted with gastric carcinoma in three generations. Our data show that microsatellite instability is a genetic event in 11 to 24% of tumors of the upper gastrointestinal tract. The observation of microsatellite instability and a familial clustering of gastric tumors may suggest a genetic predisposition for a subset of gastric tumors, which may be identified by microsatellite analysis. Images Figure 1 PMID:7677173

  3. Primary vaginal adenocarcinoma arising in vaginal adenosis after CO2 laser vaporization and 5-fluorouracil therapy.

    PubMed

    Paczos, Tamera A; Ackers, Stacey; Odunsi, Kunle; Lele, Shashikant; Mhawech-Fauceglia, Paulette

    2010-03-01

    We present a case of a 45-year-old woman with a long-standing history of persistent cervical dysplasia that resulted in a hysterectomy. Subsequent vaginal smears revealed high-grade vaginal intraepithelial neoplasia (VAIN III) on Pap smear with positive human papilloma virus (HPV) testing. Over the course of 2 years, the patient underwent 2 CO(2) laser vaporization procedures of the upper vagina and intermittent 5-fluorouracil therapy. A biopsy performed at the time of the second laser procedure revealed endocervical-type well-differentiated adenocarcinoma, associated with VAIN III. HPV in situ hybridization for HPV types 16 and 18 was positive in both the glandular and squamous mucosa. The patient has no known history of intrauterine diethylstilbestrol exposure or mullerian developmental abnormalities. Subsequently, the patient underwent a radical upper vaginetcomy with bilateral pelvic lymph nodes dissection and bilateral salpingo-oophorectomy. The vaginectomy specimen showed residual adenocarcinoma associated with VAIN-III and extensive vaginal adenosis with free resection margins. This is the second reported case in the literature of adenocarcinoma arising in vaginal adenosis after 5-fluorouracil. Herein, we highlight these important findings and shed some light on the pathogenesis of vaginal adenosis and the subsequent development of vaginal adenocarcinoma.

  4. Loss of Par3 promotes lung adenocarcinoma metastasis through 14-3-3ζ protein.

    PubMed

    Song, Tong; Tian, Xia; Kai, Fan; Ke, Jiang; Wei, Zhai; Jing-Song, Li; Si-Hua, Wang; Jian-Jun, Wang

    2016-09-27

    Partitioning defective protein 3 (Par3) can activate the Tiam1/Rac pathway to inhibit invasion and metastasis in many cancers; however, the role of Par3 in lung adenocarcinoma remains unknown. Here we show that Par3 is downregulated in lung adenocarcinoma tissues and is associated with higher rates of lymph node metastasis and recurrence. Our functional study demonstrated that knock-down of Par3 promoted lung adenocarcinoma cell growth, cell migration, tumor formation, and metastasis, all of which were effectively inhibited when 14-3-3ζ was silenced. We found that Par3 binded with 14-3-3ζ protein and also showed that Par3 abrogated the binding of 14-3-3ζ to Tiam1, which was responsible for Rac1 activation. Knock-down of 14-3-3ζ inhibited Tiam1/Rac-GTP activation and blocked the invasive behavior of cells lacking Par3. These data suggest that loss of Par3 promotes metastatic behavior in lung adenocarcinoma cells through 14-3-3ζ protein.

  5. Prostate adenocarcinoma mandibular metastasis associated with numb chin syndrome: a case report

    PubMed Central

    2016-01-01

    The purpose of this study is to report a rare case of mandibular adenocarcinoma that was diagnosed due to metastasis from the prostate. Numb chin syndrome (NCS), which was associated with this case, is also discussed. Computed tomography (CT) and an intraoral incisional biopsy of the left mandibular area were performed. Urology consultation, hormone therapy, chemotherapy and follow-up radiographic images were administered. Histological examination of the incised specimen revealed moderately differentiated adenocarcinoma. The Gleason score was 8 (primary 4/secondary 4). Immunohistochemical features and radiographic results confirmed the diagnosis of metastasis from prostate adenocarcinoma, moderately differentiated. The patient's prostate-specific antigen (PSA) level was very high. After hormone treatment, the patient's PSA levels dropped gradually. Seventeen months later, in May 2015, the PSA level was elevated. The 18-month follow-up CT image indicated that the patient's condition was aggravated. Docetaxel chemotherapy was started in June 2015 (18 months later), and the sixth cycle of the therapy is in progress. Oral metastases that originate from prostate adenocarcinoma are rare and can induce various periosteal reactions. Hormone therapy, chemotherapy and close follow-up could be additional, appropriate treatment, and were applied in this case. Finally, NCS is a valuable indicator of metastatic disease in the mandible. PMID:27847740

  6. TAK1-regulated expression of BIRC3 predicts resistance to preoperative chemoradiotherapy in oesophageal adenocarcinoma patients

    PubMed Central

    Piro, G; Giacopuzzi, S; Bencivenga, M; Carbone, C; Verlato, G; Frizziero, M; Zanotto, M; Mina, M M; Merz, V; Santoro, R; Zanoni, A; De Manzoni, G; Tortora, G; Melisi, D

    2015-01-01

    Background: About 20% of resectable oesophageal carcinoma is resistant to preoperative chemoradiotherapy. Here we hypothesised that the expression of the antiapoptotic gene Baculoviral inhibitor of apoptosis repeat containing (BIRC)3 induced by the transforming growth factor β activated kinase 1 (TAK1) might be responsible for the resistance to the proapoptotic effect of chemoradiotherapy in oesophageal carcinoma. Methods: TAK1 kinase activity was inhibited in FLO-1 and KYAE-1 oesophageal adenocarcinoma cells using (5Z)-7-oxozeaenol. The BIRC3 mRNA expression was measured by qRT–PCR in 65 pretreatment frozen biopsies from patients receiving preoperatively docetaxel, cisplatin, 5-fluorouracil, and concurrent radiotherapy. Receiver operator characteristic (ROC) analyses were performed to determine the performance of BIRC3 expression levels in distinguishing patients with sensitive or resistant carcinoma. Results: In vitro, (5Z)-7-oxozeaenol significantly reduced BIRC3 expression in FLO-1 and KYAE-1 cells. Exposure to chemotherapeutic agents or radiotherapy plus (5Z)-7-oxozeaenol resulted in a strong synergistic antiapoptotic effect. In patients, median expression of BIRC3 was significantly (P<0.0001) higher in adenocarcinoma than in the more sensitive squamous cell carcinoma subtype. The BIRC3 expression significantly discriminated patients with sensitive or resistant adenocarcinoma (AUC-ROC=0.7773 and 0.8074 by size-based pathological response or Mandard's tumour regression grade classifications, respectively). Conclusions: The BIRC3 expression might be a valid biomarker for predicting patients with oesophageal adenocarcinoma that could most likely benefit from preoperative chemoradiotherapy. PMID:26291056

  7. Association of distinct mutational signatures with correlates of increased immune activity in pancreatic ductal adenocarcinoma

    DOE PAGES

    Connor, Ashton A.; Denroche, Robert E.; Jang, Gun Ho; ...

    2016-10-20

    Outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) remain poor. In addition, advances in next-generation sequencing provide a route to therapeutic approaches, and integrating DNA and RNA analysis with clinicopathologic data may be a crucial step toward personalized treatment strategies for this disease.

  8. A Speculative Role for Stromal Gastrin Signaling in Development and Dissemination of Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Matters, Gail L; Clawson, Gary A

    2013-01-01

    The peptide growth factor gastrin and its receptor, the G-protein coupled cholecystokinin receptor type B (CCKBR), play an integral role in the growth and progression of pancreatic ductal adenocarcinoma (PDAC). Gastrin immunoreactivity is found in the fetal pancreas but its expression is not detected in normal pancreas after birth, except when it is re-expressed in malignant lesions. PMID:25346875

  9. Size- and dose-dependent toxicity of cellulose nanocrystals (CNC) on human fibroblasts and colon adenocarcinoma.

    PubMed

    Hanif, Zahid; Ahmed, Farrukh R; Shin, Seung Won; Kim, Young-Kee; Um, Soong Ho

    2014-07-01

    A controlled preparation of cellulose nanocrystals of different sizes and shapes has been carried out by acid hydrolysis of microcrystalline cellulose. The size- and concentration-dependent toxicity effects of the resulting cellulose nanocrystals were evaluated against two different cell lines, NIH3T3 murine embryo fibroblasts and HCT116 colon adenocarcinoma. It could serve as a therapeutic platform for cancer treatment.

  10. Should the involvement of skeletal muscle by prostatic adenocarcinoma be reported on biopsies?

    PubMed

    Sadimin, Evita T; Ye, Huihui; Epstein, Jonathan I

    2016-03-01

    Skeletal muscle is seen at the distal part of the prostate apex, where benign glands may reside as part of normal anatomy and histology, and extends more proximally anteriorly. At times, prostatic adenocarcinoma can be seen admixed with skeletal muscle, raising the question of extraprostatic extension. Although there has been increased attention regarding biopsy sampling of the distal apex to guide the performing of the apical dissection on radical prostatectomy, the finding of skeletal muscle involvement by prostatic adenocarcinoma has not been consistently reported by pathologists on biopsies. We searched our database spanning 12 years from 2000 to 2012 for all patients who had prostatic adenocarcinoma Gleason score 3 + 3 = 6 involving skeletal muscle on biopsy. We identified 220 patients who met the criteria. Of the 220 patients, 101 underwent prostatectomy, which comprised the "study group." Prostatectomy reports from these patients were compared with those of a "control group," which consisted of 201 contemporaneous patients with Gleason score 3 + 3 = 6 prostatic adenocarcinoma on biopsy without skeletal muscle involvement. The results showed a significantly higher percentage of positive margins in the study group compared with the control group (P = .006). The study group also had a higher percentage of positive margins at the apex admixed with skeletal muscle (P = .008). In summary, the findings in this study support that pathologists should report the involvement of skeletal muscle by tumor, and recommend that urologists performing radical prostatectomies on these patients try to ensure adequate excision in the apical area to avoid positive apical margin.

  11. Migration and invasion of drug-resistant lung adenocarcinoma cells are dependent on mitochondrial activity

    PubMed Central

    Jeon, Ji Hoon; Kim, Dong Keon; Shin, Youngmi; Kim, Hee Yeon; Song, Bomin; Lee, Eun Young; Kim, Jong Kwang; You, Hye Jin; Cheong, Heesun; Shin, Dong Hoon; Kim, Seong-Tae; Cheong, Jae-Ho; Kim, Soo Youl; Jang, Hyonchol

    2016-01-01

    A small proportion of cancer cells have stem-cell-like properties, are resistant to standard therapy and are associated with a poor prognosis. The metabolism of such drug-resistant cells differs from that of nearby non-resistant cells. In this study, the metabolism of drug-resistant lung adenocarcinoma cells was investigated. The expression of genes associated with oxidative phosphorylation in the mitochondrial membrane was negatively correlated with the prognosis of lung adenocarcinoma. Because the mitochondrial membrane potential (MMP) reflects the functional status of mitochondria and metastasis is the principal cause of death due to cancer, the relationship between MMP and metastasis was evaluated. Cells with a higher MMP exhibited greater migration and invasion than those with a lower MMP. Cells that survived treatment with cisplatin, a standard chemotherapeutic drug for lung adenocarcinoma, exhibited increased MMP and enhanced migration and invasion compared with parental cells. Consistent with these findings, inhibition of mitochondrial activity significantly impeded the migration and invasion of cisplatin-resistant cells. RNA-sequencing analysis indicated that the expression of mitochondrial complex genes was upregulated in cisplatin-resistant cells. These results suggested that drug-resistant cells have a greater MMP and that inhibition of mitochondrial activity could be used to prevent metastasis of drug-resistant lung adenocarcinoma cells. PMID:27932791

  12. Distinct metaplastic and inflammatory phenotypes in autoimmune and adenocarcinoma-associated chronic atrophic gastritis

    PubMed Central

    Jeong, Sangho; Choi, Eunyoung; Petersen, Christine P; Roland, Joseph T; Federico, Alessandro; Ippolito, Rossana; D'Armiento, Francesco P; Nardone, Gerardo; Nagano, Osamu; Saya, Hideyuki; Romano, Marco

    2016-01-01

    Background Autoimmune gastritis (AIG) and adenocarcinoma-associated chronic atrophic gastritis (CAG) are both associated with oxyntic atrophy, but AIG patients demonstrate an increased risk of carcinoid tumors rather than the elevated risk of adenocarcinoma observed with CAG. We therefore sought to compare the characteristics of the metaplastic mucosa in AIG and CAG patients. Methods We examined markers for metaplasia (spasmolytic polypeptide expressing metaplasia (SPEM) and intestinal metaplasia) as well as proliferation (Ki67) and immune cell populations (neutrophils, macrophages, and eosinophils) in gastric sections from 16 female patients with autoimmune thyroiditis and AIG and 17 patients with CAG associated with gastric adenocarcinoma. Results Both AIG and CAG patients demonstrated prominent SPEM and intestinal metaplasia. However, AIG patients displayed significantly lower numbers of infiltrating macrophages and significantly reduced mucosal cell proliferation as compared to CAG patients. Conclusions These findings indicate that, while both AIG and CAG patients display prominent oxyntic atrophy and metaplasia, the AIG patients do not show proliferative metaplastic lineages that would predispose to adenocarcinoma.

  13. Immunophenotype and human papillomavirus status of serous adenocarcinoma of the uterine cervix.

    PubMed

    Togami, Shinichi; Sasajima, Yuko; Kasamatsu, Takahiro; Oda-Otomo, Rie; Okada, Satoshi; Ishikawa, Mitsuya; Ikeda, Shun-ichi; Kato, Tomoyasu; Tsuda, Hitoshi

    2015-04-01

    Serous adenocarcinoma of the cervix (SACC) is a very rare tumor. Our study aimed to characterize the immune profile and human papillomavirus (HPV) status of SACC, in comparison with other serous adenocarcinomas arising in the female genital tract. The pathological specimens obtained from 81 patients with serous carcinoma of the uterine cervix (n = 12), 29 endometrium, 20 ovary and 20 patients with mucinous carcinoma of the uterine cervix were reviewed. We assessed the expression of WT-1, p53, p16, HER2, CEA, and CA125 by immunohistochemistry and HPV DNA by PCR in 12 SACC samples. Their immune profile was compared with that of uterine papillary serous carcinoma (UPSC), ovarian serous adenocarcinoma (OSA), and mucinous endocervical adenocarcinoma (MEA). WT-1 and HER2 were expressed in very few SACC samples (0 and 0%, respectively), but p16, CA125, CEA and p53 were present in 100, 92, 58 and 50%, respectively. The difference in WT-1 expression between SACC and UPSC, MEA is not significant, but SACC differ significantly from OSA (p < 0.01). HPV DNA (type 16 or 18) was detected in 4 of the 12 SACC. The immunophenotype of SACC was similar to UPSC, whereas the frequency of expression of WT-1 was significantly lower in SACC than OSA. It appeared that p53 expression was associated with worse clinical outcome in patients with SACC, and that HPV infection was related to its occurrence.

  14. Mesothelin Expression in Gastric Adenocarcinoma and Its Relation to Clinical Outcomes

    PubMed Central

    Han, Song-Hee; Joo, Mee; Kim, Hanseong; Chang, Sunhee

    2017-01-01

    Background Although surgical resection with chemotherapy is considered effective for patients with advanced gastric cancer, it remains the third leading cause of cancer-related death in South Korea. Several studies have reported that mesothelial markers including mesothelin, calretinin, and Wilms tumor protein 1 (WT1) were positive in variable carcinomas, associated with prognosis, and were evaluated as potential markers for targeted therapy. The aim of this study was to assess the immunohistochemical expression of mesothelial markers (mesothelin, calretinin, and WT1) in gastric adenocarcinoma and their relations to clinocopathological features and prognosis. Methods We evaluated calretinin, WT1, and mesothelin expression by immunohistochemical staining in 117 gastric adenocarcinomas. Results Mesothelin was positively stained in 30 cases (25.6%). Mesothelin expression was related to increased depth of invasion (p = .002), lymph node metastasis (p = .013), and presence of lymphovascular (p = .015) and perineural invasion (p = .004). Patients with mesothelin expression had significantly worse disease-free survival rate compared with that of nonmesothelin expression group (p = .024). Univariate analysis showed that mesothelin expression is related to short-term survival. None of the 117 gastric adenocarcinomas stained for calretinin or WT1. Conclusions Mesothelin expression was associated with poor prognosis. Our results suggest that mesothelin-targeted therapy should be considered as an important therapeutic alternative for gastric adenocarcinoma patients with mesothelin expression. PMID:28196410

  15. Loss of Par3 promotes lung adenocarcinoma metastasis through 14-3-3ζ protein

    PubMed Central

    Tong, Song; Xia, Tian; Fan, Kai; Jiang, Ke; Zhai, Wei; Li, Jing-Song; Wang, Si-Hua; Wang, Jian-Jun

    2016-01-01

    Partitioning defective protein 3 (Par3) can activate the Tiam1/Rac pathway to inhibit invasion and metastasis in many cancers; however, the role of Par3 in lung adenocarcinoma remains unknown. Here we show that Par3 is downregulated in lung adenocarcinoma tissues and is associated with higher rates of lymph node metastasis and recurrence. Our functional study demonstrated that knock-down of Par3 promoted lung adenocarcinoma cell growth, cell migration, tumor formation, and metastasis, all of which were effectively inhibited when 14-3-3ζ was silenced. We found that Par3 binded with 14-3-3ζ protein and also showed that Par3 abrogated the binding of 14-3-3ζ to Tiam1, which was responsible for Rac1 activation. Knock-down of 14-3-3ζ inhibited Tiam1/Rac-GTP activation and blocked the invasive behavior of cells lacking Par3. These data suggest that loss of Par3 promotes metastatic behavior in lung adenocarcinoma cells through 14-3-3ζ protein. PMID:27588399

  16. Primary clitoral adenocarcinoma with secondary hypercalcemia of malignancy in a dog.

    PubMed

    Neihaus, Steven A; Winter, Jennifer E; Goring, Robert L; Kennedy, F A; Kiupel, Matti

    2010-01-01

    This report describes a primary clitoral adenocarcinoma in a dog with secondary hypercalcemia of malignancy. A 10-year-old, spayed female basset hound was evaluated for a mass protruding from the vulva. The mass was excised, and a histological diagnosis of clitoral adenocarcinoma was made. No evidence of metastasis on thoracic radiographs or abdominal ultrasound was seen. Preoperative hypercalcemia resolved following excision of the mass. Cellular features were similar to an apocrine gland anal sac adenocarcinoma, and immunohistochemistry exhibited features noted with apocrine gland anal sac adenocarcinoma. No further treatment was elected by the owner. Internal iliac lymph-node metastasis was identified 4 weeks postoperatively, and hypercalcemia recurred 8 weeks postoperatively. The dog was euthanized 22 weeks postoperatively for signs related to hypercalcemia, including polyuria/polydipsia, lethargy, and weakness. A necropsy was performed and confirmed the presence of internal iliac lymph-node metastasis. The colon, rectum, and anal sacs were grossly and histologically normal. To our knowledge, this is the first reported case of clitoral neoplasia in the dog.

  17. Association of the DNMT3B polymorphism with colorectal adenomatous polyps and adenocarcinoma.

    PubMed

    Guo, Xiaoqing; Zhang, Liwei; Wu, Mingli; Wang, Na; Liu, Yanfeng; Er, Limian; Wang, Shunping; Gao, Yang; Yu, Weifang; Xue, Hui; Xu, Zhibin; Wang, Shijie

    2010-01-01

    DNMT3B is an important enzyme to modulate the methylation status in mammalian cells. The aim of this study is to investigate the correlation of the DNMT3B G39179T polymorphism with the susceptibilities of colorectal adenomatous polyps and adenocarcinoma. This case-control study included 146 colorectal adenomatous polyps, 170 colorectal adenocarcinoma patients, and 157 normal controls. DNMT3B polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Family history of colorectal cancer significantly increases the risk of developing colorectal adenomatous polyps and adenocarcinoma. The genotype frequency of DNMT3B polymorphism (T/T and G/T + G/G) in adenocarcinoma patients was significantly different from that in controls (P value = 0.01). Compared with DNMT3B T/T genotype, the G allelotype (G/T + G/G genotype) had lower risk to develop colorectal adenocarcinoma (OR = 0.50, 95% CI = 0.29-0.87); while there was no significant difference between the colorectal adenomatous polyps patients and controls (OR = 0.63, 95% CI = 0.37-1.09), although descending tendency could be found in this polyps group. In the stratification analysis, a significant association was confined to subgroups of age < 55 (OR = 0.31, 95% CI = 0.12-0.84) and males (OR = 0.35, 95% CI = 0.17-0.71). Meanwhile, combined G/T + G/G genotypes were found to have a lower risk in non-drinkers to develop both colorectal adenomatous polyps and adenocarcinoma (OR = 0.54, 95% CI = 0.31-0.96 and OR = 0.48, 95% CI = 0.27-0.84, respectively). This study also showed a distinct difference in the distribution of DNMT3B G39179T SNP in different ethnics. DNMT3B G39179T SNP may be a potential genetic susceptibility factor for adenocarcinoma of the colon, especially in younger Chinese Han non-drinker men.

  18. Aryl hydrocarbon receptor protects lung adenocarcinoma cells against cigarette sidestream smoke particulates-induced oxidative stress

    SciTech Connect

    Cheng, Ya-Hsin; Huang, Su-Chin; Lin, Chun-Ju; Cheng, Li-Chuan; Li, Lih-Ann

    2012-03-15

    Environmental cigarette smoke has been suggested to promote lung adenocarcinoma progression through aryl hydrocarbon receptor (AhR)-signaled metabolism. However, whether AhR facilitates metabolic activation or detoxification in exposed adenocarcinoma cells remains ambiguous. To address this question, we have modified the expression level of AhR in two human lung adenocarcinoma cell lines and examined their response to an extract of cigarette sidestream smoke particulates (CSSP). We found that overexpression of AhR in the CL1-5 cell line reduced CSSP-induced ROS production and oxidative DNA damage, whereas knockdown of AhR expression increased ROS level in CSSP-exposed H1355 cells. Oxidative stress sensor Nrf2 and its target gene NQO1 were insensitive to AhR expression level and CSSP treatment in human lung adenocarcinoma cells. In contrast, induction of AhR expression concurrently increased mRNA expression of xenobiotic-metabolizing genes CYP1B1, UGT1A8, and UGT1A10 in a ligand-independent manner. It appeared that AhR accelerated xenobiotic clearing and diminished associated oxidative stress by coordinate regulation of a set of phase I and II metabolizing genes. However, the AhR-signaled protection could not shield cells from constant oxidative stress. Prolonged exposure to high concentrations of CSSP induced G0/G1 cell cycle arrest via the p53–p21–Rb1 signaling pathway. Despite no effect on DNA repair rate, AhR facilitated the recovery of cells from growth arrest when CSSP exposure ended. AhR-overexpressing lung adenocarcinoma cells exhibited an increased anchorage-dependent and independent proliferation when recovery from exposure. In summary, our data demonstrated that AhR protected lung adenocarcinoma cells against CSSP-induced oxidative stress and promoted post-exposure clonogenicity. -- Highlights: ► AhR expression level influences cigarette sidestream smoke-induced ROS production. ► AhR reduces oxidative stress by coordinate regulation of

  19. Validation of microRNA pathway polymorphisms in esophageal adenocarcinoma survival.

    PubMed

    Faluyi, Olusola O; Eng, Lawson; Qiu, Xin; Che, Jiahua; Zhang, Qihuang; Cheng, Dangxiao; Ying, Nanjiao; Tse, Alvina; Kuang, Qin; Dodbiba, Lorin; Renouf, Daniel J; Marsh, Sharon; Savas, Sevtap; Mackay, Helen J; Knox, Jennifer J; Darling, Gail E; Wong, Rebecca K S; Xu, Wei; Azad, Abul Kalam; Liu, Geoffrey

    2017-02-01

    Polymorphisms in miRNA and miRNA pathway genes have been previously associated with cancer risk and outcome, but have not been studied in esophageal adenocarcinoma outcomes. Here, we evaluate candidate miRNA pathway polymorphisms in esophageal adenocarcinoma prognosis and attempt to validate them in an independent cohort of esophageal adenocarcinoma patients. Among 231 esophageal adenocarcinoma patients of all stages/treatment plans, 38 candidate genetic polymorphisms (17 biogenesis, 9 miRNA targets, 5 pri-miRNA, 7 pre-miRNA) were genotyped and analyzed. Cox proportional hazard models adjusted for sociodemographic and clinicopathological covariates helped assess the association of genetic polymorphisms with overall survival (OS) and progression-free survival (PFS). Significantly associated polymorphisms were then evaluated in an independent cohort of 137 esophageal adenocarcinoma patients. Among the 231 discovery cohort patients, 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis, and median OS and PFS were 20 and 12 months, respectively. GEMIN3 rs197412 (aHR = 1.37, 95%CI: [1.04-1.80]; P = 0.02), hsa-mir-124-1 rs531564 (aHR = 0.60, 95% CI: [0.53-0.90]; P = 0.05), and KIAA0423 rs1053667 (aHR = 0.51, 95% CI: [0.28-0.96]; P = 0.04) were found associated with OS. Furthermore, GEMIN3 rs197412 (aHR = 1.33, 95% CI: [1.03-1.74]; P = 0.03) and KRT81 rs3660 (aHR = 1.29, 95% CI: [1.01-1.64]; P = 0.04) were found associated with PFS. Although none of these polymorphisms were significant in the second cohort, hsa-mir-124-1 rs531564 and KIAA0423 rs1053667 had trends in the same direction; when both cohorts were combined together, GEMIN3 rs197412, hsa-mir-124-1 rs531564, and KIAA0423 rs1053667 remained significantly associated with OS. We demonstrate the association of multiple miRNA pathway polymorphisms with esophageal adenocarcinoma prognosis in a discovery cohort of patients, which did not validate in a separate cohort

  20. Discovery and validation of vascular endothelial growth factor (VEGF) pathway polymorphisms in esophageal adenocarcinoma outcome.

    PubMed

    Eng, Lawson; Azad, Abul Kalam; Qiu, Xin; Kong, Qin Quinn; Cheng, Dangxiao; Ying, Nanjiao; Tse, Alvina; Kuang, Qin; Dodbiba, Lorin; Renouf, Daniel J; Marsh, Sharon; Savas, Sevtap; Mackay, Helen J; Knox, Jennifer J; Darling, Gail E; Wong, Rebecca K S; Xu, Wei; Liu, Geoffrey; Faluyi, Olusola O

    2015-09-01

    Polymorphisms in the vascular endothelial growth factor (VEGF)/angiogenesis pathway have been implicated previously in cancer risk, prognosis and response to therapy including in esophageal adenocarcinoma. Prior esophageal adenocarcinoma studies focused on using candidate polymorphisms, limiting the discovery of novel polymorphisms. Here, we applied the tagSNP (single nucleotide polymorphism) approach to identify new VEGF pathway polymorphisms associated with esophageal adenocarcinoma prognosis and validated them in an independent cohort of esophageal adenocarcinoma patients. In 231 esophageal adenocarcinoma patients of all stages/treatment plans, 58 genetic polymorphisms (18 KDR, 7 VEGFA and 33 FLT1) selected through tagging and assessment of predicted function were genotyped. Cox-proportional hazard models adjusted for important socio-demographic and clinico-pathological factors were applied to assess the association of genetic polymorphisms with overall survival (OS) and progression-free survival (PFS). Significantly associated polymorphisms were then validated in an independent cohort of 137 esophageal adenocarcinoma patients. Among the 231 discovery cohort patients, 86% were male, median diagnosis age was 64 years, 34% were metastatic at diagnosis and median OS and PFS were 20 and 12 months, respectively. KDR rs17709898 was found significantly associated with PFS (adjusted hazard ratio, aHR = 0.69, 95% confidence interval (CI): 0.53-0.90; P = 5.9E-3). FLT1 rs3794405 and rs678714 were significantly associated with OS (aHR = 1.44, 95% CI: 1.04-1.99; P = 0.03 and aHR = 1.50, 95% CI: 1.01-2.24; P = 0.045, respectively). No VEGFA polymorphisms were found significantly associated with either outcome. Upon validation, FLT1 rs3794405 remained strongly associated with OS (aHR = 1.59, 95% CI: 1.04-2.44; P = 0.03). FLT1 rs3794405 is significantly associated with OS in esophageal adenocarcinoma, whereby each variant allele confers a 45-60% increased risk of mortality

  1. Expression of SNCG, MAP2, SDF-1 and CXCR4 in gastric adenocarcinoma and their clinical significance

    PubMed Central

    Zheng, Shufang; Shi, Lifang; Zhang, Yi; He, Tao

    2014-01-01

    Objectives: The purpose of the study was to detect the expression of SNCG, MAP2, SDF-1 and CXCR4 in gastric adenocarcinoma, and to evaluate their roles in the carcinogenesis of gastric adenocarcinoma, development, invasion and metastasis as well as their clinical significance. Methods: The expression of SNCG, MAP2, SDF-1 and CXCR4 was detected by SP immunohistochemical method in 225 cases of gastric adenocarcinoma and 105 cases of nonneoplastic adjacent gastric tissue. The expression of SNCG, MAP2, SDF-1 and CXCR4 mRNA was also detected by RT-PCR method in 50 cases of gastric adenocarcinoma and 30 cases of nonneoplastic adjacent gastric tissue. Results: The expression of SNCG, MAP2, SDF-1 and CXCR4 in the gastric adenocarcinoma was remarkably higher than those in the nonneoplastic adjacent gastric tissue (P < 0.01); The positive expression of SNCG and MAP2 was correlated with the depth of tumor invasion and the metastasis of lymph nodes (P < 0.05), and that of SDF-1 and CXCR4 was correlated with the metastasis of lymph nodes (P < 0.05). Conclusions: SNCG, MAP2, SDF-1 and CXCR4 may play an important role in the carcinogenesis, progression, invasion and metastasis of gastric adenocarcinoma. However, it still needs more exploration whether they can serve as promising therapeutic targets of gastric adenocarcinoma. PMID:25400739

  2. Management of primary adenocarcinoma of the female urethra: Report of two cases and review of the literature.

    PubMed

    Wang, Xinjun; Bai, Peiming; Su, Hanzhong; Luo, Guangcheng; Zhong, Zhaohui; Zhao, Xiaokun

    2012-11-01

    Primary adenocarcinoma of the female urethra is rare and only a few retrospective cases have been published. The origin of urethral adenocarcinomas remains unclear. Certain authors have suggested that urethral adenocarcinomas in females originate at the periurethral Skene's glands. We report one case of urethral adenocarcinoma of the proximal urethra in a 44-year-old female who presented with painless urethral bleeding. Abdominal and pelvic CT scan with contrast and chest radiology were unremarkable. Biopsy of the mass revealed adenocarcinoma of the urethra. The patient was treated with partial urethrectomy and was free of disease for more than 5 years. We also present another rare case of mucinous adenocarcinoma in a 52-year-old female who complained of an enlarged urethral mass. Pelvic MRI revealed a tumor surrounding the whole urethra and bilateral inguinal lymph nodes. A puncture biopsy later revealed that the tumor was mucinous adenocarcinoma. Anterior pelvic exenteration with pelvic and bilateral lymph node dissection was performed and chemotherapy was administered. The patient was followed up for 12 months and did not experience local recurrence or distant metastasis. In conclusion, for the diagnosis of urethral cancer, a biopsy is necessary for any suspicious urethral lesions. MRI is recommended for tumor staging. Small, superficial, distal urethral tumors may be treated with excision of the distal urethra. For advanced female urethral cancer, a combination of chemotherapy, radiation therapy and surgery is recommended for optimal local and distant disease control. Regular follow-up is required in these patients.

  3. Jackstone: A rare entity of vesical calculus

    PubMed Central

    Singh, Kamal Jeet; Tiwari, Anuj; Goyal, Adarsh

    2011-01-01

    Jackstone calculi are urinary tract stones that have a specific appearance resembling toy jacks. They are almost always composed of calcium oxalate dihydrate consist of a dense central core and radiating spicules. They are usually light brown with dark patches and are usually described to occur in the urinary bladder and rarely in the upper urinary tract. Their appearance on plain radiographs and computed tomography in human patients has been described. PMID:22279326

  4. Vesicant Therapeutics Collaborative Core Research Program

    DTIC Science & Technology

    2012-12-01

    could stabilize siRNA nanoparticles in a solution with physiological ionic strength. Nanoparticle Stability in the Presence of 50% Bovine Serum To test ... tested the efficiency of chitosan-siRNA nanoparticles and found that the transfection and gene knockdown efficiency is much lower than linear PEI/siRNA...leading to particle aggregation and uptake by macrophages. Enhanced stability of nanoparticles at physiological ionic strength. The complex

  5. Gastric type endocervical adenocarcinoma: an aggressive tumor with unusual metastatic patterns and poor prognosis

    PubMed Central

    Karamurzin, Yevgeniy S.; Kiyokawa, Takako; Parkash, Vinita; Jotwani, Anjali R.; Patel, Prusha; Pike, Malcolm C.; Soslow, Robert A.; Park, Kay J.

    2016-01-01

    Gastric type adenocarcinoma of the uterine cervix (GAS) is a rare variant of mucinous endocervical adenocarcinoma not etiologically associated with human papillomavirus (HPV) infection, with minimal deviation adenocarcinoma (MDA) at the well-differentiated end of the morphologic spectrum. These tumors are reported to have worse prognosis than usual HPV-associated endocervical adenocarcinoma (UEA). A retrospective review of GAS was performed from the pathology databases of three institutions spanning 20 years. Stage, metastatic patterns, and overall survival were documented. Forty GAS cases were identified, with clinical follow-up data available for 38. The tumors were subclassified as MDA (n=13) and non-MDA GAS (n=27). Two patients were syndromic (one Li-Fraumeni, one Peutz-Jeghers). At presentation, 59% were advanced stage (FIGO II–IV), 50% had lymph node metastases, 35% had ovarian involvement, 20% had abdominal disease, 39% had at least one site of metastasis at the time of initial surgery, and 12% of patients experienced distant recurrence. The metastatic sites included lymph nodes, adnexa, omentum, bowel, peritoneum, diaphragm, abdominal wall, bladder, vagina, appendix, and brain. Follow-up ranged from 1.4 to 136.0 months (mean, 33.9 months); 20/38 (52.6%) had no evidence of disease, 3/38 (7.9%) were alive with disease, and 15/38 (39.5%) died of disease. Disease specific survival at 5 years was 42% for GAS vs. 91% for UEA. There were no survival differences between MDA and non-MDA GAS. GAS represents a distinct, biologically aggressive type of endocervical adenocarcinoma. The majority of patients present at advanced stage and pelvic, abdominal, and distant metastases are not uncommon. PMID:26457350

  6. Association of STAT3 with Cx26 and Cx43 in human uterine endometrioid adenocarcinoma

    PubMed Central

    SULKOWSKA, URSZULA; FEBP, ANDRZEJ WINCEWICZ; SULKOWSKI, STANISLAW

    2016-01-01

    Signal transducer and activator of transcription-3 (STAT3) drives endometrial carcinogenesis, while signaling via gap junctions gets weakened during cancer progression. Connexin 26 (Cx26), Cx43 and STAT3 were immunohistochemically evaluated in 78 endometrioid adenocarcinomas: Nuclear expression of STAT3 positively correlated with cytoplasmic immunoreactivity to Cx43 (P=0.004, r=0.318) and Cx26 (P=0.006, r=0.309). STAT3 correlated with Cx43 (P=0.022, r=0.411) and Cx26 (P=0.008 r=0.466) in G1 tumors. A statistically significant linkage remained in G2 cancers between STAT3 and Cx43 (P=0.061, r=0.262) and Cx26 (P=0.016, r=0.331); however, no correlations were observed in G3 tumors. STAT3 was significantly associated with Cx 43 (p=0.003, r=0.684) and Cx26 (p=0.049, r=0.500) in estrogen receptor (ER) negative adenocarcinomas. STAT3 did not correlate with Cx43 in ER positive adenocarcinomas; however, STAT3 expression remained correlated with Cx26 expression (P=0.035, r=0.268). In progesterone receptor negative tumors STAT3 was significantly associated with Cx43 (P=0.035, r=0.451) and Cx26 (P<0.0001, r=0.707). However, in PgR positive adenocarcinomas STAT3 correlated with Cx43 (P=0.03, r=0.290) but not with Cx26. Thus, it appears that hormone dependent acceleration of cancer growth breaks the association between STAT3 and Cx expression. These associations become weaker as the tumors dedifferentiate from G1 to G3 endometrioid adenocarcinomas. The present study provides evidence that the loss of correlation between STAT3 and selected Cx proteins occurs in tumors with more aggressive behavior. PMID:27313754

  7. NR4A2 Is Regulated by Gastrin and Influences Cellular Responses of Gastric Adenocarcinoma Cells

    PubMed Central

    Misund, Kristine; Selvik, Linn-Karina Myrland; Rao, Shalini; Nørsett, Kristin; Bakke, Ingunn; Sandvik, Arne K.; Lægreid, Astrid; Bruland, Torunn; Prestvik, Wenche S.; Thommesen, Liv

    2013-01-01

    The peptide hormone gastrin is known to play a role in differentiation, growth and apoptosis of cells in the gastric mucosa. In this study we demonstrate that gastrin induces Nuclear Receptor 4A2 (NR4A2) expression in the adenocarcinoma cell lines AR42J and AGS-GR, which both possess the gastrin/CCK2 receptor. In vivo, NR4A2 is strongly expressed in the gastrin responsive neuroendocrine ECL cells in normal mucosa, whereas gastric adenocarcinoma tissue reveals a more diffuse and variable expression in tumor cells. We show that NR4A2 is a primary early transient gastrin induced gene in adenocarcinoma cell lines, and that NR4A2 expression is negatively regulated by inducible cAMP early repressor (ICER) and zinc finger protein 36, C3H1 type-like 1 (Zfp36l1), suggesting that these gastrin regulated proteins exert a negative feedback control of NR4A2 activated responses. FRAP analyses indicate that gastrin also modifies the nucleus-cytosol shuttling of NR4A2, with more NR4A2 localized to cytoplasm upon gastrin treatment. Knock-down experiments with siRNA targeting NR4A2 increase migration of gastrin treated adenocarcinoma AGS-GR cells, while ectopically expressed NR4A2 increases apoptosis and hampers gastrin induced invasion, indicating a tumor suppressor function of NR4A2. Collectively, our results uncover a role of NR4A2 in gastric adenocarcinoma cells, and suggest that both the level and the localization of NR4A2 protein are of importance regarding the cellular responses of these cells. PMID:24086717

  8. The new IASLC-ATS-ERS lung adenocarcinoma classification: what the surgeon should know.

    PubMed

    Eguchi, Takashi; Kadota, Kyuichi; Park, Bernard J; Travis, William D; Jones, David R; Adusumilli, Prasad S

    2014-01-01

    In 2011, a new histologic classification of lung adenocarcinomas was proposed from a joint working group of the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society, based on the recommendation of an international and multidisciplinary panel. This classification proposed a method of comprehensive histologic subtyping (lepidic, acinar, papillary, micropapillary, and solid pattern) based on semiquantitative assessment of histologic patterns (in 5% increments), with the ultimate goal of choosing a single, predominant pattern. Prognostic subsets could then be described for the classification. Patients with completely resected adenocarcinoma in situ and minimally invasive adenocarcinomas experienced low risk of recurrence. Patients with micropapillary or solid predominant tumors have a high risk of recurrence or cancer-related death. Patients with acinar and papillary predominant tumors comprise an intermediate-risk group. Herein, we review the outline of the proposed International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society classification, a summary of published validation studies of this new classification, and then discuss the key surgical issues; we mainly focused on limited resection as an adequate treatment for early-stage lung adenocarcinomas, as well as preoperative and intraoperative diagnoses. We also review the published studies that identified the importance of histologic subtypes in predicting recurrence, both rates and patterns, in early-stage lung adenocarcinomas. This new classification for the most common type of lung cancer is useful for surgeons, as its implementation would require only hematoxylin-and-eosin histology slides, which is the common type of stain used in hospitals. It can be implemented with routine pathology evaluation and with no additional costs.

  9. Expression profiling of CEACAM6 associated with the tumorigenesis and progression in gastric adenocarcinoma.

    PubMed

    Deng, X; Liu, P; Zhao, Y; Wang, Q

    2014-09-26

    Carcinoembryonic antigen-related cellular adhesion molecule 6 (CEACAM6) is a member of the immunoglobulin superfamily and has been recently reported to affect the neoplastic, metastatic, and invasive ability of malignant cells by regulating intracellular signaling pathways during tumorigenesis and progression. We investigated the expression and amplification of CEACAM6 in relation to the clinicopathological and biological significance of gastric adenocarcinoma. Expression of CEACAM6 mRNA in 75 primary gastric adenocarcinom and 20 adjacent tissues compared to normal gastric mucosas were explored using real-time quantitative-polymerase chain reaction. Immunohistochemical assays were conducted to evaluate the expression and tissue distribution of CEACAM6 protein. Overexpression of CEACAM6 mRNA in both gastric adenocarcinoma (2.513 ± 0.869) and adjacent tissues (1.171 ± 0.428) was significantly higher than the relative expressions in non-neoplastic specimens (0.594 ± 0.513) (P < 0.01). CEACAM6 protein was present in 52 (69.33%) gastric adenocarcinomas, but not in normal gastric tissues. Adenocarcinomas with elevated CEACAM6 expression were significantly associated with lymph node metastases and advanced stages. There were no relationships between CEACAM6 expression and tumor size, histological differentiation, or different subtypes, respectively. Moreover, higher expression of CEACAM6 was found to be correlated with short postoperative survival time of patients with gastric cancer. Amplification and upregulation of CEACAM6 expression was observed in human gastric adenocarcinomas, which may be correlated with the generation or transformation of malignant cells, tumor aggressive progression, and clinical outcome. CEACAM6 may be a valuable biomarker screening for gastric tumor and novel predictor for patients in advanced stages of gastric cancer.

  10. NR4A2 is regulated by gastrin and influences cellular responses of gastric adenocarcinoma cells.

    PubMed

    Misund, Kristine; Selvik, Linn-Karina Myrland; Rao, Shalini; Nørsett, Kristin; Bakke, Ingunn; Sandvik, Arne K; Lægreid, Astrid; Bruland, Torunn; Prestvik, Wenche S; Thommesen, Liv

    2013-01-01

    The peptide hormone gastrin is known to play a role in differentiation, growth and apoptosis of cells in the gastric mucosa. In this study we demonstrate that gastrin induces Nuclear Receptor 4A2 (NR4A2) expression in the adenocarcinoma cell lines AR42J and AGS-GR, which both possess the gastrin/CCK2 receptor. In vivo, NR4A2 is strongly expressed in the gastrin responsive neuroendocrine ECL cells in normal mucosa, whereas gastric adenocarcinoma tissue reveals a more diffuse and variable expression in tumor cells. We show that NR4A2 is a primary early transient gastrin induced gene in adenocarcinoma cell lines, and that NR4A2 expression is negatively regulated by inducible cAMP early repressor (ICER) and zinc finger protein 36, C3H1 type-like 1 (Zfp36l1), suggesting that these gastrin regulated proteins exert a negative feedback control of NR4A2 activated responses. FRAP analyses indicate that gastrin also modifies the nucleus-cytosol shuttling of NR4A2, with more NR4A2 localized to cytoplasm upon gastrin treatment. Knock-down experiments with siRNA targeting NR4A2 increase migration of gastrin treated adenocarcinoma AGS-GR cells, while ectopically expressed NR4A2 increases apoptosis and hampers gastrin induced invasion, indicating a tumor suppressor function of NR4A2. Collectively, our results uncover a role of NR4A2 in gastric adenocarcinoma cells, and suggest that both the level and the localization of NR4A2 protein are of importance regarding the cellular responses of these cells.

  11. Body size and composition and the risk of gastric and oesophageal adenocarcinoma.

    PubMed

    MacInnis, Robert J; English, Dallas R; Hopper, John L; Giles, Graham G

    2006-05-15

    Although evidence has been mounting that obesity may be related to the increased incidence of oesophageal and gastric cardia malignancies, these reports (mainly case-control studies) have relied on imperfect measures of obesity such as body mass index (BMI), and generally have not clearly distinguished between anatomical subsites within the oesophagus and stomach. In a prospective study of people aged 27-75 years, we directly measured fat mass and fat-free mass (using bioelectrical impedance analysis), height, weight and waist and hip circumferences. Among 41,295 people followed on average for 11.3 years, 30 cases with cancers in the gastric cardia or lower third of the oesophagus and 68 cases with noncardia gastric adenocarcinomas were ascertained via the population cancer registry. The risk of adenocarcinoma of the lower oesophagus and gastric cardia was positively associated with BMI with a hazards ratio (HR) and (95% confidence interval) for people with BMI>or=30 kg/m2 compared with those<25 kg/m2, of 3.7 (1.1-12.4), an HR per 10 cm increase in waist circumference of 1.46 (1.05-2.04), and a HR per 10 kg increase on fat-free mass of 2.06 (1.15-3.69). Noncardia gastric adenocarcinoma showed little relationship with body size. We observed an increased risk of adenocarcinoma of the lower oesophagus and gastric cardia associated with increased BMI, central adiposity and the nonfat component of weight, but found no association with noncardia gastric adenocarcinoma. An increasing prevalence of obesity may be associated with the increasing incidence of gastro-oesophageal cancer observed in many populations.

  12. Unique microRNA-profiles in EGFR-mutated lung adenocarcinomas.

    PubMed

    Bjaanaes, Maria Moksnes; Halvorsen, Ann Rita; Solberg, Steinar; Jørgensen, Lars; Dragani, Tommaso A; Galvan, Antonella; Colombo, Francesca; Anderlini, Marco; Pastorino, Ugo; Kure, Elin; Børresen-Dale, Anne-Lise; Brustugun, Odd Terje; Helland, Aslaug

    2014-10-15

    The findings of mutations and the development of targeted therapies have improved lung cancer management. Still, the prognosis remains poor, and we need to know more about the genetic and epigenetic alterations in lung cancer. MicroRNAs are involved in crucial biological processes like carcinogenesis by regulating gene expression at the post-transcriptional level. In this project, we have studied the microRNA expression of lung adenocarcinomas and corresponding normal lung tissue and correlated the expression with clinical data and EGFR- and KRAS-mutational status. Agilent microarrays have been used, examining microRNA expression in 154 surgically resected lung adenocarcinomas and 20 corresponding normal lung tissue samples. Findings were confirmed by RT-qPCR in the same cohort and in an independent cohort of 103 lung cancer patients. EGFR and KRAS mutation analyses were also performed. 129 microRNAs were significantly differentially expressed in lung adenocarcinomas compared with normal lung tissue, and 17 microRNAs were differentially expressed between EGFR-mutated and EGFR wildtype tumors. We identified microRNAs associated with time to progression. We have identified several aberrantly expressed microRNAs that discriminate lung adenocarcinomas from normal lung tissue, and hence may be potential biomarkers for early detection. We have found microRNAs that are differentially expressed between EGFR-mutated and EGFR wildtype lung adenocarcinomas, suggesting that microRNAs can be used as molecular biomarkers in classification. We hypothesize that microRNA expression can be used as biomarkers for clinical course.

  13. The frequency and clinical impact of HER2 alterations in lung adenocarcinoma

    PubMed Central

    Kim, Eun Kyung; Kim, Kyung A.; Lee, Chang Young

    2017-01-01

    Human epidermal growth factor receptor 2 (HER2 or ErbB2) can be overexpressed, amplified and/or mutated in malignant tumors, and is a candidate for therapeutic targeting. However, molecular associations and clinical significances of these alterations were controversial in lung cancer. In this study, we investigated the frequency and clinicopathological significance of HER2 dysregulation in patients with lung adenocarcinoma. HER2 protein overexpression, gene amplification, and gene mutation were evaluated by immunohistochemistry (IHC), silver in situ hybridization, and direct sequencing, respectively. The H-scoring method and American Society of Clinical Oncology/College of American Pathologists breast cancer guidelines were used to interpret IHC results. Genetic analyses of EGFR and KRAS mutations, and of ALK and ROS1 rearrangements, were also performed. Of the 321 adenocarcinoma patients identified, HER2 overexpression (H-score ≥200) and gene amplification were found in 6 (1.9%) and 46 (14.3%), respectively. HER2 overexpression was correlated with papillary predominant histology; furthermore, it indicated poor overall survival and was an independent prognostic factor. HER2 amplification was associated with pleural invasion and showed a tendency towards shorter overall and disease-free survival. High-level gene amplification (HER2/CEP17 ratio ≥5 or copy number ≥10) was a poor prognostic factor for disease-free survival. HER2 mutations were detected in 6.7% (7 of 104) of driver oncogene-negative adenocarcinomas. Our study suggests that HER2 overexpression or amplification is a poor prognostic factor in lung adenocarcinoma, although the frequency of such events is low. Since molecular targeted agents are being tested in clinical trials, awareness of the specific HER2 status can influence the prognostic stratification and treatment of patients with molecularly defined subsets of lung adenocarcinoma. PMID:28146588

  14. Significance of interstitial tumor-associated macrophages in the progression of lung adenocarcinoma

    PubMed Central

    Sun, Bing-Sheng; Pei, Bao-Xiang; Zhang, Kang; Zhang, Lu-Chang; Zhang, Guang-Jing; Liu, Ji-Kuan; Cui, Hong-Wei; Pan, Fen; Zhang, Zhen-Fa

    2016-01-01

    Stepwise progression from adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) to lepidic predominant adenocarcinoma (LPA) was proposed by various scholars. Interstitial tumor-associated macrophages (TAMs) and various potential chemokines involved in the progression from AIS/MIA to LPA were hypothesized. In the present study, immunohistochemistry or immunofluorescent double staining was used to detect the expression of the TAMs marker cluster of differentiation (CD) 68, tumor-derived colony-stimulating factor (CSF)-1, interleukin (IL)-6, matrix metalloproteinase (MMP)-2, E-cadherin and Snail in lung adenocarcinoma specimens, including AIS/MIA, LPA and other types. It was observed that infiltrating TAMs were negatively associated with the prognosis of patients, and that the infiltration degree of interstitial TAMs was higher in LPA than that in AIS/MIA. In addition, E-cadherin, Snail and MMP-2 expression were significantly correlated with the infiltration degree of TAMs. Survival analysis revealed that co-expression of CD68, CSF-1 and IL-6 was an independent prognostic factor. Stratified analysis demonstrated that, in AIS/MIA patients, there was a statistically significant difference between the number of TAMs (TAMs ≤25 and TAMs >25) in the CD68+CSF-1+IL-6+ group compared with other groups (including CD68+CSF-1-IL-6-, CD68+CSF-1+IL-6-, CD68+CSF-1-IL-6+ and CD68- groups). By contrast, in patients with TAMs >25 and in patients with positive CD68, CSF-1 and IL-6 expression, the survival rates were not significantly different between AIS/MIA and LPA. These results suggested that co-expression of TAMs marker CD68, CSF-1 and IL-6 may be a valuable independent prognostic predictor in lung adenocarcinoma. TAMs may facilitate AIS/MIA progression to LPA, which may be closely associated with the induction of the epithelial-mesenchymal transition. PMID:28101209

  15. Mutation analysis of the p53, APC, and p16 genes in the Barrett's oesophagus, dysplasia, and adenocarcinoma.

    PubMed Central

    González, M V; Artímez, M L; Rodrigo, L; López-Larrea, C; Menéndez, M J; Alvarez, V; Pérez, R; Fresno, M F; Pérez, M J; Sampedro, A; Coto, E

    1997-01-01

    AIMS: To study the loss of heterozygosity and the presence of mutations at the p53, p16/CDKN2, and APC genes in Barrett's oesophagus, low grade dysplastic oesophageal epithelium, and adenocarcinoma of the oesophagus; to relate the presence of alterations at these genes with the progression from Barrett's oesophagus to adenocarcinoma. METHODS: DNA was extracted from paraffin blocks containing tissue from Barrett's oesophagus (12 samples), low grade dysplasia (15 cases), and adenocarcinoma (14 cases). Loss of heterozygosity (LOH) at the p53, p16, and APC genes was determined by comparing the autoradiographic patterns of several microsatellite markers between the normal tissue and the malignant tissue counterpart. SSCP was used to determine the presence of mutations at p53 (exons 5 to 8), p16 (exon 2), and APC. Homozygous deletion of the p16 gene was defined through polymerase chain reaction followed by Southern blot. RESULTS: LOH at the p53, p16, and APC genes was not observed in Barrett's oesophagus without dysplasia, and increased to 90% (p53), 89% (p16), and 60% (APC) in the adenocarcinomas. The p53 gene was mutated in only two adenocarcinomas (codons 175 and 245). In one case a mutation at the APC gene (codon 1297) was found. No patient had mutation at the second exon of p16. However, this gene was homozygously deleted in three of the 12 adenocarcinomas. CONCLUSIONS: The tumour suppressor genes p53, p16, and APC are often deleted in adenocarcinomas derived from Barrett's oesophagus. Mutations at these genes are also found in the adenocarcinomas, including the homozygous deletion of the p16 gene. However, the absence of genetic alterations in the Barrett's oesophagus and the low grade dysplastic epithelia suggest that mutations at these genes develop later in the progression from Barrett's oesophagus to adenocarcinoma. Images PMID:9155671

  16. A Rare Case of an Adult with Untreated Bladder Exstrophy Presenting with Signet-Ring Cell Adenocarcinoma of Urinary Bladder

    PubMed Central

    Kumar, Vikash; Kasat, Gaurav; Sawant, Ajit

    2016-01-01

    Untreated bladder exstrophy in an adult is rare, as the defect is obvious and primary reconstruction is usually done in infancy. There are less than 90 reported cases of primary adenocarcinoma in an untreated bladder exstrophy in literature and only two such case reports from India. Of these, only one case was of signet-ring cell type of mucinous adenocarcinoma. Here we report the second case of signet-ring cell adenocarcinoma in a 63 year old male with untreated bladder exstrophy (oldest patient in literature), to highlight the extreme rarity, yet distinct possibility and challenges faced in surgical management of such cases. PMID:28050437

  17. Hypercalcemia as Initial Presentation of Metastatic Adenocarcinoma of Gastric Origin: A Case Report and Review of the Literature

    PubMed Central

    Kumar, Abhishek; Kumar, Vinod; Kaur, Supreet; Maroules, Michael

    2016-01-01

    Hypercalcemia of malignancy due to metastatic gastric adenocarcinoma is extremely rare; in fact, to the best of our knowledge, only three case reports of hypercalcemia associated with metastatic gastric adenocarcinoma have been published in the literature to date. Herein, we report a rare case involving a 61-year-old African-American female who had hypercalcemia at initial presentation and who was later diagnosed with poorly differentiated gastric adenocarcinoma with extensive liver metastases, without bone involvement. She was found to have elevated parathyroid hormone-related peptide and normal parathyroid hormone levels. Despite aggressive treatment, she died within a few months of diagnosis. PMID:27752397

  18. A Subset of Sinonasal Non-Intestinal Type Adenocarcinomas are Truly Seromucinous Adenocarcinomas: A Morphologic and Immunophenotypic Assessment and Description of a Novel Pitfall.

    PubMed

    Purgina, Bibianna; Bastaki, Jassem M; Duvvuri, Umamaheswar; Seethala, Raja R

    2015-12-01

    While sinonasal intestinal type adenocarcinoma (ITAC) is defined by an intestinal phenotype, non-intestinal type adenocarcinoma (non-ITAC) is traditionally viewed as a diagnosis of exclusion, despite previous implication of a seromucinous phenotype and similarity to sinonasal seromucinous hamartomas (SSH). We performed a comparison of clinicopathologic and immunophenotypic features of ITAC, non-ITAC and SSH using traditional discriminatory markers and new markers of seromucinous differentiation. Twenty-three non-ITAC, 17 ITAC, and 5 SSH were retrieved (1987-2014). As expected, ITAC occurred predominantly in the nasal cavity in elderly patients (mean age 65 years) with a striking male predilection (15:2). Regardless of grade/subtype, all ITAC were invariably CK20 and CDX2 positive, and many (11/15) showed some CK7 positivity. Non-ITAC occurred in younger individuals (mean age 51 years) with a slight female predilection (male to female ratio: 10:13) and showed diverse morphologic patterns and grades, some with morphologic similarity to SSH. SSH occurred in younger individuals (mean age 33 years). Non-ITAC and SSH were invariably CK7 positive and CK20 negative, however, 4/22 non-ITAC and 2/5 SSH showed squamoid morular metaplasia that aberrantly expressed CDX2 and co-expressed nuclear β-catenin. Markers of seromucinous differentiation (S100, DOG1, and SOX10) were essentially absent in ITAC, but present to varying degrees in the majority of non-ITAC and all SSH. Thus, the term 'seromucinous adenocarcinoma' is the more appropriate designation for non-ITAC. Squamoid morules in non-ITAC and SSH may be an immunophenotypic pitfall given the aberrant CDX2 expression.

  19. Loss of heterozygosity at chromosomes 1p35-pter, 4q, and 18q and protein expression differences between adenocarcinomas of the distal stomach and gastric cardia.

    PubMed

    Xu, Yan; Man, Xiaohui; Lv, Zhi; Li, Deming; Sun, Zhe; Chen, Hong; Wang, Zhenning; Luo, Yang; Xu, Huimian

    2012-12-01

    Loss of heterozygosity of 1p35-pter, 4q, and 18q is frequent in gastric carcinoma, suggesting that these regions harbor tumor suppressor genes. However, the differences in these genetic alterations between adenocarcinoma of the gastric cardia and adenocarcinoma of the distal stomach remain unclear. In this study, loss of heterozygosity at chromosomes 1p35-pter, 4q, and 18q were analyzed in adenocarcinoma of the gastric cardia and adenocarcinoma of the distal stomach samples acquired by laser capture microdissection. The expression of several tumor suppressor gene proteins, runt-related transcription factor 3 (1p36), annexin A10 (4q33), SMAD family member 4 (18q21.1), and deleted in colorectal carcinoma (18q21.3), was evaluated immunohistochemically. The adenocarcinoma of the distal stomach and adenocarcinoma of the gastric cardia lesions had a similar trend in total deletion frequency for chromosomes 1p35-pter (36.5% for adenocarcinoma of the distal stomach and 32.5% for adenocarcinoma of the gastric cardia), 4q (42.3% for adenocarcinoma of the distal stomach and 47.5% for adenocarcinoma of the gastric cardia), and 18q (38.5% for adenocarcinoma of the distal stomach and 45% for adenocarcinoma of the gastric cardia). However, loss of heterozygosity patterns were clearly different in the 2 adenocarcinomas. Deletion mapping indicated that 4q32.2-4q34.3, 18q21.2-21.31, 18q22.3-23, and 1p35.2-1p36.13 were involved in adenocarcinoma of the distal stomach, whereas 4q13.3-4q22.3, 4q31.21-4q32.2, 18q21.31-18q22.1, and 1p35.2-1p36.13 were involved in adenocarcinoma of the gastric cardia. Expression of ANXA10 (P = .038), SMAD family member 4 (P = .028), and deleted in colorectal carcinoma (P = .004) was less common in adenocarcinoma of the distal stomach than in adenocarcinoma of the gastric cardia. Expression of runt-related transcription factor 3 (P = .795) showed no significant difference in the 2 tumors. The tumors differed in the profile of genetic alterations and

  20. Primary vaginal adenocarcinoma of intestinal type arising from an adenoma: case report and review of the literature.

    PubMed

    Mudhar, H S; Smith, J H; Tidy, J

    2001-04-01

    A 1 cm polypoid lesion was encountered on the posterior vaginal wall in a 56-year-old woman with no history of diethylstilbestrol exposure that on microscopic examination was a moderately differentiated adenocarcinoma of intestinal type. The tumor was cytokeratin 20 and carcinoembryonic antigen positive and negative for cytokeratin 7. Mucin histochemistry demonstrated the presence of o-acetylated sialomucin, a specific marker of large intestinal differentiation. The initial interpretation favored a metastasis from a colonic adenocarcinoma, but clinical investigations showed no evidence of a primary gastrointestinal lesion. The morphology, histochemical, and differential cytokeratin profile led to the lesion being reinterpreted as a primary intestinal-type adenocarcinoma of the vagina arising from a tubular adenoma. Although a very rare tumor, awareness of this lesion is important as it must be distinguished from metastatic adenocarcinomas from other sites.

  1. Inhibition of hydrogen sulfide biosynthesis sensitizes lung adenocarcinoma to chemotherapeutic drugs by inhibiting mitochondrial DNA repair and suppressing cellular bioenergetics

    PubMed Central

    Szczesny, Bartosz; Marcatti, Michela; Zatarain, John R.; Druzhyna, Nadiya; Wiktorowicz, John E.; Nagy, Péter; Hellmich, Mark R.; Szabo, Csaba

    2016-01-01

    Therapeutic manipulation of the gasotransmitter hydrogen sulfide (H2S) has recently been proposed as a novel targeted anticancer approach. Here we show that human lung adenocarcinoma tissue expresses high levels of hydrogen sulfide (H2S) producing enzymes, namely, cystathionine beta-synthase (CBS), cystathionine gamma lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST), in comparison to adjacent lung tissue. In cultured lung adenocarcinoma but not in normal lung epithelial cells elevated H2S stimulates mitochondrial DNA repair through sulfhydration of EXOG, which, in turn, promotes mitochondrial DNA repair complex assembly, thereby enhancing mitochondrial DNA repair capacity. In addition, inhibition of H2S-producing enzymes suppresses critical bioenergetics parameters in lung adenocarcinoma cells. Together, inhibition of H2S-producing enzymes sensitize lung adenocarcinoma cells to chemotherapeutic agents via induction of mitochondrial dysfunction as shown in in vitro and in vivo models, suggesting a novel mechanism to overcome tumor chemoresistance. PMID:27808278

  2. Metastasis of colonic adenocarcinoma to the external ear canal: an unusual case with a complex-pattern of disease progression.

    PubMed

    Carson, Henry J; Krivit, Jeffrey S; Eilers, Stanley G

    2005-01-01

    We report on a patient who developed far-ranging metastases of adenocarcinoma of the colon that followed a gradual cephalad progression, including the right external ear canal, and led to hearing loss. The patient was a 63-year-old white male with stage III adenocarcinoma of the colon. After 2 years with metastases elsewhere, he developed hearing loss on the right side. Physical examination of the head and neck showed a mass in the external ear canal, and biopsy confirmed adenocarcinoma. After removal, the patient's hearing improved. This case is interesting not only because of the unusual metastasis to the external ear canal, but also because of the patient's previous history of metastasis over the course of more than 2 years. The significance of such wide-ranging metastases is that metastasis of adenocarcinoma to the ear did not signal imminent death, and relief of the hearing loss it caused was possible.

  3. The new IASLC/ATS/ERS lung adenocarcinoma classification from a clinical perspective: current concepts and future prospects

    PubMed Central

    Enguita, Ana Belen; Nuñez, Juan Antonio; Iglesias, Lara; Ponce, Santiago

    2014-01-01

    The new the International Association for the Study of Lung Cancer (IASLC)/the American Thoracic Society (ATS)/the European Respiratory Society (ERS) pathologic classification of lung cancer has markedly changed the pathologic diagnosis of lung adenocarcinoma. This classification deals with many aspects that directly affect clinical practice, and opens new gateways for future research. By means of a multidisciplinary approach, it differs significantly from the former 2004 the World Health Organization (WHO) classification, which was mainly written by pathologist. The present review, in line with the consensus article, is divided in two components: the diagnosis and classification of lung adenocarcinoma in resection specimens and the diagnosis of lung cancer in small biopsies and cytology. Resection specimens are currently classified according to the predominant histologic pattern after comprehensive subtyping in 5% increments. This approach has led to the addition of new pathologic subtypes [adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and micropapillary predominant adenocarcinoma)] and to the discontinuation of some heterogeneous entities included in the former 2004 WHO classification (mixed subtype adenocarcinoma and bronchioloalveolar carcinoma). Overall, these changes have resulted in a better stratification of lung adenocarcinoma tumors in more homogeneous morphologic, clinical and biological subgroups. Pathologic subtyping has demonstrated prognostic utility in resected stage I-III patients, and recent data support their predictive role for the benefit of adjuvant chemotherapy. Moreover, comprehensive pathologic subtyping may potentially affect TNM staging and surgical management or early-stage tumors. On the other hand, for the first time, the novel pathologic classification provides standardized terminology and diagnostic criteria of small biopsies and cytology. Criteria are proposed not only for adenocarcinoma but also for other

  4. FOXM1 confers resistance to gefitinib in lung adenocarcinoma via a MET/AKT-dependent positive feedback loop.

    PubMed

    Wang, Yu; Zhang, Weiwei; Wen, Li; Yang, Huiling; Wen, Mingling; Yun, Yuyu; Zhao, Lisheng; Zhu, Xiaofei; Tian, Li; Luo, Erping; Li, Yu; Liu, Wenchao; Wen, Ning

    2016-09-13

    Gefitinib resistance remains a major problem in the treatment of lung adenocarcinoma. However, the molecular mechanisms of gefitinib resistance are not fully understood. In this study, we characterized the critical role of transcription factor Forkhead box protein M1 (FOXM1) in gefitinib resistance of lung adenocarcinoma cells. In vitro drug sensitivity assays demonstrated that FOXM1 inhibition sensitized PC9/GR and HCC827/GR cells to gefitinib, whereas FOXM1 overexpression enhanced PC9 and HCC827 cell resistance to gefitinib. Increased FOXM1 resulted in the upregulation of hepatocyte growth factor receptor (MET), which led to activation of the protein kinase B (AKT) pathway, whereas knockdown of FOXM1 did the opposite. FOXM1 bound directly to the MET promoter regions and regulated the promoter activities and the expression of MET at the transcriptional level. Moreover, MET/AKT pathway upregulated the expression of FOXM1 in lung adenocarcinoma cells. Inhibition of pAKT by LY294002 or inhibition of pMET by PHA-665752 significantly inhibited the expression of FOXM1 in lung adenocarcinoma cells. Importantly, we further demonstrated that the expression levels of FOXM1, pAKT and MET were significantly increased in lung adenocarcinoma tissues relative to normal lung tissues, and these three biomarkers were concomitantly overexpressed in lung adenocarcinoma tissues. Taken together, our results indicate that FOXM1 promotes acquired resistance to gefitinib of lung adenocarcinoma cells, and FOXM1 crosstalks with MET/AKT signaling to form a positive feedback loop to promote lung adenocarcinoma development.

  5. Twist1 correlates with poor differentiation and progression in gastric adenocarcinoma via elevation of FGFR2 expression

    PubMed Central

    Zhu, Dong-Yuan; Guo, Qi-Sen; Li, Yan-Liang; Cui, Bin; Guo, Jun; Liu, Ji-Xiao; Li, Peng

    2014-01-01

    AIM: To explore the correlation between Twist-related protein (Twist)1, fibroblast growth factor receptor (FGFR)2 and gastric adenocarcinoma differentiation and progression. METHODS: We evaluated Twist1 and FGFR2 in 52 gastric adenocarcinoma samples by immunohistochemistry and quantitative real time polymerase chain reaction, and analyzed the correlation between Twist1, FGFR2 and cancer differentiation. We also detected Twist1 and FGFR2 expression in gastric adenocarcinoma cell lines, and evaluated Twist1 influence on FGFR2 expression. In addition, we studied the role of FGFR2 in Twist1-promoted cancer progression, including proliferation, invasion and epithelial-mesenchymal transition (EMT). RESULTS: Twist1 and FGFR2 were detected in almost all the gastric adenocarcinoma samples. Twist1 (P = 0.0213) and FGFR2 (P = 0.0310) mRNA levels had a significant association with gastric adenocarcinoma differentiation. Moreover, Twist1 and FGFR2 expression in poorly differentiated cells (SNU-1 and SNU-16) was notably higher than in well-differentiated cells (MKN-7 and MKN-28). In poorly differentiated gastric adenocarcinomas, FGFR2 mRNA level was significantly positively correlated with Twist1 mRNA level (P = 0.004). Twist1 was proved to promote FGFR2 by regulating Twist1 expression by knockdown and overexpression. Additionally, Twist1 could induce proliferation, invasion and EMT in gastric cancer; of these, FGFR2 was required for invasion and EMT, rather than proliferation. CONCLUSION: Twist1 and FGFR2 are highly associated with differentiation of gastric adenocarcinoma; Twist1 can facilitate invasion and EMT in gastric adenocarcinoma via promotion of FGFR2 expression. PMID:25561797

  6. FOXM1 confers resistance to gefitinib in lung adenocarcinoma via a MET/AKT-dependent positive feedback loop

    PubMed Central

    Wen, Mingling; Yun, Yuyu; Zhao, Lisheng; Zhu, Xiaofei; Tian, Li; Luo, Erping; Li, Yu; Liu, Wenchao; Wen, Ning

    2016-01-01

    Gefitinib resistance remains a major problem in the treatment of lung adenocarcinoma. However, the molecular mechanisms of gefitinib resistance are not fully understood. In this study, we characterized the critical role of transcription factor Forkhead box protein M1 (FOXM1) in gefitinib resistance of lung adenocarcinoma cells. In vitro drug sensitivity assays demonstrated that FOXM1 inhibition sensitized PC9/GR and HCC827/GR cells to gefitinib, whereas FOXM1 overexpression enhanced PC9 and HCC827 cell resistance to gefitinib. Increased FOXM1 resulted in the upregulation of hepatocyte growth factor receptor (MET), which led to activation of the protein kinase B (AKT) pathway, whereas knockdown of FOXM1 did the opposite. FOXM1 bound directly to the MET promoter regions and regulated the promoter activities and the expression of MET at the transcriptional level. Moreover, MET/AKT pathway upregulated the expression of FOXM1 in lung adenocarcinoma cells. Inhibition of pAKT by LY294002 or inhibition of pMET by PHA-665752 significantly inhibited the expression of FOXM1 in lung adenocarcinoma cells. Importantly, we further demonstrated that the expression levels of FOXM1, pAKT and MET were significantly increased in lung adenocarcinoma tissues relative to normal lung tissues, and these three biomarkers were concomitantly overexpressed in lung adenocarcinoma tissues. Taken together, our results indicate that FOXM1 promotes acquired resistance to gefitinib of lung adenocarcinoma cells, and FOXM1 crosstalks with MET/AKT signaling to form a positive feedback loop to promote lung adenocarcinoma development. PMID:27494877

  7. Discriminating between Terminal- and Non-Terminal Respiratory Unit-Type Lung Adenocarcinoma Based on MicroRNA Profiles.

    PubMed

    Kim, Mi-Hyun; Cho, Jeong Su; Kim, Yeongdae; Lee, Chang Hun; Lee, Min Ki; Shin, Dong Hoon

    2016-01-01

    Lung adenocarcinomas can be classified into terminal respiratory unit (TRU) and non-TRU types. We previously reported that non-TRU-type adenocarcinoma has unique clinical and morphological features as compared to the TRU type. Here we investigated whether micro (mi)RNA expression profiles can be used to distinguish between these two subtypes of lung adenocarcinoma. The expression of 1205 human and 144 human viral miRNAs was analyzed in TRU- and non-TRU-type lung adenocarcinoma samples (n = 4 each) by microarray. Results were validated by quantitative real-time (qRT-)PCR and in situ hybridization. A comparison of miRNA profiles revealed 29 miRNAs that were differentially expressed between TRU- and non-TRU adenocarcinoma types. Specifically, hsa-miR-494 and ebv-miR-BART19 were up regulated by > 5-fold, whereas hsa-miR-551b was down regulated by > 5-fold in the non-TRU relative to the TRU type. The miRNA signature was confirmed by qRT-PCR analysis using an independent set of paired adenocarcinoma (non-TRU-type, n = 21 and TRU-type, n = 12) and normal tissue samples. Non-TRU samples showed increased expression of miR-494 (p = 0.033) and ebv-miR-BART19 (p = 0.001) as compared to TRU-type samples. Both miRNAs were weakly expressed in the TRU type but strongly expressed in the non-TRU type. Neither subtype showed miR-551b expression. TRU- and non-TRU-type adenocarcinomas have distinct miRNA expression profiles, suggesting that tumorigenesis in lung adenocarcinoma occur via different pathways.

  8. Intrapancreatic distal common bile duct carcinoma: Analysis, staging considerations, and comparison with pancreatic ductal and ampullary adenocarcinomas.

    PubMed

    Gonzalez, Raul S; Bagci, Pelin; Basturk, Olca; Reid, Michelle D; Balci, Serdar; Knight, Jessica H; Kong, So Yeon; Memis, Bahar; Jang, Kee-Taek; Ohike, Nobuyuki; Tajiri, Takuma; Bandyopadhyay, Sudeshna; Krasinskas, Alyssa M; Kim, Grace E; Cheng, Jeanette D; Adsay, N Volkan

    2016-11-01

    Distal common bile duct carcinoma is a poorly characterized entity for reasons such as variable terminology and difficulty in determining site of origin of intrapancreatic lesions. We compared clinicopathologic features of pancreatobiliary-type adenocarcinomas within the pancreas, but arising from the distal common bile duct, with those of pancreatic and ampullary origin. Upon careful review of 1017 pancreatoduodenectomy specimens with primary adenocarcinoma, 52 (5%) qualified as intrapancreatic distal common bile duct carcinoma. Five associated with an intraductal papillary neoplasm were excluded; the remaining 47 were compared to 109 pancreatic ductal adenocarcinomas and 133 ampullary carcinomas. Distal common bile duct carcinoma patients had a younger median age (58 years) than pancreatic ductal adenocarcinoma patients (65 years) and ampullary carcinoma patients (68 years). Distal common bile duct carcinoma was intermediate between pancreatic ductal adenocarcinoma and ampullary carcinoma with regard to tumor size and rates of node metastases and margin positivity. Median survival was better than for pancreatic ductal adenocarcinoma (P=0.0010) but worse than for ampullary carcinoma (P=0.0006). Distal common bile duct carcinoma often formed an even band around the common bile duct and commonly showed intraglandular neutrophil-rich debris and a small tubular pattern. Poor prognostic indicators included node metastasis (P=0.0010), lymphovascular invasion (P=0.0299), and margin positivity (P=0.0069). Categorizing the tumors based on size also had prognostic relevance (P=0.0096), unlike categorization based on anatomic structures invaded. Primary distal common bile duct carcinoma is seen in younger patients than pancreatic ductal adenocarcinoma or ampullary carcinoma. Its prognosis is significantly better than pancreatic ductal adenocarcinoma and worse than ampullary carcinoma, at least partly because of differences in clinical presentation. Use of size-based criteria

  9. Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma

    PubMed Central

    Shiraishi, Kouya; Okada, Yukinori; Takahashi, Atsushi; Kamatani, Yoichiro; Momozawa, Yukihide; Ashikawa, Kyota; Kunitoh, Hideo; Matsumoto, Shingo; Takano, Atsushi; Shimizu, Kimihiro; Goto, Akiteru; Tsuta, Koji; Watanabe, Shun-ichi; Ohe, Yuichiro; Watanabe, Yukio; Goto, Yasushi; Nokihara, Hiroshi; Furuta, Koh; Yoshida, Akihiko; Goto, Koichi; Hishida, Tomoyuki; Tsuboi, Masahiro; Tsuchihara, Katsuya; Miyagi, Yohei; Nakayama, Haruhiko; Yokose, Tomoyuki; Tanaka, Kazumi; Nagashima, Toshiteru; Ohtaki, Yoichi; Maeda, Daichi; Imai, Kazuhiro; Minamiya, Yoshihiro; Sakamoto, Hiromi; Saito, Akira; Shimada, Yoko; Sunami, Kuniko; Saito, Motonobu; Inazawa, Johji; Nakamura, Yusuke; Yoshida, Teruhiko; Yokota, Jun; Matsuda, Fumihiko; Matsuo, Keitaro; Daigo, Yataro; Kubo, Michiaki; Kohno, Takashi

    2016-01-01

    Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30–50%) than in European/Americans (10–20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10−17, per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10−9, per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations. PMID:27501781

  10. Clinicopathologic and prognostic factors of young and elderly patients with esophageal adenocarcinoma: is there really a difference?

    PubMed

    Vallböhmer, D; Hölscher, A H; Brabender, J; Prenzel, K; Gutschow, C; Schröder, W; Metzger, R; Bollschweiler, E

    2008-01-01

    Evidence suggests a significant difference in the incidence, presentation, and outcome of young and elderly patients with esophageal adenocarcinoma. We aimed to compare clinicopathologic and prognostic factors of young and elderly patients with esophageal adenocarcinoma at a surgical department in Europe. From 1996 to 2006, 223 patients with a resectable esophageal adenocarcinoma were analyzed and divided in three groups: (i) patients 70 years (n = 52). Clinicopathological and prognostic factors were compared between these groups. The total number of patients with esophageal adenocarcinoma increased significantly. Although the total number of patients adenocarcinoma was rather constant. The number of patients with a pT1-tumor was similar among all groups. Young patients had a significantly lower comorbidity and received more often a neoadjuvant radio-chemotherapy. The 5-year survival rate of young patients was significantly higher compared with elderly patients. In this European population, the total number of patients with adenocarcinoma of the esophagus increased dramatically in recent years, but the number of young patients remained rather constant. The better prognosis of young patients is mainly caused by less comorbidity and more frequent use of neoadjuvant therapy.

  11. [Adenocarcinoma of the gastro-esophagus junction associated to endobrachyesophagus. Two case reports. Review of the literature].

    PubMed

    Kreiker, Joseph; Daou, Robert

    2004-01-01

    Barrett esophagus (BE) is intestinal metaplasia (MI) within the distal tubular esophagus. The BE results in replacement of the normal squamous-lined epithelium with a columnar type epithelium. This metaplastic lesion is a clearly defined risk factor for the development of esophageal adenocarcinoma (ADC). In the western countries the incidence of adenocarcinoma of the lower esophagus and the gastro-esophagus junction have rapidly increased during the past twenty years. The 5-year survival is very poor. Although the relative risk of individuals in the United States with BE developing esophageal adenocarcinoma is very high, the absolute risk is extremely low due to the small number of cases. This lesion is caused by a persistent gastro-esophageal reflux. The nature of the reflux liquid is mixed acid and alkaline in the big majority of cases. A familial aggregation of BE and esophageal adenocarcinoma are present in 14% of patients with BE and esophageal adenocarcinoma. The diagnosis, the surveillance, the new tools of characterization of BE and the therapy remain an actual problem. We present 2 cases of endobrachyesophagus associated to an adenocarcinoma of the lower esophagus and a review of the main actual problem.

  12. Identification of Factors for the Preoperative Prediction of Tumour Subtype and Prognosis in Patients with T1 Lung Adenocarcinoma

    PubMed Central

    Zhang, Yong-Kui; Chai, Zhen-da; Hu, Xiao-fei; Tan, Lin-lin; Wang, Zhao-yu; Chen, Zhi-jun

    2016-01-01

    Aims. Identification of factors that can predict the subtypes of lung adenocarcinoma preoperatively is important for selecting the appropriate surgical procedure and for predicting postoperative survival. Methods. We retrospectively evaluated 87 patients with lung adenocarcinomas ≤30 mm. Results. Preoperative radiological findings, serum CEA level, serum microRNA-183 (miR-183) level, and tumour size differed significantly between patients with adenocarcinoma in situ (AIS) or minimally invasive adenocarcinoma (MIA) and those with invasive adenocarcinoma (IAC). Receiver operating characteristic curves and univariate analysis revealed that patients who were older than 57 years or had a pure solid nodule or a tumour with mixed ground-glass opacity (mGGO), a tumour >11 mm, a serum CEA level >2.12 ng/mL, or a serum miR-183 level >1.233 (2−ΔΔCt) were more likely to be diagnosed with IAC than with AIS or MIA. The combination of all five factors had an area under the curve of 0.946, with a sensitivity of 89.13% and a specificity of 95.12%. Moreover, patients with a cut-off value >0.499 for the five-factor combination had poor overall survival. Conclusions. The five-factor combination enables clinicians to distinguish AIS or MIA from IAC, thereby aiding in selecting the appropriate treatment, and to predict the prognosis of lung adenocarcinoma patients. PMID:28115792

  13. Effect of silencing SATB1 on proliferation, invasion and apoptosis of A549 human lung adenocarcinoma cells

    PubMed Central

    Huang, Bo; Zhou, Hongli; Wang, Siwang; Lang, Xian Ping; Wang, Xiaodong

    2016-01-01

    The present study aimed to explore the clinical characteristics of special adenine-thymine-rich sequence-binding protein 1 (SATB1) in lung adenocarcinoma and its role in the proliferation, invasion, migration and apoptosis of the lung adenocarcinoma cell line A549. The expression of SATB1 was first studied in tumor tissues of lung adenocarcinoma and adjacent non-tumor tissues. The siRNA green fluorescent protein expression vector of SATB1 was constructed and transfected into the lung adenocarcinoma cell line A549, then a fluorescence microscope was used to study the transfection efficiency. Western blot analysis was adopted to measure the silencing efficiency. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Transwell and scratch assays were used to study cell proliferation, invasion and migration activity, and the apoptosis rate was tested by flow cytometry. SATB1 expression was low in the adjacent non-tumor tissues but high in lung adenocarcinoma tissues, and it was reversely proportional to the differentiation degree. Following transfection with SATB1-siRNA, the expression of SATB1 in A549 cells was blocked (P<0.01). In addition, the proliferation, invasion and migration abilities of cells decreased significantly while the apoptosis rate increased significantly (P<0.01). In conclusion SATB1 is closely associated with the pathogenesis and development of lung adenocarcinoma. PMID:27895736

  14. Immunohistochemical and histopathological findings of ovine pulmonary adenocarcinoma (Jaagsiekte) in Egyptian sheep.

    PubMed

    Oda, Samah Shehata; Youssef, Sameh Ahmed

    2011-12-01

    Ovine pulmonary adenocarcinoma (OPA) is a naturally occurring retrovirus-induced transmissible lung cancer in sheep. Lungs and associated (bronchial and mediastinal) lymph nodes of seven sheep with OPA were examined. Lungs had few multifocal consolidated slightly elevated gray to white masses ranging from 0.5 to 3 cm in diameter. Histopathologically, these masses appeared as well-differentiated acinar adenocarcinoma with little evidence of anaplasia. The acini composed of well-differentiated cuboidal to low columnar epithelium with clear or vacuolated cytoplasm and low mitotic index. No metastases were observed in the bronchial and mediastinal lymph nodes of any animal. The presence of Jaagsiekte sheep retrovirus (JSRV) was demonstrated in the lungs by immunohistochemistry. JSRV protein was detected in all tumor epithelial cells, histologically normal alveolar type II cells, and few bronchiolar epithelial cells, alveolar macrophages, lymphocytes, and plasma cells. This study is the first to confirm the presence of natural OPA in Egypt.

  15. Adenocarcinoma of Mullerian origin: review of pathogenesis, molecular biology, and emerging treatment paradigms.

    PubMed

    Cobb, Lauren Patterson; Gaillard, Stephanie; Wang, Yihong; Shih, Ie-Ming; Secord, Angeles Alvarez

    2015-01-01

    Traditionally, epithelial ovarian, tubal, and peritoneal cancers have been viewed as separate entities with disparate origins, pathogenesis, clinical features, and outcomes. Additionally, previous classification systems for ovarian cancer have proposed two primary histologic groups that encompass the standard histologic subtypes. Recent data suggest that these groupings no longer accurately reflect our knowledge surrounding these cancers. In this review, we propose that epithelial ovarian, tubal, and peritoneal carcinomas represent a spectrum of disease that originates in the Mullerian compartment. We will discuss the incidence, classification, origin, molecular determinants, and pathologic analysis of these cancers that support the conclusion they should be collectively referred to as adenocarcinomas of Mullerian origin. As our understanding of the molecular and pathologic profiling of adenocarcinomas of Mullerian origin advances, we anticipate treatment paradigms will shift towards genomic driven therapeutic interventions.

  16. Pathogenic PALB2 mutation in metastatic pancreatic adenocarcinoma and neuroendocrine tumour: A case report

    PubMed Central

    CHAN, DAVID; CLARKE, STEPHEN; GILL, ANTHONY J.; CHANTRILL, LORRAINE; SAMRA, JAS; LI, BOB T.; BARNES, TRISTAN; NAHAR, KAZI; PAVLAKIS, NICK

    2015-01-01

    Adenocarcinoma of the pancreas is an aggressive malignancy with poor prognosis. Pancreatic neuroendocrine tumours (PNET) comprise ~3% of primary pancreatic neoplasms and they are more heterogeneous in their histological character and outcome. This is the case report of a 73-year-old female patient with synchronously diagnosed pancreatic adenocarcinoma and PNET, which is likely associated with a pathogenic partner and localizer of breast cancer 2, early onset (PALB2) mutation. The potential pathogenic significance of PALB2 and its association with various malignancies were investigated and the potential role of PALB2 in conferring sensitivity to chemotherapeutic agents, such as mitomycin C and cisplatin, was discussed. This case report highlights the significance of ongoing research into the molecular pathogenesis of pancreatic cancer, which may help guide the selection of optimal treatments for this disease, as well as the need for ongoing study of PALB2 as a possible predictive marker of response to DNA-damaging agents. PMID:26171187

  17. Genetic Diversity of Pancreatic Ductal Adenocarcinoma and Opportunities for Precision Medicine

    PubMed Central

    Knudsen, Erik S.; O’Reilly, Eileen M.; Brody, Jonathan R.; Witkiewicz, Agnieszka K.

    2016-01-01

    Patients with pancreatic ductal adenocarcinoma (PDA) have a poor prognosis—in spite of new treatments, approximately 7% survive for 5 years. Although there have been advances in systemic, primarily cytotoxic, therapies, it has been a challenge to treat patients with PDA using targeted therapies. Sequence analyses have provided a wealth of information about the genetic features of PDA and identified potential therapeutic targets. Preclinical and early-phase clinical studies have found specific pathways could be rationally targeted; it might also be possible to take advantage of the genetic diversity of PDAs to develop therapeutic agents. The genetic diversity and instability of PDA cells have long been thought of as obstacles to treatment, but now are considered exploitable features. We review the latest findings in pancreatic cancer genetics and the promise of targeted-approaches in pancreatic ductal adenocarcinoma therapy. PMID:26385075

  18. Scrotal Apocrine Adenocarcinoma with Pagetoid Phenomenon and Inguinal Lymph Node Metastases

    PubMed Central

    Fyllos, Apostolos Haralampos; Havaki, Sophia; Sotiriou, Sotirios; Kotakidis, Georgios; Arvanitis, Dimitrios Leonidas

    2016-01-01

    We report a case of scrotal apocrine adenocarcinoma in a 72-year-old Caucasian male which was initially presented as a reddish superficial lesion which in time became an ulcerated nodule. The initial pathological examination showed an apocrine adenocarcinoma with pagetoid phenomenon. The tumor recurred after four months and then excision biopsy showed tumor with pagetoid phenomenon which reached all the surgical margins. Three months later an ulcerated nodule in the scrotum and greatly enlarged ipsilateral inguinal lymph nodes were noticed. The final pathological examination showed multiple separated malignant foci, some with overlying pagetoid phenomenon and inguinal lymph node metastases. Immunohistochemistry showed positivity for Gross Cystic Disease Fluid Protein-15 (GCDFP-15), androgen receptors, and score 3+ for the Human Epidermal growth factor Receptor-2 (HER2). The aggressive behavior of the present tumor goes along with previous reports showing that HER2 high score cases exhibit a worse prognosis. PMID:27818816

  19. A case of very well-differentiated adenocarcinoma with carcinoid tumor in the ascending colon.

    PubMed

    Yamauchi, Hayato; Sakurai, Shinji; Tsukagoshi, Ritsuko; Suzuki, Masaki; Tabe, Yuichi; Fukasawa, Takaharu; Kiriyama, Shinsuke; Fukuchi, Minoru; Naitoh, Hiroshi; Kuwano, Hiroyuki

    2014-01-01

    Malignant tumors with mixed glandular and neuroendocrine characteristics with at least 30% of each component are classified as mixed adenoneuroendocrine carcinoma (MANEC) by the World Health Organization 2010 classification. We report here a case of very well-differentiated adenocarcinoma accompanied by carcinoid tumor, categorized as MANEC. A 41-year-old Japanese man was clinically diagnosed with ascending colon cancer and underwent right hemicolectomy. Using an immunohistologic technique, the pathologic diagnosis was very well-differentiated adenocarcinoma accompanied by carcinoid tumor and marked eosinophil infiltration, which was categorized as MANEC. By immunohistochemical analysis, tumor cells of the carcinoid component exhibited very low proliferation activity. Our case was thought to be MANEC without high malignant potential. MANEC as per the World Health Organization 2010 classification seems to include tumors with diverse grades of malignancy, and it might need to have subclassifications according to the malignancy potential of the tumor cells.

  20. [Mucinous adenocarcinoma of the nose and paranasal sinuses, an occupational disease?].

    PubMed

    Rüttner, J R; Makek, M

    1985-12-21

    In Great Britain and other countries there have been reports of an increased frequency of adenocarcinoma of the nose and paranasal sinuses, mimicking histologically mucinous colonic carcinoma, among workers exposed to wood dust and workers in the leather industry. No such cases have been reported so far in Switzerland. 31 patients with this type of adenocarcinoma of the nose and paranasal sinuses observed between 1953 and 1984 have been reviewed. In 13 of these patients there was occupational exposure to wood dust, and 4 were shoemakers. The study suggests an association of this type of nasal carcinoma with occupational exposure to wood dust and leatherwork. The nature of the postulated carcinogen is unknown. The authors propose further investigations to define the magnitude of the cancer risk associated with exposure to wood dust and leather.

  1. Radiologic presentation of chronic granulomatous prostatitis mimicking locally advanced prostate adenocarcinoma.

    PubMed

    Lee, Su-Min; Joshi, Jay; Wolfe, Konrad; Acher, Peter; Liyanage, Sidath H

    2016-06-01

    We present a case of nonspecific granulomatous prostatitis (GP), a clinical mimic of prostate adenocarcinoma. A 54-year-old man presented with lower urinary tract symptoms and raised prostate-specific antigen. Magnetic resonance imaging showed features consistent with prostate cancer, including low T2-signal intensity in the peripheral and transition zones with signs of extracapsular extension. Diffusion-weighted imaging showed high-signal intensity, with low apparent diffusion coefficient values, whereas dynamic contrast enhancement demonstrated a type 3 washout curve, similar to that found in prostate cancer. Transperineal sector-guided prostate biopsy confirmed nonspecific GP, and the patient was treated conservatively. We discuss and compare nonspecific, chronic GP as a radiologic mimic of prostate adenocarcinoma patient.

  2. A case of gastric adenocarcinoma in a Shih Tzu dog: successful treatment of early gastric cancer.

    PubMed

    Lee, Hee-Chun; Kim, Ji-Hyun; Jee, Cho-Hee; Lee, Jae-Hoon; Moon, Jong-Hyun; Kim, Na-Hyun; Sur, Jung-Hyang; Cho, Kyu-Woan; Kang, Byeong-Teck; Ha, Jeongim; Jung, Dong-In

    2014-07-01

    A 9-year-old castrated male Shih Tzu dog was referred to us, because of chronic vomiting. The patient's hematological, radiographic, ultrasonographic, endoscopic and histological examinations were evaluated for diagnosis. Hematologic analysis indicated moderate anemia and azotemia. Based on the imaging studies, an oval-shaped mass was identified in the gastric pylorus area. A proliferative mass was found on endoscopic examination, and we performed biopsy using grasping forceps. The histopathological findings of the biopsy specimens indicated hypertrophic gastritis, and Y-U pyloroplasty was performed. However, histopathological examination of the surgically resected mass revealed tubular adenocarcinoma of the stomach. Then, carboplatin chemotherapy was performed 4 times for 13 weeks. Clinical signs, such as vomiting, were resolved gradually after surgery and chemotherapy, and the patient's condition was managed favorably until recently (30 months after surgery). This case report describes clinical features, imaging studies, endoscopic characteristics and histopathological and immunohistochemical features of gastric tubular adenocarcinoma as early gastric cancer in a dog.

  3. Coexistence of Gastric Adenocarcinoma and Choriocarcinoma: Complete Response to Trastuzumab and Chemotherapy

    PubMed Central

    Gunduz, Seyda; Elpek, Gulsum Ozlem; Uysal, Mukremin; Goksu, Sema Sezgin; Tatli, Murat; Arslan, Deniz; Coskun, Hasan Senol; Bozcuk, Hakan; Savas, Burhan; Ozdogan, Mustafa

    2012-01-01

    Gastric choriocarcinoma is a rare neoplasm and usually accompanies gastric adenocarcinoma. The prognosis is poor due to the aggressive course of the disease. A 57-year-old female patient with weight loss and abdominal pain was examined. The patient was operated following the examination, and pathological analysis revealed the presence of a gastric adenocarcinoma associated with choriocarcinoma. Immunohistochemical analysis showed a positive reaction with antibodies to beta-human chorionic gonadotropin and overexpression of the cErbB2 proto-oncogene. Staging revealed multiple metastases in the liver. A complete response was obtained with a combination of trastuzumab and chemotherapy. The diagnosis of gastric choriocarcinomas without pathological examination is difficult due to their rare occurrence. A complete response can be obtained with trastuzumab in the treatment of cases with overexpression of the cErbB2 protein. PMID:23525369

  4. Paraneoplastic Evans syndrome in a patient with adenocarcinoma of the lung: A case report

    PubMed Central

    Yu, Hong; Fu, Rong; Wang, Huaquan; Liu, Hui

    2016-01-01

    We present a rare case of newly diagnosed Evans syndrome associated with lung papillary adenocarcinoma in which the patient showed prompt restoration of blood cell count and long‐lasting complete remission of Evans syndrome after lung cancer resection. Detailed investigation led to a diagnosis of Evans syndrome. In the first year of the disease, left lower lung papillary adenocarcinoma was diagnosed. Pulmonary lobectomy and three courses of chemotherapy were performed. Six months after the initial visit, the primary lung cancer and the autoimmune diseases appeared to be well controlled. We hypothesized that our patient's initial presentation of hematological manifestation was a paraneoplastic phenomenon associated to her underlying malignancy. This rare case report illustrates the unique relationship between primary lung cancer and the development of paraneoplastic Evans syndrome. PMID:28055149

  5. Case of metachronous bilateral isolated adrenal metastasis from colorectal adenocarcinoma and review of the literature.

    PubMed

    Liu, Yu-Yi; Chen, Zhi-Hui; Zhai, Er-Tao; Yang, Jie; Xu, Jian-Bo; Cai, Shi-Rong; Song, Wu

    2016-04-14

    Rarely has a solitary, metachronous bilateral adrenal metastasis of colorectal cancer been reported. We depict a 41-year-old man who underwent sigmoid colon cancer radical surgery followed by adjuvant chemotherapy for a locally ulcerative sigmoid adenocarcinoma with metachronous bilateral adrenal metastasis revealed by a computed tomography scan. Histopathological examination showed adenocarcinoma, compatible with metastasis from the rectal cancer. The level of serum carcinoembryonic antigen had indicative significance for the presence of adrenal metastasis in the reported series. We performed a literature analysis related to this pathological characteristic and attach importance to consistent, vigilant radiological surveillance of the adrenal glands in the patients' follow up for colorectal cancer with or without subsequent adrenal metastasis.

  6. Identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line, LC-2/ad.

    PubMed

    Matsubara, Daisuke; Kanai, Yoshihiko; Ishikawa, Shumpei; Ohara, Shiori; Yoshimoto, Taichiro; Sakatani, Takashi; Oguni, Sachiko; Tamura, Tomoko; Kataoka, Hiroaki; Endo, Shunsuke; Murakami, Yoshinori; Aburatani, Hiroyuki; Fukayama, Masashi; Niki, Toshiro

    2012-12-01

    Rearranged during transfection (RET) fusions have been newly identified in approximately 1% of patients with primary lung tumors. However, patient-derived lung cancer cell lines harboring RET fusions have not yet been established or identified, and therefore, the effectiveness of an RET inhibitor on lung tumors with endogenous RET fusion has not yet been studied. In this study, we report identification of CCDC6-RET fusion in the human lung adenocarcinoma cell line LC-2/ad. LC-2/ad showed distinctive sensitivity to the RET inhibitor, vandetanib, among 39 non-small lung cancer cell lines. The xenograft tumor of LC-2/ad showed cribriform acinar structures, a morphologic feature of primary RET fusion-positive lung adenocarcinomas. LC-2/ad cells could provide useful resources to analyze molecular functions of RET-fusion protein and its response to RET inhibitors.

  7. Molecular biology of adenocarcinoma of the pancreatic duct, current state and future therapeutic avenues.

    PubMed

    Abbas, Saleh

    2013-06-01

    Pancreatic adenocarcinoma is a lethal disease; currently surgery offers five years survival of less than 5%. Any improvement in the outcome is likely to be through novel therapeutic agents that will target the genetic machinery of the cell. Knowledge of genetic alterations in the process of carcinogenesis is expanding rapidly, the targeted therapy, however, is progressing slowly. Pancreatic adenocarcinoma displays a variety of molecular changes that evolve exponentially with time and lend the cancer cells their ability not only to survive, but also to invade the surrounding tissues and metastasise to distant sites. These changes involve genetic alteration in oncogenes, cancer suppressor genes, changes in cell cycle, pathways of apoptosis and also changes in epithelial to mesenchymal transition. Monotherapeutic targeted agents seem(s) to have limited effect on cancer cells. The near future is likely to show an improvement in the treatment outcome, which is likely to be a result of the combination of targeted agents with surgery and chemotherapy.

  8. Diagnosis potential of near infrared Mueller Matrix imaging for colonic adenocarcinoma

    NASA Astrophysics Data System (ADS)

    Wang, Jianfeng; Zheng, Wei; Lin, Kan; Huang, Zhiwei

    2016-03-01

    Mueller matrix imaging along with polar decomposition method was employed for the colonic adenocarcinoma detection by polarized light in the near-infrared spectral range (700-1100 nm). A high-speed (<5s) Muller matrix imaging system with dual-rotating waveplates was developed. 16 (4 by 4) full Mueller matrices of the colonic tissues (i.e., normal and caner) were acquired. Polar decomposition was further implemented on the 16 images to derive the diattentuation, depolarization, and the retardance images. The decomposed images showed clear margin between the normal and adenocarcinomaous colon tissue samples. The work shows the potential of near-infrared Mueller matrix imaging for the early diagnosis and detection of malignant lesions in the colon.

  9. Bilateral Aural Adenocarcinoma in a Congo African Grey Parrot ( Psittacus erithacus erithacus).

    PubMed

    Houck, Emma L; Keller, Krista A; Hawkins, Michelle G; Burton, Andrew G; Casey, Keriann M; Keel, Kevin; Tong, Nathan; Guzman, David Sanchez-Migallon

    2016-09-01

    A 28-year-old female Congo African grey parrot ( Psittacus erithacus erithacus) was evaluated because of a mass in the left external auditory meatus. Results of a computed tomography scan revealed an osteolytic left hemimandibular mass with irregular bone production and a soft tissue mass in the left external auditory meatus. Results of cytologic examination of fine needle aspirates of the hemimandible were interpreted as adenocarcinoma with reactive osteoblasts. The owner chose palliative treatment, and a debulking procedure was performed on the left external auditory meatus mass 52 days after initial presentation to control self-trauma. Euthanasia was elected 67 days after initial presentation because of poor prognosis associated with the development of bilateral masses of the external auditory meatus and lateral deviation of the mandible, findings that were confirmed by postmortem examination. Histopathologic results confirmed the diagnosis of bilateral aural adenocarcinoma with invasion of both temporal bones and hemimandibles.

  10. Paraneoplastic Evans syndrome in a patient with adenocarcinoma of the lung: A case report.

    PubMed

    Yu, Hong; Fu, Rong; Wang, Huaquan; Liu, Hui; Shao, Zonghong

    2017-01-01

    We present a rare case of newly diagnosed Evans syndrome associated with lung papillary adenocarcinoma in which the patient showed prompt restoration of blood cell count and long-lasting complete remission of Evans syndrome after lung cancer resection. Detailed investigation led to a diagnosis of Evans syndrome. In the first year of the disease, left lower lung papillary adenocarcinoma was diagnosed. Pulmonary lobectomy and three courses of chemotherapy were performed. Six months after the initial visit, the primary lung cancer and the autoimmune diseases appeared to be well controlled. We hypothesized that our patient's initial presentation of hematological manifestation was a paraneoplastic phenomenon associated to her underlying malignancy. This rare case report illustrates the unique relationship between primary lung cancer and the development of paraneoplastic Evans syndrome.

  11. Primary adenocarcinoma of the jejunum and ileum: clinicopathological review of 25 cases.

    PubMed Central

    Lioe, T F; Biggart, J D

    1990-01-01

    Between 1954 and 1988 only a total of twenty five cases of primary adenocarcinoma of the small bowel (excluding periampillary tumours) were recorded at the Department of Histopathology, Belfast City Hospital. Of these, 14 tumours were located in the jejunum: the remainder arose in the ileum. The average age at presentation was 61.3 years and a slight female to male preponderance of 1:7:1 was noted. The adenocarcinoma arose from a preexisting villous adenoma in six cases. The overall prognosis was poor, with a five year survival of 15.7%. All the survivors had tumours located in the jejunum. The single most important prognostic indicator was the depth of tumour invasion or stage at the time of diagnosis. Tumour size and grade did not seem to correlate well with survival. It is concluded that the rarity of these tumours and their inaccessibility hinder detection and treatment and that surgical resection is more effective than chemotherapy. Images PMID:2380402

  12. Cutaneous adenocarcinoma of sebaceous gland in a captive male jaguar Panthera onca: a case report.

    PubMed

    Majie, Arnab K; Mondal, Parswanath; Ghosh, Swapan K; Banerjee, Dayanarayan

    2014-02-24

    High incidence of neoplasia in captive jaguar (Panthera onca) has been recorded but there have been no reports of cutaneous adenocarcinoma of the sebaceous gland. A high incidence of neoplasia has been detected in captive jaguars, possibly associated with longevity and husbandry practices in captivity. Neoplasm is a major cause of mortality in jaguar. Tumours of sebaceous gland are common in older domestic felids. A case of cutaneous adenocarcinoma of the sebaceous gland was diagnosed in a male captive jaguar in the Zoological Garden, Alipore, Kolkata, India and was managed successfully. The tumour was observed as a superficial, ulcerated, multilobulated intradermal mass. After preoperative haematological evaluation the tumour was excised through routine surgical procedure under chemical immobilisation. Post-operative management was uneventful. Local tumour recurrence was not noticed till one year after post-operation.

  13. Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach

    PubMed Central

    Jiang, Meng-jie; Weng, Shan-Shan; Cao, Ying; Li, Xiao-Fen; Wang, Liu-Hong; Xu, Jing-Hong; Yuan, Ying

    2015-01-01

    Abstract Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common. Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes. Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients. PMID:26356712

  14. Advances in the management of Barrett’s esophagus and early esophageal adenocarcinoma

    PubMed Central

    Singh, Ajaypal; Chak, Amitabh

    2015-01-01

    The incidence of esophageal adenocarcinoma (EAC) has markedly increased in the United States over the last few decades. Barrett’s esophagus (BE) is the most significant known risk factor for this malignancy. Theoretically, screening and treating early BE should help prevent EAC but the exact incidence of BE and its progression to EAC is not entirely known and cost-effectiveness studies for Barrett’s screening are lacking. Over the last few years, there have been major advances in our understanding of the epidemiology, pathogenesis and endoscopic management of BE. These developments focus on early recognition of advanced histology and endoscopic treatment of high-grade dysplasia. Advanced resection techniques now enable us to endoscopically treat early esophageal cancer. In this review, we will discuss these recent advances in diagnosis and treatment of Barrett’s esophagus and early esophageal adenocarcinoma. PMID:26486568

  15. Small bowel adenocarcinoma and Crohn's disease: any further ahead than 50 years ago?

    PubMed

    Cahill, Caitlin; Gordon, Philip H; Petrucci, Andrea; Boutros, Marylise

    2014-09-07

    This review of the literature on small bowel carcinoma associated with Crohn's disease specifically addresses the incidence, risk factors, and protective factors which have been identified. It also reviews the clinical presentation, the current modalities of diagnosis, the pathology, treatment, and surveillance. Finally, the prognosis and future direction are addressed. Our experience with small bowel adenocarcinoma in Crohn's disease is reported. Readers will be provided with a better understanding of this rare and often poorly recognized complication of Crohn's disease.

  16. YBX1 regulates tumor growth via CDC25a pathway in human lung adenocarcinoma

    PubMed Central

    Yu, Wendan; Li, Jinxiu; Tang, Zhipeng; Yu, Zhenlong; Zhao, Lei; Zhang, Yixiang; Wang, Ziyi; Wang, Peng; Li, Yechi; Li, Fengzhou; Sun, Zhe; Xuan, Yang; Tang, Ranran; Deng, Wu-guo; Guo, Wei; Gu, Chundong

    2016-01-01

    Y-box binding protein 1 (YBX1) is involved in the multi-tumor occurrence and development. However, the regulation of YBX1 in lung tumorigenesis and the underlying mechanisms, especially its relationship with CDC25a, was remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and CDC25a in lung adenocarcinoma and identified their roles in the regulation of lung cancer growth. The retrospective analysis of 116 patients with lung adenocarcinoma indicated that YBX1 was positively correlated with CDC25a expression. The Cox-regression analysis showed only high-ranking TNM stage and low CDC25a expression were an independent risk factor of prognosis in enrolled patients. High expression of YBX1 or CDC25a protein was also observed in lung adenocarcinoma cells compared with HLF cells. ChIP assay demonstrated the binding of endogenous YBX1 to the CDC25a promoter region. Overexpression of exogenous YBX1 up-regulated the expression of the CDC25a promoter-driven luciferase. By contrast, inhibition of YBX1 by siRNA markedly decreased the capability of YBX1 binding to CDC25a promoter in A549 and H322 cells. Inhibition of YBX1 expression also blocked cell cycle progression, suppressed cell proliferation and induced apoptosis via the CDC25a pathway in vitro. Moreover, inhibition of YBX1 by siRNA suppressed tumorigenesis in a xenograft mouse model and down-regulated the expression of YBX1, CDC25a, Ki67 and cleaved caspase 3 in the tumor tissues of mice. Collectively, these results demonstrate inhibition of YBX1 suppressed lung cancer growth partly via the CDC25a pathway and high expression of YBX1/CDC25a predicts poor prognosis in human lung adenocarcinoma. PMID:27384875

  17. Transcriptionally targeted in vivo gene therapy for carcinoembrionic antigen-producing adenocarcinoma.

    PubMed

    Konishi, F; Maeda, H; Yamanishi, Y; Hiyama, K; Ishioka, S; Yamakido, M

    1999-09-01

    Inoperable adenocarcinoma in colon or lung shows resistance to conventional anti-cancer therapy. For these cancers, the feasibility of transcriptionally targeted killing of carcinoembryonic antigen (CEA)-producing adenocarcinoma cells was investigated. Adenovirus vectors carrying a CEA promoter to express E. coli lacZ (AdCEALacZ) or herpes simplex thymidine kinase (AdCEATK) were made and their in vitro and in vivo tumoricidal effects on CEA-producing or non-producing colon and lung cancer cells were evaluated. In vitro infection with AdCEALacZ showed significantly higher CEA promoter-driven lacZ expression in CEA-producing adenocarcinoma cells including VMRC-LCD and LoVo than in CEA-non-producing cells. AdCEATK-infected LoVo showed higher sensitivity to ganciclovir than control vector-infected LoVo or AdCEATK-infected HeLa both in vitro and in subcutaneously implanted tumors of nude mice. Moreover, total tumor elimination in vivo was achieved by either pre-infection of as few as 30% of cells comprising tumors or by direct in vivo injection of AdCEATK to pre-established LoVo tumors. In addition, CEA promoter-driven lacZ expression in LoVo cells was enhanced by the addition of interleukin-6 (IL-6) in vitro. These results provide a rationale for CEA-promoter-driven, adenovirus-mediated gene therapy for CEA-producing adenocarcinomas in colon and lung with reduced toxicity to normal cells.

  18. Contrast-enhanced ultrasound improves accurate identification of appendiceal mucinous adenocarcinoma in an old patient

    PubMed Central

    Shang, Jing; Ruan, Li-tao; Dang, Ying; Wang, Yun-yue; Song, Yan; Lian, Jie

    2016-01-01

    Abstract Background: Adenocarcinoma of appendiceal origin is far rarer than other colorectal carcinomas and its preoperative diagnosis is challenging. To our knowledge, utility of contrast-enhanced ultrasound (CEUS) to diagnose it is much less. Method: A 61-year-old man presented with abdominal pain in the right lower quadrant for 20 days. In order to fulfill an accurately preoperative diagnosis, he received laboratory and imaging tests such as carcinoembryonic antigen (CEA), computer tomography (CT), CEUS and endoscope. Diagnosis and Intervention: He was initially suspected of suffering appendicitis, while his white blood cell count was normal and carcinoembryonic antigen (CEA) in serum was remarkably increased. Both routine ultrasound and computer tomography (CT) examinations supported suppurative appendicitis. The overall data, however, failed to excluded neoplastic pathology thoroughly. Therefore, CEUS was carried out and showed an inhomogeneous enhancement intra the lesion located in the body of the appendix, which made our consideration of neoplasm. The result of the follow-up biopsy guided by endoscope was consistent with appendiceal tumor. The patient received laparoscopic right hemicolectomy. Histopathology confirmed as well differentiated mucinous adenocarcinoma of appendix origin. His postoperative course was uneventful, and he had a regular diet again without any complaint. Result: Serum CEA was remarkably increased (12.00 ng/mL). Both routine ultrasound and CT examinations supported suppurative appendicitis. However, CEUS examination showed an inhomogeneous enhancement intra the lesion located in the body of the appendix, which made our consideration of neoplasm. The follow-up biopsy guided by endoscope and surgical specimens confirmed as well differentiated mucinous adenocarcinoma of appendix origin. Conclusion: Most mucinous adenocarcinoma mimicking appendicitis results in difficult diagnosis preoperatively. Clinician and radiologist should be

  19. Integrative transcriptome analysis identifies deregulated microRNA-transcription factor networks in lung adenocarcinoma

    PubMed Central

    Cinegaglia, Naiara C.; Andrade, Sonia Cristina S.; Tokar, Tomas; Pinheiro, Maísa; Severino, Fábio E.; Oliveira, Rogério A.; Hasimoto, Erica N.; Cataneo, Daniele C.; Cataneo, Antônio J.M.; Defaveri, Júlio; Souza, Cristiano P.; Marques, Márcia M.C.; Carvalho, Robson F.; Coutinho, Luiz L.; Gross, Jefferson L.; Rogatto, Silvia R.; Lam, Wan L.; Jurisica, Igor; Reis, Patricia P.

    2016-01-01

    Herein, we aimed at identifying global transcriptome microRNA (miRNA) changes and miRNA target genes in lung adenocarcinoma. Samples were selected as training (N = 24) and independent validation (N = 34) sets. Tissues were microdissected to obtain >90% tumor or normal lung cells, subjected to miRNA transcriptome sequencing and TaqMan quantitative PCR validation. We further integrated our data with published miRNA and mRNA expression datasets across 1,491 lung adenocarcinoma and 455 normal lung samples. We identified known and novel, significantly over- and under-expressed (p ≤ 0.01 and FDR≤0.1) miRNAs in lung adenocarcinoma compared to normal lung tissue: let-7a, miR-10a, miR-15b, miR-23b, miR-26a, miR-26b, miR-29a, miR-30e, miR-99a, miR-146b, miR-181b, miR-181c, miR-421, miR-181a, miR-574 and miR-1247. Validated miRNAs included let-7a-2, let-7a-3, miR-15b, miR-21, miR-155 and miR-200b; higher levels of miR-21 expression were associated with lower patient survival (p = 0.042). We identified a regulatory network including miR-15b and miR-155, and transcription factors with prognostic value in lung cancer. Our findings may contribute to the development of treatment strategies in lung adenocarcinoma. PMID:27081085

  20. Enhanced expression of hydroxylated ceramide in well-differentiated endometrial adenocarcinoma

    PubMed Central

    Tajima, Toshiki; Miyazawa, Masaki; Hayashi, Masaru; Asai, Satoshi; Ikeda, Masae; Shida, Masako; Hirasawa, Takeshi; Iwamori, Masao; Mikami, Mikio

    2017-01-01

    Based on our previous analysis of neutral glycolipids in the human endometrium, the present authors already reported that the concentrations of glucosylceramide, lactosylceramide and globotriaosylceramide (Gb3Cer), in which both fatty acids and sphingosines in the ceramides are hydroxylated, exhibit a marked increase during the luteal phase of the menstrual cycle. It is also well known that poorly differentiated endometrial adenocarcinoma exhibits a more rapid progression and a worse response to therapy than well-differentiated endometrial adenocarcinoma. To examine the molecular background of well-differentiated and poorly differentiated cancers, the levels of neutral glycolipids in tumor tissues from endometrial carcinoma displaying different degrees of differentiation were measured. The composition of neutral glycolipids in tumor tissues was determined, and ceramide structures that were specifically expressed in well-differentiated endometrial carcinomas were investigated using biochemical analytical methods, including lipid extraction, enzyme digestion, thin-layer chromatography (TLC), gas-liquid chromatography and mass spectrometry. Well-differentiated adenocarcinoma contained numerous structurally unknown glycolipids that exhibited slower migration than globotetraosylceramide (Gb4Cer). In the case of Gb3Cer, three bands appeared on TLC in well-differentiated cancer, but only two bands appeared in the poorly-differentiated cancer. This difference was associated with the fatty acid composition of ceramide, since non-hydroxy fatty acids with ≥20 carbon atoms were increased in well-differentiated cancer, while α-hydroxy fatty acids were increased in poorly differentiated cancer. Similarly, there were two bands on TLC of Gb4Cer from well-differentiated cancer, but only one band in poorly differentiated cancer, and the long-chain base of ceramide was observed to contain phytosphingosine in well-differentiated cancer. It was demonstrated in endometrial cancer

  1. The IASLC/ATS/ERS classification of lung adenocarcinoma-a surgical point of view.

    PubMed

    Fang, Wentao; Xiang, Yangwei; Zhong, Chenxi; Chen, Qunhui

    2014-10-01

    Adenocarcinoma has become the most common histologic type of lung cancers. Ground glass nodules (GGN), most of them early stage noninvasive or minimally invasive adenocarcinomas (MIA), have been encountered more frequently with the application of computed tomography (CT) screening. The International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) histologic lung adenocarcinoma classification combines radiologic, histologic, clinic, and molecular features to form a diagnostic approach for different subgroups of diseases. One of the major focuses of this new classification is the introduction of adenocarcinoma in situ (AIS) and MIA, to replace the old term of bronchioloalveolar carcinoma (BAC). Not all GGNs are malignant lesions that should be surgically resected upon first presentation. A management approach different to solid nodules has been suggested based on the understanding that these lesions tend to have a more indolent nature. Hasty intervention should be avoided and potential surgical risks, radiation exposure, patient psychology, and socio-economical burden must be balanced comprehensively before surgery is decided upon. In the mean time, surgical issues concerning extent of resection and lymphadenectomy should also be carefully contemplated once intervention is deemed necessary. Extremely good prognosis with a near 100% disease-free survival could be expected when a pure GGN is completely resected. This has led to re-evaluation of sublobar resections, including both segmentectomy and big wedge resection, for small (≤2 cm) less invasive histology (AIS or MIA) appearing as GGN on CT scan. Evidences are accumulating that these limited resections are oncologically equivalent to standard lobectomy. And extensive lymph node dissection may not have additional staging or prognostic benefit. These would add new meaning to the contemporary definition of minimally invasive surgery for lung cancers

  2. Primary mucinous adenocarcinoma of the female urethra: a contemporary clinicopathologic analysis.

    PubMed

    Harari, Saul E; Cheng, Liang; Osunkoya, Adeboye O

    2016-01-01

    Primary mucinous adenocarcinoma of the female urethra is very rare and may lead to both diagnostic and therapeutic challenges. Although primary mucinous adenocarcinoma of the prostate and prostatic urethra has been well characterized in men, this is the largest clinicopathologic study to date of primary mucinous adenocarcinoma of the female urethra. A search was made through the files of 2 major academic institutions for cases of confirmed primary mucinous adenocarcinoma arising from the female urethra. Tumors arising from adjacent organs were excluded both clinically and pathologically in all cases. Five cases were identified. The mean patient age was 67 years (range, 54-74 years). All patients presented with a polypoid/papillary mass arising from the urethra. Pathologic stages were as follows: pT4 3 (60%) of 5 cases; pT3 1 (20%) of 5 cases, and pT2 1 (20%) of 5 cases. Immunohistochemical stains for GATA3, p63, CK7, CK20, CDX2, ER, PAX8, and β-catenin were performed on all cases. Immunohistochemical stains were positive in the tumor cells for CDX2 in 4/5 (80%) cases; focally positive for CK20 in 4/5 (80%) cases; focally positive for CK7 in 4/5 cases (80%); and negative for p63, GATA3, ER, PAX8 and β-catenin in all cases. In the 4 patients with available follow-up data, mean follow-up was 25 months (range, 4-54 months). It is critical for pathologists to be aware of this entity in light of potential diagnostic pitfalls and therapeutic implications.

  3. Identification of Epigenetic Biomarkers of Lung Adenocarcinoma through Multi-Omics Data Analysis.

    PubMed

    Kikutake, Chie; Yahara, Koji

    2016-01-01

    Epigenetic mechanisms such as DNA methylation or histone modifications are essential for the regulation of gene expression and development of tissues. Alteration of epigenetic modifications can be used as an epigenetic biomarker for diagnosis and as promising targets for epigenetic therapy. A recent study explored cancer-cell specific epigenetic biomarkers by examining different types of epigenetic modifications simultaneously. However, it was based on microarrays and reported biomarkers that were also present in normal cells at a low frequency. Here, we first analyzed multi-omics data (including ChIP-Seq data of six types of histone modifications: H3K27ac, H3K4me1, H3K9me3, H3K36me3, H3K27me3, and H3K4me3) obtained from 26 lung adenocarcinoma cell lines and a normal cell line. We identified six genes with both H3K27ac and H3K4me3 histone modifications in their promoter regions, which were not present in the normal cell line, but present in ≥85% (22 out of 26) and ≤96% (25 out of 26) of the lung adenocarcinoma cell lines. Of these genes, NUP210 (encoding a main component of the nuclear pore complex) was the only gene in which the two modifications were not detected in another normal cell line. RNA-Seq analysis revealed that NUP210 was aberrantly overexpressed among the 26 lung adenocarcinoma cell lines, although the frequency of NUP210 overexpression was lower (19.3%) in 57 lung adenocarcinoma tissue samples studied and stored in another database. This study provides a basis to discover epigenetic biomarkers highly specific to a certain cancer, based on multi-omics data at the cell population level.

  4. Something Old, Something New, Something Borrowed, Something Fused: Novel EGFR Rearrangements in Lung Adenocarcinomas

    PubMed Central

    Paik, Paul K.

    2016-01-01

    Summary Mutations in the epidermal growth factor receptor (EGFR) stand as the archetype for somatic alterations that lead to oncogene addiction and that predict for response to targeted therapies. In this issue of Cancer Discovery, Konduri and colleagues report on a pair of novel oncogenic and actionable EGFR fusion events in a series of patients with lung adenocarcinomas, casting new light on this model gene. PMID:27261479

  5. Image based detection and targeting of therapy resistance in pancreatic adenocarcinoma

    PubMed Central

    Jaquish, Dawn V.; Park, Frederick D.; Ito, Takahiro; Bajaj, Jeevisha; Koechlein, Claire S.; Zimdahl, Bryan; Yano, Masato; Kopp, Janel; Kritzik, Marcie; Sicklick, Jason; Sander, Maike; Grandgenett, Paul M.; Hollingsworth, Michael A.; Shibata, Shinsuke; Pizzo, Donald; Valasek, Mark; Sasik, Roman; Scadeng, Miriam; Okano, Hideyuki; Kim, Youngsoo; MacLeod, A. Robert

    2016-01-01

    Pancreatic intraepithelial neoplasia (PanIN) is a premalignant lesion that can progress to pancreatic ductal adenocarcinoma, a highly lethal malignancy marked by its late stage at clinical presentation and profound drug resistance1. The genomic alterations that commonly occur in pancreatic cancer include activation of KRAS2 and inactivation of p53, and SMAD42-4. To date, however, it has been challenging to target these pathways therapeutically; thus the search for other key mediators of pancreatic cancer growth remains an important endeavor. Here we show that the stem cell determinant Musashi (Msi) is a critical element of pancreatic cancer progression in both genetic models and patient derived xenografts. Specifically, we developed Msi reporter mice that allowed image based tracking of stem cell signals within cancers, revealing that Msi expression rises as PanIN progresses to adenocarcinoma, and that Msi-expressing cells are key drivers of pancreatic cancer: they preferentially harbor the capacity to propagate adenocarcinoma, are enriched in circulating tumor cells, and are markedly drug resistant. This population could be effectively targeted by deletion of either Msi1 or Msi2, which led to a striking defect in PanIN progression to adenocarcinoma and an improvement in overall survival. Msi inhibition also blocked the growth of primary patient-derived tumors, suggesting that this signal is required for human disease. To define the translational potential of this work we developed antisense oligonucleotides against Msi; these showed reliable tumor penetration, uptake and target inhibition, and effectively blocked pancreatic cancer growth. Collectively, these studies highlight Msi reporters as a unique tool to identify therapy resistance, and define Msi signaling as a central regulator of pancreatic cancer. PMID:27281208

  6. Metachronous bilateral isolated adrenal metastasis from rectal adenocarcinoma: a case report.

    PubMed

    Jabir, H; Tawfiq, N; Moukhlissi, M; Akssim, M; Guensi, A; Kadiri, B; Bouchbika, Z; Taleb, A; Benchekroun, N; Jouhadi, H; Sahraoui, S; Zamiati, S; Benider, A

    2014-01-01

    We report a case of adrenal metastasis from colorectal cancer in a 54-year-old woman. Nine months after resection for advanced rectal carcinoma, a computed tomography scan revealed bilateral adrenal metastasis. The level of serum carcinoembryonic antigen was normal. A bilateral adrenalectomy was performed after chemotherapy. Histopathological examination showed adenocarcinoma, compatible with metastasis from the rectal cancer. Adrenal metastasis should be considered in the patients' follow-up for colorectal cancer.

  7. Breast metastasis from recurrent gallbladder adenocarcinoma: a case report with review of the literature

    PubMed Central

    Faouzi, Houssin; Salmi, Nariman; Ettahri, Hamza; Elghissassi, Ibrahim; Mrabti, Hind; Errihani, Hassan

    2016-01-01

    Gallbladder adenocarcinoma has a poor prognostic. The leading modes of dissemination in gallbladder cancer (GBC) are lymphatic, vascular, neural, intraperitoneal, and intraductal. The most common site of dissemination is liver. Breast metastasis in GBC is an unusual site of dissemination. Only few cases have been reported in the literature. We report a rare case of solitary breast metastasis from recurrent gallbladder carcinoma in light of existing literature. PMID:27512606

  8. Lung adenocarcinoma: Sustained subtyping with immunohistochemistry and EGFR, HER2 and KRAS mutational status.

    PubMed

    Sousa, Vitor; Rodrigues, Carolina; Silva, Maria; Alarcão, Ana Maria; Carvalho, Lina

    2015-01-01

    Pulmonary adenocarcinomas are still in the process of achieving morphological, immunohistochemical and genetic standardization. The ATS/ERS/IASLC proposed classification for lung adenocarcinomas supports the value of the identification of histological patterns, specifically in biopsies. Thirty pulmonary adenocarcinomas were subjected to immunohistochemical study (CK7, CK5, 6, 18, CK20, TTF1, CD56, HER2, EGFR and Ki-67), FISH and PCR followed by sequencing and fragment analysis for EGFR, HER2 and KRAS. Solid pattern showed lower TTF1 and higher Ki-67 expression. TTF1 expression was higher in non-mucinous lepidic and micropapillary patterns when compared to acinar and solid and acinar, solid and mucinous respectively. Higher Ki67 expression was present in lepidic and solid patterns compared to mucinous. EGFR membranous staining had increasing expression from non-mucinous lepidic/BA pattern to solid pattern and micropapillary until acinar pattern. EGFR mutations, mainly in exon 19, were more frequent in females, together with non-smoking status, while KRAS exon 2 mutations were statistically more frequent in males, especially in solid pattern. FISH EGFR copy was correlated gross, with mutations. HER2 copy number was raised in female tumours without mutations, in all cases. Although EGFR and KRAS mutations are generally considered mutually exclusive, in rare cases they can coexist as it happened in one of this series, and was represented in acinar pattern with rates of 42.9% and 17.9%, respectively. EGFR mutations were more frequent in lepidic/BA and acinar patterns. Some cases showed different EGFR mutations. The differences identified between the adenocarcinoma patterns reinforce the need to carefully identify the patterns present, with implications in diagnosis and in pathogenic understanding. EGFR and KRAS mutational status can be determined in biopsies representing bronchial pulmonary carcinomas because when a mutation is present it is generally present in all the

  9. Something Old, Something New, Something Borrowed, Something Fused: Novel EGFR Rearrangements in Lung Adenocarcinomas.

    PubMed

    Paik, Paul K

    2016-06-01

    Mutations in EGFR stand as the archetype for somatic alterations that lead to oncogene addiction and that predict for response to targeted therapies. In this issue of Cancer Discovery, Konduri and colleagues report on a pair of novel oncogenic and actionable EGFR fusion events in a series of patients with lung adenocarcinomas, casting new light on this model gene. Cancer Discov; 6(6); 574-5. ©2016 AACRSee related article by Konduri et al., p. 601.

  10. Evidence for Treatment and Survival Disparities by Age in Pancreatic Adenocarcinoma

    PubMed Central

    Amin, Sunil; Lucas, Aimee L.; Frucht, Harold

    2013-01-01

    Objectives Studies demonstrate safety and survival benefits of surgical resection in older individuals with pancreatic adenocarcinoma. We investigated treatment disparities by age. Methods The Surveillance, Epidemiology, and End Results database for survival and treatment of pancreatic adenocarcinoma between 1983 and 2007 stratified by age: younger than 50 years, between 50 and 70 years, or older than 70 years. Kaplan-Meier curves and Cox proportional hazards models were used for survival differences, and logistic regression models were used for treatment disparities and the decision to refuse surgery. Results A total of 45,509 patients had microscopically confirmed pancreatic adenocarcinoma. Of these, 7374 (16%) received surgery and 9842 (22%) received radiation. Younger patients were more likely to receive both surgery and radiation. The prevalence of surgery decreased from 21% for those younger than 50 years to 19% for those between 50 and 70 years to 13% for those older than 70 years (P < 0.001). Radiation decreased from 28% to 25% to 17% (P < 0.001). Overall survival decreased with increasing age at diagnosis, 10.4 months (age <50 years) to 9.1 months (age 50–70 years) to 6.4 months (age >70 years) controlling for stage, sex, race, radiation, and surgery (P < 0.001). Increasing age negatively predicted the odds of receiving both surgery and radiation and increased the likelihood of refusing surgery. Conclusions Treatment disparities exist by age despite advances in radiation and surgical treatment. Increased treatment in the elderly will increase overall survival from pancreatic adenocarcinoma. PMID:22836862

  11. Genetic and Epigenetic Determinants of Lung Cancer Subtype: Adenocarcinoma to Small Cell Conversion

    DTIC Science & Technology

    2015-08-01

    AWARD NUMBER: W81XWH-14-1-0223 TITLE: Genetic and Epigenetic Determinants of Lung Cancer Subtype: Adenocarcinoma to Small Cell Conversion...COVERED 1Aug2014 - 31Jul2015 4. TITLE AND SUBTITLE Genetic and Epigenetic Determinants of Lung Cancer Subtype: 5a. CONTRACT NUMBER W81XWH-14-1-0223...histologies of lung cancer is made difficult in part because of the extensive genetic and epigenetic changes that occur in lung carcinogenesis, the

  12. Mismatch repair status may predict response to adjuvant chemotherapy in resectable pancreatic ductal adenocarcinoma.

    PubMed

    Riazy, Maziar; Kalloger, Steve E; Sheffield, Brandon S; Peixoto, Renata D; Li-Chang, Hector H; Scudamore, Charles H; Renouf, Daniel J; Schaeffer, David F

    2015-10-01

    Deficiencies in DNA mismatch repair have been associated with inferior response to 5-FU in colorectal cancer. Pancreatic ductal adenocarcinoma is similarly treated with pyrimidine analogs, yet the predictive value of mismatch repair status for response to these agents has not been examined in this malignancy. A tissue microarray with associated clinical outcome, comprising 254 resected pancreatic ductal adenocarcinoma patients was stained for four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2). Mismatch repair deficiency and proficiency was determined by the absence or presence of uniform nuclear staining in tumor cells, respectively. Cases identified as mismatch repair deficient on the tissue microarray were confirmed by immunohistochemistry on whole slide sections. Of the 265 cases, 78 (29%) received adjuvant treatment with a pyrimidine analog and 41 (15%) showed a mismatch repair-deficient immunoprofile. Multivariable disease-specific survival in the mismatch repair-proficient cohort demonstrated that adjuvant chemotherapy, regional lymph-node status, gender, and the presence of tumor budding were significant independent prognostic variables (P≤0.04); however, none of the eight clinico-pathologic covariates examined in the mismatch repair-deficient cohort were of independent prognostic significance. Univariable assessment of disease-specific survival revealed an almost identical survival profile for both treated and untreated patients with a mismatch repair-deficient profile, while treatment in the mismatch repair-proficient cohort conferred a greater than 10-month median disease-specific survival advantage over their untreated counterparts (P=0.0018). In this cohort, adjuvant chemotherapy with a pyrimidine analog conferred no survival advantage to mismatch repair-deficient pancreatic ductal adenocarcinoma patients. Mismatch repair immunoprofiling is a feasible predictive marker in pancreatic ductal adenocarcinoma patients, and further prospective

  13. Ureteroiliac fistula secondary to radiotherapy in a patient with single renal metastasis of colon adenocarcinoma

    PubMed Central

    Dormeus, Sarah; Hernández, Erick A.; Nicolazzi, Mickaël; Barba, Javier F.; Algarra, Rubén; Tienza, Antonio; Pascual, Juan I.; Berián, José M.; Zudaire, Juan J.

    2013-01-01

    We report the case of a 61-year-old man diagnosed in 2001 with rectal cancer (stage T3N1M0). The patient was treated with surgery, adjuvant chemotherapy and radiotherapy. In 2009, he was admitted to the urology department with a complaint of right hemiabdominal pain. The anatomopathological investigation reported renal metastasis of colon adenocarcinoma. After surgery, he received adjuvant chemotherapy. No tumour recurrence or metastasis was reported at the 22-month follow-up. PMID:23671507

  14. Increased expression of S100A4, a metastasis-associated gene, in human colorectal adenocarcinomas.

    PubMed

    Takenaga, K; Nakanishi, H; Wada, K; Suzuki, M; Matsuzaki, O; Matsuura, A; Endo, H

    1997-12-01

    The S100A4 gene (also known as pEL98/mts1/p9Ka/18A2/42A/calvasculin /FSP1/CAPL) encoding an S100-related calcium-binding protein is implied to be involved in the invasion and metastasis of murine tumor cells. In the present study, the expression of S100A4 in human colorectal adenocarcinoma cell lines (SW837, LoVo, DLD-1, HT-29, SW480, SW620, WiDr, and Colo201) and surgically resected neoplastic tissues was examined to investigate whether S100A4 plays a role in the invasion and metastasis of human tumor cells. Northern blot analysis using total RNA isolated from the adenocarcinoma cell lines revealed that five of the eight cell lines expressed substantial amounts of S100A4 mRNA. Normal colon fibroblasts (CCD-18Co) expressed little of the RNA. Using surgically resected specimens, it seemed that the amount of S100A4 mRNA in adenomas was nearly equal to that in normal colonic mucosa, whereas adenocarcinomas expressed a significantly higher amount of the RNA than did the adjacent normal colonic mucosa. Immunohistochemical analysis using formalin-fixed paraffin-embedded surgical specimens and monoclonal anti-S100A4 antibody demonstrated that none of 12 adenoma specimens were immunopositive, whereas 8 of 18 (44%) focal carcinomas in carcinoma in adenoma specimens and 50 of 53 (94%) adenocarcinoma specimens were immunopositive. Interestingly, the incidence of immunopositive cells increased according to the depth of invasion, and nearly all of the carcinoma cells in 14 metastases in the liver were positive. These results suggest that S100A4 may be involved in the progression and the metastatic process of human colorectal neoplastic cells.

  15. Preclinical Modeling of KIF5B-RET Fusion Lung Adenocarcinoma.

    PubMed

    Huang, Qingling; Schneeberger, Valentina E; Luetteke, Noreen; Jin, Chengliu; Afzal, Roha; Budzevich, Mikalai M; Makanji, Rikesh J; Martinez, Gary V; Shen, Tao; Zhao, Lichao; Fung, Kar-Ming; Haura, Eric B; Coppola, Domenico; Wu, Jie

    2016-10-01

    RET fusions have been found in lung adenocarcinoma, of which KIF5B-RET is the most prevalent. We established inducible KIF5B-RET transgenic mice and KIF5B-RET-dependent cell lines for preclinical modeling of KIF5B-RET-associated lung adenocarcinoma. Doxycycline-induced CCSP-rtTA/tetO-KIF5B-RET transgenic mice developed invasive lung adenocarcinoma with desmoplastic reaction. Tumors regressed upon suppression of KIF5B-RET expression. By culturing KIF5B-RET-dependent BaF3 (B/KR) cells with increasing concentrations of cabozantinib or vandetanib, we identified cabozantinib-resistant RET(V804L) mutation and vandetanib-resistant-RET(G810A) mutation. Among cabozantinib, lenvatinib, ponatinib, and vandetanib, ponatinib was identified as the most potent inhibitor against KIF5B-RET and its drug-resistant mutants. Interestingly, the vandetanib-resistant KIF5B-RET(G810A) mutant displayed gain-of-sensitivity (GOS) to ponatinib and lenvatinib. Treatment of doxycycline-induced CCSP-rtTA/tetO-KIF5B-RET bitransgenic mice with ponatinib effectively induced tumor regression. These results indicate that KIF5B-RET-associated lung tumors are addicted to the fusion oncogene and ponatinib is the most effective inhibitor for targeting KIF5B-RET in lung adenocarcinoma. Moreover, this study finds a novel vandetanib-resistant RET(G810A) mutation and identifies lenvatinib and ponatinib as the secondary drugs to overcome this vandetanib resistance mechanism. Mol Cancer Ther; 15(10); 2521-9. ©2016 AACR.

  16. Pulmonary adenocarcinoma mutation profile in smokers with smoking-related interstitial fibrosis.

    PubMed

    Primiani, Andrea; Dias-Santagata, Dora; Iafrate, A John; Kradin, Richard L

    2014-01-01

    Cigarette smoking is an established cause of lung cancer. However, pulmonary fibrosis is also an independent risk factor for the development of lung cancer. Smoking-related interstitial fibrosis (SRIF) has recently been reported. We hypothesized that adenocarcinomas in lungs with SRIF might show distinct molecular changes and examined the molecular phenotype of 168 resected lung adenocarcinomas in lungs with and without SRIF. The diagnosis of SRIF was determined by histological examination, based on the presence of alveolar septal thickening, due to pauci-inflamed, hyalinized, "ropy" collagen, in areas of lung greater than 1 cm away from the tumor. Tumors were concomitantly examined genotypically for mutations in genes frequently altered in cancer, including EGFR and KRAS, by SNaPshot and by fluorescence in situ hybridization for possible ALK rearrangements. Fluorescence in situ hybridization for ROS1 rearrangement (n=36) and/or MET amplification (n=31) were performed when no mutation was identified by either SNaPshot or ALK analysis. Sixty-five cases (38.7%) showed SRIF, which was distributed in all lobes of the lungs examined. No differences were observed in sex, average age, or smoking history in patients with and without SRIF. There was no difference in either the percent or types of adenocarcinoma genetic mutations in patients with SRIF versus those without. This data suggests that SRIF does not represent an independent risk factor for the development of the major known and targeted mutations seen in pulmonary adenocarcinoma. However, additional research is required to investigate the potential significance of SRIF in the pathogenesis of lung cancer.

  17. Laparoscopic transhiatal approach for resection of an adenocarcinoma in long-segment Barrett’s esophagus

    PubMed Central

    Shiozaki, Atsushi; Fujiwara, Hitoshi; Konishi, Hirotaka; Kinoshita, Osamu; Kosuga, Toshiyuki; Morimura, Ryo; Murayama, Yasutoshi; Komatsu, Shuhei; Kuriu, Yoshiaki; Ikoma, Hisashi; Nakanishi, Masayoshi; Ichikawa, Daisuke; Okamoto, Kazuma; Sakakura, Chouhei; Otsuji, Eigo

    2015-01-01

    Barrett’s esophagus (BE) is a precursor of esophageal adenocarcinoma and is associated with gastroesophageal reflux disease, which is often preceded by a hiatal hernia. We describe a case of esophageal adenocarcinoma arising in long-segment BE (LSBE) associated with a hiatal hernia that was successfully treated with a laparoscopic transhiatal approach (LTHA) without thoracotomy. The patient was a 42-year-old male who had previously undergone laryngectomy and tracheal separation to avoid repeated aspiration pneumonitis. An ulcerative lesion was found in a hiatal hernia by endoscopy and superficial esophageal cancer was also detected in the lower thoracic esophagus. The histopathological diagnosis of biopsy samples from both lesions was adenocarcinoma. There were difficulties with the thoracic approach because the patient had severe kyphosis and muscular contractures from cerebral palsy. Therefore, we performed subtotal esophagectomy by LTHA without thoracotomy. Using hand-assisted laparoscopic surgery, the esophageal hiatus was divided and carbon dioxide was introduced into the mediastinum. A hernial sac was identified on the cranial side of the right crus of the diaphragm and carefully separated from the surrounding tissues. Abruption of the thoracic esophagus was performed up to the level of the arch of the azygos vein via LTHA. A cervical incision was made in the left side of the permanent tracheal stoma, the cervical esophagus was divided, and gastric tube reconstruction was performed via a posterior mediastinal route. The operative time was 175 min, and there was 61 mL of intra-operative bleeding. A histopathological examination revealed superficial adenocarcinoma in LSBE. Our surgical procedure provided a good surgical view and can be safely applied to patients with a hiatal hernia and kyphosis. PMID:26269688

  18. Cryptolepine, isolated from Sida acuta, sensitizes human gastric adenocarcinoma cells to TRAIL-induced apoptosis.

    PubMed

    Ahmed, Firoj; Toume, Kazufumi; Ohtsuki, Takashi; Rahman, Mahmudur; Sadhu, Samir Kumar; Ishibashi, Masami

    2011-01-01

    Bioassay guided separation of Sida acuta whole plants led to the isolation of an alkaloid, cryptolepine (1), along with two kaempferol glycosides (2-3). Compound 1 showed strong activity in overcoming TRAIL-resistance in human gastric adenocarcinoma (AGS) cells at 1.25, 2.5 and 5 μm. Combined treatment of 1 and TRAIL sensitized AGS cells to TRAIL-induced apoptosis at the aforementioned concentrations.

  19. Pleural LDH as a prognostic marker in adenocarcinoma lung with malignant pleural effusion

    PubMed Central

    Verma, Akash; Phua, Chee Kiang; Sim, Wen Yuan; Algoso, Reyes Elmer; Tee, Kuan Sen; Lew, Sennen J. W.; Lim, Albert Y. H.; Goh, Soon Keng; Tai, Dessmon Y. H.; Kor, Ai Ching; Ho, Benjamin; Abisheganaden, John

    2016-01-01

    Abstract To study the performance of serum and pleural lactate dehydrogenase (LDH) level in predicting survival in patients with adenocarcinoma lung presenting with malignant pleural effusions (MPE) at initial diagnosis. Retrospective cohort study of the patient hospitalized for adenocarcinoma lung with MPE in year 2012. Univariate analyses showed lower pleural fluid LDH 667 (313–967) versus 971 (214–3800), P = 0.04, female gender 9 (100%) versus 27 (41.5%), P = 0.009, never smoking status 9 (100%) versus 36 (55.3%), P = 0.009, and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy 8 (89%) versus 26 (40%), P = 0.009 to correlate with survival of more than 1.7 year versus less than 1.7 year. In multivariate analysis, low pleural fluid LDH and female gender maintained significance. The pleural LDH level of ≤1500 and >1500 U/L discriminated significantly (P = 0.009) between survival. High pleural LDH (>1500 IU/L) predicts shorter survival (less than a year) in patients with adenocarcinoma lung presenting with MPE at the time of initial diagnosis. This marker may be clinically applied for selecting therapeutic modality directed at prevention of reaccumulation of MPE. Patients with low pleural LDH may be considered suitable for measures that provide more sustained effect on prevention of reaccumulation such as chemical pleurodesis or tunneled pleural catheter. PMID:27368006

  20. [Adenocarcinoma of anal canal. Report of a case and review of the literature].

    PubMed

    Pollastri, E; Brosutti, O; Montenovo, A; Bergero, A; Moroni, J

    1994-01-01

    Carcinomas of the anal channel includes only 2 to 6 per cent of all colorectal tumors. They are squamous cell carcinomas, cloacogenic carcinoma and unusually, adenocarcinomas. A 41 year old man in which an adenocarcinoma of the anal channel developed within a chronic perianal fistula, is presented. A review of the literature about adenocarcinoma or the anus is made, and then the incidence, probable etiologies, biologic behavior, clinical features, diagnosis, differential diagnosis and treatment are enunciated. This rare tumor is associated with chronic inflammatory disease of the anal channel because of its etiology (fistula-in-ano, condyloma acuminata), because of cellular changes that are perpetuated by local immunologic blockade. We conclude that any chronic inflammatory disease must be treated early and adequately to avoid metaplastic and frank neoplastic changes. A deep and early biopsy of any benign lesion must be made if it does not respond to treatment, and a histopathologic exam of any tissue resected in orificial surgery must be performed. We suggest to use the classification of histological typing used by the W.H.O. and the staging of cancer by the U.I.C.C. and A.J.C.C. (1987).

  1. Pathologic stratification of operable lung adenocarcinoma using radiomics features extracted from dual energy CT images

    PubMed Central

    Lee, Ho Yun; Sohn, Insuk; Kim, Hye Seung; Son, Ji Ye; Kwon, O Jung; Choi, Joon Young; Lee, Kyung Soo; Shim, Young Mog

    2017-01-01

    Purpose To evaluate the usefulness of surrogate biomarkers as predictors of histopathologic tumor grade and aggressiveness using radiomics data from dual-energy computed tomography (DECT), with the ultimate goal of accomplishing stratification of early-stage lung adenocarcinoma for optimal treatment. Results Pathologic grade was divided into grades 1, 2, and 3. Multinomial logistic regression analysis revealed i-uniformity and 97.5th percentile CT attenuation value as independent significant factors to stratify grade 2 or 3 from grade 1. The AUC value calculated from leave-one-out cross-validation procedure for discriminating grades 1, 2, and 3 was 0.9307 (95% CI: 0.8514–1), 0.8610 (95% CI: 0.7547–0.9672), and 0.8394 (95% CI: 0.7045–0.9743), respectively. Materials and Methods A total of 80 patients with 91 clinically and radiologically suspected stage I or II lung adenocarcinoma were prospectively enrolled. All patients underwent DECT and F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT, followed by surgery. Quantitative CT and PET imaging characteristics were evaluated using a radiomics approach. Significant features for a tumor aggressiveness prediction model were extracted and used to calculate diagnostic performance for predicting all pathologic grades. Conclusions Quantitative radiomics values from DECT imaging metrics can help predict pathologic aggressiveness of lung adenocarcinoma. PMID:27880938

  2. Mucinous adenocarcinoma of perianal region: an uncommon disease treated with neo-adjuvant chemo-radiation.

    PubMed

    Purkayastha, Abhishek; Sharma, Neelam; Dutta, Vibha; Bisht, Niharika; Pandya, Tejas

    2016-01-01

    Mucinous adenocarcinoma of the perianal region is an oncologic rarity posing a diagnostic and therapeutic dilemma for treating oncologists due to very few reported cases without definite therapeutic guidelines. It accounts for 2% to 3% of all gastrointestinal malignancies and are historically known to arise from chronic anal fistulas and ischiorectal or perianal abscesses. We hereby report a sporadic and interesting case of perianal mucinous adenocarcinoma in a 56-year-old male initially treated with alternative medicines and local surgery for recurrent fistula in ano of 2 years duration. He presented with complaints of discharging growth in perianal region, painful defecation associated with occasional blood mixed stools of 6 months duration. Incisional biopsy from the ulcer revealed mucinous adenocarcinoma. Contrast enhanced computed tomography (CT) scan and whole body positron emission tomography (PET) scan showed a localized perianal growth which was further confirmed with colonoscopy. With no pre-set treatment protocol for this rare entity, he was managed with neo-adjuvant concurrent chemo-radiation (CCRT) followed by abdominoperineal resection (APR) and adjuvant chemotherapy. Presently he is on 3 monthly follow-up since last 1 year post APR and adjuvant chemotherapy without any evidence of recurrence or distant metastasis. To the best of knowledge, our report may be one of the rarest cases of this disease entity where the duration of anal fistula was merely 2 years in contrast to the established criteria that the fistula precedes carcinoma by at least 10 years.

  3. The role of contrast-enhanced endoscopic ultrasound in pancreatic adenocarcinoma

    PubMed Central

    Săftoiu, Adrian; Vilmann, Peter; Bhutani, Manoop S.

    2016-01-01

    Contrast-enhanced endoscopic ultrasound (CE-EUS) allows characterization, differentiation, and staging of focal pancreatic masses. The method has a high sensitivity and specificity for the diagnosis of pancreatic adenocarcinoma which is visualized as hypo-enhanced as compared to the rest of the parenchyma while chronic pancreatitis and neuroendocrine tumors are generally either iso-enhanced or hyper-enhanced. The development of contrast-enhanced low mechanical index harmonic imaging techniques used in real time during endoscopic ultrasound (EUS) allowed perfusion imaging and the quantification of intensity of the contrast signal through time-intensity curve analysis. Thus, contrast harmonic imaging-EUS has been used to differentiate pancreatic adenocarcinoma based on lower values of the peak enhancement. Future applications of CE-EUS in pancreatic adenocarcinoma include not only use of targeted contrast agents for early detection, tridimensional and fusion techniques for enhanced staging and resectability assessment but also novel applications of perfusion imaging for monitoring ablative therapy, improved local detection through EUS-guided sampling of portal vein flow or enhanced drug delivery through sonoporation and ultrasound-induced release of the drugs locally. PMID:28000627

  4. Identification of feature genes for smoking-related lung adenocarcinoma based on gene expression profile data

    PubMed Central

    Liu, Ying; Ni, Ran; Zhang, Hui; Miao, Lijun; Wang, Jing; Jia, Wenqing; Wang, Yuanyuan

    2016-01-01

    This study aimed to identify the genes and pathways associated with smoking-related lung adenocarcinoma. Three lung adenocarcinoma associated datasets (GSE43458, GSE10072, and GSE50081), the subjects of which included smokers and nonsmokers, were downloaded to screen the differentially expressed feature genes between smokers and nonsmokers. Based on the identified feature genes, we constructed the protein–protein interaction (PPI) network and optimized feature genes using closeness centrality (CC) algorithm. Then, the support vector machine (SVM) classification model was constructed based on the feature genes with higher CC values. Finally, pathway enrichment analysis of the feature genes was performed. A total of 213 down-regulated and 83 up-regulated differentially expressed genes were identified. In the constructed PPI network, the top ten nodes with higher degrees and CC values included ANK3, EPHA4, FGFR2, etc. The SVM classifier was constructed with 27 feature genes, which could accurately identify smokers and nonsmokers. Pathways enrichment analysis for the 27 feature genes revealed that they were significantly enriched in five pathways, including proteoglycans in cancer (EGFR, SDC4, SDC2, etc.), and Ras signaling pathway (FGFR2, PLA2G1B, EGFR, etc.). The 27 feature genes, such as EPHA4, FGFR2, and EGFR for SVM classifier construction and cancer-related pathways of Ras signaling pathway and proteoglycans in cancer may play key roles in the progression and development of smoking-related lung adenocarcinoma. PMID:27994470

  5. Hyperplastic-like colon polyps that preceded microsatellite-unstable adenocarcinomas.

    PubMed

    Goldstein, Neal S; Bhanot, Punam; Odish, Eva; Hunter, Susan

    2003-06-01

    We compared hyperplastic-like polyps that preceded microsatellite-unstable adenocarcinomas to incidental hyperplastic polyps to identify distinguishing morphologic criteria. The study group included 106 hyperplastic-like, nonadenomatous, serrated polyps, most from the ascending colon in 91 patients; the control group included 106 rectosigmoid hyperplastic polyps from 106 patients in whom adenocarcinoma did not develop. Study group polyps had an expanded crypt proliferative zone, a serrated architectural outline that became apparent in the basilar crypt regions, basilar crypt dilation, inverted crypts, and a predominance of dysmaturational crypts (crypts with minimal cell maturation). In contrast, control group polyps had a proliferative zone confined to the basal crypt region, serrated architecture that became apparent in the superficial crypt region, rare to no basilar crypt dilation, and rare or no dysmaturational crypts. Hyperplastic-like polyps that preceded microsatellite-unstable adenocarcinomas had a distinctive constellation of morphologic features related to altered and decreased cell function and control that resulted in dysmaturational crypts. Dysmaturation constitutes a range of morphologic alterations, some of which overlap with incidental-type innocuous hyperplastic polyps. The morphologic features described herein provide initial guidelines to identify this potentially important subset of premalignant serrated-like polyps.

  6. [A case of poorly differentiated lung adenocarcinoma showing air-space consolidation caused by aerogenic metastasis].

    PubMed

    Fujita, Kazue; Kurihara, Takeyuki; Ohba, Hideo; Nakamura, Junichi; Okimoto, Niro

    2004-05-01

    A 78-year-old woman was admitted to our hospital because of dyspnea. A chest radiograph and a computed tomogram on admission showed air-space consolidation in the left upper lung field, and so pneumonia was diagnosed. Although antibiotics were administered, the air-space consolidation did not improve. A transbronchial lung biopsy was performed, yielding a pathologic diagnosis of poorly differentiated lung adenocarcinoma. Despite combination chemotherapy with docetaxel and UFT, the air-space consolidation expanded, and the patient finally died of respiratory failure 3 months after diagnosis. Autopsy revealed air-space consolidation due to poorly differentiated lung adenocarcinoma, with large atypical cells diffusely floating in the alveolar spaces. It has been recognized that bronchiolo-alveolar carcinoma and well-differentiated lung adenocarcinoma present with air-space consolidation, reflecting the cancer cells lining the alveolar walls. However, in this case, the air-space consolidation was due to cancer cells diffusely floating in the alveolar spaces in aerogenic metastasis. It was considered that this is a rare case, which presented with a very interesting development pattern.

  7. Roles of histamine on the expression of aldehyde dehydrogenase 1 in endometrioid adenocarcinoma cell line.

    PubMed

    Wang, Yi; Jiang, Yang; Ikeda, Jun-Ichiro; Tian, Tian; Sato, Atsushi; Ohtsu, Hiroshi; Morii, Eiichi

    2014-10-01

    Cancer-initiating cells (CICs) are a limited number of cells that are essential for maintenance, recurrence, and metastasis of tumors. Aldehyde dehydrogenase 1 (ALDH1) has been recognized as a marker of CICs. We previously reported that ALDH1-high cases of uterine endometrioid adenocarcinoma showed poor prognosis, and that ALDH1 high population was more tumorigenic, invasive, and resistant to apoptosis than ALDH1 low population. Histamine plays a critical role in cancer cell proliferation, migration, and invasion. Here, we examined the effect of histamine on ALDH1 expression in endometrioid adenocarcinoma cell line. The addition of histamine increased ALDH1 high population, which was consistent with the result that histamine enhanced the invasive ability and the resistance to anticancer drug. Among 4 types of histamine receptors, histamine H1 and H2 receptor (H1R and H2R) were expressed in endometrioid adenocarcinoma cell line. The addition of H1R agonist but not H2R agonist increased ALDH1. The antagonist H1R but not H2R inhibited the effect of histamine on ALDH1 expression. These results indicated that histamine increased the expression of ALDH1 via H1R but not H2R. These findings may provide the evidence for exploring a new strategy to suppress CICs by inhibiting ALDH1 expression with histamine.

  8. External assessment of the Early Mortality Risk Score in patients with adenocarcinoma undergoing pancreaticoduodenectomy

    PubMed Central

    Joliat, Gaëtan-Romain; Petermann, David; Demartines, Nicolas; Schäfer, Markus

    2015-01-01

    Background Pancreaticoduodenectomies (PD) still have a substantial mortality rate. Recently, different scores have been published to predict the mortality risk pre-operatively after PD. This retrospective study was designed to perform an external assessment of an Early Mortality Risk Score (EMRS). Methods From 2000 to 2012, all PD cases performed at our institution were documented. Only patients treated for pancreatic head adenocarcinomas were included. Survival time and EMRS (based on age, tumour size, tumour differentiation and comorbidities) were calculated for every patient. Relative risks (RR) of early death 9 and 12 months after PD were then calculated. Results Of 270 PD for various aetiologies, 120 PD for adenocarcinomas were included. The median follow-up was 37 months, and the overall median survival was 19 months. EMRS of 4 showed a mortality RR of 5.1 at 9 months (P = 0.048) and of 4.5 at 12 months (P = 0.020). Conclusions EMRS of 4 is a predictor of tumour-related mortality at 9 and 12 months after PD for adenocarcinoma. The EMRS was externally assessed in our patient cohort and can be implemented in clinical practice. Clinical implications of this score still need to be studied. PMID:25906918

  9. Simultaneous Occurrence of Pancreatic Adenocarcinoma and Brunner's Gland Adenoma in a Siberian Tiger (Panthera tigris altaica).

    PubMed

    Gombač, M; Dolenšek, T; Jaušovec, D; Kvapil, P; Švara, T; Pogačnik, M

    2015-11-01

    We describe a case of pancreatic adenocarcinoma and Brunner's gland adenoma in an 18-year-old male Siberian tiger (Panthera tigris altaica) from the Ljubljana Zoo. The tiger was humanely destroyed due to weakness and progressive weight loss. Necropsy examination revealed a large, grey, predominantly necrotic mass replacing the major part of the pancreatic body. Microscopically, the mass was unencapsulated, poorly demarcated, highly cellular and composed of highly pleomorphic, cuboidal to tall columnar cells with basal, round or oval, moderately anisokaryotic nuclei with prominent nucleoli and moderate to large amounts of eosinophilic cytoplasm. The tumour was diagnosed as pancreatic tubular adenocarcinoma with infiltration into the duodenum and mesentery. There were tumour emboli in mesenteric blood vessels and hepatic metastases. The non-affected part of the pancreas exhibited severe chronic pancreatitis. In addition, one firm white neoplastic nodule was observed in the duodenal wall. The nodule was set in the tunica muscularis and was unencapsulated, well demarcated and highly cellular, and consisted of a closely packed layer of normal Brunner's glands and a centrally positioned group of irregularly branched tubules with small amounts of debris in the lumen. The neoplastic nodule was diagnosed as Brunner's gland adenoma. The present case is, to the best of our knowledge, the first report of concurrent pancreatic adenocarcinoma and Brunner's gland adenoma, most probably induced by chronic pancreatitis, either in man or animals.

  10. N-terminal truncated carboxypeptidase E expression is associated with poor prognosis of lung adenocarcinoma

    PubMed Central

    Sun, Jing; Meng, Dawei; Li, Li; Tian, Xin; Jia, Yunji; Wang, Hongyue; Yu, Huihui; Sun, Tiemin; Qu, Aibing; Shen, Hui; Bao, Jimin; Zhang, Guirong

    2016-01-01

    Lung cancer is a malignant tumor with high morbidity and mortality rates. To date, no suitable molecular diagnostic tool to predict disease recurrence and metastasis has been identified. The current study aimed to evaluate the potential of N-terminal truncated carboxypeptidase E (CPEΔN) to predict the recurrence and metastasis of lung adenocarcinoma. Western blotting revealed the co-expression of CPE and CPEΔN in the surgically collected pathological and pericarcinoma tissues tissues of 62.1% (59/95) lung adenocarcinoma patients. The full length CPE protein was predominantly expressed in pericarcinoma tissues and CPEΔN expression was identified in the pericarcinoma normal tissues of only 5.26% (5/95) patients. The 3-year postoperative recurrence and metastasis rates were significantly higher in patients with positive CPEΔN expression than in patients with negative CPEΔN expression (P=0.009). Furthermore, the overall survival rate of patients with predominant nuclear CPE expression was lower than that of patients with predominant cytoplasmic CPE expression (46.3 vs. 64.7%); however, no statistically significant difference was identified (P=0.125). Thus, the results of the current study indicated that CPEΔN may present a novel molecular biomarker for predicting recurrence and metastasis of lung adenocarcinoma, which may aid with stratifying patients by risk and thus, may facilitate individualized therapy. PMID:28101219

  11. Synchronous coexistence of liver metastases from cecal leiomyosarcoma and rectal adenocarcinoma: A case report

    PubMed Central

    Aoki, Hideki; Arata, Takashi; Utsumi, Masashi; Mushiake, Yutaka; Kunitomo, Tomoyoshi; Yasuhara, Isao; Taniguchi, Fumitaka; Katsuda, Koh; Tanakaya, Kohji; Takeuchi, Hitoshi; Yamasaki, Rie

    2017-01-01

    Multiple liver tumors represent a challenging condition for abdominal surgeons both in the selection of technique and the rarity of diagnosis. There are no case reports on co-existence of liver metastases from both intestinal leiomyosarcoma and adenocarcinoma. The patient described in this report successfully underwent resection of both primary lesions and liver metastases in combination with chemotherapy. As for the leiomyosarcoma, the primary cecal lesion was revealed more than three years after the patient's first visit. Peritoneal, lymph-node, and lung recurrences were observed afterward, and thus surgeries on those regions were performed. Pathologically, the peritoneal and lung recurrences comprised leiomyosarcoma and the lymph-node recurrence was diagnosed as adenocarcinoma. Despite newly discovered multiple lung recurrences and regional lymph-node metastases, the patient lived a normal life for 73 mo after the initial operation based on multidisciplinary therapy. He ultimately died of liver failure due to invasive lymph-node recurrence from the rectal adenocarcinoma, in addition to multiple lung recurrences from the leiomyosarcoma. Hepatic recurrence did not occur in this patient's case, which appears to be one reason for his long-term survival. PMID:28321173

  12. Metastatic Colonic Adenocarcinoma in Breast: Report of Two Cases and Review of the Literature

    PubMed Central

    Kothadia, Jiten P.; Arju, Rezina; Kaminski, Monica; Ankireddypalli, Arvind; Duddempudi, Sushil; Chow, Jonathan; Giashuddin, Shah

    2015-01-01

    Metastatic adenocarcinoma to the breast from an extramammary site is extremely rare. In the literature, the most current estimate is that extramammary metastases account for only 0.43% of all breast malignancies and that, of these extramammary sites, colon cancer metastases form a very small subset. Most commonly seen metastasis in breast is from a contralateral breast carcinoma, followed by metastasis from hematopoietic neoplasms, malignant melanoma, sarcoma, lung, prostate, and ovary and gastric neoplasms. Here we present two rare cases, in which colonic adenocarcinomas were found to metastasize to the breast. In both cases, core biopsies were obtained from the