Science.gov

Sample records for desmoid tumors results

  1. [Desmoid tumors].

    PubMed

    Montagliani, L; Duverger, V

    2008-01-01

    Desmoid tumors are a rare form of malignancy with a great propensity for local extension and recurrence. They typically occur in the abdominal wall or within the abdomen but also may occur extra-abdominally. Most cases are sporadic but traumatic, hormonal, and genetic etiologies have been implicated. The only curative treatment is wide surgical excision, but the risk of local recurrence is high. Several adjuvant or complementary treatments have been proposed and the results show promise; the authors review all these therapies. PMID:18438278

  2. Genetics Home Reference: desmoid tumor

    MedlinePlus

    ... in my area? Other Names for This Condition aggressive fibromatosis deep fibromatosis desmoid fibromatosis familial infiltrative fibromatosis ... catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumors). Am J Pathol. 1997 Aug; ...

  3. Desmoid Tumors in Pregnant and Postpartum Women

    PubMed Central

    Robinson, William A.; McMillan, Colette; Kendall, Amy; Pearlman, Nathan

    2012-01-01

    We report here a review of the current medical literature on pregnancy associated desmoids, including 10 cases of our own. The pertinent findings are that a large percentage of desmoids in females arise in and around pregnancy. Most occur in the abdominal muscles, particularly the right rectus abdominus, perhaps related to trauma from abdominal stretching and fetal movement. While these tumors may regress spontaneously after delivery most can be surgically resected with low recurrence rates even with R1 resections and this is clearly the treatment of choice. Subsequent pregnancies do not appear to result in recurrence in either FAP or non FAP patients. It is not clear from currently available data whether pregnancy associated desmoids are molecularly distinct from other desmoids. PMID:24213235

  4. The Role of Radiotherapy in the Treatment of Primary or Recurrent Desmoid Tumors and Long-Term Results

    PubMed Central

    Ergen, Şefika Arzu; Tiken, Elif Eda; Öksüz, Didem Çolpan; Dinçbaş, Fazilet Öner; Dervişoğlu, Sergülen; Mandel, Nil Molinas; Hız, Murat; Koca, Sedat

    2016-01-01

    Background: Desmoid tumors are uncommon and benign mesenchymal neoplasms. The optimal treatment of patients with desmoid tumors is still controversial. Surgery is the primary treatment for locally invasive or recurrent desmoid tumors. Also, radiotherapy is a treatment option for patients at high risk for local failure such as those with positive margins or recurrent and unresectable tumors. Aims: To report our institutional experience and long-term results of patients with desmoid tumors who received radiotherapy. Study Design: Retrospective cross-sectional study. Methods: Between 1980 and 2009, 20 patients who received radiotherapy (RT) in our institution were analyzed. The majority of patients (80%) were referred with a recurrent tumor after previous surgery. Thirteen patients underwent marginal resection, 4 had wide local excision and 3 patients had only biopsy. Resection margin was positive in 15 (75%) patients. All patients received radiation therapy. The median prescribed dose was 60 Gy. Five patients received less than 54 Gy. Results: The median follow-up time was 77.5 months (28–283 months). Nine patients developed local recurrence after RT. Seven local failures (78%) were in field. Time to local recurrence ranged from 3–165 months (median 33 months). The 2–5 year local control (LC) rates were 80% and 69%, respectively. On univariate analysis, the 5 year local control rate was significantly better in the patients treated with ≥54 Gy than in patients who received <54 Gy (p=0.023). The most common acute side effect was grade 1–2 skin toxicity. As a late side effect of radiotherapy, soft tissue fibrosis was detected in 10 patients and lymphangitis was seen in 1 patient. One patient developed radiation-induced sarcoma. Conclusion: According to our results, radiotherapy is especially effective in recurrent disease and provides a high local control rate in the patients received more than 54 Gy. PMID:27308076

  5. Laparoscopic excision of abdominal wall desmoid tumor.

    PubMed

    Meshikhes, Abdul-Wahed; Al-Zahrani, Hana; Ewies, Tarek

    2016-02-01

    Open surgical resection is the mainstay treatment for desmoid tumors. Laparoscopic resection is rarely used and not well described in the literature. We report a case of a single, 35-year-old woman who presented with palpable abdominal wall desmoid tumor. The patient had had laparoscopic cholecystectomy 2 years earlier, and the tumor was at the insertion site of the right upper quadrant trocar. The diagnosis was made by a Tru-Cut biopsy at another institution, after the lesion had increased in size and caused increased discomfort. The patient underwent successful laparoscopic resection of the tumor. This report aimed to promote laparoscopic resection of abdominal wall desmoid tumors, whenever feasible, and describe the laparoscopic technique. We believe this is the second case of laparoscopic excision of desmoid tumor reported in the English-language literature. PMID:26781534

  6. Clinical significance of midkine expression in sporadic desmoid tumors

    PubMed Central

    KIM, HEE SUNG; KIM, JIN; NAM, KYUNG HAN; KIM, WOO HO

    2016-01-01

    The aim of the present study was to identify the prognostic factors for the propensity for recurrence in sporadic desmoid tumors. The catenin (cadherin-associated protein) β1 (CTNNB1) genotypes and expression of Wnt pathway proteins and midkine (also termed neurite growth-promoting factor 2) were investigated in 159 patients with sporadic desmoid tumors. Formalin-fixed paraffin-embedded tissues of the surgically resected desmoid tumors were examined by direct sequencing of CTNNB1 exon 3, and immunostained for the expression of β-catenin, T-cell factor 4 (TCF-4), phosphorylated protein kinase B (pAkt), midkine and menin using a tissue microarray method. Among the samples, 70% (111/159) exhibited point mutations of the CTNNB1 gene, including T41A (56%), S45F (8%), S45P (2%), S45N (2%) and T42A (1%). In addition, 100, 57, 24, 15 and 92% of the tumors expressed β-catenin, TCF-4, midkine, pAkt and menin, respectively. Positive midkine expression was significantly associated with the recurrence of tumors (P=0.001). The multivariate analysis of recurrence demonstrated that an extra-abdominal tumor site [hazard ratio (HR), 2.625; P=0.001] and midkine expression (HR, 2.077; P<0.009) were independent prognostic factors of tumor recurrence. In conclusion, the present results suggest that the tumor site and midkine expression may be predictive markers for the recurrence of sporadic desmoid tumors. PMID:26998061

  7. Simple resection of truncal desmoid tumors: A case series

    PubMed Central

    Nishida, Yoshihiro; Tsukushi, Satoshi; Urakawa, Hiroshi; Hamada, Shunsuke; Kozawa, Eiji; Ikuta, Kunihiro; Ishiguro, Naoki

    2016-01-01

    Desmoid tumors of the extra-abdominal and abdominal wall have been associated with morbidity due to the aggressive nature of the surgery and high recurrence rates. Surgery that does not cause functional impairment is desired for patients with desmoid tumors. In the present study, among patients with desmoid tumors who were prospectively and consecutively treated with identical conservative treatment with meloxicam, a selected patients of patients were treated with less invasive surgery than wide-resection. Out of 60 patients pathologically diagnosed with desmoid tumors, 9 patients with tumors refractory to conservative treatment and 4 patients who refused to receive this type of treatment were treated with planned simple resection. Subsequently, the clinical outcome of the patients and the mutational status of the catenin β-1 (CTNNB1) gene in the tumors were analyzed. The mean age of the 13 patients that underwent planned simple resection was 39 years, and the tumors were located in the abdominal wall in 6 cases, the chest wall in 4 cases and the neck in 3 cases. All excised specimens were evaluated and positive microscopic margins were identified; however, during the mean follow-up period of 30 months, 12/13 cases, 7 of which had T41A mutations and 5 of which had no mutations (wild-type), did not develop recurrence. Only 1 initial case with an S45F mutation in the CTNNB1 gene developed recurrence. The results of the present prospectively treated with simple resection and retrospectively analyzed study suggest that planned simple resection could serve as a therapeutic modality for extraperitoneal desmoid tumors, particularly truncal ones with a wild-type or T41A mutational status. PMID:27446472

  8. Bilateral desmoid tumor of the breast: case seriesand literature review

    PubMed Central

    Wongmaneerung, Phanchaporn; Somwangprasert, Areewan; Watcharachan, Kirati; Ditsatham, Chagkrit

    2016-01-01

    Background Desmoid tumor of the breast is very rare and locally aggressive but has no distant metastasis. Bilateral lesions are extremely rare, found in only 4% of patients. Two cases of bilateral desmoid tumor of the breast are reported. The clinical presentation, diagnosis, imaging, treatment, and follow-up outcomes of recurrence as well as a brief literature review are provided. Case reports Case 1 is a 31-year-old woman who presented with nipple retraction. An ultrasound revealed BIRAD V in both breasts. She underwent a bilateral excisional biopsy under ultrasound mark with the pathology result of extra-abdominal desmoid tumor in both breasts. The patient had a bilateral mastectomy with silicone implantation due to the involved margins by excision. She remained tumor free after 7-year follow-up. Case 2 is a 28-year-old woman who presented with a lump on her right breast that she had discovered ~2 months earlier. An ultrasound showed a spiculated mass in the right breast and some circumscribed hypoechoic masses in both breasts. A bilateral breast excision was done. The pathology result was an extra-abdominal desmoid tumor. She had recurrence on both sides and underwent a mastectomy and silicone implantation. The tumor has not recurred after 1-year follow-up. Conclusion Imaging cannot distinguish between benign breast lesions and malignancy. Pathology results are helpful in making a definitive diagnosis. Given that the desmoid tumor is locally aggressive, a local excision with clear margins is recommended. Chemotherapy and hormonal treatment are controversial. PMID:27578999

  9. Renographic Demonstration of Desmoid Tumor-Ureteral Fistula.

    PubMed

    Kim, David U; McQuinn, Garland; Lin, Eugene; Lee, Marie

    2016-01-01

    A 20-year-old woman with Gardner syndrome and intra-abdominal desmoid tumors presented with increasing abdominal pain. CT demonstrated a new area of central hypodensity in a presumed desmoid tumor, compressing the left ureter. Findings were suspicious for abscess or fistula to the ureter. Subsequent 99mTc-MAG3 renogram demonstrated persistent extraureteral radiotracer activity in the region of the tumor, confirming a desmoid tumor-ureteral fistula. Desmoid tumors are benign but locally aggressive fibrous neoplasms that can be sporadic or associated with familial adenomatous polyposis syndromes, specifically Gardner syndrome. Fistula formation to the ureter has been reported infrequently. PMID:26284772

  10. Desmoid Tumors: A Review of the Literature and Pharmacologic Management.

    PubMed

    Sivanesan, Eellan; Gitlin, Melvin C

    2016-06-01

    Desmoid tumors represent a nonmalignant proliferation of fibroblast-related cells. These rare tumors are difficult to treat and often persist as indolent, lifelong conditions. There are a number of treatments available for both anatomic and symptom regression. Some of these treatments, unfortunately, may not provide long-lasting results and may result in further complications. Pain is a distressing symptom that may be due to the tumor itself or the result of utilized treatments. Pharmacologic therapies represent a noninvasive alternative to surgical resection. Pain symptoms require therapeutic regimens that must be modified as the tumor evolves in expression. The individualized pain treatment program utilized may often reflect principles used in both nonmalignant and malignant pain management models. This review seeks to increase awareness of desmoid tumors through a review of the literature and discussion of its pharmacotherapeutic management. PMID:27159399

  11. EXTRA-ABDOMINAL DESMOID TUMOR: LOCAL RECURRENCE AND TREATMENT OPTIONS

    PubMed Central

    TEIXEIRA, LUIZ EDUARDO MOREIRA; ARANTES, EUGÊNIO COSTA; VILLELA, RAFAEL FREITAS; SOARES, CLAUDIO BELING GONÇALVES; COSTA, ROBERTO BITARÃES DE CARVALHO; ANDRADE, MARCO ANTÔNIO PERCOPE DE

    2016-01-01

    ABSTRACT Objective: To evaluate the rate of local recurrence of extra-abdominal desmoid tumor and compare the outcomes of surgical treatment and conservative treatment. Methods: Twenty one patients (14 women and seven men), mean age 33.0±8.7 years old, with a diagnosis of desmoid tumor were evaluated. The mean follow-up period was 58.5±29.0 months. Fourteen cases involved the lower limbs, four cases involved the upper limbs, and three cases involved the trunk. The average tumor size was 12.7±7.5 cm. Of the 21 patients, 14 did not undergo previous treatment and seven patients relapsed before the initial evaluation. Surgical treatment was performed in 16 patients and conservative treatment was performed in five patients. Results: Recurrence occurred in seven patients (33%) and six of them relapsed within the first 18 months. No significant difference was observed between conservative and surgical treatment. However, a significant difference was observed among patients undergoing wide resection and who experienced improved local control. Conclusion: The recurrence rate of desmoid tumor was 33.3%. There was no difference in recurrence between conservative and surgical treatment. In surgical treatment, wide margins showed better results for recurrence control. Level of Evidence III. Retrospective Observational Study. PMID:27217816

  12. Sporadic intra-abdominal desmoid tumor: a unusual presentation.

    PubMed

    Lasseur, Antoinette; Pasquer, Arnaud; Feugier, Patrick; Poncet, Gilles

    2016-01-01

    Desmoid tumors are rare potentially aggressive benign tumors. Various etiologies and recurrent factors have been presented and discussed. A case of an abdominal desmoid tumor with vascular mesenteric invasion in a 32-year-old female, over 2 years after pregnancy is presented. Pre-operative biopsy was not contributive, diagnosis was made after surgery. Resection required two vascular bypasses. Desmoid tumors appear frequently in women of child-bearing age (during or after pregnancy), hormonal signaling is probably involved, but pathways remain unknown. Multiple predictive factors of recurrence are discussed but not strongly identified due to underpowered studies: resection margins, age, sex, tumor's size and location. Recent development is in favor of a non-aggressive treatment such as 'wait and see' procedures. Without radical treatment, these tumors could generate bowel compression or perforation. Due to their location and high risk of complication, surgery is the most fitted option. PMID:27150282

  13. Sporadic intra-abdominal desmoid tumor: a unusual presentation

    PubMed Central

    Lasseur, Antoinette; Pasquer, Arnaud; Feugier, Patrick; Poncet, Gilles

    2016-01-01

    Desmoid tumors are rare potentially aggressive benign tumors. Various etiologies and recurrent factors have been presented and discussed. A case of an abdominal desmoid tumor with vascular mesenteric invasion in a 32-year-old female, over 2 years after pregnancy is presented. Pre-operative biopsy was not contributive, diagnosis was made after surgery. Resection required two vascular bypasses. Desmoid tumors appear frequently in women of child-bearing age (during or after pregnancy), hormonal signaling is probably involved, but pathways remain unknown. Multiple predictive factors of recurrence are discussed but not strongly identified due to underpowered studies: resection margins, age, sex, tumor’s size and location. Recent development is in favor of a non-aggressive treatment such as ‘wait and see’ procedures. Without radical treatment, these tumors could generate bowel compression or perforation. Due to their location and high risk of complication, surgery is the most fitted option. PMID:27150282

  14. Clinical outcomes of systemic therapy for patients with deep fibromatoses (desmoid tumors)

    PubMed Central

    de Camargo, Veridiana Pires; Keohan, Mary L.; D’Adamo, David R.; Antonescu, Cristina R.; Brennan, Murray F.; Singer, Samuel; Ahn, Linda S.; Maki, Robert G.

    2010-01-01

    Objectives We examined outcomes of patients with desmoid tumors receiving systemic therapy at a single institution to provide a basis for examination of newer agents. Methods We reviewed records of patients with desmoid tumors treated with chemotherapy at our institution. The activity of NSAIDs was not addressed. Patients without measurable disease, those receiving therapy we could not document, and those receiving prophylactic therapy were excluded. Results Sixty-eight patients received 157 lines of therapy. Nine patients died, 7 of progressive disease. The cohort was 62% female with median age 32.5, 32% with Gardner syndrome, median follow-up 63 months, and median of 2 lines of therapy. Intra-abdominal primary location was most common (44%). The greatest RECIST response rate was observed with anthracyclines and hormonal therapy and lowest with single agent dacarbazine/temozolomide or tyrosine kinase inhibitors, principally imatinib. In a multivariate analysis, only nodular gross morphology and presence of Gardner syndrome were the only tumor factors associated with greater time to progression. Conclusions Anti-estrogens and anthracycline-containing regimens are associated with a higher radiological response rate against desmoid tumors than other agents. Systemic therapy for desmoid tumors can be successful in patients with desmoids, and is a viable option in lieu of morbid or disabling surgery. PMID:20187095

  15. Desmoid tumor in Gardner's Syndrome presented as acute abdomen

    PubMed Central

    Hatzimarkou, Andreas; Filippou, Dimitrios; Papadopoulos, Vasilios; Filippou, Georgios; Rizos, Spiros; Skandalakis, Panagiotis

    2006-01-01

    Background Gardner's syndrome can occasionally be complicated with intra-abdominal desmoid tumor. These tumors usually remain asymptomatic but can exhibit symptoms due to intestinal, vascular and ureteral compression and obstruction. Case presentation A rare case of a 41-year-old male patient with Gardner's syndrome complicated with intra-abdominal desmoid tumor, which first presented as acute abdomen, is presented. Conclusion Extra-abdominal manifestations of Gardner's syndrome along with a palpable abdominal mass would raise suspicion for the presence of a desmoid tumor in the majority of cases. In life-threatening cases, surgical treatment should be considered as a palliative approach, though the extent of excision remains debatable PMID:16569244

  16. Desmoid tumor occurring after reconstruction mammaplasty for breast carcinoma.

    PubMed

    Dale, P S; Wardlaw, J C; Wootton, D G; Resnick, J I; Giuliano, A E

    1995-11-01

    We present a case of desmoid tumor associated with prior alloplastic breast reconstruction. Wide local excision that includes chest wall resection, if necessary, is the primary treatment of choice. Patients with extensive nonresectable or recurrent disease may benefit from radiation therapy. Systemic therapy is a possibility in certain cases, but its toxicity generally precludes its use with this nonmetastatic tumor. Although this is the fourth reported case of desmoid tumor arising after implantation of a silicone prosthesis, we cannot claim a causal relationship. Careful follow-up consisting of yearly physical and mammagraphic examinations may facilitate early diagnosis and treatment of locally aggressive desmoid tumors but is not warranted, except in the context of routine screening for breast carcinoma. PMID:8579271

  17. Role of Radiotherapy in the Management of Desmoid Tumors

    SciTech Connect

    Gluck, Iris; Griffith, Kent A.; Biermann, J. Sybil; Feng, Felix Y.; Lucas, David R.; Ben-Josef, Edgar

    2011-07-01

    Purpose: To identify high-risk patients with desmoid tumors who could benefit from postoperative radiotherapy (RT) and to determine the efficacy of postoperative and definitive RT. Materials and Methods: Retrospective analysis of clinical data for all patients with desmoid tumors who underwent definitive local therapy at the University of Michigan from 1984 through 2008. Estimates for local control were calculated using the product-limit method of Kaplan and Meier, and associations with patient, tumor, and RT characteristics were explored using Cox proportional hazard regression. Results: Treatment for 95 patients who qualified for the study included surgery, RT, or both in 54, 13, and 28 cases, respectively. With a median follow-up of 38 months, the actuarial 3-year local control (95% confidence interval [CI]) was not significantly different (p = 0.3) among the three treatment groups: 84.6% (70.2-92.4), 92.3% (56.6-98.9), and 69.0% (43.1-84.9), respectively. Tumor site in the head/neck (p = 0.03) and history of previous surgical therapy (p = 0.01) were associated with increased recurrence risk (HR = 2.8, 95% CI 1.1-7.4, and HR = 3.2, 95% CI = 1.3-7.8), whereas gender, age, use of RT, and positive margins were not (p > 0.2). Conclusions: Our findings suggest equivalent local control rates after surgery, RT, or a combination of both. Although history of previous surgical therapy or site of origin in the head/neck region were found to be associated with increased risk of recurrence after local therapy, there was no clear association between surgical margin status and local control.

  18. Desmoid tumors of the bilateral breasts in a patient without Gardner syndrome: a case report and review of literature.

    PubMed

    Brown, Charles S; Jeffrey, Brenda; Korentager, Richard; Hughes, Kenneth

    2012-08-01

    Desmoid tumors constitute 0.02% to 0.03% of all tumors. Consequently, few case reports exist for breast desmoids, even fewer identifying bilateral disease. We present a case report of a patient with bilateral breast desmoids and shoulder desmoid without evidence of FAP or Gardner syndrome. This case report explores the clinical, radiographic, pathologic, and treatment elements for desmoid tumors as well as a review of the literature. PMID:21629058

  19. Resection and Abdominal Wall Reconstruction of a Desmoid Tumor with Endometrioma Features

    PubMed Central

    Majors, Jaqueline; Stoikes, Nathaniel F.; Nejati, Reza

    2016-01-01

    Desmoid tumors are rare, musculoaponeurotic mesenchymal origin tumors arising from the proliferation of well-differentiated fibroblasts. Desmoid tumors may arise from any location with the abdominal cavity, abdominal wall and extremity locations being most frequent. We present the case of a 35-year-old female with a history of endometriosis who presented palpable abdominal mass and cyclic abdominal pain. Resection was performed for a presumed desmoid soft tissue tumor. Final pathology demonstrated desmoid histology admixed with abdominal wall endometriosis (endometrioma). This unique pathologic finding has only been rarely reported and is discussed with a brief review of the literature. PMID:27247824

  20. Resection and Abdominal Wall Reconstruction of a Desmoid Tumor with Endometrioma Features.

    PubMed

    Majors, Jaqueline; Stoikes, Nathaniel F; Nejati, Reza; Deneve, Jeremiah L

    2016-01-01

    Desmoid tumors are rare, musculoaponeurotic mesenchymal origin tumors arising from the proliferation of well-differentiated fibroblasts. Desmoid tumors may arise from any location with the abdominal cavity, abdominal wall and extremity locations being most frequent. We present the case of a 35-year-old female with a history of endometriosis who presented palpable abdominal mass and cyclic abdominal pain. Resection was performed for a presumed desmoid soft tissue tumor. Final pathology demonstrated desmoid histology admixed with abdominal wall endometriosis (endometrioma). This unique pathologic finding has only been rarely reported and is discussed with a brief review of the literature. PMID:27247824

  1. Multidisciplinary treatment of intra-thoracic desmoid tumors: Case series and narrative review

    PubMed Central

    Mátrai, Zoltán; Tóth, László; Szentirmay, Zoltán; Papp, János; Langmár, Zoltán; Kásler, Miklós

    2012-01-01

    Summary Background Primary intra-thoracic desmoids are exceedingly rare borderline tumors, with 34 reported cases in the English-language literature. The characteristic localized infiltrative growth and the high rate of recurrence can result in life-threatening conditions. Radical surgical resection is considered to be the primary treatment. Achieving negative surgical margins is a challenge. Cases with positive surgical margins are associated with a high rate of local recurrence; therefore, other multimodal approaches play a large role in their therapy. Case Reports The authors reviewed the relevant literature and presented examples of long-term follow-up of 3 intra-thoracic desmoid tumour patients, multidisciplinarily treated between 2000 and 2008. All reports of intra-thoracic desmoid tumors that the authors could find on PubMed or in the reference sections of these PubMed located articles were included using the search terms: intra-thoracic, desmoid, aggressive fibromatoses. Conclusions Because of the rarity of the disease and the heterogeneity of the cases, it is difficult to assess the importance of the information for everyday clinical practice. It does however provide a useful guide for reference. PMID:22367132

  2. Desmoid tumors: local control and patterns of relapse following radiation therapy

    SciTech Connect

    Leibel, S.A.; Wara, W.M.; Hill, D.R.; Bovill, E.G. Jr.; De Lorimier, A.A.; Beckstead, J.H.; Phillips, T.L.

    1983-08-01

    Desmoid tumors are benign neoplasms, arising from musculoaponeurotic tissues, which tend to be locally infiltrative, resulting in a high rate of local recurrence following surgical resection. Nineteen patients with desmoid tumors underwent radiation therapy at the University of California, San Francisco, between 1970 and 1980. Fifteen patients were referred with local recurrence following one or more surgical resections. Three patients were referred for initial radiation therapy with unresectable tumors, and one patient received planned postoperative irradiation following subtotal tumor resection. At the time of treatment, 8 patients had nonresectable disease measuring greater than 10 cm. The majority of patients were treated to a tumor dose of 50 to 55 Gy at 1.6 to 1.8 Gy per fraction. With a median follow-up of 8 years, 13 patients remained free of recurrent disease following radiation therapy. Local control was not related to the amount of disease present at the time of treatment. Of the 6 patients who developed recurrent disease, only 1 patient had a true in-field recurrence. Four patients recurred at the margin of the radiation field 1 to 5 years following therapy. Moderate dose radiation therapy to desmoid tumors can result in lasting local control when surgical resection is not possible. Post operative radiation can improve the rate of local control for patients with a high risk of recurrence. As desmoid tumors tend to be locally infiltrative, fields must be very generous to prevent marginal recurrence. Systemic chemotherapy offers an alternative to ablative surgery in the event of local failure following radiation therapy.

  3. Radiation-induced Sarcomas Occurring in Desmoid-type Fibromatosis Are Not Always Derived From the Primary Tumor.

    PubMed

    Verschoor, Arie J; Cleton-Jansen, Anne-Marie; Wijers-Koster, Pauline; Coffin, Cheryl M; Lazar, Alexander J; Nout, Remi A; Rubin, Brian P; Gelderblom, Hans; Bovée, Judith V M G

    2015-12-01

    Desmoid-type fibromatosis is a rare, highly infiltrative, locally destructive neoplasm that does not metastasize, but recurs often after primary surgery. Activation of the Wnt/β-catenin pathway is the pathogenic mechanism, caused by an activating mutation in exon 3 of CTNNB1 (85% of the sporadic patients). Radiotherapy is a frequent treatment modality with a local control rate of approximately 80%. In very rare cases, this may result in the development of radiation-induced sarcoma. It is unclear whether these sarcomas develop from the primary tumor or arise de novo in normal tissue. In 4 tertiary referral centers for sarcoma, 6 cases of desmoid-type fibromatosis that subsequently developed sarcoma after radiotherapy were collected. The DNA sequence of CTNNB1 exon 3 in the desmoid-type fibromatosis and the subsequent postradiation sarcoma was determined. Sarcomas developed 5 to 21 years after the diagnosis of desmoid-type fibromatosis and included 2 osteosarcomas, 2 high-grade undifferentiated pleomorphic sarcomas, 1 fibrosarcoma, and 1 undifferentiated spindle cell sarcoma. Three patients showed a CTNNB1 hotspot mutation (T41A, S45F, or S45N) in both the desmoid-type fibromatosis and the radiation-induced sarcoma. The other 3 patients showed a CTNNB1 mutation in the original desmoid-type fibromatosis (2 with a T41A and 1 with an S45F mutation), which was absent in the sarcoma. In conclusion, postradiation sarcomas that occur in the treatment area of desmoid-type fibromatosis are extremely rare and can arise through malignant transformation of CTNNB1-mutated desmoid fibromatosis cells, but may also originate from CTNNB1 wild-type normal cells lying in the radiation field. PMID:26414222

  4. Current Perspectives on Desmoid Tumors: The Mayo Clinic Approach

    PubMed Central

    Joglekar, Siddharth B.; Rose, Peter S.; Sim, Franklin; Okuno, Scott; Petersen, Ivy

    2011-01-01

    Desmoid tumors are a rare group of locally aggressive, non malignant tumors of fibroblastic origin that can lead to significant morbidity due to local invasion. Despite advances in the understanding of these tumors, their natural history is incompletely understood and the optimal treatment is still a matter of debate. Local control is the main goal of treatment and there has been a change in philosophy regarding the management of these tumors from aggressive surgical resection to function preservation. A multidisciplinary approach is essential to plan local control with acceptable morbidity. The current Mayo Clinic algorithm for the treatment of these tumors is based on institutional experience and the available evidence in the literature: asymptomatic/non progressive lesions away from vital structures are managed with observation and regular imaging; primary or recurrent desmoid tumors which are symptomatic or progressive or near vital structures are managed with wide surgical resection when wide surgical margins are possible with minimal functional and cosmetic loss. When positive or close surgical margins are likely, surgical resection with adjuvant radiotherapy or definitive radiotherapy is preferred. If likely functional or cosmetic deficit is unacceptable, radiotherapy is the treatment of choice. Unresectable lesions are considered for radiotherapy, chemotherapy or newer modalities however an unresectable lesion associated with a painful, functionless, infected extremity is managed with an amputation. PMID:24212949

  5. Mediastinal Desmoid Tumor With Remarkably Rapid Growth: A Case Report.

    PubMed

    Lee, Joon Hyung; Jeong, Jae Seok; Kim, So Ri; Jin, Gong Yong; Chung, Myoung Ja; Kuh, Ja Hong; Lee, Yong Chul

    2015-12-01

    Desmoid tumors (DTs) are a group of rare and benign soft tissue tumors that result from monoclonal proliferation of well-differentiated fibroblasts. Since DTs tend to infiltrate and compress adjacent structures, the location of DTs is one of the most crucial factors for determining the severity of the disease. Furthermore, DTs can further complicate the clinical course of patients when the growth is remarkably rapid, especially for DTs occurring in anatomically critical compartments, including the thoracic cavity.The authors report a case of a 71-year-old man with a known mediastinal mass incidentally detected 4 months ago, presenting dyspnea with right-sided atelectasis and massive pleural effusion. Imaging studies revealed a 16.4 × 9.4-cm fibrous mass with high glucose metabolism in the anterior mediastinum. The mass infiltrated into the chest wall and also displaced the mediastinum contralaterally. Interestingly, the tumor had an extremely rapid doubling time of 31.3 days.En bloc resection of the tumor was performed as a curative as well as a diagnostic measure. Histopathologic examination showed spindle cells with low cellularity and high collagen deposition in the stroma. Immunohistochemical staining was positive for nuclear β-catenin. Based on these pathologic findings, the mass was diagnosed as DT. After surgery, there has been no evidence of recurrence of disease in the patient.This patient presents a mediastinal DT with extremely rapid growth. Notably, the doubling time of DT in our case was the shortest among reported cases of DT. Our experience also highlights the benefits of early interventional strategy, especially for rapidly growing DTs in the thoracic cavity. PMID:26717381

  6. [A Case of a Desmoid Tumor the Developed Around Ileostomy in a Patient with FAP].

    PubMed

    Chika, Noriyasu; Kumamoto, Kensuke; Suzuki, Okihide; Yamamoto, Azusa; Tajima, Yusuke; Watanabe, Yuichiro; Onozawa, Hisashi; Matsuzawa, Takeaki; Eguchi, Hidetaka; Ishibashi, Keiichiro; Mochiki, Erito; Ishida, Hideyuki

    2015-11-01

    A 21-year-old woman who underwent laparoscopic total colectomy for familial adenomatous polyposis (FAP) 1 year 3 months previously presented with a mass larger than 10 cm around the ileostomy. Multiple tumors in the mesentery around the ileostomy and anterior to the sacrum, accompanied by bilateral hydronephrosis, were detected by computed tomography. The patient was diagnosed with intraabdominal desmoid tumors, stage Ⅳ according to the Church's classification. The desmoid tumor (15×9 cm) around the ileostomy was completely resected surgically, whereas another desmoid tumor (5×4 cm) was incompletely resected. We found a desmoid tumor of more than 10 cm in size and many fibromatous plaques in the mesentery. We then performed 4 courses of systemic chemotherapy with dacarbazine and doxorubicin in for the residual desmoid tumors after surgery. There was no growth of the residual desmoid tumors for 12 months after chemotherapy. Genetic tests detected a pathogenic germline mutation of the APC gene in the high-risk region of the desmoid tumor. We also confirmed somatic mutations in the resected specimens. PMID:26805226

  7. Desmoid Tumor of the Pancreas: Case Report and Review of a Rare Entity.

    PubMed

    Gerleman, Roxana; Mortensen, Michael Bau; Detlefsen, Sönke

    2015-10-01

    Desmoid tumors, also known as desmoid-type fibromatoses or aggressive fibromatoses, are clonal fibroblastic proliferations that arise in the deep soft tissues. They are characterized by infiltrative growth, a tendency toward local recurrence and the inability to metastasize. We present a case of a 63-year-old woman who complained of abdominal pain, and a contrast-enhanced computed tomography scan revealed a well-circumscribed tumor in the pancreatic tail, measuring 5.1 cm. A left-sided, spleen-preserving pancreatic resection was performed, and pathological analysis showed a mesenchymal tumor. The diagnosis of a pancreatic desmoid tumor was made based on the characteristic morphology and the immune phenotype of the tumor. The English-language literature on pancreatic desmoid tumors was reviewed. In total, 16 previous cases were identified. PMID:26215223

  8. Desmoid tumors: clinical features and treatment options: a case report and a review of literature

    PubMed Central

    Jenayah, Amel Achour; Bettaieb, Hajer; Saoudi, Sarra; Gharsa, Anissa; Sfar, Ezzeddine; Boudaya, Fethia; Chelli, Dalenda

    2015-01-01

    Desmoid tumors are a rare group of locally aggressive, non malignant tumors of fibroblastic origin that can lead to significant morbidity due to local invasion and may even result in a fatal outcome when located around vital organs. Their clinical presentation, biological behavior and natural history can be quite varied and is incompletely understood at the present time. The optimal therapeutic approach depends on various factors, and a multidisciplinary approach is necessary to achieve local control with acceptable morbidity. Despite progress in the understanding of these tumors and the treatment options, local recurrence remains a major problem. PMID:26516394

  9. Recurrent desmoid tumor of the mediastinum: A case report

    PubMed Central

    XIE, YUXIN; XIE, KEQI; GOU, QIHENG; HE, JINLAN; ZHONG, LAN; WANG, YONGSHENG

    2014-01-01

    Desmoid tumors (DTs) are rare, benign soft-tissue tumors that have the potential for local invasion, but not for metastasis. The tumors are commonly characterized by a palpable mass, but present a variable and unpredictable clinical course. The current study presents the case of a giant mediastinal DT exhibiting lung involvement. A 50-year-old female was referred to the West China Hospital (Chengdu, Sichuan, China) due to a recurrent DT that was identified one year following radical surgery. The patient subsequently received radiation therapy. The DT arose from the mediastinum, unlike the usual presentation, and recurrence presented as extensive invasion into the lung tissue, almost being misdiagnosed as lung cancer with brain metastasis. Tumor recurrence was diagnosed through contrast-enhanced computed tomography and histological examination of the tumor. A routine follow-up revealed no further tumor progression at 9 months post-admission. Taking into account the unpredictable treatment complications, recurrent DTs can be managed simply and efficiently. A ‘wait-and-see’ policy could be a viable therapeutic option for this disease. PMID:25295113

  10. Long-Term Outcomes for Desmoid Tumors Treated With Radiation Therapy

    SciTech Connect

    Guadagnolo, B. Ashleigh Zagars, Gunar K.; Ballo, Matthew T.

    2008-06-01

    Purpose: To evaluate long-term outcomes in patients with desmoid fibromatosis treated with radiation therapy (RT), with or without surgery. Methods and Materials: Between 1965 and 2005, 115 patients with desmoid tumors were treated with RT at our institution. The median age was 29 years (range, 8-73 years). Of the patients, 41 (36%) received RT alone (median dose, 56 Gy) for gross disease, and 74 (64%) received combined-modality treatment (CMT) consisting of a combination of surgery and RT (median dose, 50.4 Gy). Results: Median follow-up was 10.1 years. Local control (LC) rates at 5 and 10 years were 75% and 74%, respectively. On univariate analysis, LC was significantly influenced by tumor size ({<=}5 cm vs. 5-10 cm vs. >10 cm) (p = 0.02) and age ({<=} 30 vs. >30 years) (p = 0.02). There was no significant difference in LC for patients treated with RT alone for gross disease vs. CMT. For patients treated with CMT, only tumor size significantly influenced LC (p = 0.02). Patients with positive margins after surgery did not have poorer LC than those with negative margins (p = 0.38). Radiation-related complications occurred in 20 (17%) of patients and were associated with dose >56 Gy (p = 0.001), age {<=}30 years (p = 0.009), and receipt of RT alone vs. CMT (p = 0.01). Conclusions: Desmoid tumors are effectively controlled with RT administered either as an adjuvant to surgery when resection margins are positive or alone for gross disease when surgical resection is not feasible. Doses >56 Gy may not be necessary to control gross disease and are associated with high rates of radiation-related complications.

  11. Pedicled TRAM Flap in Presence of Desmoid Tumor of the Rectus Sheath; a Case Report.

    PubMed

    Khater, Ashraf

    2015-12-01

    Creating TRAM flap in obese patient is a challenging issue with a hazard of flap ischemia and breast envelope loss or sepsis. In this case we show our experience in doing an interval TRAM flap in markedly obese patient (BMI index 39) in the presence of Desmoid tumor of the anterior abdominal wall on top of previous mesh hernioplasty in the contralateral side of the tumor. Interval TRAM was decided with achieving of a complete vascular delay in the same sitting with skin sparing mastectomy. On doing abdominal ultrasonography for perforator mapping a desmoid tumor was encountered in the contralateral side. The decision was to elevate the flap together with excision of the desmoid tumor with the flap to be sutured in situ at the end of operation and after 5 days to transfer the flap to the mastectomy site. There was no major complications apart from mild wound sepsis of the breast pocket that was controlled medically. According to our proposed aesthetical score, our patient expressed the outcome as good (8/10 points). Pedicled TRAM flap creation in markedly obese patients is hazardous and we recommend this new concept of interval TRAM for this situation. Moreover the presence of desmoid tumor in the rectus sheath is not a contraindication to this flap elevation. The presence of abdominal desmoid tumor is not a contraindication for TRAM flap provided that it can be resected with sparing of perforators on one side of the rectus sheath. PMID:27065672

  12. Desmoid tumor of the anterior abdominal wall in female patients: comparison with endometriosis.

    PubMed

    Krentel, H; Tchartchian, G; De Wilde, R L

    2012-01-01

    In female patients presenting a tumor of the lower abdominal wall especially after cesarian section, an endometriotic tumor as well as an aggressive desmoid tumor should be considered. Symptoms in correlation with the monthly period can facilitate the presurgical differentiation between endometriosis and fibromatosis. Ultrasound reveals the typical location of both tumors and its remarkable sonographic appearance. In the clinical practice, the desmoid fibromatosis of the lower abdominal wall is a very rare disease. We present a case of a 25-year-old pregnant and discuss diagnostic and therapeutic options by a PubMed literature review. With the knowledge of the prognosis of the desmoid fibromatosis and the respective treatment options including wait and see, complete surgical resection with macroscopically free margins and adjuvant approaches is essential to avoid further interventions and progression of the locally destructive tumor. PMID:22778752

  13. Desmoid Tumor of the Anterior Abdominal Wall in Female Patients: Comparison with Endometriosis

    PubMed Central

    Krentel, H.; Tchartchian, G.; De Wilde, R. L.

    2012-01-01

    In female patients presenting a tumor of the lower abdominal wall especially after cesarian section, an endometriotic tumor as well as an aggressive desmoid tumor should be considered. Symptoms in correlation with the monthly period can facilitate the presurgical differentiation between endometriosis and fibromatosis. Ultrasound reveals the typical location of both tumors and its remarkable sonographic appearance. In the clinical practice, the desmoid fibromatosis of the lower abdominal wall is a very rare disease. We present a case of a 25-year-old pregnant and discuss diagnostic and therapeutic options by a PubMed literature review. With the knowledge of the prognosis of the desmoid fibromatosis and the respective treatment options including wait and see, complete surgical resection with macroscopically free margins and adjuvant approaches is essential to avoid further interventions and progression of the locally destructive tumor. PMID:22778752

  14. A Sporadic Desmoid Tumor: an Exceptional Pancreatic Cystic-Solid Mass.

    PubMed

    Ardakani, Jalal Vahedian; Mehrjardi, Ali Zare; Wadji, Massoud Baghai; Saraee, Amir

    2016-08-01

    Desmoid tumors are locally aggressive and non-metastatic neoplasms with a high rate of recurrence. Desmoid tumors of the pancreas are, however, very rare, and only a few cases have been reported in the literature. This paper reports an anecdotal case of a diffuse pancreatic desmoid tumor with the involvement of the pancreatic head, body, and-partially-tail. The patient underwent the Whipple procedure and subtotal pancreatectomy. Histopathological assessment showed that the tissues were partly positive for smooth muscle actin, but not for S100 or PanCK. The Ki67 index of the cells was only 1 %. Unfortunately, the patient died on the 10th postoperative day due to massive upper gastrointestinal bleeding. PMID:27574352

  15. Genotype and phenotype factors as determinants of desmoid tumors in patients with familial adenomatous polyposis.

    PubMed

    Bertario, L; Russo, A; Sala, P; Eboli, M; Giarola, M; D'amico, F; Gismondi, V; Varesco, L; Pierotti, M A; Radice, P

    2001-03-20

    Desmoids represent the most important cause of death, after colorectal cancer, in patients affected with familial adenomatous polyposis (FAP), an inherited disease due to mutations in the APC gene. The aims of our study were to estimate the risk of developing desmoids in FAP patients and to evaluate the association between desmoids and different risk factors. The occurrence of desmoids, colorectal cancer and other extra-colonic manifestations were assessed in 897 FAP patients, 653 of whom were also investigated for APC mutations. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were computed using an unconditional multiple logistic regression model. Desmoids developed in 107 patients (11.9%), with a cumulative risk of 20.6%. Females had a significantly higher risk than males (OR = 2.1; 95% CI 1.4-3.1). Family history of desmoids (OR = 8.75; 95% CI 5.66-13.51), osteomas (OR = 2.9; 95% CI 1.8-4.8) and epidermoid cysts (OR = 1.8; 95% CI 1.1-3.2) was also significantly associated with the occurrence of disease. Subjects with APC mutations beyond codon 1444 had a 12-fold increased risk, compared with patients with mutations located upstream. Mutations beyond codon 1309 conferred a 17-fold higher risk, compared with mutations upstream codon 452. Multivariate analysis identified as independent predictors mutation beyond codon 1444 (OR = 6.2; 95% CI 2.5-15.8), family history of desmoids (OR = 5.8; 95% CI 3.1-10.6), female gender (OR = 2.1; 95% CI 1.1-3.8) and the presence of osteomas (OR = 1.9; 95% CI 1.1-3.4). Our results indicate that integrating genetic and clinical data is helpful in defining subgroups of patients at higher risk for desmoids, who may benefit from specific prevention programs. PMID:11241320

  16. [A Case of Intra-Abdominal Desmoid Tumor with Abacterial Peritonitis].

    PubMed

    Sumiyama, Fusao; Inada, Ryo; Nakamura, Fumiko; Ryota, Hironori; Miki, Hirokazu; Oishi, Masaharu; Matsumoto, Tomoko; Iwamoto, Shigeyoshi; Mukaide, Yumi; Ozaki, Takeshi; Michiura, Taku; Inoue, Kentaro; Kon, Masanori; Miyasaka, Chika; Uemura, Yoshiko; Hamada, Madoka

    2016-03-01

    A woman in her 50s visited our hospital in February 2015 with a complaint of dull abdominal pain in the right lower quadrant. She had a medical history of appendectomy for appendicitis in her 20s. Computed tomography(CT)revealed a tumor 90 mm in diameter near the ileocecum. Elective surgery was planned under the suspicion of gastrointestinal tumor, malignant lymphoma, or ileal cancer. She was emergently hospitalized 1 day earlier than scheduled because of high fever and severe abdominal pain. CT revealed that the tumor had increased to 120 mm in diameter without free air. Her white blood cell count was not elevated, and her symptoms improved readily with medical treatment. Thus, we performed the operation as scheduled. A tumor with a dark red recess on the surface had invaded the transverse colon intraoperatively, and a small amount of purulent ascites was present at the pouch of Douglas. We performed ileocecal resection with partial transverse colectomy. Histopathological examination led to the diagnosis of desmoid tumor in the mesentery of the terminal ileum. The surgical margins were negative for tumor cells. The tumor surface around the recess showed peritonitis, and the ascites showed no bacteria or tumor cells. The patient had been doing well without recurrence after discharge. Some cases of desmoid tumor with peritonitis have been reported, but most were caused by tumor penetration into the intestinal tract. We report herein a rare case of intra-abdominal desmoid tumor with abacterial peritonitis. PMID:27067862

  17. [A Case of Abdominal Wall Desmoid Tumor after Radical Nephrectomy for Renal Cancer].

    PubMed

    Ohtake, Shinji; Namura, Kazuhiro; Fujikawa, Atsushi; Sawada, Takuto; Ohta, Junichi; Moriyama, Masatoshi; Hayashi, Hiroyuki

    2015-09-01

    A 71-year-old man with a right renal tumor underwent nephrectomy. The procedure was converted from laparoscopy to open surgery due to profound bleeding from the renal vein. Pathological diagnosis was clear cell carcinoma G2pT3b v1 ly1 INFα. Three years after surgery, a 5 cm tumor in the abdominal wall was found on computed tomography (CT). A mild uptake was shown on positron emission tomography/CT and as the tumor was located near the surgical wound, recurrence of the renal cell carcinoma was suspected. However, desmoid tumor was suggested by the pathological examination of the tumor biopsy. En-bloc resection of the mass was carried out and the pathological examination showed an array of proliferating and tangling atypical spindle-shaped tumor cells. Immunohistochemical staining of the tumor cells was positive for vimentin, but negative for CD34, c-kit, and s100. Pathological diagnosis was desmoid tumor. There has been no recurrence so far. Desmoid tumor, despite its extremely low incidence, should be considered in a postoperative neoplasm. PMID:26497861

  18. Desmoid tumor of lung with pleural involvement - the case of unique location of aggressive fibromatosis.

    PubMed

    Tokarek, Tomasz; Szpor, Joanna; Pankowski, Juliusz; Okoń, Krzysztof

    2015-01-01

    Desmoid tumors (DTs) are rare mesenchymal neoplasms with unpredictable natural history. There is a high risk of recurrence despite adequate surgical resection, however DTs do not have the capacity to metastasize. The estimated incidence in general population is 2-4 cases/million/year. They may occur at any age but most commonly in the third and fourth decades. Both sexes may be affected, but there is a slight female predominance. DTs can occur at any body site. The exact etiology remains unclear, but trauma, hormonal disturbances, pregnancy, genetic and hereditary factors are postulated to be in association with its' development. Potential to attain large size, infiltration and destruction of adjacent vital structures and tendency to recur are main management problems and important causes of morbidity and mortality. Wide excision is standard first-line treatment of primary or recurrent symptomatic desmoids. We present case of 33-years-old Caucasian female patient admitted to hospital with 2 months history of squeezing pain in right upper quadrant which appeared after meals. The patient was in general good condition. There were no abnormalities on basic laboratory tests on admission. CT of chest revealed hydrothorax to the level of the apex of the right lung and tumor sized 7 × 13 × 13 cm located in the lower lobe of right lung. Histopathological diagnosis of desmoid tumor of right lung was formulated. We report, to our knowledge for the first time in Poland, case of aggressive fibromatosis of lung with invasion of pleura. PMID:26774632

  19. Desmoid Tumor Showing Intense Uptake on 68Ga PSMA-HBED-CC PET/CT.

    PubMed

    Kanthan, Gowri L; Hsiao, Edward; Kneebone, Andrew; Eade, Thomas; Schembri, Geoffrey Paul

    2016-06-01

    Ga-PSMA PET/CT is a new imaging technique that is highly sensitive to metastatic prostate cancer lesions compared with other conventional imaging modalities. We report a case of a 77-year-old man with newly diagnosed prostate carcinoma who had a PSMA PET/CT scan for staging of his disease. An intensely PSMA-avid right pelvic mass was identified abutting the cecum and terminal ileum. Surgical removal and histopathologic examination of this lesion revealed the diagnosis of a desmoid tumor. It is important to be aware that many tumors other than prostate carcinoma may also show avid uptake on PSMA PET/CT scan. PMID:26909712

  20. High-intensity focused ultrasound treatment for intra-abdominal desmoid tumors: a report of four cases.

    PubMed

    Shi, Yulan; Huang, Yanqin; Zhou, Meiqi; Ying, Xiao; Hu, Xiaoye

    2016-04-01

    Desmoid tumors are rare clonal fibroblastic proliferations that can arise at abdominal or extra-abdominal sites. Complete surgical resection is the primary treatment for resectable desmoid tumors, but a high rate of local recurrence has been reported even after complete resection. For patients with a recurrent tumor, the goals of treatment are to control the recurrence, maintain quality of life, and prolong survival. Radiofrequency ablation, radiotherapy, chemotherapy, and other medical therapies can be used as alternative methods, but there are considerable controversies over the roles of these methods in the management of desmoid tumors. High-intensity focused ultrasound (HIFU) is a minimally invasive and effective method for treatment of solid tumors. We used HIFU to treat four patients with intra-abdominal desmoid tumors from June 2011 to September 2013. Post-procedural pain was seen in all patients. One patient had an intra-abdominal abscess and another suffered a slight injury to the femoral nerve. The patients were followed up for 19-46 months (mean 34 months) until April 2015. The tumor in one patient disappeared, and no tumor progression was observed in the other patients. PMID:27033872

  1. [A Case in Which a Patient Was Operated for Intra-Abdominal Desmoid Tumors after Total Colectomy in FAP].

    PubMed

    Hoshi, Minako; Ikeda, Kimimasa; Higashiguchi, Kimiya; Kobayashi, Teruyuki; Sakai, Kenji; Koyama, Taichi; Doi, Takasi; Taniguchi, Hirokazu; Murakami, Masakazu; Kurokawa, Eiji; Nakamichi, Itsuko

    2015-11-01

    The patient was a 22-year-old woman with FAP, who had undergone laparoscopic total colectomy 3 years previously. She presented to our hospital with a high fever and abdominal pain. Large hard tumors were palpated in the right lower abdomen and pelvis. Blood examination showed an inflammatory response. CT scan revealed 17 cm diameter solid tumors. At surgery, 2 tumors arising from the mesentery of the small intestine were found, neither of which invaded any organs. We performed tumor extirpation with partial resection of the duodenum, ileum, right fallopian tube and rectum. A jejunal stoma was formed, leaving a length of remnant intestine of about 120 cm. The histopathological diagnosis was given as desmoid tumor with infection. The patient was discharged from the hospital on the 9th postoperative day. Desmoid tumor is the second most common cause of death in FAP patients. Although desmoids can also occur in the extremities, most FAP patients develop intra-abdominal tumors. Despite being histologically benign, they are locally infiltrative and can cause death through invasion and destruction of adjacent vital structures and organs. Here, we report a case of desmoid tumors with FAP with reference to the literature. PMID:26805225

  2. Concomitant surgical treatment of a chondrosarcoma of the chest wall and a desmoid tumor of the gastrointestinal tract

    PubMed Central

    Sadowski, Andrzej; Chruścicka, Iwona; Rak, Piotr; Ptach, Anna; Maliszewski, Daniel; Pęksa, Rafał; Haponiuk, Ireneusz

    2015-01-01

    The co-existence of a chondrosarcoma of the chest wall and a desmoid tumor in the gastrointestinal tract is rare. In both Polish and global literature, cases of chest wall chondrosarcomas are presented in the form of case reports. Desmoids of the gastrointestinal tract are more common; notwithstanding, their incidence in Europe is estimated at approximately 2 cases per 1 million inhabitants per year. We present the case of a 62-year-old female patient who suffered from both a chest wall chondrosarcoma and a desmoid tumor of the intestine; both neoplasms were operated on simultaneously. The former tumor was located in the region of the right costal margin, whereas the latter was located in the mesojejunum. The surgery was performed with two independent surgical incisions. The postoperative period was uneventful. The case is noteworthy in view of the extremely rare synchronous occurrence of the described tumors and due to the fact that any such operation requires an individualized surgical approach. PMID:26336503

  3. Desmoid tumors in adults: the role of radiotherapy in their management

    SciTech Connect

    Bataini, J.P.; Belloir, C.; Mazabraud, A.; Pilleron, J.P.; Cartigny, A.; Jaulerry, C.; Ghossein, N.A.

    1988-06-01

    Twenty-six adult patients with the pathologic diagnosis of desmoid tumor were treated between 1964 and 1983 at the Institut Curie in Paris with megavoltage irradiation. Twenty of these patients (76 percent) had extraabdominal tumors. Definitive surgical resection was performed on nine patients (one received preoperative radiotherapy). At last follow-up 1 1/2 to 10 years after treatment, all of the patients had no evidence of disease. Seven of the nine had follow-up examinations from 5 to 10 years after treatment. Seven patients had postoperative radiotherapy with doses from 4,700 to 6,500 rads (47 to 65 Gy) for either microscopic (three patients) or gross (four patients) residual disease. All but one patient had no evidence of disease from 2 to 8 years after treatment. Nine patients had radiotherapy for recurrent inoperable tumors and six had no evidence of disease from 3 to 20 years after treatment. Recurrences developed in three patients; outside the treatment portal in one, and the other two had received less than 5,000 rads (50 Gy). Clinical regression of tumors after treatment was slow, with complete regression taking up to 2 years. Postoperative radiotherapy with doses of at least 5,000 to 6,000 rads (50 to 60 Gy) was effective in achieving local control of inoperable or incompletely resected tumors, thus the need for repeated resections was avoided. Computerized tomography has greatly improved the assessment of tumor extension and should be used routinely before either operation or radiotherapy to obtain adequate margins and minimize the chance of missing disease.

  4. Management of Desmoids.

    PubMed

    Grignol, Valerie P; Pollock, Raphael; Howard, John Harrison

    2016-10-01

    Desmoid tumors are rare, comprising 3% of soft tissue tumors. Surgical resection has been the standard of care; however, this has begun to evolve into a movement of watchful waiting as observational studies have shown long-term stability of many tumors without treatment and even spontaneous regression in 5% to 10% of cases. When surgical therapy is used, wide local excision with microscopically negative margins is the goal of resection but should not be at the expense of organ or limb function. Recurrence rates after surgical resection are approximately 20%; a variety of multimodal therapies are useful in controlling disease. PMID:27542640

  5. Splenic Artery Aneurysm Invaded by Desmoid-Type Fibromatosis.

    PubMed

    Tatsumi, Kanayo; Bundock, Elizabeth A

    2015-09-01

    Despite the benign histologic appearance and negligible metastatic potential, desmoid tumors can be locally aggressive, invading into adjacent structures and organs. We report an unusual case of desmoid-type fibromatosis causing the death of an otherwise healthy individual by rupturing the splenic artery. PMID:26017693

  6. Inflammatory myofibroblastic tumor with RANBP2 and ALK gene rearrangement with bland cytological features mimicking desmoid-type fibromatosis: A case report and review of the literature

    PubMed Central

    HUANG, YU-HUA; TIAN, YU-FENG; LI, CHIEN-FENG

    2016-01-01

    Here, we present an uncommon case of inflammatory myofibroblastic tumor (IMT) involving the mesentery. The tumor was composed of loosely arranged round-to-spindle-shaped tumor cells with amphophilic cytoplasm in an inflammatory and myxoid background. The mitotic activity was low (1 per 50 high-power fields) and the tumor cells lacked cellular atypism. Immunohistochemically, the tumor cells demonstrated strong nuclear membranous staining with anaplastic lymphoma kinase (ALK). In situ hybridization for ALK gene rearrangement revealed a splitting apart of the two signals within the tumor cells. Reverse transcription-polymerase chain reaction revealed that the tumor harbored a ran-binding protein 2 (RANBP2)-ALK rearrangement. IMTs are usually characterized by epithelioid-to-round cells featuring increased mitotic activity, occasionally demonstrating unusual tumor cells and more aggressive clinical behavior. To date, 23 IMTs have been reported with RANBP2 and ALK gene rearrangements. However, the present case demonstrated indolent cytological features, leading to a difficulty in differentiating it from desmoid-type fibromatosis. PMID:26893756

  7. Near universal detection of alterations in CTNNB1 and Wnt pathway regulators in desmoid-type fibromatosis by whole-exome sequencing and genomic analysis.

    PubMed

    Crago, Aimee M; Chmielecki, Juliann; Rosenberg, Mara; O'Connor, Rachael; Byrne, Caitlin; Wilder, Fatima G; Thorn, Katherine; Agius, Phaedra; Kuk, Deborah; Socci, Nicholas D; Qin, Li-Xuan; Meyerson, Matthew; Hameed, Meera; Singer, Samuel

    2015-10-01

    CTNNB1 mutations or APC abnormalities have been observed in ∼85% of desmoids examined by Sanger sequencing and are associated with Wnt/β-catenin activation. We sought to identify molecular aberrations in "wild-type" tumors (those without CTNNB1 or APC alteration) and to determine their prognostic relevance. CTNNB1 was examined by Sanger sequencing in 117 desmoids; a mutation was observed in 101 (86%) and 16 were wild type. Wild-type status did not associate with tumor recurrence. Moreover, in unsupervised clustering based on U133A-derived gene expression profiles, wild-type and mutated tumors clustered together. Whole-exome sequencing of eight of the wild-type desmoids revealed that three had a CTNNB1 mutation that had been undetected by Sanger sequencing. The mutation was found in a mean 16% of reads (vs. 37% for mutations identified by Sanger). Of the other five wild-type tumors sequenced, two had APC loss, two had chromosome 6 loss, and one had mutation of BMI1. The finding of low-frequency CTNNB1 mutation or APC loss in wild-type desmoids was validated in the remaining eight wild-type desmoids; directed miSeq identified low-frequency CTNNB1 mutation in four and comparative genomic hybridization identified APC loss in one. These results demonstrate that mutations affecting CTNNB1 or APC occur more frequently in desmoids than previously recognized (111 of 117; 95%), and designation of wild-type genotype is largely determined by sensitivity of detection methods. Even true CTNNB1 wild-type tumors (determined by next-generation sequencing) may have genomic alterations associated with Wnt activation (chromosome 6 loss/BMI1 mutation), supporting Wnt/β-catenin activation as the common pathway governing desmoid initiation. PMID:26171757

  8. Pediatric desmoid fibromatosis of the parapharyngeal space: A case report and review of literature.

    PubMed

    Zheng, Zhong; Jordan, Adrienne C; Hackett, Alyssa M; Chai, Raymond L

    2016-01-01

    Desmoid fibromatosis, or aggressive fibromatosis, is a benign but locally infiltrative fibroblastic neoplasm arising from fascial or musculoaponeurotic tissues. Although lacking metastatic potential, head and neck fibromatosis can have significant functional or cosmetic morbidities. 7%-15% of all desmoid tumors are seen in the head and neck region, 57% of which occur in the pediatric population. The incidence of pediatric desmoid tumor peaks around age 8. Treatment of choice is complete surgical resection; however, local recurrence is common. We present a case of a 14-month-old male with an 8-cm desmoid tumor in the right parapharyngeal space and provide an overview of diagnosis and management of pediatric head and neck fibromatosis. This is the largest desmoid tumor of the parapharyngeal space in the youngest patient described in the literature. PMID:27040413

  9. Desmoid-Type Fibromatosis: Evolving Treatment Standards.

    PubMed

    Fiore, Marco; MacNeill, Andrea; Gronchi, Alessandro; Colombo, Chiara

    2016-10-01

    Desmoid-type fibromatosis is a rare nonmetastasizing neoplasm with variable behavior. Recent discoveries into the biology of this disease hold promise for identifying prognostic and predictive features and novel therapeutic targets. Surgery has been the historical standard of care but carries considerable drawbacks in terms of high local recurrence rates and poor functional outcomes. Improved understanding of the natural history of desmoid-type fibromatosis has resulted in a paradigm shift toward nonoperative management. Effective medical treatment options include nonsteroidal antiinflammatory drugs, hormone therapy, cytotoxic chemotherapy, and targeted agents. A treatment algorithm has been proposed with the objective of optimizing treatment. PMID:27591500

  10. Attenuated familial adenomatous polyposis with desmoids caused by an APC mutation.

    PubMed

    Ikenoue, Tsuneo; Yamaguchi, Kiyoshi; Komura, Mitsuhiro; Imoto, Seiya; Yamaguchi, Rui; Shimizu, Eigo; Kasuya, Shinichi; Shibuya, Tetsuo; Hatakeyama, Seira; Miyano, Satoru; Furukawa, Yoichi

    2015-01-01

    We present here a case of attenuated familial adenomatous polyposis (AFAP) with a family history of desmoids and thyroid tumors. This patient had no colonic polyps but did have multiple desmoids. Genetic analysis identified a 4-bp deletion in codon 2644 (c.7932_7935delTTAT: p.Tyr2645LysfsX14) of the adenomatous polyposis coli (APC) gene. In cases with limited numbers of colonic polyps and desmoids, AFAP may be caused by a mutation in the 3' region of APC. PMID:27081525

  11. Attenuated familial adenomatous polyposis with desmoids caused by an APC mutation

    PubMed Central

    Ikenoue, Tsuneo; Yamaguchi, Kiyoshi; Komura, Mitsuhiro; Imoto, Seiya; Yamaguchi, Rui; Shimizu, Eigo; Kasuya, Shinichi; Shibuya, Tetsuo; Hatakeyama, Seira; Miyano, Satoru; Furukawa, Yoichi

    2015-01-01

    We present here a case of attenuated familial adenomatous polyposis (AFAP) with a family history of desmoids and thyroid tumors. This patient had no colonic polyps but did have multiple desmoids. Genetic analysis identified a 4-bp deletion in codon 2644 (c.7932_7935delTTAT: p.Tyr2645LysfsX14) of the adenomatous polyposis coli (APC) gene. In cases with limited numbers of colonic polyps and desmoids, AFAP may be caused by a mutation in the 3′ region of APC. PMID:27081525

  12. Chemotherapy for desmoid tumours in association with familial adenomatous polyposis: a report of three cases

    PubMed Central

    Hamilton, Lisa; Blackstein, Martin; Berk, Terri; McLeod, Robin S.; Gallinger, Steven; Madlensky, Lisa; Cohen, Zane

    1996-01-01

    Objective To determine the efficacy of chemotherapy for inoperable desmoid tumours associated with familial adenomatous polyposis. Design A review of three cases of unresectable desmoid tumours and of the literature on the subject. Setting The Steven Atanas Stavro Polyposis Registry at Mount Sinai Hospital in Toronto. Patients Three patients with symptomatic, unresectable desmoid tumours associated with familial adenomatous polyposis and unresponsive to conventional hormone therapy. Intervention A chemotherapy regimen of seven cycles of doxorubicin (dose ranging from 60 to 90 mg/m2) and dacarbazine (1000 mg/m2), followed by carboplatin (400 mg/m2) and dacarbazine. Outcome Measures Clinical improvement and tumour regression demonstrated by computed tomography. Results In each of the three cases significant tumour regression was seen clinically and radiologically. Conclusions Cytotoxic chemotherapy is an effective treatment for desmoid tumours associated with familial adenomatous polyposis. The chemotherapy should be started early in cases of symptomatic desmoid tumour unresponsive to conventional medical therapy. PMID:8640627

  13. Characteristics of cultured desmoid cells with different CTNNB1 mutation status.

    PubMed

    Hamada, Shunsuke; Urakawa, Hiroshi; Kozawa, Eiji; Arai, Eisuke; Ikuta, Kunihiro; Sakai, Tomohisa; Ishiguro, Naoki; Nishida, Yoshihiro

    2016-02-01

    Desmoid tumors are benign mesenchymal neoplasms with a locally aggressive nature. The mutational status of β-catenin gene (CTNNB1) is presumed to affect the tumorous activity of the cells. In this study, we isolated three kinds of desmoid cell with different CTNNB1 status, and compared their characteristics. Cells were isolated from three patients with abdominal wall desmoid during surgery, all of which were resistant to meloxicam treatment. The mutational status of the CTNNB1 exon 3 was determined for both parental tumor tissues and isolated cultured cells. β-catenin expression was determined with immunohistochemistry. Responsiveness to meloxicam was investigated with MTS assay together with COX-2 immunostaining. mRNA expressions of downstream molecules of Wnt/β-catenin pathway were determined with real-time RT-PCR. Three kinds of cell isolated from desmoid tumors harboring different CTNNB1 mutation status (wild type, T41A, and S45F), all exhibited a spindle shape. These isolated cells could be cultured until the 20th passage with unchanged proliferative activity. Nuclear accumulation of β-catenin was observed in all cultured cells, particularly in those with S45F. Proliferating activity was significantly suppressed by meloxicam (25 μmol/L, P < 0.007) in all three cell cultures, of which parental desmoid was resistant to meloxicam clinically. The mRNA expressions of Axin2, c-Myc, and Cyclin D1 differently increased in the three cultured cell types as compared with those in human skin fibroblast cells (HDF). Inhibitors of Wnt/β-catenin pathway downregulated Axin2, c-Myc, and Cyclin D1 significantly. Isolated and cultured desmoid tumor cells harboring any one of the CTNNB1 mutation status had unique characteristics, and could be useful to investigate desmoid tumors with different mutation status of CTNNB1. PMID:26686699

  14. Diagnosis and treatment of extraabdominal desmoid fibromatosis

    PubMed Central

    Ghanem, Mohamed; Heinisch, Antje; Heyde, Christoph-E.; Freiherr von Salis-Soglio, Georg

    2014-01-01

    Introduction: The desmoid fibromatosis is a very rare connective tissue disease which is recognized as semimalignant. The aim of this work is to review the relevant literature and to analyze the management of our patient collective. Material and Method: Surgery was performed on 7 patients with extraabdominal desmoid fibromatosis between August 1998 and May 2007. MRI examination as well as biopsy was carried out in all cases. All patients were operated on; the mean follow up was 4 years (1–7). Upon follow up, every patient has undergone clinical and MRI examination. Results: The results show that we have achieved R0 resection in 4 cases and R1 in two cases and Rx in one case. In 4 patients, no recurrence was observed after the single surgery performed in our hospital. In 2 patients a single revision surgery was performed in each case and yielded no further recurrence. In only one case, multiple surgeries (one primary and two revision surgeries) were necessary, after which no recurrence was reported. Conclusion: The early diagnosis of the disease is of utmost importance to the success of the outcome. MRI examination and biopsy are mandatory. Surgery is the therapy of choice. The recurrence rate is high and is linked to the difficulty of recognition of the exact infiltrative extent of the tumour. This necessitates a close follow-up. PMID:26504712

  15. Hereditary desmoid disease due to a frameshift mutation at codon 1924 of the APC gene.

    PubMed Central

    Eccles, D. M.; van der Luijt, R.; Breukel, C.; Bullman, H.; Bunyan, D.; Fisher, A.; Barber, J.; du Boulay, C.; Primrose, J.; Burn, J.; Fodde, R.

    1996-01-01

    Desmoid tumors are slowly growing fibrous tumors highly resistant to therapy and often fatal. Here, we report hereditary desmoid disease (HDD), a novel autosomal dominant trait with 100% penetrance affecting a three-generation kindred. Desmoid tumors are usually a complication of familial adenomatous polyposis, a predisposition to the early development of premalignant adenomatous polyps in the colorectum due to chain-terminating mutations of the APC gene. In general, one or more members in approximately 10% of the FAP families manifest desmoid tumors. Affected individuals from the HDD kindred are characterized by multifocal fibromatosis of the paraspinal muscles, breast, occiput, arms, lower ribs, abdominal wall, and mesentery. Osteomas, epidermal cysts, and other congenital features were also observed. We show that HDD segregates with an unusual germ-line chain-terminating mutation at the 3' end of the APC gene (codon 1924) with somatic loss of the wild-type allele leading to tumor development. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:8940264

  16. Human desmoid fibroblasts: matrix metalloproteinases, their inhibitors and modulation by Toremifene

    PubMed Central

    Balducci, Chiara; Lilli, Cinzia; Stabellini, Giordano; Marinucci, Lorella; Giustozzi, Giammario; Becchetti, Alessio; Cagini, Lucio; Locci, Paola

    2005-01-01

    Background Desmoid tumour is a benign, non metastasising neoplasm characterised by an elevated deposition of organic macromolecules in the extracellular matrix (ECM). The matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the degradation of ECM macromolecules. The MMPs and their natural inhibitors (TIMPs) have been implicated in tumour growth, invasion and metastasis. In this study we provide evidence that the in vitro cultured cell line from desmoid tumour accumulates more collagen fibres in the ECM than healthy fibroblasts. Methods We investigated collagen accumulation by 3H-thymidine incorporation, MMP expression by substrate gel zymography and TIMP expression by Western blot analysis. Results Desmoid fibroblasts showed a reduction in MMP activity and an increase of type I and III collagen and TIMPs compared to normal fibroblasts. Conclusion The increase in collagen in desmoid fibroblasts was due to inhibited collagen degradation (reduction of MMP activity) rather than to increased collagen synthesis. Adding toremifene, an anti-estrogen triphenylethylene derivate, to desmoid fibroblasts reduced collagen accumulation by decreasing mRNA expression and increasing collagen degradation. PMID:15740610

  17. The challenge of extraabdominal desmoid tumour management in patients with Gardner's syndrome: radiofrequency ablation, a promising option.

    PubMed

    Cobianchi, Lorenzo; Ravetta, Valentina; Viera, Francesca Torello; Filisetti, Claudia; Siri, Barbara; Segalini, Edoardo; Maestri, Marcello; Dominioni, Tommaso; Alessiani, Mario; Rossi, Sandro; Dionigi, Paolo

    2014-01-01

    Desmoid tumours are benign, myofibroblastic stromal neoplasms common in Gardner's syndrome, which is a subtype of familial adenomatous polyposis characterized by colonic polyps, osteomas, thyroid cancer, epidermoid cysts, fibromas and sebaceous cysts. The primary treatment is surgery, followed by adjuvant radiotherapy, but the local recurrence rate is high, and wide resection can result in debilitating loss of function. We report the case of a 39-year-old man with Gardner's syndrome who had already undergone a total prophylactic colectomy. He developed desmoid tumours localized in the mesenteric root, abdominal wall and dorsal region, which were treated from 2003 through 2013 with several surgical procedures and percutaneous radiofrequency ablation. In 2008 and 2013, RFA was applied under ultrasonographic guidance to two desmoid tumours localized in the dorsal thoracic wall. The outcomes were low-grade pain and one case of superficial skin necrosis, but so far there has been no recurrence of desmoid tumours in these locations. Surgical resection remains the first-line therapy for patients with desmoid tumours, but wide resection may lead to a poor quality of life. Radiofrequency ablation is less invasive and expensive and is a possible therapeutic option for desmoid tumours in patients with Gardner's syndrome. PMID:25429890

  18. Desmoid-Type Fibromatosis of the Mesentery: Report of a Sporadic Case with Emphasis on Differential Diagnostic Problems

    PubMed Central

    Pennisi, Monica

    2014-01-01

    Desmoid-type fibromatosis is a rare mesenchymal neoplasm with local aggressiveness. The incidence of desmoid-type fibromatosis is 2–5/million/year with intra-abdominal fibromatosis, such as that which is reported in this clinical case, occurring only in 12–18% of cases. After having analyzed the pathogenetic hypotheses of desmoid-type fibromatosis, the authors point out that the diagnosis of this disease, especially in the intra-abdominal form, is often late, specifically when highly demolitive interventions are needed or when the limits of radical surgery have been exceeded. In the clinical case reported, the tumor was infiltrating both ileus and sigma. The authors consider the differential diagnosis of desmoid-type fibromatosis, especially with GISTs, with regard to both the radiological preoperative diagnostic and histological studies on the surgical specimen. Radical surgical excision is not always, for this disease, a sign of healing; in fact, even when the resection margins are negative, the incidence of recurrence is between 13 and 68%. The average time of recurrence is between 15 and 24 months; in this case report, the patient, who has not been subjected to complementary therapies, is tumor-free for over 30 months since surgery; his prognosis may be satisfactory if we consider the negativity of resection margins, which in any case remains the most important prognostic factor. PMID:25349618

  19. An Abdominal Wall Desmoid Tumour Mimicking Cesarean Scar Endometriomas: A Case Report and Review of the Literature

    PubMed Central

    Vural, Fisun; Müezzinoglu, Bahar

    2015-01-01

    Abdominal wall desmoid tumours (DT) are rare, slow-growing benign muscular-aponeurotic fibrous tumours with the tendency to locally invade and recur. They constitute 0.03% of all neoplasms and high infiltration and recurrence rate, but there is no metastatic potential. Although surgery is the primary treatment modality, the optimal treatment remains unclear. Abdominal wall endometriosis is also an unusual disease, and preoperative clinical diagnosis is not always easy. The preoperative radiologic imaging modalities may not aid all the time. Herein, we report an abdominal mass presenting as cyclic pain. Forty-two years old woman who gave birth by cesarean section admitted the complaints of painful abdominal mass (78x45 mm in size) under her cesarean incision scar. She had severe pain, particularly during menstruation. The clinical and radiological imaging findings mimicking endometrioma. We performed wide surgical excision of mass with a 1 cm tumor-free margin with the diagnosis of a benign mesenchymal tumor in the frozen section. The postoperative course was uneventful and recovered without any complication and recurrence three years after surgery. This report presents a case of abdominal wall desmoid tumor mimicking endometrioma. In this paper, shortcomings in diagnosis, abdominal wall endometriomas, and DTs were discussed in the view of literature. PMID:26500967

  20. Klatskin tumor--results of surgical therapy.

    PubMed

    Zovak, Mario; Doko, Marko; Glavan, Elizabet; Hochstädter, Hrvoje; Roić, Goran; Ljubicić, Neven

    2004-06-01

    Between January 1st 1990 and December 31st 1999, 24 patients affected by Klatskin tumor underwent operation in our department of surgery. According to Bismuth's classification, there were 0 (0%) type I, 5 (21%) type II, 6 (25%) type IIIa, 4 (17%) type IIIb and 9 (37%) type IV tumors. Five patients (21%) were treated by curative resection (group I) while in 14 patients (58%) palliative surgical procedure was performed (group II). In 5 cases (21%) the extension of malignancy did not allowed any procedure (group III). Curative resection for malignant tumors of the hepatic duct bifurcation included wide tumor excision and bile duct resection at the liver hilum (with wedge hepatic resection in one patient) and creation of biliary-enteric anastomosis. Palliative surgical procedure included stent insertion. Jaundice was completely relieved in all patients undergoing resection, since 3 patients (21%) after stenting hadn't satisfactory biliary drainage. There was 1 (20%) perioperative death in the group 1, while in group 2, 5 patients (36%) died postoperatively. In this series, the mean postoperative survival of all patients was 16 months. The mean postoperative survival of patients undergoing localized tumor resection with curative intent was 38 months, in contrast to 10 months for those undergoing operative stent insertion. in addition, only 1 patient from group III, in whom only exploratory surgery were performed survived 7 months, while other 4 patients died in the hospital. This retrospective review suggests that aggressive surgical treatment could improve survival and quality of life in patients suffering from Klatskin tumor. PMID:15636089

  1. A systematic review of active treatment options in patients with desmoid tumours

    PubMed Central

    Yao, X.; Corbett, T.; Gupta, A.A.; Kandel, R.A.; Verma, S.; Werier, J.; Ghert, M.

    2014-01-01

    Introduction We conducted a systematic review to determine the optimal treatment options in patients with desmoid tumours who have declined observational management. Methods A search was conducted of the medline and embase databases (1990 to September 2012), the Cochrane Library, and relevant guideline Web sites and conference materials. Results One systematic review and forty-six studies met the preplanned study selection criteria; data from twenty-eight articles were extracted and analyzed. For local control, three studies reported a statistically significant difference in favour of surgery plus radiotherapy (rt) compared with surgery alone, and one study did not; two studies reported the lack of a statistical difference between surgery plus rt and rt alone in maintaining local control. Multivariate risk factors for local recurrence included positive surgical margins and young patient age. Single-agent imatinib led to a progression-free survival rate of 55% at 2 years and 58% at 3 years. Methotrexate plus vinblastine led to a progression-free survival rate of 67% at 10 years. Significant toxicities were reported for all treatment modalities, including surgical morbidity, and rt- and chemotherapy-related toxicities. Conclusions In patients who have declined observational management, the local control rate was higher with surgery plus rt than with surgery alone. However, the additional rt-related complications should be considered in treatment decision-making. Surgery, rt, and systemic therapy are all reasonable treatment options for patients with desmoid tumours. PMID:25089111

  2. Cortical desmoids in adolescent top-level athletes

    PubMed Central

    Biedert, Roland M; Gal, Imre

    2015-01-01

    Two adolescent, highly active athletes are presented with unspecific symptoms of anterior knee pain. Conventional radiographs and magnetic resonance imaging (MRI) showed a suspicious but pathognomonic cortical irregularity of the dorsal, medial femoral condyle. Cortical desmoid is one of the most common incidental osseous findings on conventional radiographs and MRI of the knee. It often needs no follow-up examination in asymptomatic patients. Malignancy needs however to be ruled out. PMID:25992301

  3. Infantile desmoid-type fibromatosis in an Akita puppy.

    PubMed

    Cook, J L; Turk, J R; Pope, E R; Jordan, R C

    1998-01-01

    A 10-week-old Akita puppy was evaluated for a reported umbilical hernia. Repair of the hernia had been attempted three times prior to referral. A defect in the ventral abdominal wall with an associated soft-tissue mass was identified on abdominal radiographs. Exploratory surgery was performed; the mass was resected and the abdominal wall defect was repaired. Histopathological evaluation of the mass was consistent with infantile desmoid-type fibromatosis. PMID:9657161

  4. Magnetic Resonance Elastography of Liver Tumors- Preliminary Results

    PubMed Central

    Venkatesh, Sudhakar K; Yin, Meng; Glockner, James F; Takahashi, Naoki; Araoz, Philip A; Talwalkar, Jayant A; Ehman, Richard L

    2010-01-01

    Aim To evaluate the potential value of magnetic resonance elastography (MRE) for characterizing solid liver tumors. Materials and Methods Forty-four liver tumors (metastases-14, hepatocellular carcinoma- 12, hemangioma-9, cholangiocarcinoma-5, focal nodular hyperplasia-3, and hepatic adenoma-1) were evaluated with MRE. MRE was performed on a 1.5 T scanner with a modified phase-contrast, gradient echo sequence to collect axial wave images sensitized along the through-plane motion direction. The tumors were identified in T2-, T1-weighted and gadolinium enhanced T1-weighted images and the MRE images were obtained through the tumor. A stiffness map (elastogram) was generated by an automated process using an inversion algorithm. The mean shear stiffness of the tumor was calculated using a manually specified region of interest placed over the tumor in the stiffness map. The stiffness value of non-tumor bearing hepatic parenchyma was also calculated. Statistical analysis was performed on the stiffness values for differentiation between normal liver, fibrotic liver, benign tumors and malignant tumors. Results Malignant liver tumors had significantly higher mean shear stiffness than benign tumors, fibrotic liver and normal liver (10.1kPa vs. 2.7kpa (p<0.001), vs. 5.9kPa (p<0.001) and vs. 2.3kPa (p<0.001) respectively). Fibrotic livers had stiffness values overlapping both the benign and malignant tumors. Cut-off values of 5kPa accurately differentiate malignant tumors from benign tumors and normal liver parenchyma in this preliminary investigation. Conclusions MR elastography is a promising, non-invasive technique for assessing solid liver tumors. MRE may provide new, quantitative tissue characterization parameters for differentiating benign and malignant liver tumors. PMID:18492904

  5. Desmoid tumour: a rare etiology of intestinal obstruction

    PubMed Central

    Aggarwal, Gaurav; Shukla, Sumit; Maheshwari, Ankur; Mathur, Rajkumar

    2015-01-01

    Intestinal obstruction is a frequently encountered entity in surgical practice. The signs & symptoms, many a times, are suggestive of the level of obstruction, making the diagnosis of obstruction evident. There are various causes of intestinal obstruction which diversify to an enormous extent, stamping on the famous paradigm for the mysterious nature of the abdomen being referred to as the Pandora's Box. In accordance with the above saying, we report a rare case of a desmoid tumour, presenting as intestinal obstruction, which entices us to strongly believe the same. PMID:26889339

  6. Mesenchymal Tumors Can Derive from Ng2/Cspg4-Expressing Pericytes with β-Catenin Modulating the Neoplastic Phenotype.

    PubMed

    Sato, Shingo; Tang, Yuning J; Wei, Qingxia; Hirata, Makoto; Weng, Angela; Han, Ilkyu; Okawa, Atsushi; Takeda, Shu; Whetstone, Heather; Nadesan, Puvindran; Kirsch, David G; Wunder, Jay S; Alman, Benjamin A

    2016-07-26

    The cell of origin for most mesenchymal tumors is unclear. One cell type that contributes to this lineages is the pericyte, a cell expressing Ng2/Cspg4. Using lineage tracing, we demonstrated that bone and soft tissue sarcomas driven by the deletion of the Trp53 tumor suppressor, or desmoid tumors driven by a mutation in Apc, can derive from cells expressing Ng2/Cspg4. Deletion of the Trp53 tumor suppressor gene in these cells resulted in the bone and soft tissue sarcomas that closely resemble human sarcomas, while stabilizing β-catenin in this same cell type caused desmoid tumors. Comparing expression between Ng2/Cspg4-expressing pericytes lacking Trp53 and sarcomas that arose from deletion of Trp53 showed inhibition of β-catenin signaling in the sarcomas. Activation of β-catenin inhibited the formation and growth of sarcomas. Thus, pericytes can be a cell of origin for mesenchymal tumors, and β-catenin dysregulation plays an important role in the neoplastic phenotype. PMID:27425618

  7. Extra-abdominal desmoid fibromatosis: A review of management, current guidance and unanswered questions.

    PubMed

    Eastley, N; McCulloch, T; Esler, C; Hennig, I; Fairbairn, J; Gronchi, A; Ashford, R

    2016-07-01

    Extra abdominal desmoid fibromatosis is a complex condition with many recognised treatments including active observation, hormonal therapy, chemotherapy, radiotherapy and surgical resection. There is large variation in the natural history of individual desmoid tumours, with some cases progressing aggressively and others regressing spontaneously when observed alone. This combined with an absence of accurate clinical predictors of a desmoid tumour's behaviour has led to difficulties in identifying which patients would benefit most from aggressive treatment, and which could be adequately managed with a policy of active observation alone. This review explores the aetiology and common presentation of extra-abdominal desmoid fibromatosis including the condition's histopathological, clinical and radiological characteristics. The current evidence for potential predictors of desmoid tumour behaviour is also reviewed, along with the indications and evidence for the multitude of treatments available. We also summarise the published guidelines that are currently available for oncologists and surgeons managing extra-abdominal desmoid fibromatosis, and highlight some of the unanswered questions that need to be addressed to optimise the management of this condition. PMID:26965303

  8. Spatio-temporal genetic heterogeneity of CTNNB1 mutations in sporadic desmoid type fibromatosis lesions.

    PubMed

    Doyen, Jérôme; Duranton-Tanneur, Valérie; Hostein, Isabelle; Karanian-Philippe, Marie; Chevreau, Christine; Breibach, Florence; Coutts, Michael; Dadone, Bérengère; Saint-Paul, Marie-Christine; Gugenheim, Jean; Duffaud, Florence; Pedeutour, Florence

    2016-03-01

    Desmoid type fibromatosis (DT) is a rare lesion of unclear pathogenesis that most often presents a mutation of the (β-catenin) gene. The natural history and clinical evolution are highly variable between patients and to date there is no consensus on optimal therapy. We report two cases of a patient with multiple DT lesions. Molecular investigations performed in both patients on multiple tumors at different anatomical sites revealed non-identical CTNNB1 mutations. The first patient was a 39-year-old man with a history of recurrent DT. In two of the DT lesions, three different mutations were found in codons 41 and 45, respectively. The lesions showed marked inflammatory features, characterized by IgG4 positive lymphoplasmacytic infiltrates and a foreign body reaction, which increased in intensity over time. The patient was eventually treated with a COX-2 inhibitor and the remaining mass was stabilized. In the two DT lesions of the second patient, CTNNB1 mutations S45P and T41A were found. The presence of different mutations in multiple focally recurrent sporadic DT lesions indicates that they do not have a clonal relationship. Our data suggest that a CTNNB1 mutation is a necessary event probably by providing a selective growth advantage. An IgG4 host antigen response is discussed as a potential predisposing factor for one of the patients. PMID:26666421

  9. No Detectable Hypoxia in Malignant Salivary Gland Tumors: Preliminary Results

    SciTech Connect

    Wijffels, Karien; Hoogsteen, Ilse J.; Lok, Jasper; Rijken, Paulus F.J.W.; Marres, Henri A.M.; Wilde, Peter C.M. de; Kogel, Albert J. van der; Kaanders, Johannes H.A.M.

    2009-04-01

    Purpose: Hypoxia is detected in most solid tumors and is associated with malignant progression and adverse treatment outcomes. However, the oxygenation status of malignant salivary gland tumors has not been previously studied. The aim of this study was to investigate the potential clinical relevance of hypoxia in this tumor type. Methods and Materials: Twelve patients scheduled for surgical resection of a salivary gland tumor were preoperatively injected with the hypoxia marker pimonidazole and the proliferation marker iododeoxyuridine. Tissue samples of the dissected tumor were immunohistochemically stained for blood vessels, pimonidazole, carbonic anhydrase-IX, glucose transporters-1 and -3 (Glut-1, Glut-3), hypoxia-inducible factor-1{alpha}, iododeoxyuridine, and epidermal growth factor receptor. The tissue sections were quantitatively assessed by computerized image analysis. Results: The tissue material from 8 patients was of sufficient quality for quantitative analysis. All tumors were negative for pimonidazole binding, as well as for carbonic anhydrase-IX, Glut-1, Glut-3, and hypoxia-inducible factor-1{alpha}. The vascular density was high, with a median value of 285 mm{sup -2} (range, 209-546). The iododeoxyuridine-labeling index varied from <0.1% to 12.2% (median, 2.2%). Epidermal growth factor receptor expression levels were mostly moderate to high. In one-half of the cases, nuclear expression of epidermal growth factor receptor was observed. Conclusion: The absence of detectable pimonidazole binding, as well as the lack of expression of hypoxia-associated proteins in all tumors, indicates that malignant salivary gland tumors are generally well oxygenated. It is unlikely that hypoxia is a relevant factor for their clinical behavior and treatment responsiveness.

  10. Syndromes resulting from ectopic hormone-producing tumors.

    PubMed

    Gomez-Uria, A; Pazianos, A G

    1975-03-01

    Among the malignant tumors of nonendocrine origin that are capable of producing polypeptide hormones and of manifesting as different endocrine syndromes discussed here are ectopic ACTH syndrome, SIADH, and ectopic gonadotropin-producing tumors. PMID:163945

  11. Mechanical Disruption of Tumors by Iron Particles and Magnetic Field Application Results in Increased Anti-Tumor Immune Responses

    PubMed Central

    Bouchlaka, Myriam N.; Sckisel, Gail D.; Wilkins, Danice; Maverakis, Emanual; Monjazeb, Arta M.; Fung, Maxwell; Welniak, Lisbeth; Redelman, Doug; Fuchs, Alan; Evrensel, Cahit A.; Murphy, William J.

    2012-01-01

    The primary tumor represents a potential source of antigens for priming immune responses for disseminated disease. Current means of debulking tumors involves the use of cytoreductive conditioning that impairs immune cells or removal by surgery. We hypothesized that activation of the immune system could occur through the localized release of tumor antigens and induction of tumor death due to physical disruption of tumor architecture and destruction of the primary tumor in situ. This was accomplished by intratumor injection of magneto-rheological fluid (MRF) consisting of iron microparticles, in Balb/c mice bearing orthotopic 4T1 breast cancer, followed by local application of a magnetic field resulting in immediate coalescence of the particles, tumor cell death, slower growth of primary tumors as well as decreased tumor progression in distant sites and metastatic spread. This treatment was associated with increased activation of DCs in the draining lymph nodes and recruitment of both DCs and CD8(+)T cells to the tumor. The particles remained within the tumor and no toxicities were observed. The immune induction observed was significantly greater compared to cryoablation. Further anti-tumor effects were observed when MRF/magnet therapy was combined with systemic low dose immunotherapy. Thus, mechanical disruption of the primary tumor with MRF/magnetic field application represents a novel means to induce systemic immune activation in cancer. PMID:23133545

  12. Mesenteric desmoid-type fibromatosis causing secondary hypertension in a young woman

    PubMed Central

    Kim, Mi-Seon; Jung, Myung-Chul; Kim, Yong-Bong

    2014-01-01

    This report describes an 18-year-old woman presenting with abdominal distension, left flank pain, and hypertension. She had a huge abdominal mass, diagnosed as a mesenteric desmoid-type fibromatosis, causing compression of the left external iliac vessels and ureter, as well as elevated renin concentration and hypertension. After surgical removal of the mass, all signs improved including hypertension. PMID:25264535

  13. Radiation-guided drug delivery to tumor blood vessels results in improved tumor growth delay.

    PubMed

    Geng, Ling; Osusky, Katherine; Konjeti, Sekhar; Fu, Allie; Hallahan, Dennis

    2004-10-19

    Tumor blood vessels are biological targets for cancer therapy. In this study, a tumor vasculature targeting system that consisted of liposomes and lectin (WGA) was built. Liposomes were used to carry a number of liposome-friendly anti-tumoral agents along with WGA, a lectin which posseses a specific affinity for binding to inflamed endothelial cells. In order to target tumor vasculature, inflammation of endothelial cells was induced by radiation. Because ionizing radiation induces an inflammatory response in tumor vasculature, lectin-conjugates were utilized to determine whether radiation can be used to target drug delivery to tumor vessels. Wheat germ agglutinin (WGA) is one such lectin that binds to inflamed microvasculature. WGA was conjugated to liposomes containing cisplatin and administered to tumor bearing mice. Tumor growth delay was used to analyze the efficacy of cytotoxicity. FITC-conjugated WGA accumulated within irradiated tumor microvasculature. WGA was conjugated to liposomes and labeled with 111In. This demonstrated radiation-inducible tumor-selective binding. WGA-liposome-conjugates were loaded with Cisplatin and administered to mice bearing irradiated tumors. Tumors treated with a combination of liposome encapsulated cisplatin together with radiation showed a significant increase in tumor growth delay as compared to radiation alone. These findings demonstrate that ionizing radiation can be used to guide drug delivery to tumor microvasculature. PMID:15451595

  14. Interstitial laser photocoagulation therapy for liver tumors: clinical results

    NASA Astrophysics Data System (ADS)

    Amin, Zahir; Donald, J. J.; Masters, A.; Kant, R.; Lees, William R.; Bown, Stephen G.

    1993-07-01

    Interstitial laser photocoagulation is a new technique of tumor ablation using low power (2 W) laser light over a long time (500 s) via thin (0.2 mm) optical fibers. We have treated 26 patients with 70 liver metastases measuring 1 to 15 cm (median 2.5 cm). There were 1 to 8 treatment sessions per patient (median 3). Each tumor was treated via 1 to 4 optical fibers. The median energy used was 16000 J (range 3000 to 34000 J). Treatment effects were monitored in real-time with ultrasound, and the extent of tumor necrosis evaluated 1 to 3 days later using dynamic enhanced CT which showed laser-induced necrosis as well-defined new areas of non-enhancement. Greater than 50% necrosis of tumor volume was achieved in 86% (60 out of 70) of the tumors treated, and 100% necrosis in 53% (37 out of 70). Metastases under 4 cm were treated more effectively and required fewer treatment sessions than those over 4 cm. In eleven patients there was evidence of disease progression (follow-up 14 months or longer) and in 15 patients there has been overall tumor reduction (follow-up less than 1 year, median 4 months). Conclusion: With further development, ILP may offer a practical and minimally invasive alternative to major surgery for eradicating small, deep seated tumors, and debulking larger ones.

  15. Hypofractionation Results in Reduced Tumor Cell Kill Compared to Conventional Fractionation for Tumors With Regions of Hypoxia

    SciTech Connect

    Carlson, David J.; Keall, Paul J.; Loo, Billy W.; Chen, Zhe J.; Brown, J. Martin

    2011-03-15

    Purpose: Tumor hypoxia has been observed in many human cancers and is associated with treatment failure in radiation therapy. The purpose of this study is to quantify the effect of different radiation fractionation schemes on tumor cell killing, assuming a realistic distribution of tumor oxygenation. Methods and Materials: A probability density function for the partial pressure of oxygen in a tumor cell population is quantified as a function of radial distance from the capillary wall. Corresponding hypoxia reduction factors for cell killing are determined. The surviving fraction of a tumor consisting of maximally resistant cells, cells at intermediate levels of hypoxia, and normoxic cells is calculated as a function of dose per fraction for an equivalent tumor biological effective dose under normoxic conditions. Results: Increasing hypoxia as a function of distance from blood vessels results in a decrease in tumor cell killing for a typical radiotherapy fractionation scheme by a factor of 10{sup 5} over a distance of 130 {mu}m. For head-and-neck cancer and prostate cancer, the fraction of tumor clonogens killed over a full treatment course decreases by up to a factor of {approx}10{sup 3} as the dose per fraction is increased from 2 to 24 Gy and from 2 to 18 Gy, respectively. Conclusions: Hypofractionation of a radiotherapy regimen can result in a significant decrease in tumor cell killing compared to standard fractionation as a result of tumor hypoxia. There is a potential for large errors when calculating alternate fractionations using formalisms that do not account for tumor hypoxia.

  16. Primary tumors of the trachea. Results of radiation therapy

    SciTech Connect

    Fields, J.N.; Rigaud, G.; Emami, B.N.

    1989-06-15

    From 1959 to 1986, 24 patients with primary malignant tumors of the trachea received radiotherapy as all or part of treatment. Common presentations included respiratory symptoms in 20 patients and hemoptysis in 15. Thirteen patients had squamous carcinomas with undifferentiated and adenoid cystic cancers in five and four patients, respectively. Overall actuarial survival was 45% at 1 year, 25% at 5 years, and 13% at 10 years. Survival was significantly correlated to histologic type (adenoid cystic versus squamous, P less than 0.03), but not to tumor extent or to patient age or sex. Local control was attained in 10 of 24 patients overall and was more frequent for patients with tumors localized to the trachea and for patients who were treated with combined surgery and radiotherapy. For the 18 patients treated with radiotherapy alone, complete response (CR) was seen to be significantly (P less than 0.001) related to dose: six of seven (86%) patients receiving greater than or equal to 6000 cGy attained CR versus one of 11 (9%) receiving less than 6000 cGy. Three patients developed complications related to radiotherapy. Radiotherapy can provide durable local control of localized tracheal tumors and should be considered for medically inoperable patients with localized tumors and for patients with high risk of recurrence after resection.

  17. Desmoid tumour. The risk of recurrent or new disease with subsequent pregnancy: a case report

    PubMed Central

    Way, Jeffrey C.; Culham, Beverley A.

    1999-01-01

    Desmoid tumours are rare, benign tumours arising from fibrous tissue in muscle fascia or aponeurosis. They are most common in women of child-bearing age and most often appear during or after pregnancy in this age group. The recommended treatment is wide surgical excision, if possible, but unresectable tumours may be treated with radiotherapy, anticancer drugs, nonsteroidal anti-inflammatory agents or antiestrogenic compounds. The recurrence rate is high and seems to be related to the achievement of resection margins free of tumour. The literature is not specific about how to counsel woment who have had a desmoid tumour and subsequently wish to have a child. Patients should be advised that these tumours may be estrogen sensitive but subsequent pregnancy is not necessarily a risk factor for recurrence or development of new disease. PMID:10071588

  18. Direct endothelial junction restoration results in significant tumor vascular normalization and metastasis inhibition in mice

    PubMed Central

    Agrawal, Vijayendra; Maharjan, Sony; Kim, Kyeojin; Kim, Nam-Jung; Son, Jimin; Lee, Keunho; Choi, Hyun-Jung; Rho, Seung-Sik; Ahn, Sunjoo; Won, Moo-Ho; Ha, Sang-Jun; Koh, Gou Young; Kim, Young-Myeong; Suh, Young-Ger; Kwon, Young-Guen

    2014-01-01

    Tumor blood vessels are leaky and immature, which causes inadequate blood supply to tumor tissues resulting in hypoxic microenvironment and promotes metastasis. Here we have explored tumor vessel modulating activity of Sac-1004, a recently developed molecule in our lab, which directly potentiates VE-cadherin-mediated endothelial cell junction. Sac-1004 could enhance vascular junction integrity in tumor vessels and thereby inhibit vascular leakage and enhance vascular perfusion. Improved perfusion enabled Sac-1004 to have synergistic anti-tumor effect on cisplatin-mediated apoptosis of tumor cells. Interestingly, characteristics of normalized blood vessels namely reduced hypoxia, improved pericyte coverage and decreased basement membrane thickness were readily observed in tumors treated with Sac-1004. Remarkably, Sac-1004 was also able to inhibit lung and lymph node metastasis in MMTV and B16BL6 tumor models. This was in correlation with a reduction in epithelial-to-mesenchymal transition of tumor cells with considerable diminution in expression of related transcription factors. Moreover, cancer stem cell population dropped substantially in Sac-1004 treated tumor tissues. Taken together, our results showed that direct restoration of vascular junction could be a significant strategy to induce normalization of tumor blood vessels and reduce metastasis. PMID:24811731

  19. Image-Guided Percutaneous Ablation of Bone and Soft Tissue Tumors

    PubMed Central

    Kurup, A. Nicholas; Callstrom, Matthew R.

    2010-01-01

    Image-guided percutaneous ablation of bone and soft tissue tumors is an effective minimally invasive alternative to conventional therapies, such as surgery and external beam radiotherapy. Proven applications include treatment of benign primary bone tumors, particularly osteoid osteoma, as well as palliation of painful bone metastases. Use of percutaneous ablation in combination with cementoplasty can provide stabilization of metastases at risk for fracture. Local control of oligometastatic disease and treatment of desmoid tumors are emerging applications. PMID:22550367

  20. Pancreatic desmoid-type fibromatosis with beta-catenin gene mutation-Report of a case and review of the literature.

    PubMed

    Tsukamoto, Yoshitane; Imakita, Masami; Nishitani, Akiko; Ito, Toshikazu; Izukura, Masaaki; Hirota, Seiichi

    2016-05-01

    We experienced a rare case of pancreatic desmoid-type fibromatosis (DTF) in a 75-year-old Japanese woman. She was asymptomatic but routine examination including ultrasonography revealed a mass in the abdomen. For precise examination, she was referred to the regional hospital. Computed tomography showed that the mass was protruding anteriorly from the left-sided pancreas. Because of the enlargement of the mass lesion, distal pancreatectomy with splenectomy was performed after about 3 months. Macroscopically, the mass was encapsulated and approximately 8cm in diameter. Histological examination revealed that spindle or blunt stellate cells were proliferating in parallel or storiform fashion with myxoid and fibrous background. The tumor cells did not show prominent atypia and mitoses were rarely seen, suggesting that the tumor was low grade or borderline. Immunohistochemistry showed obvious nuclear staining of beta-catenin. Furthermore, analysis of beta-catenin gene revealed that the tumor had a typical missense mutation of threonine to alanine at colon 41 (T41A) in exon 3. These findings confirmed the pathological diagnosis of DTF of the pancreas. To the best of our knowledge, 18 cases of pancreatic DTF have been reported in the English literature and beta-catenin gene mutation had been examined in only one case among them. Thus, our case is the 19th pancreatic DTF and the second case with confirmed beta-catenin gene mutation. PMID:26907785

  1. Vascular Normalization Induced by Sinomenine Hydrochloride Results in Suppressed Mammary Tumor Growth and Metastasis

    PubMed Central

    Zhang, Huimin; Ren, Yu; Tang, Xiaojiang; Wang, Ke; Liu, Yang; Zhang, Li; Li, Xiao; Liu, Peijun; Zhao, Changqi; He, Jianjun

    2015-01-01

    Solid tumor vasculature is characterized by structural and functional abnormality and results in a hostile tumor microenvironment that mediates several deleterious aspects of tumor behavior. Sinomenine is an alkaloid extracted from the Chinese medicinal plant, Sinomenium acutum, which has been utilized to treat rheumatism in China for over 2000 years. Though sinomenine has been demonstrated to mediate a wide range of pharmacological actions, few studies have focused on its effect on tumor vasculature. We showed here that intraperitoneally administration of 100 mg/kg sinomenine hydrochloride (SH, the hydrochloride chemical form of sinomenine) in two orthotopic mouse breast cancer models for 14 days, delayed mammary tumor growth and decreased metastasis by inducing vascular maturity and enhancing tumor perfusion, while improving chemotherapy and tumor immunity. The effects of SH on tumor vessels were caused in part by its capability to restore the balance between pro-angiogenic factor (bFGF) and anti-angiogenic factor (PF4). However 200 mg/kg SH didn't exhibit the similar inhibitory effect on tumor progression due to the immunosuppressive microenvironment caused by excessive vessel pruning, G-CSF upregulation, and GM-CSF downregulation. Altogether, our findings suggest that SH induced vasculature normalization contributes to its anti-tumor and anti-metastasis effect on breast cancer at certain dosage. PMID:25749075

  2. Clinical Outcomes of Patients with Rare and Heavily Pretreated Solid Tumors Treated according to the Results of Tumor Molecular Profiling

    PubMed Central

    Hayden, Ingrid

    2016-01-01

    Patients with heavily pretreated advanced cancer or with rare tumors are difficult to treat. Molecular profiling (MP) of tumors to identify biomarkers that predict potential outcomes with individual therapies is an emerging strategy to guide treatment decisions. Patients with rare tumors for which standard-of-care therapy was unavailable or more common tumors for which standard-of-care options had been exhausted underwent MP at a single Australian center. Data regarding treating physicians' choice of therapy, MP results and recommendations, and patient outcomes were collected. Seven patients had received prior standard first-line therapy (PST), 16 had rare tumors, and 31 had been heavily pretreated (HPT; ≥2 prior lines). Most treatments suggested by MP (541/594; 91.1%) were common chemotherapy drugs available in generic formulations. MP-guided therapy recommendations differed from physician's recommendations in 48 patients (88.9%). MP-guided therapy produced clinical benefit (improved QOL and/or performance status, symptoms, bodyweight, or RECIST) in 19/31 (61.3%), 11/16 (68.8%), and 3/7 (42.9%) patients with HPTs, rare tumors, and PSTs, respectively, and had a PFS ratio ≥1.3 in 22/37 evaluable patients (59.5%; 95% confidence interval 44–76%). The null hypothesis that ≤15% of these patients would have a PFS ratio ≥1.3 was rejected (one-sided p < 0.0001). In conclusion, using MP to guide therapy selection is feasible in clinical practice and may improve patient outcomes. PMID:27525268

  3. Clinical Outcomes of Patients with Rare and Heavily Pretreated Solid Tumors Treated according to the Results of Tumor Molecular Profiling.

    PubMed

    Dean, Andrew; Byrne, Aisling; Marinova, Mira; Hayden, Ingrid

    2016-01-01

    Patients with heavily pretreated advanced cancer or with rare tumors are difficult to treat. Molecular profiling (MP) of tumors to identify biomarkers that predict potential outcomes with individual therapies is an emerging strategy to guide treatment decisions. Patients with rare tumors for which standard-of-care therapy was unavailable or more common tumors for which standard-of-care options had been exhausted underwent MP at a single Australian center. Data regarding treating physicians' choice of therapy, MP results and recommendations, and patient outcomes were collected. Seven patients had received prior standard first-line therapy (PST), 16 had rare tumors, and 31 had been heavily pretreated (HPT; ≥2 prior lines). Most treatments suggested by MP (541/594; 91.1%) were common chemotherapy drugs available in generic formulations. MP-guided therapy recommendations differed from physician's recommendations in 48 patients (88.9%). MP-guided therapy produced clinical benefit (improved QOL and/or performance status, symptoms, bodyweight, or RECIST) in 19/31 (61.3%), 11/16 (68.8%), and 3/7 (42.9%) patients with HPTs, rare tumors, and PSTs, respectively, and had a PFS ratio ≥1.3 in 22/37 evaluable patients (59.5%; 95% confidence interval 44-76%). The null hypothesis that ≤15% of these patients would have a PFS ratio ≥1.3 was rejected (one-sided p < 0.0001). In conclusion, using MP to guide therapy selection is feasible in clinical practice and may improve patient outcomes. PMID:27525268

  4. [Functional results of partial nephrectomy for kidney tumors].

    PubMed

    Petrov, S B; Shpilenia, E S; Shkarupa, D D

    2009-01-01

    The aim of the investigation was to analyze functional results of organ-sparing operations using radioisotopic method in combination with the investigation of serum creatinine in 31 patients. The data obtained suggest that the functional results of organ-sparing operations for neoplasms of the kidney directly depend on the time of warm renal ischemia. Warm ischemia about 15 minutes long is able to result in an ultrastructural damage of the nephron and decreased filtration level by 20-30%. A sudden change of serum creatinine on the next day after operation can be taken as a long-term prognostic factor of the kidney function. If the suggested time of stopped renal blood flow is more than 10-15 minutes, local hypothermia is advisable to protect the kidney. PMID:19947426

  5. Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study.

    PubMed

    Du, Yeting; Ter-Minassian, Monica; Brais, Lauren; Brooks, Nichole; Waldron, Amanda; Chan, Jennifer A; Lin, Xihong; Kraft, Peter; Christiani, David C; Kulke, Matthew H

    2016-08-01

    The etiology of neuroendocrine tumors remains poorly defined. Although neuroendocrine tumors are in some cases associated with inherited genetic syndromes, such syndromes are rare. The majority of neuroendocrine tumors are thought to be sporadic. We performed a genome-wide association study (GWAS) to identify potential genetic risk factors for sporadic neuroendocrine tumors. Using germline DNA from blood specimens, we genotyped 909,622 SNPs using the Affymetrix 6.0 GeneChip, in a cohort comprising 832 neuroendocrine tumor cases from Dana-Farber Cancer Institute and Massachusetts General Hospital and 4542 controls from the Harvard School of Public Health. An additional 241 controls from Dana-Farber Cancer Institute were used for quality control. We assessed risk associations in the overall cohort, and in neuroendocrine tumor subgroups. We identified no potential risk associations in the cohort overall. In the small intestine neuroendocrine tumor subgroup, comprising 293 cases, we identified risk associations with three SNPs on chromosome 12, all in strong LD. The three SNPs are located upstream of ELK3, a transcription factor implicated in angiogenesis. We did not identify clear risk associations in the bronchial or pancreatic neuroendocrine subgroups. This large-scale study provides initial evidence that presumed sporadic small intestine neuroendocrine tumors may have a genetic etiology. Our results provide a basis for further exploring the role of genes implicated in this analysis, and for replication studies to confirm the observed associations. Additional studies to evaluate potential genetic risk factors for sporadic pancreatic and bronchial neuroendocrine tumors are warranted. PMID:27492634

  6. Quantitative CT for volumetric analysis of medical images: initial results for liver tumors

    NASA Astrophysics Data System (ADS)

    Behnaz, Alexander S.; Snider, James; Chibuzor, Eneh; Esposito, Giuseppe; Wilson, Emmanuel; Yaniv, Ziv; Cohen, Emil; Cleary, Kevin

    2010-03-01

    Quantitative CT for volumetric analysis of medical images is increasingly being proposed for monitoring patient response during chemotherapy trials. An integrated MATLAB GUI has been developed for an oncology trial at Georgetown University Hospital. This GUI allows for the calculation and visualization of the volume of a lesion. The GUI provides an estimate of the volume of the tumor using a semi-automatic segmentation technique. This software package features a fixed parameter adaptive filter from the ITK toolkit and a tumor segmentation algorithm to reduce inter-user variability and to facilitate rapid volume measurements. The system also displays a 3D rendering of the segmented tumor, allowing the end user to have not only a quantitative measure of the tumor volume, but a qualitative view as well. As an initial validation test, several clinical cases were hand-segmented, and then compared against the results from the tool, showing good agreement.

  7. TNF Neutralization Results in the Delay of Transplantable Tumor Growth and Reduced MDSC Accumulation

    PubMed Central

    Atretkhany, Kamar-Sulu N.; Nosenko, Maxim A.; Gogoleva, Violetta S.; Zvartsev, Ruslan V.; Qin, Zhihai; Nedospasov, Sergei A.; Drutskaya, Marina S.

    2016-01-01

    Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells (IMCs) that, under normal conditions, may differentiate into mature macrophages, granulocytes, and dendritic cells. However, under pathological conditions associated with inflammation, cancer, or infection, such differentiation is inhibited leading to IMC expansion. Under the influence of inflammatory cytokines, these cells become MDSCs, acquire immunosuppressive phenotype, and accumulate in the affected tissue, as well as in the periphery. Immune suppressive activity of MDSCs is partly due to upregulation of arginase 1, inducible nitric oxide synthase, and anti-inflammatory cytokines, such as IL-10 and TGF-β. These suppressive factors can enhance tumor growth by repressing T-cell-mediated anti-tumor responses. TNF is a critical factor for the induction, expansion, and suppressive activity of MDSCs. In this study, we evaluated the effects of systemic TNF ablation on tumor-induced expansion of MDSCs in vivo using TNF humanized (hTNF KI) mice. Both etanercept and infliximab treatments resulted in a delayed growth of MCA 205 fibrosarcoma in hTNF KI mice, significantly reduced tumor volume, and also resulted in less accumulated MDSCs in the blood 3 weeks after tumor cell inoculation. Thus, our study uncovers anti-tumor effects of systemic TNF ablation in vivo. PMID:27148266

  8. TNF Neutralization Results in the Delay of Transplantable Tumor Growth and Reduced MDSC Accumulation.

    PubMed

    Atretkhany, Kamar-Sulu N; Nosenko, Maxim A; Gogoleva, Violetta S; Zvartsev, Ruslan V; Qin, Zhihai; Nedospasov, Sergei A; Drutskaya, Marina S

    2016-01-01

    Myeloid-derived suppressor cells (MDSCs) represent a heterogeneous population of immature myeloid cells (IMCs) that, under normal conditions, may differentiate into mature macrophages, granulocytes, and dendritic cells. However, under pathological conditions associated with inflammation, cancer, or infection, such differentiation is inhibited leading to IMC expansion. Under the influence of inflammatory cytokines, these cells become MDSCs, acquire immunosuppressive phenotype, and accumulate in the affected tissue, as well as in the periphery. Immune suppressive activity of MDSCs is partly due to upregulation of arginase 1, inducible nitric oxide synthase, and anti-inflammatory cytokines, such as IL-10 and TGF-β. These suppressive factors can enhance tumor growth by repressing T-cell-mediated anti-tumor responses. TNF is a critical factor for the induction, expansion, and suppressive activity of MDSCs. In this study, we evaluated the effects of systemic TNF ablation on tumor-induced expansion of MDSCs in vivo using TNF humanized (hTNF KI) mice. Both etanercept and infliximab treatments resulted in a delayed growth of MCA 205 fibrosarcoma in hTNF KI mice, significantly reduced tumor volume, and also resulted in less accumulated MDSCs in the blood 3 weeks after tumor cell inoculation. Thus, our study uncovers anti-tumor effects of systemic TNF ablation in vivo. PMID:27148266

  9. Endoscopic Ultrasonography-Guided Ethanol Ablation for Small Pancreatic Neuroendocrine Tumors: Results of a Pilot Study

    PubMed Central

    Choi, Jun-Ho; Oh, Dongwook; Lee, Sang Soo; Seo, Dong-Wan; Lee, Sung Koo; Kim, Myung-Hwan

    2015-01-01

    Background/Aims Endoscopic ultrasonography (EUS)-guided ethanol ablation is gaining popularity for the treatment of focal pancreatic lesions. The aim of this study was to evaluate the safety, feasibility, and treatment response after EUS-guided ethanol injection for small pancreatic neuroendocrine tumors (p-NETs). Methods This was a retrospective analysis of a prospectively collected database including 11 consecutive patients with p-NETs who underwent EUS-guided ethanol injection. Results EUS-guided ethanol injection was successfully performed in 11 patients with 14 tumors. The final diagnosis was based on histology and clinical signs as follows: 10 non-functioning neuroendocrine tumors and four insulinomas. During follow-up (median, 370 days; range, 152 to 730 days), 10 patients underwent clinical follow-up after treatment, and one patient was excluded because of loss to follow-up. A single treatment session with an injection of 0.5 to 3.8 mL of ethanol resulted in complete responses (CRs) at the 3-month radiologic imaging for seven of 13 tumors (response rate, 53.8%). Multiple treatment sessions performed in three tumors with residual viable enhancing tissue increased the number of tumors with CRs to eight of 13 (response rate, 61.5%). Mild pancreatitis occurred in three of 11 patients. Conclusions EUS-guided ethanol injection appears to be a safe, feasible, and potentially effective method for treating small p-NETs in patients who are poor surgical candidates. PMID:25844345

  10. Evaluation of the results of surgery treatment in patients with benign lung tumors

    PubMed Central

    Bagheri, Reza; Haghi, Seyed Ziaollah; Dalouee, Marziyeh Nouri; Nasiri, Zakiyeh; Rajabnejad, Ata’ollah

    2015-01-01

    Background: Lung tumors are among the common tumors and can be benign or malignant. Benign lung tumors are less common compared to the malignant types. Recognition of the clinical symptoms, types of tumors, paraclinical findings, and treatment approaches can bring better therapeutic results. The present study aims to evaluate the characteristics, diagnosis methods, and therapeutic approaches of different benign lung tumors. Materials and Methods: In this retrospective study, 32 patients with a diagnosis of benign lung tumor, who had been referred to the Mashhad University of Medical Sciences between 1981 and 2009, were studied. Some of the studied variables were symptoms, the pulmonary location involved, surgery technique, pathology findings, recurrence, and surgery complications. Data were analyzed by SPSS package version 16. Results: The average age of the patients was 51.69 ± 20.5 years. Prevalence of benign lung tumors was equal in both genders. The most common symptom was cough (31.2%); right lung involvement was more common (71.9%), and the most common sampling technique was transbronchial lung biopsy (TBLB) (62.5%); 53.1% of the patients were operated on by thoracotomy and the wedge resection technique. In 78.1% of the patients, no complications occurred after surgery. There was no recurrence. Most operations were performed in one month after the start of the symptoms (68.8%). Conclusions: Benign lung tumors are commonly diagnosed by routine radiography because most of them are asymptomatic. The most common finding in radiography is the presence of mass in the lungs. Transbronchial lung biopsy is a valuable technique to be used for diagnosis. We chose thoracotomy and wedge resection for the treatment of patients. We recommend this approach as a useful method. PMID:25624593

  11. Intra-Abdominal Desmoid Tumour (DT) with Pelvic Extension-A Case Report

    PubMed Central

    Kumar, Sathish Selva; Ramachandran, Padmini; G, Veena; Madhusudhan, Napa; Kumbhar, Uday

    2014-01-01

    Desmoid Tumour (DT) is a rare benign, myofibroblastic tumour originating from muscle fascia with tendency to recur but, it rarely metastasizes. We are reporting here a case of DT that presented as an intra-abdominal mass with pelvic extension in a patient who underwent hysterectomy for fibroid uterus seventeen years ago. A clinical diagnosis of ovarian malignancy was made. Ovarian tumour markers for surface epithelial and germ cell tumours were negative. Imaging studies suggested DT and the same was excised surgically. A histopathological diagnosis of DT was made and confirmed with immunohistochemistry (IHC) markers. DT should always be considered especially in female patients with previous history of surgery. A complete surgical excision is the treatment of choice with recurrent cases requiring radiotherapy. A differential diagnosis like sarcoma and further toxic chemotherapy can be avoided with careful histopathological evaluation and IHC confirmation of DTs. PMID:24596759

  12. A gene expression signature that distinguishes desmoid tumours from nodular fasciitis.

    PubMed

    Bacac, M; Migliavacca, E; Stehle, J-C; McKee, T; Delorenzi, M; Coindre, J-M; Guillou, L; Stamenkovic, I

    2006-03-01

    Nodular fasciitis (NF) is a rapidly growing cellular mass composed of fibroblasts/myofibroblasts, usually localized in subcutaneous tissues, that typically undergoes fibrosis and almost never recurs. Desmoid tumours (DTs) are rare forms of fibroblastic/myofibroblastic growth that arise in deep soft tissues, display a propensity for local infiltration and recurrence, but fail to metastasize. Given that both entities are primarily fibroblastic/myofibroblastic lesions with overlapping histological features, their gene expression profiles were compared to identify differentially expressed genes that may provide not only potential diagnostic markers, but also clues as to the pathogenesis of each disorder. Differentially expressed transcripts (89 clones displaying increased expression in DTs and 246 clones displaying increased expression in NF) included genes encoding several receptor and non-receptor tyrosine kinases (EPHB3, PTPRF, GNAZ, SYK, LYN, EPHA4, BIRC3), transcription factors (TWIST1, PITX2, EYA2, OAS1, MITF, TCF20), and members of the Wnt signalling pathway (AXIN2, WISP1, SFRP). Remarkably, almost one-quarter of the differentially expressed genes encode proteins associated with inflammation and tissue remodelling, including members of the interferon (IFN), tumour necrosis factor (TNF), and transforming growth factor beta (TGF-beta) signalling pathways as well as metalloproteinases (MMP1, 9, 13, 23), urokinase plasminogen activator (PLAU), and cathepsins. The observations provide the first comparative molecular characterization of desmoid tumours and nodular fasciitis and suggest that selected tyrosine kinases, transcription factors, and members of the Wnt, TGF-beta, IFN, and TNF signalling pathways may be implicated in influencing and distinguishing their fate. PMID:16440290

  13. Radiation induction of drug resistance in RIF-1: Correlation of tumor and cell culture results

    SciTech Connect

    Moulder, J.E.; Hopwood, L.E.; Volk, D.M.; Davies, B.M. )

    1991-02-01

    The RIF-1 tumor line contains cells that are resistant to various anti-neoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), adriamycin (ADR), and etoposide (VP16). The frequency of these drug-resistant cells is increased after irradiation. The frequency of drug-resistant cells and the magnitude of radiation-induced drug resistance are different in cell culture than in tumors. The dose-response and expression time relationships for radiation induction of drug resistance observed in RIF-1 tumors are unusual.We hypothesize that at high radiation doses in vivo, we are selecting for cells that are both drug resistant and radiation resistant due to microenvironmental factors, whereas at low radiation doses in vivo and all radiation doses in vitro, we are observing true mutants. These studies indicate that there can be significant differences in drug-resistance frequencies between tumors and their cell lines of origin, and that radiation induction of drug resistance depends significantly on whether the induction is done in tumors or in cell culture. These results imply that theories about the induction of drug resistance that are based on cell culture studies may be inapplicable to the induction of drug resistance in tumors.

  14. Current results from treatment of bladder tumors with total cystectomy at roswell park memorial institute.

    PubMed

    Wajsman, Z; Merrin, C; Moore, R; Murphy, G P

    1975-06-01

    Results of our recent cystectomy series revealed good survival for patients with superficial bladder tumors. The morbidity rate was low, 8.6 per cent. Our series showed a statistically significant postoperative morbidity rate in a high risk patient group, then justifying preoperative selection of patients as condidates for this major operation. However, we believe that despite relatively good results in reducing the morbitidy and mortality rates and improvement in survival, the over-all results in treatment of bladder tumors with operation alone are still unsatisfactory and there is an urgent need to develop and to investigate new and combined modalities of treatment. PMID:807747

  15. Occurrence of Multiple Tumors in a Patient.

    PubMed

    Tan, Elaine; Friedman, Mark; Coppola, Domenico

    2015-10-01

    An 81-year-old man initially presented with a right forearm mass that was found to be myxofibrosarcoma. In addition, he was found to have gastric and intragastric masses identified as neuroendocrine tumor (NET) and gastrointestinal stromal tumor (GIST; presenting synchronously), respectively, as well as a new left upper quadrant mass identified as desmoid tumor in the colon. The patient complained of melena, which was found to be due to metastatic myxofibrosarcoma in the transverse colon. Several reports have associated GIST with NET and some reports have associated GIST with sarcomas and NET with sarcomas; however, this is the first report to document all these tumors in a single patient. Several factors may have contributed to the development of these tumors, including growth factors secreted by NET, KIT mutation of GIST predisposing to additional tumors, immunosuppressed state, or an underlying genetic syndrome. This case highlights the importance of investigating for additional malignancies when a primary malignancy is discovered. PMID:26678978

  16. Next-generation sequencing is highly sensitive for the detection of beta-catenin mutations in desmoid-type fibromatoses.

    PubMed

    Aitken, Sarah J; Presneau, Nadège; Kalimuthu, Sangeetha; Dileo, Palma; Berisha, Fitim; Tirabosco, Roberto; Amary, M Fernanda; Flanagan, Adrienne M

    2015-08-01

    Desmoid-type fibromatoses are locally aggressive and frequently recurrent tumours, and an accurate diagnosis is essential for patient management. The majority of sporadic lesions harbour beta-catenin (CTNNB1) mutations. We used next-generation sequencing to detect CTNNB1 mutations and to compare the sensitivity and specificity of next-generation sequencing with currently employed mutation detection techniques: mutation-specific restriction enzyme digestion and polymerase chain reaction amplification. DNA was extracted from formalin-fixed paraffin-embedded needle biopsy or resection tissue sections from 144 patients with sporadic desmoid-type fibromatoses, four patients with syndrome-related desmoid-type fibromatoses and 11 morphological mimics. Two primer pairs were designed for CTNNB1 mutation hotspots. Using ≥10 ng of DNA, libraries were generated by Fluidigm and sequenced on the Ion Torrent Personal Genome Machine. Next-generation sequencing had a sensitivity of 92.36 % (133/144, 95 % CIs: 86.74 to 96.12 %) and a specificity of 100 % for the detection of CTNNB1 mutations in desmoid-type fibromatoses-like spindle cell lesions. All mutations detected by mutation-specific restriction enzyme digestion were identified by next-generation sequencing. Next-generation sequencing identified additional mutations in 11 tumours that were not detected by mutation-specific restriction enzyme digestion, two of which have not been previously described. Next-generation sequencing is highly sensitive for the detection of CTNNB1 mutations. This multiplex assay has the advantage of detecting additional mutations compared to those detected by mutation-specific restriction enzyme digestion (sensitivity 82.41 %). The technology requires minimal DNA and is time- and cost-efficient. PMID:25838078

  17. Tumor

    MedlinePlus

    ... be removed because of their location or harmful effect on the surrounding normal brain tissue. If a tumor is cancer , possible treatments may include: Chemotherapy Radiation Surgery Targeted cancer therapy Biologic therapy Other treatment options

  18. Breast Carcinomatous Tumoral Emboli Can Result From Encircling Lymphovasculogenesis Rather Than Lymphovascular Invasion

    PubMed Central

    Mahooti, Sepi; Porter, Kyle; Alpaugh, Mary L.; Ye, Yin; Xiao, Yi; Jones, Susie; Tellez, Joseph D.; Barsky, Sanford H.

    2010-01-01

    The canonical view of the origin of tumor lymphovascular emboli is that they usually originate from lymphovascular invasion as part of a multistep metastatic process. Recent experimental evidence has suggested that metastasis can occur earlier than previously thought and we found evidence that tumor emboli formation can result from the short-circuiting step of encircling lymphovasculogenesis. Experimentally, we used a xenograft of human inflammatory breast cancer (MARY-X), a model that exhibited florid tumor emboli, to generate tumoral spheroids in vitro. In observational studies, we chose human breast carcinoma cases where there appeared to be a possible transition of in situ carcinoma to lymphovascular emboli without intervening stromal invasion. These cases were studied by morphometry as well as IHC with tumor proliferation (Ki-67) and adhesion (E-cadherin) markers, myoepithelial (p63), as well as endothelial (podoplanin [D2-40], CD31, VEGFR-3, Prox-1) markers. Unlabelled spheroids coinjected with either GFP or RFP-human myoepithelial cells or murine embryonal fibroblasts (MEFs) gave rise to tumors which exhibited GFP/RFP immunoreactivity within the cells lining the emboli-containing lymphovascular channels. In vitro studies demonstrated that the tumoral spheroids induced endothelial differentiation of cocultured myoepithelial cells and MEFs, measured by real time PCR and immunofluorescence. In humans, the in situ clusters exhibited similar proliferation, E-cadherin immunoreactivity and size as the tumor emboli (p =.5), suggesting the possibility that the latter originated from the former. The in situ clusters exhibited a loss (50%-100%) of p63 myoepithelial immunoreactivity but not E-cadherin epithelial immunoreactivity. The tumor emboli were mainly present within lymphatic channels whose dual p63/CD31, p63/D2-40 and p63/VEGFR-3 and overall weak patterns of D2-40/CD31/VEGFR-3 immunoreactivities suggested that they represented immature and newly created

  19. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    SciTech Connect

    Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E.

    2015-08-14

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

  20. Sequential Salinomycin Treatment Results in Resistance Formation through Clonal Selection of Epithelial-Like Tumor Cells.

    PubMed

    Kopp, Florian; Hermawan, Adam; Oak, Prajakta Shirish; Ulaganathan, Vijay Kumar; Herrmann, Annika; Elnikhely, Nefertiti; Thakur, Chitra; Xiao, Zhiguang; Knyazev, Pjotr; Ataseven, Beyhan; Savai, Rajkumar; Wagner, Ernst; Roidl, Andreas

    2014-12-01

    Acquiring therapy resistance is one of the major obstacles in the treatment of patients with cancer. The discovery of the cancer stem cell (CSC)-specific drug salinomycin raised hope for improved treatment options by targeting therapy-refractory CSCs and mesenchymal cancer cells. However, the occurrence of an acquired salinomycin resistance in tumor cells remains elusive. To study the formation of salinomycin resistance, mesenchymal breast cancer cells were sequentially treated with salinomycin in an in vitro cell culture assay, and the resulting differences in gene expression and salinomycin susceptibility were analyzed. We demonstrated that long-term salinomycin treatment of mesenchymal cancer cells resulted in salinomycin-resistant cells with elevated levels of epithelial markers, such as E-cadherin and miR-200c, a decreased migratory capability, and a higher susceptibility to the classic chemotherapeutic drug doxorubicin. The formation of salinomycin resistance through the acquisition of epithelial traits was further validated by inducing mesenchymal-epithelial transition through an overexpression of miR-200c. The transition from a mesenchymal to a more epithelial-like phenotype of salinomycin-treated tumor cells was moreover confirmed in vivo, using syngeneic and, for the first time, transgenic mouse tumor models. These results suggest that the acquisition of salinomycin resistance through the clonal selection of epithelial-like cancer cells could become exploited for improved cancer therapies by antagonizing the tumor-progressive effects of epithelial-mesenchymal transition. PMID:25500079

  1. Silencing of Doublecortin-Like (DCL) Results in Decreased Mitochondrial Activity and Delayed Neuroblastoma Tumor Growth

    PubMed Central

    Verissimo, Carla S.; Elands, Rachel; Cheng, Sou; Saaltink, Dirk-Jan; ter Horst, Judith P.; Alme, Maria N.; Pont, Chantal; van de Water, Bob; Håvik, Bjarte; Fitzsimons, Carlos P.; Vreugdenhil, Erno

    2013-01-01

    Doublecortin-like (DCL) is a microtubule-binding protein crucial for neuroblastoma (NB) cell proliferation. We have investigated whether the anti-proliferative effect of DCL knockdown is linked to reduced mitochondrial activity. We found a delay in tumor development after DCL knockdown in vivo in doxycycline-inducible NB tumor xenografts. To understand the mechanisms underlying this tumor growth retardation we performed a series of in vitro experiments in NB cell lines. DCL colocalizes with mitochondria, interacts with the mitochondrial outer membrane protein OMP25/ SYNJ2BP and DCL knockdown results in decreased expression of genes involved in oxidative phosphorylation. Moreover, DCL knockdown decreases cytochrome c oxidase activity and ATP synthesis. We identified the C-terminal Serine/Proline-rich domain and the second microtubule-binding area as crucial DCL domains for the regulation of cytochrome c oxidase activity and ATP synthesis. Furthermore, DCL knockdown causes a significant reduction in the proliferation rate of NB cells under an energetic challenge induced by low glucose availability. Together with our previous studies, our results corroborate DCL as a key player in NB tumor growth in which DCL controls not only mitotic spindle formation and the stabilization of the microtubule cytoskeleton, but also regulates mitochondrial activity and energy availability, which makes DCL a promising molecular target for NB therapy. PMID:24086625

  2. Total enbloc spondylectomy for metastatic high grade spinal tumors: Early results

    PubMed Central

    Patil, Sanganagouda S; Nene, Abhay M

    2016-01-01

    Background: High grade metastatic spinal tumors are most common and are invasive. These patients can succumb to disease progression if not treated timely. Although considered as invasive and morbid, total enbloc spondylectomy (TES) in selected cases has better survival rates. The authors describe the results of TES for high grade metastatic spinal tumors. Materials and Methods: Five patients (four females and one male) underwent TES for solitary metastatic vertebral lesion between November 2012 and January 2014. These patients presented to us with spinal instability, unrelenting severe spinal pain and/or with severe progressive radiculopathy. Average age was 46.2 years (range 39–62 years). After complete investigations, computed tomography scan, magnetic resonance imaging scan and positron emission tomography (PET) scan, it was confirmed that these patients had high grade solitary vertebral metastatic tumor. Results: Average duration of followup was 18 months (range 16–20 months). The average preoperative visual analog scale score of 9.4 (range 9–10) improved to 2 (range 1–4) at last followup. Average blood loss was 1440 mL (range 1000–2000 mL). Average duration of surgery was 198 min (range 180–240 min). Significant pain relief was noticed in each patient in the immediate postoperative period and during followups. These patients attained complete functional activities of daily living with in a month. The imaging showed implants in situ, no recurrence of tumor, and no activity on PET scan at the final followup. Conclusion: The present series shows favorable short term results of TES for solitary, metastatic, high grade vertebral body tumors by a team approach. PMID:27512215

  3. Obstructive hydrocephalus as a result of giant cell tumor of the thoracic spine: A case report

    PubMed Central

    WEI, CHENG-YU; CHEN, SHUO-TSUNG; TAI, HSU-CHIH; WANG, WEN-BING; CHANG, CHI-CHU; WANG, YAO-CHIN; WEI, LI; KUNG, WOON-MAN

    2016-01-01

    Giant cell tumors (GCTs) are rare bone tumors that account for ~5% of all primary bone tumors. When GCTs occur in the spine, patients usually present with localized pain and neurological symptoms, such as radiating pain or hyperesthesia. In the current report, an unusual case of a GCT of the thoracic spine associated with hydrocephalus is described. A 48-year-old male presented with urinary retention, loss of sensation in the lower limbs and inability to walk. The patient eventually developed hydrocephalus combined with altered consciousness, indicated by an inability to follow simple commands. Magnetic resonance (MR) imaging demonstrated the presence of a soft tissue mass at the T2 level, and biopsy examination of the tissue confirmed that it was a GCT. The patient experienced a sudden loss of consciousness due to an acute episode of obstructive hydrocephalus. A ventriculoperitoneal shunting procedure was performed to treat the hydrocephalus, and the patient regained normal consciousness, although the paraplegia persisted. An MR examination performed 30 months following surgery demonstrated that the tumor size was stable, consistent with the slow growth that is characteristic of GCTs. Diagnosis of GCTs may be challenging, and relies on radiographic and histopathologic findings. Although rare, acute hydrocephalus as a result of GCTs should not be excluded from a differential diagnosis. PMID:26870164

  4. [Possibilities for inhibiting tumor-induced angiogenesis: results with multi-target tyrosine kinase inhibitors].

    PubMed

    Török, Szilvia; Döme, Balázs

    2012-03-01

    Functional blood vasculature is essential for tumor progression. The main signalization pathways that play a key role in the survival and growth of tumor vessels originate from the VEGF-, PDGF- and FGF tyrosine kinase receptors. In the past decade, significant results have been published on receptor tyrosine kinase inhibitors (RTKIs). In this paper, the mechanisms of action and the results so far available of experimental and clinical studies on multi-target antiangiogenic TKIs are discussed. On the one hand, notable achievements have been made recently and these drugs are already used in clinical practice in some patient populations. On the other hand, the optimal combination and dosage of these drugs, selection of the apropriate biomarker and better understanding of the conflicting role of PDGFR and FGFR signaling in angiogenesis remain future challenges. PMID:22403757

  5. Results of fast neutron teletherapy for locally advanced head and neck tumors

    SciTech Connect

    Battermann, J.J.; Breur, K.

    1981-08-01

    An analysis is given of the results of fast neutron therapy for locally advanced tumors of the head and neck region. All patients were treated five times per week with a 14 MeV d + T neutron beam and received dosages of about 19 Gy/sub ntumors were treated in this pilot study, the survival time is rather short for most patients. Only 8 patients are alive at the time of writing. The results of treatment for inoperable malignancies of the major salivary glands are very promising, as initial complete regression was achieved in over 90% (12/13).

  6. Implementation and experimental results of 4D tumor tracking using robotic couch

    SciTech Connect

    Buzurovic, I.; Yu, Y.; Werner-Wasik, M.; Biswas, T.; Anne, P. R.; Dicker, A. P.; Podder, T. K.

    2012-11-15

    Purpose: This study presents the implementation and experimental results of a novel technique for 4D tumor tracking using a commercially available and commonly used treatment couch and evaluates the tumor tracking accuracy in clinical settings. Methods: Commercially available couch is capable of positioning the patient accurately; however, currently there is no provision for compensating physiological movement using the treatment couch in real-time. In this paper, a real-time couch tracking control technique is presented together with experimental results in tumor motion compensation in four dimensions (superior-inferior, lateral, anterior-posterior, and time). To implement real-time couch motion for tracking, a novel control system for the treatment couch was developed. The primary functional requirements for this novel technique were: (a) the treatment couch should maintain all previous/normal features for patient setup and positioning, (b) the new control system should be used as a parallel system when tumor tracking would be deployed, and (c) tracking could be performed in a single direction and/or concurrently in all three directions of the couch motion (longitudinal, lateral, and vertical). To the authors' best knowledge, the implementation of such technique to a regular treatment couch for tumor tracking has not been reported so far. To evaluate the performance of the tracking couch, we investigated the mechanical characteristics of the system such as system positioning resolution, repeatability, accuracy, and tracking performance. Performance of the tracking system was evaluated using dosimetric test as an endpoint. To investigate the accuracy of real-time tracking in the clinical setting, the existing clinical treatment couch was replaced with our experimental couch and the linear accelerator was used to deliver 3D conformal radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) treatment plans with and without tracking. The results of

  7. Surveillance Strategies for Sarcoma: Results of a Survey of Members of the Musculoskeletal Tumor Society

    PubMed Central

    2016-01-01

    Background. Surveillance is crucial to oncology, yet there is scant evidence to guide strategies. Purpose. This survey identified sarcoma surveillance strategies for Musculoskeletal Tumor Society (MSTS) members and rationales behind them. Understanding current practice should facilitate studies to generate evidence-based surveillance protocols. Methods. Permission was granted by the Research and Executive Committee of the MSTS to survey members on surveillance strategies. First, the questionnaire requested demographic and clinical practice information. Second, the survey focused on clinicians' specific surveillance soft tissue and bone sarcoma protocols. Results. 20 percent of MSTS members completed the survey. The primary rationale for protocols was training continuation, followed by published guidelines, and finally personal interpretation of the literature. 95% of the respondents believe that additional studies regarding appropriate surveillance protocols are needed. 87% reported patient concerns regarding radiation exposure from surveillance imaging. For soft tissue and bone sarcoma local recurrence, responders identified surgical margin, histologic grade, and tumor size as the most important factors. For metastases, important risk factors identified included histologic grade, tumor size, and histologic type. Protocols demonstrated wide variation. Conclusion. This survey demonstrates that surveillance strategies utilized by MSTS members are not evidence-based, providing rationale for multi-institutional studies. It also confirms the public health issue of excessive radiation exposure. PMID:27478404

  8. Results of d+T fast neutron irradiation on advanced tumors of bladder and rectum

    SciTech Connect

    Battermann, J.J.

    1982-12-01

    From November, 1975 to November, 1981, around 400 patients were irradiated with 14 MeV d+T fast neutrons at the Antoni van Leeuwenhoek Hospital in Amsterdam. Special interest was focused on inoperable tumors of bladder and rectum. During the pilot phase of the study 47 patients were treated, mostly via two parallel opposed ports with dosages that ranged from 18 to more than 22 Gy. Although persistent local control was achieved in 23 patients (48%), 14 patients (29%) died of severe complications. By the introduction of a six field technique, the fatal complication rate could be reduced significantly. Since May 1978 patients were randomized in a three arm trial, using two dose levels on the neutron site. The preliminary results of a group of 91 patients show a similar survival in the three treatment arms with a somewhat better local control rate for high dose neutrons. An attempt was made to estimate RBE values for tumor control and normal tissue reactions by comparing the data for neutron irradiation with the data obtained with photons on a similar group of patients. From the values derived it must be concluded that the gain for neutron irradiation on these tumors in the pelvis will be negligible.

  9. Results of d+T fast neutron irradiation on advanced tumors of bladder and rectum

    SciTech Connect

    Battermann, J.J.

    1982-12-01

    From November, 1975 to November, 1981, around 400 patients were irradiated with 14 MeV d+T fast neutrons at the Antoni van Leeuwenhoek Hospital in Amsterdam. Special interest was focused on inoperable tumors of bladder and rectum. During the pilot phase of the study 47 patients were treated, mostly via two parallel opposed ports with dosages that ranged from 18 to more than 22 Gy. Although persistent local control was achieved in 23 patients (48%), 14 patients (29%) died of severe complications. By the introduction of a six field technique, the fatal complication rate could be reduced significantly. Since May 1978 patients were randomized in a three arm trial, using two dose levels on the neutron site. The preliminary results of a group of 91 patients show a similar survival in the three treatment arms with a somewhat better local control rate for high dose neutrons. An attempt was made to estimate RBE values for tumor control and normal tissue reaction by comparing the data for neutron irradiation with the data obtained with photons on a similar group of patients. From the values derived it must be concluded that the gain for neutron irradiation on these tumors in the pelvis will be negligible.

  10. Evaluation of Clinical Results and Complications of Structural Allograft Reconstruction after Bone Tumor Surgery

    PubMed Central

    Gharedaghi, Mohammad; Peivandi, Mohammad Taghi; Mazloomi, Mehdi; Shoorin, Hasan Rahimi; Hasani, Mohammad; Seyf, Parham; Khazaee, Fatemeh

    2016-01-01

    Background: Massive bone allograft is an option in cases of limb preservation and reconstruction after massive benign and malignant bone tumor resection. The purpose of this study was to analyze the outcome of these procedures at Imam Reza Hospital, Mashhad University of Medical Sciences. Methods: In this study, 113 cases have been presented. Eleven cases were excluded (patients has a traumatic defect or they passed away before the completion of the study’s two-year follow up period). Each patient completed a questionnaire, went through a physical examination and, if indicated, X-ray information was collected. The patients were divided into three groups: chemotherapy, chemotherapy plus radiation therapy, and no-adjuvant-therapy. Results: Fifty-four cases were male and the mean age was 24.5±5.39. The number of cases and indications for surgery were: 33 cases of aggressive benign tumors or low grade malignant bone tumors (large bone defects) including 16 germ cell tumors, eight aneurysmal bone cysts, five low grade osteosarcomas, and four chondrosarcomas. Another 69 cases were high-grade malignant bone tumors including 42 osteosarcomas, 21 Ewing’s sarcoma, and six other high grade osteosarcomas. Patients were divided into three groups: the first group received no adjuvant therapy, the second group received chemotherapy, and the third group received chemotherapy plus radiotherapy. The location of tumors were as follows: eight cases in the pelvic bone, 12 in the proximal femur, 18 in the femoral shaft, 36 in the distal femur, 12 in the proximal tibia, and 16 in the humeral bone. The 12 cases of proximal femoral defects were reconstructed by allograft composite prosthesis, 18 diaphyseal defects with intercalary allograft, and 36 distal femoral defects were reconstructed using osteoarticular allograft. The rate of deep infection was 7:8% (eight patients) and in this regard, we found a significant difference among the three groups, such that most cases of infection

  11. Treatment of Giant Fibroadenoma in Young Women: Results after Tumor Excision without Reconstructive Surgery

    PubMed Central

    Hille-Betz, U.; Klapdor, R.; Henseler, H.; Soergel, P.; Länger, F.

    2015-01-01

    Introduction: Giant fibroadenoma (GFA) of the breast is defined as fibroadenoma larger than 5 cm, usually presenting unilaterally and manifesting as breast asymmetry or deformity of the breast. Material and Methods: A retrospective database search was done of all patients with giant fibroadenoma who underwent surgery for GFA in the breast center of Hanover Medical School between 2007 and 2014; all patients with GFA were followed up. Data were analyzed with regard to tumor and patient characteristics and esthetic outcome. Results: A total of 13 patients with symptomatic GFA underwent surgery between 2007 and 2014. Mean patient age was 21.2 years (range 14–31 years). In 8 of 13 patients the tumor had resulted in breast deformity and/or breast asymmetry. Average size of the mass was 10.2 cm (range 8.5–12 cm) and average weight was 203.6 g (range 151.2–323.5 g). Initial clinical suspicion of GFA was confirmed by ultrasound examination. Preoperative core biopsy revealed fibroadenoma in 8/13 cases, cellular fibroepithelial lesions with a differential diagnosis of benign phyllodes tumor in 3 cases and unspecific histological findings in the remaining 2 cases. Conclusion: Excision was done using an inframammary or periareolar approach without reconstructive plasty. The cosmetic results were good, as were the outcomes on follow-up. We therefore favor this surgical technique to treat giant fibroadenoma of similar size to those described above. PMID:26500369

  12. Heating stents with radio frequency energy to prevent tumor ingrowth: modeling and experimental results

    NASA Astrophysics Data System (ADS)

    Ryan, Thomas P.; Lawes, Kate; Goldberg, S. Nahum

    1998-04-01

    Stents are often inserted into internal orifices to treat blockage due to tumor ingrowth. Stents are favored due to their minimally invasive nature, possible avoidance of a surgical procedure, and their ability to palliate surgically non-resectable disease. Because of rapid tumor growth however, a treatment means to prevent overgrowth through the stent and resultant blockage is required. To further this goal, experiments were performed in which a stent was placed in tissue and heated with radiofrequency (RF) energy to coagulate a cylinder of tissue, thereby eradicating viable tissue in the proximity of the stent. Temperatures were measured at the central stent surface and edges over time during a 5 - 10 minute heating in phantom and in fresh tissue. In addition, a finite element model was used to simulate the electric field and temperature distribution. Blood flow was also introduced in the model by evaluating RF application to stents to determine effectiveness of the energy applications. Changing perfusion and tissue electrical conductivity as a function of temperature was applied as the tissue was heated to 100 degree(s)C. Results from the electric field model will be shown as well as the thermal distribution over time from the simulations. Lastly, results from the damage integral will be discussed.

  13. Increased midkine expression correlates with desmoid tumour recurrence: a potential biomarker and therapeutic target.

    PubMed

    Colombo, Chiara; Creighton, Chad J; Ghadimi, Markus P; Bolshakov, Svetlana; Warneke, Carla L; Zhang, Yiqun; Lusby, Kristelle; Zhu, Shirley; Lazar, Alexander J; West, Robert B; van de Rijn, Matt; Lev, Dina

    2011-12-01

    Desmoid tumours (DTs) are soft tissue monoclonal neoplasms exhibiting a unique phenotype, consisting of aggressive local invasiveness without metastatic capacity. While DTs can infrequently occur as part of familial adenomatosis polyposis, most cases arise sporadically. Sporadic DTs harbour a high prevalence of CTNNB1 mutations and hence increased β-catenin signalling. However, β-catenin downstream transcriptional targets and other molecular deregulations operative in DT inception and progression are currently not well defined, contributing to the lack of sensitive molecular prognosticators and efficacious targeted therapeutic strategies. We compared the gene expression profiles of 14 sporadic DTs to those of five corresponding normal tissues and six solitary fibrous tumour specimens. A DT expression signature consisting of 636 up- and 119 down-regulated genes highly enriched for extracellular matrix, cell adhesion and wound healing-related proteins was generated. Furthermore, 98 (15%) of the over-expressed genes were demonstrated to contain a TCF/LEF consensus binding site in their promoters, possibly heralding direct β-catenin downstream targets relevant to DT. The protein products of three of the up-regulated DT genes: ADAM12, MMP2 and midkine, were found to be commonly expressed in a large cohort of human DT samples assembled on a tissue microarray. Interestingly, enhanced midkine expression significantly correlated with a higher propensity and decreased time for primary DT recurrence (log-rank p = 0.0025). Finally, midkine was found to enhance the migration and invasion of primary DT cell cultures. Taken together, these studies provide insights into potential DT molecular aberrations and novel β-catenin transcriptional targets. Further studies to confirm the utility of midkine as a clinical DT molecular prognosticator and a potential therapeutic target are therefore warranted. Raw gene array data can be found at: http://smd.stanford.edu/ PMID:21826666

  14. Preliminary oncological results of endosopic laser surgery in advanced head and neck tumors

    NASA Astrophysics Data System (ADS)

    Baker-Schreyer, Antonio; Sadick, Haneen; Juncker, Cathrine; Bergler, Wolfgang; Hoermann, Karl

    1998-01-01

    Lasersurgery has established itself in the treatment of minor tumors (T1 - T2) of the upper aerodigestive tract. However, advanced carcinomas of the head and neck (T3 - T4) are generally treated with conventional surgical procedures which include pharyngolaryngectomy. The purpose of this study was to evaluate the oncological outcome of endoscopic lasersurgery in advanced head and neck tumors and to compare the results with conventional surgical procedures. Between January 1994 to December 1996, 86 patients with advanced squamous cell carcinomas of the larynx and hypopharynx underwent endoscopic lasersurgery instead of pharyngolaryngectomy as a curative measure. Besides the recurrence and survival rate, the necessity of tracheostomy, postoperative complications and the mean duration of hospitalization were documented. The results showed that the recurrence and survival rate were similar or even better after conventional pharyngolaryngectomy, whereas the patients' postoperative rehabilitation was better after lasersurgery. In this contribution the indication for lasersurgical intervention or pharyngolaryngectomy in advanced carcinomas of the head and neck is discussed.

  15. Antigen targeting to dendritic cells combined with transient regulatory T cell inhibition results in long-term tumor regression

    PubMed Central

    Unger, Wendy WJ; Mayer, Christian T; Engels, Steef; Hesse, Christina; Perdicchio, Maurizio; Puttur, Franz; Streng-Ouwehand, Ingeborg; Litjens, Manja; Kalay, Hakan; Berod, Luciana; Sparwasser, Tim; van Kooyk, Yvette

    2014-01-01

    Therapeutic vaccinations against cancer are still largely ineffective. Major caveats are inefficient delivery of tumor antigens to dendritic cells (DCs) and excessive immune suppression by Foxp3+ regulatory T cells (Tregs), resulting in defective T cell priming and failure to induce tumor regression. To circumvent these problems we evaluated a novel combinatorial therapeutic strategy. We show that tumor antigen targeting to DC-SIGN in humanized hSIGN mice via glycans or specific antibodies induces superior T cell priming. Next, this targeted therapy was combined with transient Foxp3+ Treg depletion employing hSIGNxDEREG mice. While Treg depletion alone slightly delayed B16-OVA melanoma growth, only the combination therapy instigated long-term tumor regression in a substantial fraction of mice. This novel strategy resulted in optimal generation of antigen-specific activated CD8+ T cells which accumulated in regressing tumors. Notably, Treg depletion also allowed the local appearance of effector T cells specific for endogenous B16 antigens. This indicates that antitumor immune responses can be broadened by therapies aimed at controlling Tregs in tumor environments. Thus, transient inhibition of Treg-mediated immune suppression potentiates DC targeted antigen vaccination and tumor-specific immunity. PMID:26405564

  16. Giant Cell Tumor of Tendon Sheath in Guyon's Canal Causing Ulnar Tunnel Syndrome A Case Report and Review of the Literature

    PubMed Central

    Francisco, Ben S.; Agarwal, Jayant P.

    2009-01-01

    Objective: Giant cell tumor of tendon sheath is a rare cause of ulnar tunnel syndrome. We present a case of a 37-year-old woman who presented with decreased sensation and weakness of grip of the right hand. Magnetic resonance imaging indicated the presence of a mass in the hypothenar eminence and showed that the mass was associated with the flexor carpi ulnaris tendon and displacing the ulnar neurovascular bundle. A differential diagnosis included desmoid tumor and sarcoma. Methods: Surgical examination showed a mass that was associated with the flexor carpi ulnaris tendon and flexor retinaculum located in the distal portion of Guyon's canal and intertwined with the ulnar nerve and displacing the ulnar artery. The mass was removed and Guyon's canal was released. Results: Histological examination indicated a diagnosis of giant cell tumor of tendon sheath (GCTTS). Postoperatively, the patient had fully restored sensory and motor function of the right hand. Conclusions: Although GCTTS is the most common solid, soft-tissue lesion of the hand, it is rarely diagnosed properly preoperatively. Therefore, it is imperative to always include GCTTS in the differential diagnosis of any mass of the hand. PMID:19252681

  17. Pediatric Fibroblastic and Myofibroblastic Tumors: A Pictorial Review.

    PubMed

    Sargar, Kiran M; Sheybani, Elizabeth F; Shenoy, Archana; Aranake-Chrisinger, John; Khanna, Geetika

    2016-01-01

    Pediatric fibroblastic and myofibroblastic tumors are a relatively common group of soft-tissue proliferations that are associated with a wide spectrum of clinical behavior. These tumors have been divided into the following categories on the basis of their biologic behavior: benign (eg, myositis ossificans, myofibroma, fibromatosis colli), intermediate-locally aggressive (eg, lipofibromatosis, desmoid fibroma), intermediate-rarely metastasizing (eg, inflammatory myofibroblastic tumors, infantile fibrosarcoma, low-grade myofibroblastic sarcoma), and malignant (eg, fibromyxoid sarcoma, adult fibrosarcoma). Imaging has a key role in the evaluation of lesion origin, extent, and involvement with adjacent structures, and in the treatment management and postresection surveillance of these tumors. The imaging findings of these tumors are often nonspecific. However, certain imaging features, such as low or intermediate signal intensity on T2-weighted magnetic resonance images and extension along fascial planes, support the diagnosis of a fibroblastic or myofibroblastic tumor. In addition, certain tumors have characteristic imaging findings (eg, multiple subcutaneous or intramuscular lesions in infantile myofibromatosis, plaquelike growth pattern of Gardner fibroma, presence of adipose tissue in lipofibromatosis) or characteristic clinical manifestations (eg, great toe malformations in fibrodysplasia ossificans fibroma, neonatal torticollis in fibromatosis colli) that suggest the correct diagnosis. Knowledge of the syndrome associations of some of these tumors-for example, the association between familial adenomatous polyposis syndrome and both Gardner fibroma and desmoid fibromatosis, and that between nevoid basal cell carcinoma syndrome and cardiac fibroma-further facilitate a diagnosis. The recognition of key imaging findings can help guide treatment management and help avoid unnecessary intervention in cases of benign lesions such as myositis ossificans and fibromatosis

  18. Complications of Microwave Ablation for Liver Tumors: Results of a Multicenter Study

    SciTech Connect

    Livraghi, Tito; Meloni, Franca; Solbiati, Luigi; Zanus, Giorgio; Collaboration: For the Collaborative Italian Group using AMICA system

    2012-08-15

    Purpose: New technologies for microwave ablation (MWA) have been conceived, designed to achieve larger areas of necrosis compared with radiofrequency ablation (RFA). The purpose of this study was to report complications by using this technique in patients with focal liver cancer. Methods: Members of 14 Italian centers used a 2.45-GMHz generator delivering energy through a cooled miniature-choke MW antenna and a standardized protocol for follow-up. They completed a questionnaire regarding number and type of deaths, major and minor complications and side effects, and likelihood of their relationship to the procedure. Enrollment included 736 patients with 1.037 lesions: 522 had hepatocellular carcinoma with cirrhosis, 187 had metastases predominantly from colorectal cancer, and 27 had cholangiocellular carcinoma. Tumor size ranged from 0.5 to 10 cm. In 13 centers, the approach used was percutaneous, in 4 videolaparoscopic, and in 3 laparotomic. Results: No deaths were reported. Major complications occurred in 22 cases (2.9%), and minor complications in 54 patients (7.3%). Complications of MWA do not differ from those RFA, both being based on the heat damage. Conclusion: Results of this multicenter study confirmed those of single-center experiences, indicating that MWA is a safe procedure, with no mortality and a low rate of major complications. The low rate of complications was probably due to precautions adopted, knowing in advance possible risk conditions, on the basis of prior RFA experience.

  19. Gastrointestinal stromal tumors of the duodenum: Surgical management and survival results

    PubMed Central

    Liang, Xiao; Yu, Hong; Zhu, Lin-Hua; Wang, Xian-Fa; Cai, Xiu-Jun

    2013-01-01

    AIM: To provide long-term survival results of operable duodenal gastrointestinal stromal tumors (DGISTs) in a tertiary center in China. METHODS: In this retrospective study, the pathological data of 28 patients with DGISTs who had been treated surgically at the Second Department of General Surgery, Sir Run Run Shaw Hospital (SRRSH) from June 1998 to December 2006 were reviewed. All pathological slides were examined by a single pathologist to confirm the diagnosis. In patients whose diagnosis was not confirmed by immunohistochemistry at the time of resection, representative paraffin blocks were reassembled, and sections were studied using antibodies against CD117 (c-kit), CD34, smooth muscle actin (SMA), vimentin, S-100, actin (HHF35), and desmin. Operative procedures were classified as wedge resection (WR, local resection with pure closure, without duodenal transection or anastomosis), segmental resection [SR, duodenal transection with Roux-Y or Billroth II gastrojejunostomy (G-J), end-to-end duodenoduodenostomy (D-D), end-to-end or end-to-side duodenojejunostomy (D-J)], and pancreaticoduodenectomy (PD, Whipple operation with pancreatojejunostomy). R0 resection was pursued in all cases, and at least R1 resection was achieved. Regional lymphadenectomy was not performed. Clinical manifestations, surgery, medical treatment and follow-up data were retrospectively analyzed. Related studies in the literature were reviewed. RESULTS: There were 12 males and 16 females patients, with a median age of 53 years (20-76 years). Their major complaints were “gastrointestinal bleeding” (57.2%) and “nonspecific discomfort” (32.1%). About 14.3%, 60.7%, 17.9%, and 7.1% of the tumors originated in the first to fourth portion, respectively, with a median size of 5.8 cm (1.6-20 cm). Treatment was by WR in 5 cases (17.9%), SR in 13 cases (46.4%), and by PD in 10 cases (35.7%). The morbidity and mortality rates were 35.7% and 3.6%, respectively. The median post-operative stay was

  20. Beauty product-related exposures and childhood brain tumors in seven countries: results from the SEARCH International Brain Tumor Study.

    PubMed

    Efird, J T; Holly, E A; Cordier, S; Mueller, B A; Lubin, F; Filippini, G; Peris-Bonet, R; McCredie, M; Arslan, A; Bracci, P; Preston-Martin, S

    2005-04-01

    Data from 1218 cases of childhood brain tumors (CBT) diagnosed between 1976 and 1994 and 2223 matched controls from the general population were included in an analysis of maternal beauty product exposure and beauty-related employment in 9 centers in 7 countries. A 50% increased odds ratio (OR) [95% confidence interval (CI) = 1.0-2.1] for CBT was observed among children of mothers who were exposed via personal use of and/or possible ambient contact with beauty products during the 5 years preceding the index child's birth compared with children of mothers never exposed to beauty products during this time period. Overall maternal personal use of hair-coloring agents in the month before or during the pregnancy of the index child's birth was not associated with CBT (OR = 1.0, CI = 0.83-1.3) or with astroglial (OR = 1.1, CI = 0.85-1.4), PNET (OR = 1.0, CI = 0.71-1.5) and other glial subtypes (OR = 1.0, CI = 0.62-1.0). Similarly, no statistically increased ORs or discernable pattern of risk estimates were observed for period of use or for number of applications per year for maternal personal use of hair-coloring agents overall or by histologic type. Among children born on or after 1980, increased ORs for CBT were associated with maternal non-work-related exposure to any beauty products (OR = 2.6, CI = 1.2-5.9), hair-dyes (OR = 11, CI = 1.2-90), and hair sprays (OR = 3.4, CI = 1.0-11). No overall increased OR for CBT was observed among children of mothers employed in beauty-related jobs during the 5 years preceding the index child's birth compared with those who reported no beauty-related employment. In general, other specific beauty product-related exposures were not associated with increased ORs for CBT. Data from our study provide little evidence of an increased risk for CBT with mothers' exposures to beauty products. PMID:15925993

  1. Lost in Translation: Ambiguity in Nerve Sheath Tumor Nomenclature and Its Resultant Treatment Effect

    PubMed Central

    Bernthal, Nicholas M.; Jones, Kevin B.; Monument, Michael J.; Liu, Ting; Viskochil, David; Randall, R. Lor

    2013-01-01

    There is much ambiguity surrounding the diagnosis of nerve sheath tumors, including atypical neurofibroma and low-grade MPNST, and yet, the distinction between these entities designates either benign or malignant behavior and thus carries presumed profound prognostic importance that often guides treatment. This study reviews the diagnostic criteria used to designate atypical neurofibroma from low-grade MPNSTs and reviews existing literature the natural history of each of these tumors to see if the distinction is, in fact, of importance. PMID:24216989

  2. Tumor induction following intraoperative radiotherapy: Late results of the National Cancer Institute canine trials

    SciTech Connect

    Barnes, M.; Duray, P.; DeLuca, A.; Anderson, W.; Sindelar, W.; Kinsella, T. )

    1990-09-01

    Intraoperative radiotherapy has been employed in human cancer research for over a decade. Since 1979, trials to assess the acute and late toxicity of IORT have been carried out at the National Cancer Institute in an adult dog model in an attempt to establish dose tolerance guidelines for a variety of organs. Of the 170 animals entered on 12 studies with a minimum follow-up of 2 years, 148 dogs received IORT; 22 control animals received only surgery. Animals were sacrificed at designated intervals following IORT, usually at 1, 6, 12, 24, and 60 month intervals. 102 of 148 irradiated dogs were sacrificed less than 24 months; 46 dogs were followed greater than or equal to 24 months after IORT. To date, 34 of the 46 animals have been sacrificed; the 12 remaining animals are to be followed to 5 years. These 12 animals have minimum follow-up of 30 months. In the irradiated group followed for greater than or equal to 24 months, 10 tumors have arisen in 9 animals. One animal developed an incidental spontaneous breast carcinoma outside the IORT port, discovered only at scheduled post-mortem exam. The remaining nine tumors arose within IORT ports. Two tumors were benign neural tumors--a neuroma and a neurofibroma. One animal had a collision tumor comprised of grade I chondrosarcoma adjacent to grade III osteosarcoma arising in lumbar vertebrae. Two other grade III osteosarcomas, one grade III fibrosarcoma, and one grade III malignant fibrous histiocytoma arose in retroperitoneal/paravertebral sites. An embryonal rhabdomyosarcoma (sarcoma botryoides) arose within the irradiated urinary bladder of one animal. No sham irradiated controls nor IORT animals sacrificed less than 24 months have developed any spontaneous or radiation-induced tumors. The time range of diagnoses of tumors was 24-58 months. The IORT dose range associated with tumor development was 20-35 Gy.

  3. Radiotherapy Combined with Novel STING-Targeting Oligonucleotides Results in Regression of Established Tumors.

    PubMed

    Baird, Jason R; Friedman, David; Cottam, Benjamin; Dubensky, Thomas W; Kanne, David B; Bambina, Shelly; Bahjat, Keith; Crittenden, Marka R; Gough, Michael J

    2016-01-01

    Cytotoxic therapies prime adaptive immune responses to cancer by stimulating the release of tumor-associated antigens. However, the tumor microenvironment into which these antigens are released is typically immunosuppressed, blunting the ability to initiate immune responses. Recently, activation of the DNA sensor molecule STING by cyclic dinucleotides was shown to stimulate infection-related inflammatory pathways in tumors. In this study, we report that the inflammatory pathways activated by STING ligands generate a powerful adjuvant activity for enhancing adaptive immune responses to tumor antigens released by radiotherapy. In a murine model of pancreatic cancer, we showed that combining CT-guided radiotherapy with a novel ligand of murine and human STING could synergize to control local and distant tumors. Mechanistic investigations revealed T-cell-independent and TNFα-dependent hemorrhagic necrosis at early times, followed by later CD8 T-cell-dependent control of residual disease. Clinically, STING was found to be expressed extensively in human pancreatic tumor and stromal cells. Our findings suggest that this novel STING ligand could offer a potent adjuvant for leveraging radiotherapeutic management of pancreatic cancer. PMID:26567136

  4. French brain tumor database: 5-year histological results on 25 756 cases.

    PubMed

    Rigau, Valérie; Zouaoui, Sonia; Mathieu-Daudé, Hélène; Darlix, Amélie; Maran, Aurélie; Trétarre, Brigitte; Bessaoud, Faiza; Bauchet, Fabienne; Attaoua, Redha; Fabbro-Peray, Pascale; Fabbro, Michel; Kerr, Christine; Taillandier, Luc; Duffau, Hugues; Figarella-Branger, Dominique; Costes, Valérie; Bauchet, Luc

    2011-11-01

    This work aimed to prospectively record all primary central nervous system tumor (PCNST) cases in France, for which histological diagnosis is available. The objectives were to (i) create a national registry and a network to perform epidemiological studies; (ii) implement clinical and basic research protocols; and (iii) harmonize the health care of patients affected by PCNST. For 5 years, 25 756 cases of newly diagnosed and histologically confirmed PCNST have been recorded. Histological diagnoses included glioma (48.9%), all other neuroepithelial tumors (5%), meningioma (28.8%), nerve sheath tumors (8.4%), lymphoma (3.2%) and others (5.7%). Cryopreservation was reported for 6018 PCNST specimens. Tumor resections (R) were performed in 78% cases, while biopsies accounted for 22%. Median age (MA), sex, percentage R and number of cryopreserved tumors were detailed for each histology; for example, out of 6053 glioblastomas (MA 63 years, male 59.4%, R 62%, 1611 were cryopreserved), and out of 37 atypical teratoid/rhabdoid tumors (MA 2 years, male 56.8%, R 94%, 17 were cryopreserved). This database or databank dedicated to PCNST cases contains detailed data on clinical, histological and other characteristics, such as the inclusion of data on cryopreserved specimens that are not available in other European registries. Therefore, this is a valuable resource that can be used for planning future epidemiological and clinical research. PMID:21554472

  5. END STAGE RENAL DISEASE IN PATIENTS WITH WILMS TUMOR: RESULTS FROM THE NATIONAL WILMS TUMOR STUDY GROUP AND THE U.S. RENAL DATA SYSTEM

    PubMed Central

    Breslow, Norman E.; Grigoriev, Yevgeny A.; Peterson, Susan M.; Collins, Allan J.; Ritchey, Michael L.; Green, Daniel M.

    2006-01-01

    Purpose: To accurately assess the full spectrum of end stage renal disease (ESRD) in Wilms tumor survivors by combining the unique resources of the National Wilms Tumor Study Group (NWTSG) and the U.S. Renal Data System (USRDS), and to confirm preliminary reports of an increased incidence of ESRD in those with the Wilms tumor-aniridia (WAGR) syndrome. Material and Methods: ESRD was ascertained for 5,910 patients enrolled on NWTSG studies during 1969-1994 both by record linkage to USRDS and by direct follow-up. Cumulative ESRD incidence was estimated accounting for inter-current mortality. Results: Ten of 115 cases of ESRD (9%) were ascertained by NWTSG alone, 13 (11%) by USRDS alone and 92 (80%) by both. Cumulative incidence of ESRD at 20 years from diagnosis of unilateral Wilms tumor (WT) was 74% for 17 patients with Deny-Drash syndrome (DDS), 36% for 37 patients with WAGR syndrome, 7% for 125 male patients with hypospadias or cryptorchism (GU anomalies) and 0.6% for 5,347 patients with none of these conditions. The incidence for bilateral Wilms tumor was 50% for DDS (n=6), 90% for WAGR (n=10), 25% for GU anomaly (n=25) and 12% for other patients (n=409). ESRD for patients with WAGR syndrome or GU anomalies tended to occur relatively late, often during or after adolescence. Conclusions: The risk of ESRD is remarkably low for the majority of WT patients. Those with WAGR syndrome or associated GU anomalies, however, are at higher risk and should be screened indefinitely to facilitate prospective management of impaired renal function. PMID:16217371

  6. Neutron-capture therapy of human cancer: in vivo results on tumor localization of boron-10-labeled antibodies to carcinoembryonic antigen in the gw-39 tumor model system

    SciTech Connect

    Goldenberg, D.M.; Sharkey, R.M.; Primus, F.J.; Mizusawa, E.; Hawthorne, M.F.

    1984-01-01

    Antibody against carcinoembryonic antigen (CEA) was conjugated with p-(1,2-dicarba-closo-(1-/sup 3/H)dodecaboran(12)-2-yl)benzenediazonium ion by an azo-coupling reaction, resulting in 30 boron atoms per IgG molecule with no loss of antibody protein. Antibody immunoreactivity was not appreciably affected by this conjugation and was stable after incubation in vitro in hamster plasma for 24 hr. The efficacy of the boron-conjugated anti-CEA IgG for localizing selectively in CEA-containing human colonic carcinomas propagated in the hind leg musculature of hamsters was evaluated by labeling the antibodies with /sup 131/I and determining distribution of the radioactivity in vivo. The results show that the boron-conjugated antibodies retain selective localization in the tumors, thus indicating their suitability for transporting boron-10 to tumors for use in neutron-capture therapy of cancer. 17 references, 3 tables, 2 figures.

  7. Transurethral En Bloc Resection of Bladder Tumor Using an Endoscopic Submucosal Dissection Technique: Preliminary Results in an Animal Model

    PubMed Central

    Morizane, Shuichi; Sejima, Takehiro; Iwamoto, Hideto; Masago, Toshihiko; Honda, Masashi; Ikebuchi, Yuichiro; Matsumoto, Kazuya; Ueki, Masaru; Takenaka, Atsushi

    2016-01-01

    Background Transurethral resection of bladder tumor (TURBT) technique has been considered the routine method for removing most bladder tumors for decades. In contrast, endoscopic submucosal dissection (ESD) is the gold-standard treatment for gastrointestinal superficial tumors. We investigated the effectiveness and applicability of a new technique for en bloc bladder tumor resection using ESD procedure. Methods Four Landrace Large White Duroc female pigs were anesthetized with isoflurane prior endoscopic resection using a large-caliber prototype fiber bronchoscope. After local infiltration of the submucosa with sodium hyaluronate using an injector needle, a section of the target area (1.0–2.0 cm diameter circular area) was cut with the Dual Knife. Results In total, seven target sections were resected from the pigs. The median size of the resected sections was 1.8 cm (range 1.0–2.5 cm) and the median time taken to perform the resection of one section was 20 min (range 4–35 min). These target sections were completely resected en bloc. Although the small bladder perforations occurred on two occasions, no other short-term complications such as uncontrollable bleeding were observed. Conclusion This procedure is a slightly difficult in the pigs with thin bladder walls. However, this procedure with the slim flexible cystoscope may allow us to be able to remove bladder tumors using only light sedation, especially for cases when small tumor recurrence is observed during routine cystoscopy for the patients with non-muscle invasive bladder cancer. PMID:27493485

  8. Localized Hypoxia Results in Spatially Heterogeneous Metabolic Signatures in Breast Tumor Models1

    PubMed Central

    Jiang, Lu; Greenwood, Tiffany R; Artemov, Dmitri; Raman, Venu; Winnard, Paul T; Heeren, Ron MA; Bhujwalla, Zaver M; Glunde, Kristine

    2012-01-01

    Tumor hypoxia triggers signaling cascades that significantly affect biologic outcomes such as resistance to radiotherapy and chemotherapy in breast cancer. Hypoxic regions in solid tumor are spatially heterogeneous. Therefore, delineating the origin and extent of hypoxia in tumors is critical. In this study, we have investigated the effect of hypoxia on different metabolic pathways, such as lipid and choline metabolism, in a human breast cancer model. Human MDA-MB-231 breast cancer cells and tumors, which were genetically engineered to express red fluorescent tdTomato protein under hypoxic conditions, were used to investigate hypoxia. Our data were obtained with a novel three-dimensional multimodal molecular imaging platform that combines magnetic resonance (MR) imaging, MR spectroscopic imaging (MRSI), and optical imaging of hypoxia and necrosis. A higher concentration of noninvasively detected total choline-containing metabolites (tCho) and lipid CH3 localized in the tdTomato-fluorescing hypoxic regions indicated that hypoxia can upregulate tCho and lipid CH3 levels in this breast tumor model. The increase in tCho under hypoxia was primarily due to elevated phosphocholine levels as shown by in vitro MR spectroscopy. Elevated lipid CH3 levels detected under hypoxia were caused by an increase in mobile MR-detectable lipid droplets, as demonstrated by Nile Red staining. Our findings demonstrate that noninvasive MRSI can help delineate hypoxic regions in solid tumors by means of detecting the metabolic outcome of tumor hypoxia, which is characterized by elevated tCho and lipid CH3. PMID:22952426

  9. Photodynamic therapy (PDT) of malignant tumors by photosensitzer photosens: results of 45 clinical cases

    NASA Astrophysics Data System (ADS)

    Sokolov, Victor V.; Chissov, Valery I.; Yakubovskaya, Raisa I.; Aristarkhova, E. I.; Filonenko, E. V.; Belous, T. A.; Vorozhtsov, Georgy N.; Zharkova, Natalia N.; Smirnov, V. V.; Zhitkova, Margarita B.

    1996-01-01

    Photosensitizer Photosens is a mixture of sulphonated Al-phthalocyanines with a different number of substituents per phthalocyanine molecule. In the beginning of 1994, this photosensitizer was approved for clinical trials. Since that time till May 1995, 45 patients with 120 tumors were treated by PDT-Photosens. The main tumor localizations were lung (5/6), head and neck (4/4), esophagus (8/8), stomach (2/2), vulva (2/2), bladder (1/1), breast cancer (3/3), skin (basalioma, melanoma, sarcoma Kaposi, mts breast cancer) (20 patients/94 tumors). The lesions were photoirradiated 48-72 h after intravenous injection of Photosens in doses from 0.5 to 2.0 mg/kg b.w. (1.0 mg/kg b.w., on average). PDT was performed by laser power density from 20 to 1400 mW/sq cm (300 mW/sq.cm, on average), energy density varying from 15 to 200 J/sq cm (100 J/sq.cm, on average). The therapeutical effect of PDT was evaluated histologically, endoscopically, roentgenologically and sonographically 3 - 4 weeks after the treatment. Complete regression of tumors was reached in 56%, significant remission was reached in 34%, and partial remission was observed in 10% of cases. The follow-up of patients with complete tumor regression was to 15 months.

  10. Infant Brain Tumors: Incidence, Survival, and the Role of Radiation Based on Surveillance, Epidemiology, and End Results (SEER) Data

    SciTech Connect

    Bishop, Andrew J.; McDonald, Mark W.; Chang, Andrew L.; Esiashvili, Natia

    2012-01-01

    Purpose: To evaluate the incidence of infant brain tumors and survival outcomes by disease and treatment variables. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) Program November 2008 submission database provided age-adjusted incidence rates and individual case information for primary brain tumors diagnosed between 1973 and 2006 in infants less than 12 months of age. Results: Between 1973 and 1986, the incidence of infant brain tumors increased from 16 to 40 cases per million (CPM), and from 1986 to 2006, the annual incidence rate averaged 35 CPM. Leading histologies by annual incidence in CPM were gliomas (13.8), medulloblastoma and primitive neuroectodermal tumors (6.6), and ependymomas (3.6). The annual incidence was higher in whites than in blacks (35.0 vs. 21.3 CPM). Infants with low-grade gliomas had the highest observed survival, and those with atypical teratoid rhabdoid tumors (ATRTs) or primary rhabdoid tumors of the brain had the lowest. Between 1979 and 1993, the annual rate of cases treated with radiation within the first 4 months from diagnosis declined from 20.5 CPM to <2 CPM. For infants with medulloblastoma, desmoplastic histology and treatment with both surgery and upfront radiation were associated with improved survival, but on multivariate regression, only combined surgery and radiation remained associated with improved survival, with a hazard ratio for death of 0.17 compared with surgery alone (p = 0.005). For ATRTs, those treated with surgery and upfront radiation had a 12-month survival of 100% compared with 24.4% for those treated with surgery alone (p = 0.016). For ependymomas survival was higher in patients treated in more recent decades (p = 0.001). Conclusion: The incidence of infant brain tumors has been stable since 1986. Survival outcomes varied markedly by histology. For infants with medulloblastoma and ATRTs, improved survival was observed in patients treated with both surgery and early radiation

  11. Primary malignant bone tumors and solitary metastases of the thoracolumbar spine: results by management with total en bloc spondylectomy

    PubMed Central

    Melcher, Ingo; Khodadadyan-Klostermann, Cyrus; Tohtz, Stefan; Smolny, Mirko; Stöckle, Ulrich; Haas, Norbert P.; Schaser, Klaus-Dieter

    2007-01-01

    Primary malignant spinal tumors and solitary vertebral metastases of selected tumor entities in the thoracolumbar spine are indications for total en bloc spondylectomy (TES). This study aimed to describe our oncological and surgical management and to analyze the treatment results by management with TES for extra- and intracompartmental solitary spinal metastases and primary malignant vertebral bone tumors. In 15 patients (3 malignant bone tumors and 12 solitary metastases), tumors were distributed in the thoracic (n = 8) and lumbar (n = 7) spine. Tumors were classified as intra- (n = 8) and extracompartmental (n = 7). All patients underwent TES via a laterally extended posterior approach followed by dorsoventral reconstruction. Function and quality of life were assessed by Oswestry disability index (ODI) and SF-36 score. At follow-up (100%; mean: 33 ± 22 months), 11 patients had no evidence of disease. Two patients were alive with the disease and two were dead of the disease (no primary bone tumors). Histology revealed negative margins (R0) in all patients with wide (n = 11) and marginal (n = 4) resections. Two patients developed pulmonal metastases of which they died at 4 and 16 months of survival. No local recurrence was observed. Major complications did not occur. TES resulted in an acceptable outcome in the quality of life and function. TES is a demanding procedure reaching wide to marginal resections in a curative approach. In conjunction with multimodal therapies, local recurrences can effectively be prevented while control of distant disease needs to be improved. Proper selection of adequate patients combined with careful surgical planning are prerequisites for low complication rates, acceptable function and improved overall prognosis. PMID:17252218

  12. Boronated porphyrins in NCT: Results with a new potent tumor localizer

    SciTech Connect

    Kahl, S.B.; Koo, M.S.; Laster, B.H.; Fairchild, R.G.

    1988-01-01

    Several chemical methods are available for the solubilization of boronated porphyrins. We have previously reported the tumor localization of nido carboranyl porphyrins in which the icosahedral carborane cages have been opened to give B/sub 9/C/sub 2/ anions. One of these species has shown tumor boron levels of nearly 50 ..mu..g B/g when delivered by week-long subcutaneous infusions. We report here recent in vivo experiments with a new, highly water-soluble porphyrin based on the hematoporphyrin-type of compound in which aqueous solubility is achieved using the two propionic acid side chains of the ''natural'' porphyrin frame. 7 refs.

  13. Expression of anti-VEGF antibody together with anti-EGFR or anti-FAP enhances tumor regression as a result of vaccinia virotherapy

    PubMed Central

    Huang, Ting; Wang, Huiqiang; Chen, Nanhai G; Frentzen, Alexa; Minev, Boris; Szalay, Aladar A

    2015-01-01

    The tumor microenvironment plays an important role in tumor growth and progression. Here we demonstrate that vaccinia virus-mediated, constitutively expressed intratumoral antibodies against vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), and fibroblast activation protein (FAP) significantly improved tumor regression and oncolytic virotherapy through suppression of angiogenesis, cell proliferation, and stromagenesis in virus-colonized tumors. In contrast to the tumor growth inhibition by the three tumor growth-inhibiting antibodies individually, when two of the three antibodies were expressed simultaneously by single vaccinia virus strains tumor regression was further enhanced. These findings strongly indicate that interference with the two tumor growth-stimulating mechanisms did in fact result in enhanced therapeutic efficacy in tumor xenograft models and may lead to an effective therapy in patients with cancer. PMID:27119102

  14. T-Cell Tumor Elimination as a Result of T-Cell Receptor-Mediated Activation

    NASA Astrophysics Data System (ADS)

    Ashwell, Jonathan D.; Longo, Dan L.; Bridges, Sandra H.

    1987-07-01

    It has recently been shown that activation of murine T-cell hybridomas with antigen inhibits their growth in vitro. The ``suicide'' of these neoplastic T cells upon stimulation with antigen suggested the possibility that activation via the antigen-specific receptor could also inhibit the growth of neoplastic T cells in vivo. To test this, mice were subcutaneously inoculated with antigen-specific T-cell hybridomas and then treated intraperitoneally with antigen. Administration of the appropriate antigen immediately after inoculation with the T-cell hybridoma abrogated tumor formation; antigen administered after tumors had become established decreased the tumor burden and, in a substantial fraction of animals, led to long-term survival. The efficacy of antigen therapy was due to both a direct inhibitory effect on tumor growth and the induction of host immunity. These studies demonstrate the utility of cellular activation as a means of inhibiting neoplastic T-cell growth in vivo and provide a rationale for studying the use of less selective reagents that can mimic the activating properties of antigen, such as monoclonal antibodies, in the treatment of T-cell neoplasms of unknown antigen specificity.

  15. Does famotidine enhance tumor infiltrating lymphocytes in breast cancer? Results of a randomized prospective pilot study.

    PubMed

    Parshad, Rajinder; Kapoor, Sorabh; Gupta, Siddhartha Datta; Kumar, Arvind; Chattopadhyaya, Tushar K

    2002-01-01

    Thirty patients with breast cancer were prospectively randomized into case and control groups receiving 40 mg famotidine preoperatively for 10-14 days and routine premedication, respectively. Surgical specimens were evaluated objectively for tumor infiltrating lymphocytes in the center and in the periphery of the tumor along with evaluation of metastatic lymph nodes for reactive changes. Ten famotidine-treated cases (67%) showed significant lymphocytic infiltration in the center compared to 4 controls (27%) (p = 0.03). Eleven cases (77%) had significant lymphocytic infiltration in the periphery (p = 0.03) compared to 5 controls (33%). Considering both sites, lymphocytic response was significant in 9 (60%) cases as opposed to only 3 (20%) controls (p = 0.03). This response did not correlate with the stage, grade of tumor or menopausal status of patients in either group. Seventy-eight percent (78%) of the cases showed significant reactive changes in the metastatic lymph nodes as compared to 22% in controls (p < 0.01). This study suggests that famotidine enhances tumor infiltrating lymphocytes in breast cancer and might have potential as an immunomodulator. A larger confirmatory study is suggested. PMID:12234028

  16. Electrotransfer of Plasmid DNA Encoding an Anti-Mouse Endoglin (CD105) shRNA to B16 Melanoma Tumors with Low and High Metastatic Potential Results in Pronounced Anti-Tumor Effects.

    PubMed

    Dolinsek, Tanja; Sersa, Gregor; Prosen, Lara; Bosnjak, Masa; Stimac, Monika; Razborsek, Urska; Cemazar, Maja

    2015-01-01

    Endoglin overexpression is associated with highly proliferative tumor endothelium and also with some tumors, including melanoma. Its targeting has anti-tumor effectiveness, which can also be obtained by RNA interference. The aim of our study was to explore the anti-tumor effectiveness of endoglin silencing by electrotransfer of plasmid DNA encoding short hairpin RNA against endoglin in two murine B16 melanoma variants with different metastatic potential on cells, spheroids and subcutaneous tumors in mice. The results demonstrate that endoglin silencing with gene electrotransfer reduces the proliferation, survival and migration of melanoma cells and also has anti-tumor effectiveness, as the therapy resulted in a high percentage of tumor cures (23% and 58% on B16F1 and B16F10 tumors, respectively). The effectiveness of the therapy correlated with endoglin expression in melanoma cells; in vitro the effects were more pronounced in B16F1 cells, which express more endoglin than B16F10. However, the opposite was observed in vivo in tumors, where there was a higher expression of endoglin and better anti-tumor effectiveness in the B16F10 tumor. In conclusion, targeting endoglin for the treatment of melanoma seems to be a concept worthy of further exploration due to the increased therapeutic effect of the therapy based on simultaneous vascular targeting and its direct effect on tumor cells. PMID:26712792

  17. Electrotransfer of Plasmid DNA Encoding an Anti-Mouse Endoglin (CD105) shRNA to B16 Melanoma Tumors with Low and High Metastatic Potential Results in Pronounced Anti-Tumor Effects

    PubMed Central

    Dolinsek, Tanja; Sersa, Gregor; Prosen, Lara; Bosnjak, Masa; Stimac, Monika; Razborsek, Urska; Cemazar, Maja

    2015-01-01

    Endoglin overexpression is associated with highly proliferative tumor endothelium and also with some tumors, including melanoma. Its targeting has anti-tumor effectiveness, which can also be obtained by RNA interference. The aim of our study was to explore the anti-tumor effectiveness of endoglin silencing by electrotransfer of plasmid DNA encoding short hairpin RNA against endoglin in two murine B16 melanoma variants with different metastatic potential on cells, spheroids and subcutaneous tumors in mice. The results demonstrate that endoglin silencing with gene electrotransfer reduces the proliferation, survival and migration of melanoma cells and also has anti-tumor effectiveness, as the therapy resulted in a high percentage of tumor cures (23% and 58% on B16F1 and B16F10 tumors, respectively). The effectiveness of the therapy correlated with endoglin expression in melanoma cells; in vitro the effects were more pronounced in B16F1 cells, which express more endoglin than B16F10. However, the opposite was observed in vivo in tumors, where there was a higher expression of endoglin and better anti-tumor effectiveness in the B16F10 tumor. In conclusion, targeting endoglin for the treatment of melanoma seems to be a concept worthy of further exploration due to the increased therapeutic effect of the therapy based on simultaneous vascular targeting and its direct effect on tumor cells. PMID:26712792

  18. Thyrocyte-specific inactivation of p53 and Pten results in anaplastic thyroid carcinomas faithfully recapitulating human tumors

    PubMed Central

    Dima, Mariavittoria; Kang, Kristy S.; Dasrath, Florence; Liao, Xiao-Hui; Refetoff, Samuel; Montagna, Cristina; Di Cristofano, Antonio

    2011-01-01

    Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer, and often derives from pre-existing well-differentiated tumors. Despite a relatively low prevalence, it accounts for a disproportionate number of thyroid cancer-related deaths, due to its resistance to any therapeutic approach. Here we describe the first mouse model of ATC, obtained by combining in the mouse thyroid follicular cells two molecular hallmarks of human ATC: activation of PI3K (via Pten deletion) and inactivation of p53. By 9 months of age, over 75% of the compound mutant mice develop aggressive, undifferentiated thyroid tumors that evolve from pre-existing follicular hyperplasia and carcinoma. These tumors display all the features of their human counterpart, including pleomorphism, epithelial-mesenchymal transition, aneuploidy, local invasion, and distant metastases. Expression profiling of the murine ATCs reveals a significant overlap with genes found deregulated in human ATC, including genes involved in mitosis control. Furthermore, similar to the human tumors, [Pten, p53]thyr−/− tumors and cells are highly glycolytic and remarkably sensitive to glycolysis inhibitors, which synergize with standard chemotherapy. Taken together, our results show that combined PI3K activation and p53 loss faithfully reproduce the development of thyroid anaplastic carcinomas, and provide a compelling rationale for targeting glycolysis to increase chemotherapy response in ATC patients. PMID:22190384

  19. Treatment results of stereotactic interstitial brachytherapy for primary and metastatic brain tumors

    SciTech Connect

    Lucas, G.L.; Luxton, G.; Cohen, D.; Petrovich, Z.; Langholz, B.; Apuzzo, M.L.; Sapozink, M.D. )

    1991-08-01

    A total of 41 stereotactic interstitial brain implants in 39 patients were performed for recurrence after teletherapy (recurrence implant), or as part of initial treatment in conjunction with teletherapy (primary implant). Implanted tumors consisted of malignant gliomas (33), other primary brain tumors (3), and single metastatic lesions (3). All patients were temporarily implanted with Ir-192 using a coaxial catheter afterloading system; two patients were implanted twice. Survival post-implant for glioblastoma multiforme (GBM), 13 patients, was 10 months whether implanted primarily or for recurrence. Mean time to recurrence, measured from initiation of teletherapy to implantation, was 10 months. Twenty patients with anaplastic astrocytoma (AA) had a median survival post-implant of 23 months for primary implants (7 patients) and 11 months for recurrence implants (13 patients). Mean time to recurrence, measured from initiation of teletherapy to implantation, was 19 months. Three patients (9%) of the evaluable group required reoperation for symptomatic mass effect, all with initial diagnosis of AA. Survival for this subgroup was 14, 22, and 32 months post-implantation. Using stereotactic techniques, interstitial brachytherapy of brain tumors was technically feasible with negligible acute morbidity and mortality, and appeared to offer limited prolongation of control for a subset of patients with recurrent malignant gliomas. The role of this modality in primary treatment for malignant gliomas needs to be further defined by prospectively randomized trials.

  20. Sequential Salinomycin Treatment Results in Resistance Formation through Clonal Selection of Epithelial-Like Tumor Cells12

    PubMed Central

    Kopp, Florian; Hermawan, Adam; Oak, Prajakta Shirish; Ulaganathan, Vijay Kumar; Herrmann, Annika; Elnikhely, Nefertiti; Thakur, Chitra; Xiao, Zhiguang; Knyazev, Pjotr; Ataseven, Beyhan; Savai, Rajkumar; Wagner, Ernst; Roidl, Andreas

    2014-01-01

    Acquiring therapy resistance is one of the major obstacles in the treatment of patients with cancer. The discovery of the cancer stem cell (CSC)–specific drug salinomycin raised hope for improved treatment options by targeting therapy-refractory CSCs and mesenchymal cancer cells. However, the occurrence of an acquired salinomycin resistance in tumor cells remains elusive. To study the formation of salinomycin resistance, mesenchymal breast cancer cells were sequentially treated with salinomycin in an in vitro cell culture assay, and the resulting differences in gene expression and salinomycin susceptibility were analyzed. We demonstrated that long-term salinomycin treatment of mesenchymal cancer cells resulted in salinomycin-resistant cells with elevated levels of epithelial markers, such as E-cadherin and miR-200c, a decreased migratory capability, and a higher susceptibility to the classic chemotherapeutic drug doxorubicin. The formation of salinomycin resistance through the acquisition of epithelial traits was further validated by inducing mesenchymal-epithelial transition through an overexpression of miR-200c. The transition from a mesenchymal to a more epithelial-like phenotype of salinomycin-treated tumor cells was moreover confirmed in vivo, using syngeneic and, for the first time, transgenic mouse tumor models. These results suggest that the acquisition of salinomycin resistance through the clonal selection of epithelial-like cancer cells could become exploited for improved cancer therapies by antagonizing the tumor-progressive effects of epithelial-mesenchymal transition. PMID:25500079

  1. Bortezomib-induced unfolded protein response increases oncolytic HSV-1 replication resulting in synergistic, anti-tumor effects

    PubMed Central

    Yoo, Ji Young; Hurwitz, Brian S; Bolyard, Chelsea; Yu, Jun-Ge; Zhang, Jianying; Selvendiran, Karuppaiyah; Rath, Kellie S; He, Shun; Bailey, Zachary; Eaves, David; Cripe, Timothy P; Parris, Deborah S.; Caligiuri, Michael A.; Yu, Jianhua; Old, Matthew; Kaur, Balveen

    2014-01-01

    Background Bortezomib is an FDA-approved proteasome inhibitor, and oncolytic HSV-1 (oHSV) is a promising therapeutic approach for cancer. We tested the impact of combining bortezomib with oHSV for anti-tumor efficacy. Methods The synergistic interaction between oHSV and bortezomib was calculated using Chou-Talalay analysis. Viral replication was evaluated using plaque assay and immune fluorescence. Western-blot assays were used to evaluate induction of ER stress and unfolded protein response (UPR). Inhibitors targeting Hsp90 were utilized to investigate the mechanism of cell killing. Anti-tumor efficacy in vivo was evaluated using subcutaneous and intracranial tumor xenografts of glioma and head and neck cancer. Survival was analyzed by Kaplan-Meier curves and two-sided log rank test. Results Combination treatment with bortezomib and oHSV, 34.5ENVE, displayed strong synergistic interaction in ovarian cancer, head & neck cancer, glioma, and malignant peripheral nerve sheath tumor (MPNST) cells. Bortezomib treatment induced ER stress, evident by strong induction of Grp78, CHOP, PERK and IRE1α (western blot analysis) and the UPR (induction of hsp40, 70 and 90). Bortezomib treatment of cells at both sublethal and lethal doses increased viral replication (p value <0.001), but inhibition of Hsp90 ablated this response, reducing viral replication and synergistic cell killing. The combination of bortezomib and 34.5ENVE significantly enhanced anti-tumor efficacy in multiple different tumor models in vivo. Conclusions The dramatic synergy of bortezomib and 34.5ENVE is mediated by bortezomib- induced UPR and warrants future clinical testing in patients. PMID:24815720

  2. Different gap junction-propagated effects on cisplatin transfer result in opposite responses to cisplatin in normal cells versus tumor cells

    PubMed Central

    Zhang, Yuan; Tao, Liang; Fan, Lixia; Peng, Yuexia; Yang, Kefan; Zhao, Yifan; Song, Qi; Wang, Qin

    2015-01-01

    Previous work has shown that gap junction intercellular communication (GJIC) enhances cisplatin (Pt) toxicity in testicular tumor cells but decreases it in non-tumor testicular cells. In this study, these different GJIC-propagated effects were demonstrated in tumor versus non-tumor cells from other organ tissues (liver and lung). The downregulation of GJIC by several different manipulations (no cell contact, pharmacological inhibition, and siRNA suppression) decreased Pt toxicity in tumor cells but enhanced it in non-tumor cells. The in vivo results using xenograft tumor models were consistent with those from the above-mentioned cells. To better understand the mechanism(s) involved, we studied the effects of GJIC on Pt accumulation in tumor and non-tumor cells from the liver and lung. The intracellular Pt and DNA-Pt adduct contents clearly increased in non-tumor cells but decreased in tumor cells when GJIC was downregulated. Further analysis indicated that the opposite effects of GJIC on Pt accumulation in normal versus tumor cells from the liver were due to its different effects on copper transporter1 and multidrug resistance-associated protein2, membrane transporters attributed to intracellular Pt transfer. Thus, GJIC protects normal organs from cisplatin toxicity while enhancing it in tumor cells via its different effects on intracellular Pt transfer. PMID:26215139

  3. Systemic irradiation for selected stage IV and recurrent pediatric solid tumors: method, toxicity, and preliminary results

    SciTech Connect

    Wharam, M.D.; Kaizer, H.; Leventhal, B.G.; Munoz, L.; Tutschka, P.J.; Santos, G.W.; Elfenbein, G.J.; Order, S.E.

    1980-02-01

    Eight patients with advanced pediatric solid tumors received either sequential upper and lower half-body irradiation (HBI) (7.5 rad/min to 500 rad total) or total body irradiation (TBI) (7.5 rad/min to 800 rad total) as part of two multimodality treatment regimens. All patients received combination chemotherapy; drugs were determined by the tumor type. The TBI regimen was selected for two patients who had progression of disease with conventional chemotherapy and for two patients with stage IV neuroblastoma. This intensive regimen consisted of bone marrow harvesting, followed by local radiation to gross disease, marrow-ablative chemotherapy, TBI, and re-infusion of the cryopreserved autologous marrow. Significant acute toxicity was followed by hematologic reconstitution in each patient within seven weeks. At this writing, two patients survived, one of whom is disease free two and one half years without maintenance chemotherapy. A less intensive, outpatient regimen was selected for four patients; three had a complete or good partial response to chemotherapy. The fourth patient had tumor-involved bone marrow not responsive to chemotherapy and was therefore ineligible for marrow cryopreservation and TBI. Each of these four patients received HBI after chemotherapy and local radiation to the primary and/or metastatic sites. Acute toxicity was limited to nausea and vomiting. Significant leukopenia and thrombocytopenia occurred in three patients. All four patients were alive 10 to 26 months post HBI. This pilot study demonstrates that chemotherapy can be integrated with local fractionated radiation, and systemic radiation given as HBI or TBI with acceptable toxicity; sufficient bone marrow stem cells can be harvested after conventional chemotherapy and then cryopreserved to permit hematologic reconstitution of the patient who receives marrow ablative therapy.

  4. Evaluation of tumor angiogenesis measured with microvessel density (MVD) as a prognostic indicator in nasopharyngeal carcinoma: Results of RTOG 9505

    SciTech Connect

    Foote, Robert L. . E-mail: foote.robert@mayo.edu; Weidner, Noel; Harris, Jonathan; Hammond, Elizabeth; Lewis, Jean E.; Vuong, Te; Ang, K. Kian; Fu, Karen K.

    2005-03-01

    Purpose: The objective of this study was to evaluate tumor angiogenesis as measured by microvessel density (MVD) as an independent prognostic factor in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy alone. Methods and materials: Eligible patients included those with NPC treated with radiotherapy. Paraffin blocks of the primary tumor had a hematoxylin and eosin-stained section prepared at the block face. One representative section for tumor was stained for factor VIII-related antigen using a standard immunoperoxidase staining technique. MVD was determined by light microscopy in areas of invasive tumor containing the highest numbers of capillaries and microvessels per area. Individual microvessel counts were made on a 200x field within the area of most intense tumor neovascularization. Results were expressed as the highest number of microvessels identified within any single 200x field. Using a breakpoint of MVD < 60 vs. {>=}60, the distributions between the two MVD groups were compared by the method of Gray. Overall survival rates were estimated by the Kaplan-Meier method and compared by the log-rank test. A multivariate Cox proportional hazard model was employed to examine the relationship between MVD and disease outcomes while adjusting for other concomitant variables. Results: One hundred sixty-six were eligible, of whom 123 had values determined for MVD. The MVD values ranged from 9 to 243 with a median of 70. In the multivariate analysis of overall survival, distant metastases, and local-regional failure, MVD did not significantly improve the model containing T stage, N stage, age, radiation dose, and World Health Organization class. Conclusions: We found no significant differences in overall survival, time to distant metastasis, or time to local-regional failure using a breakpoint of MVD < 60 vs. MVD {>=}60. The study was perhaps limited by the small size of the NPC samples.

  5. The treatment of Stage III nonseminomatous testicular tumors. Roswell Park Memorial Institute results (1970-1979).

    PubMed

    Pontes, J E; Wajsman, Z; Beckley, S; Williams, P; Murphy, G P

    1983-04-01

    A review of 92 patients with Stage III nonseminomatous tumors treated at Roswell Park Memorial Institute between 1970-1979 was undertaken to verify changes in concepts as related to multiple agent chemotherapy and cytoreductive surgery. Each patient had a minimal follow-up of 18 months. Fifty-three patients were seen before 1975. Eighteen had metastasis to the lungs only. These were treated with a variety of single chemotherapeutic agents and cytoreductive surgery. The survival of this group was 38%. Among 35 patients with lung and visceral involvement seen at the same time, only one patient is alive. Thirty-nine patients were seen after 1975 and treated with multi-drug chemotherapy and cytoreductive surgery. The current survival rate of 23 patients with lung metastasis only is 69%. Among 16 patients with lung and visceral involvement, the present survival rate is 31%. This report confirms the effectiveness of multi-drug therapy in conjunction with cytoreductive surgery in the treatment of disseminated testicular tumors. PMID:6186354

  6. SU-E-J-94: Positioning Errors Resulting From Using Bony Anatomy Alignment for Treating SBRT Lung Tumor

    SciTech Connect

    Frame, C; Ding, G

    2014-06-01

    Purpose: To quantify patient setups errors based on bony anatomy registration rather than 3D tumor alignment for SBRT lung treatments. Method: A retrospective study was performed for patients treated with lung SBRT and imaged with kV cone beam computed tomography (kV-CBCT) image-guidance. Daily CBCT images were registered to treatment planning CTs based on bony anatomy alignment and then inter-fraction tumor movement was evaluated by comparing shift in the tumor center in the medial-lateral, anterior-posterior, and superior-inferior directions. The PTV V100% was evaluated for each patient based on the average daily tumor displacement to assess the impact of the positioning error on the target coverage when the registrations were based on bony anatomy. Of the 35 patients studied, 15 were free-breathing treatments, 10 used abdominal compression with a stereotactic body frame, and the remaining 10 were performed with BodyFIX vacuum bags. Results: For free-breathing treatments, the range of tumor displacement error is between 1–6 mm in the medial-lateral, 1–13 mm in the anterior-posterior, and 1–7 mm in the superior-inferior directions. These positioning errors lead to 6–22% underdose coverage for PTV - V100% . Patients treated with abdominal compression immobilization showed positional errors of 0–4mm mediallaterally, 0–3mm anterior-posteriorly, and 0–2 mm inferior-superiorly with PTV - V100% underdose ranging between 6–17%. For patients immobilized with the vacuum bags, the positional errors were found to be 0–1 mm medial-laterally, 0–1mm anterior-posteriorly, and 0–2 mm inferior-superiorly with PTV - V100% under dose ranging between 5–6% only. Conclusion: It is necessary to align the tumor target by using 3D image guidance to ensure adequate tumor coverage before performing SBRT lung treatments. The BodyFIX vacuum bag immobilization method has the least positioning errors among the three methods studied when bony anatomy is used for

  7. Bevacizumab Targeting Diffuse Intrinsic Pontine Glioma: Results of 89Zr-Bevacizumab PET Imaging in Brain Tumor Models.

    PubMed

    Jansen, Marc H A; Lagerweij, Tonny; Sewing, A Charlotte P; Vugts, Danielle J; van Vuurden, Dannis G; Molthoff, Carla F M; Caretti, Viola; Veringa, Susanna J E; Petersen, Naomi; Carcaboso, Angel M; Noske, David P; Vandertop, W Peter; Wesseling, Pieter; van Dongen, Guus A M S; Kaspers, Gertjan J L; Hulleman, Esther

    2016-09-01

    The role of the VEGF inhibitor bevacizumab in the treatment of diffuse intrinsic pontine glioma (DIPG) is unclear. We aim to study the biodistribution and uptake of zirconium-89 ((89)Zr)-labeled bevacizumab in DIPG mouse models. Human E98-FM, U251-FM glioma cells, and HSJD-DIPG-007-FLUC primary DIPG cells were injected into the subcutis, pons, or striatum of nude mice. Tumor growth was monitored by bioluminescence imaging (BLI) and visualized by MRI. Seventy-two to 96 hours after (89)Zr-bevacizumab injections, mice were imaged by positron emission tomography (PET), and biodistribution was analyzed ex vivo High VEGF expression in human DIPG was confirmed in a publically available mRNA database, but no significant (89)Zr-bevacizumab uptake could be detected in xenografts located in the pons and striatum at an early or late stage of the disease. E98-FM, and to a lesser extent the U251-FM and HSJD-DIPG-007 subcutaneous tumors, showed high accumulation of (89)Zr-bevacizumab. VEGF expression could not be demonstrated in the intracranial tumors by in situ hybridization (ISH) but was clearly present in the perinecrotic regions of subcutaneous E98-FM tumors. The poor uptake of (89)Zr-bevacizumab in xenografts located in the brain suggests that VEGF targeting with bevacizumab has limited efficacy for diffuse infiltrative parts of glial brain tumors in mice. Translating these results to the clinic would imply that treatment with bevacizumab in patients with DIPG is only justified after targeting of VEGF has been demonstrated by (89)Zr-bevacizumab immuno-PET. We aim to confirm this observation in a clinical PET study with patients with DIPG. Mol Cancer Ther; 15(9); 2166-74. ©2016 AACR. PMID:27325687

  8. An atypical presentation of small bowel obstruction and perforation secondary to sporadic synchronous intra-abdominal desmoid tumours

    PubMed Central

    Abdalla, Sala; Wilkinson, Michelle; Wilsher, Mark; Uzkalnis, Aleksandras

    2016-01-01

    Introduction Desmoid tumours (DTs) are rare, soft tissue tumours which account for 0.03% of all neoplasms. They are characteristically locally invasive but do not metastasize. There is frequent association with females of reproductive age, a history of abdominal surgery or trauma and a family history of fibromatoses. Intra-abdominal DTs are infrequently sporadic and more commonly associated with inherited disorders such as familial adenomatous polyposis (FAP), attenuated FAP and Gardener’s syndrome. Presentation of case The authors report a rare case of small bowel obstruction and perforation secondary to sporadic, synchronous intra-abdominal DTs in a 54-year old man with atypical symptoms and no risk factors or family history. Discussion Intra-abdominal DTs have a worse prognosis as they can cause intestinal bleeding, obstruction and perforation. Due to the rarity of these tumours there are no clear guidelines on their management and this is instead based on small case series from specialist centres. In the non-acute setting patients with sporadic intra-abdominal DTs should be managed in a specialist sarcoma unit by a multidisciplinary team. In the presence of FAP or other polyposis syndromes patients with DTs should be managed at a specialist colorectal unit. Emergent presentations require emergency surgery in suitable candidates. Conclusion In non-emergency presentations of DTs, it is essential to exclude FAP, AFAP and other hereditary polyposis syndromes since this affects treatment and subsequent follow-up. PMID:26866881

  9. Ultrasonic attenuation and backscatter coefficient estimates of rodent-tumor-mimicking structures: comparison of results among clinical scanners.

    PubMed

    Nam, Kibo; Rosado-Mendez, Ivan M; Wirtzfeld, Lauren A; Pawlicki, Alexander D; Kumar, Viksit; Madsen, Ernest L; Ghoshal, Goutam; Lavarello, Roberto J; Oelze, Michael L; Bigelow, Timothy A; Zagzebski, James A; O'Brien, William D; Hall, Timothy J

    2011-10-01

    In vivo estimations of the frequency-dependent acoustic attenuation (alpha) and backscatter (eta) coefficients using radiofrequency (rf) echoes acquired with clinical ultrasound systems must be independent of the data acquisition setup and the estimation procedures. In a recent in vivo assessment of these parameters in rodent mammary tumors, overall agreement was observed among alpha and eta estimates using data from four clinical imaging systems. In some cases, particularly in highly-attenuating heterogeneous tumors, multisystem variability was observed. This paper compares alpha and eta estimates of a well-characterized rodent-tumor-mimicking homogeneous phantom scanned using seven transducers with the same four clinical imaging systems: a Siemens Acuson S2000, an Ultrasonix RP, a Zonare Z.one and a VisualSonics Vevo2100. alpha and eta estimates of lesion-mimicking spheres in the phantom were independently assessed by three research groups, who analyzed their system's rf echo signals. Imaging-system-based estimates of alpha and eta of both lesion-mimicking spheres were comparable to through-transmission laboratory estimates and to predictions using Faran's theory, respectively. A few notable variations in results among the clinical systems were observed but the average and maximum percent difference between alpha estimates and laboratory-assessed values was 11% and 29%, respectively. Excluding a single outlier dataset, the average and maximum average difference between eta estimates for the clinical systems and values predicted from scattering theory was 16% and 33%, respectively. These results were an improvement over previous interlaboratory comparisons of attenuation and backscatter estimates. Although the standardization of our estimation methodologies can be further improved, this study validates our results from previous rodent breast-tumor model studies. PMID:22518954

  10. Early Significant Tumor Volume Reduction After Radiosurgery in Brain Metastases From Renal Cell Carcinoma Results in Long-Term Survival

    SciTech Connect

    Kim, Wook Ha; Kim, Dong Gyu; Han, Jung Ho; Paek, Sun Ha; Chung, Hyun-Tai; Park, Chul-Kee; Kim, Chae-Yong; Kim, Yong Hwy; Kim, Jin Wook; Jung, Hee-Won

    2012-04-01

    Purpose: To retrospectively evaluate survival of patients with brain metastasis from renal cell carcinoma (RCC) after radiosurgery. Patients and Methods: Between 1998 and 2010, 46 patients were treated with radiosurgery, and the total number of lesions was 99. The mean age was 58.9 years (range, 33-78 years). Twenty-six patients (56.5%) had a single brain metastasis. The mean tumor volume was 3.0 cm{sup 3} (range, 0.01-35.1 cm{sup 3}), and the mean marginal dose prescribed was 20.8 Gy (range, 12-25 Gy) at the 50% isodose line. A patient was classified into the good-response group when the sum of the volume of the brain metastases decreased to less than 75% of the original volume at a 1-month follow-up evaluation using MRI. Results: As of December 28, 2010, 39 patients (84.8%) had died, and 7 (15.2%) survived. The overall median survival time was 10.0 {+-} 0.4 months (95% confidence interval, 9.1-10.8). After treatment, local tumor control was achieved in 72 (84.7%) of the 85 tumors assessed using MRI after radiosurgery. The good-response group survived significantly longer than the poor-response group (median survival times of 18.0 and 9.0 months, respectively; p = 0.025). In a multivariate analysis, classification in the good-response group was the only independent prognostic factor for longer survival (p = 0.037; hazard ratio = 0.447; 95% confidence interval, 0.209-0.953). Conclusions: Radiosurgery seems to be an effective treatment modality for patients with brain metastases from RCC. The early significant tumor volume reduction observed after radiosurgery seems to result in long-term survival in RCC patients with brain metastases.

  11. Val-BoroPro Accelerates T Cell Priming via Modulation of Dendritic Cell Trafficking Resulting in Complete Regression of Established Murine Tumors

    PubMed Central

    Larabee, Shannon; Krauss, Aviva; Davis, Jessica P. E.; Cui, Yongzhi; Kim, Su Young; Guimond, Martin; Bachovchin, William; Fry, Terry J.

    2013-01-01

    Although tumors naturally prime adaptive immune responses, tolerance may limit the capacity to control progression and can compromise effectiveness of immune-based therapies for cancer. Post-proline cleaving enzymes (PPCE) modulate protein function through N-terminal dipeptide cleavage and inhibition of these enzymes has been shown to have anti-tumor activity. We investigated the mechanism by which Val-boroPro, a boronic dipeptide that inhibits post-proline cleaving enzymes, mediates tumor regression and tested whether this agent could serve as a novel immune adjuvant to dendritic cell vaccines in two different murine syngeneic murine tumors. In mice challenged with MB49, which expresses the HY antigen complex, T cell responses primed by the tumor with and without Val-boroPro were measured using interferon gamma ELISPOT. Antibody depletion and gene-deficient mice were used to establish the immune cell subsets required for tumor regression. We demonstrate that Val-boroPro mediates tumor eradication by accelerating the expansion of tumor-specific T cells. Interestingly, T cells primed by tumor during Val-boroPro treatment demonstrate increased capacity to reject tumors following adoptive transfer without further treatment of the recipient. Val-boroPro -mediated tumor regression requires dendritic cells and is associated with enhanced trafficking of dendritic cells to tumor draining lymph nodes. Finally, dendritic cell vaccination combined with Val-boroPro treatment results in complete regression of established tumors. Our findings demonstrate that Val-boroPro has antitumor activity and a novel mechanism of action that involves more robust DC trafficking with earlier priming of T cells. Finally, we show that Val-boroPro has potent adjuvant properties resulting in an effective therapeutic vaccine. PMID:23554941

  12. Val-boroPro accelerates T cell priming via modulation of dendritic cell trafficking resulting in complete regression of established murine tumors.

    PubMed

    Walsh, Meghaan P; Duncan, Brynn; Larabee, Shannon; Krauss, Aviva; Davis, Jessica P E; Cui, Yongzhi; Kim, Su Young; Guimond, Martin; Bachovchin, William; Fry, Terry J

    2013-01-01

    Although tumors naturally prime adaptive immune responses, tolerance may limit the capacity to control progression and can compromise effectiveness of immune-based therapies for cancer. Post-proline cleaving enzymes (PPCE) modulate protein function through N-terminal dipeptide cleavage and inhibition of these enzymes has been shown to have anti-tumor activity. We investigated the mechanism by which Val-boroPro, a boronic dipeptide that inhibits post-proline cleaving enzymes, mediates tumor regression and tested whether this agent could serve as a novel immune adjuvant to dendritic cell vaccines in two different murine syngeneic murine tumors. In mice challenged with MB49, which expresses the HY antigen complex, T cell responses primed by the tumor with and without Val-boroPro were measured using interferon gamma ELISPOT. Antibody depletion and gene-deficient mice were used to establish the immune cell subsets required for tumor regression. We demonstrate that Val-boroPro mediates tumor eradication by accelerating the expansion of tumor-specific T cells. Interestingly, T cells primed by tumor during Val-boroPro treatment demonstrate increased capacity to reject tumors following adoptive transfer without further treatment of the recipient. Val-boroPro -mediated tumor regression requires dendritic cells and is associated with enhanced trafficking of dendritic cells to tumor draining lymph nodes. Finally, dendritic cell vaccination combined with Val-boroPro treatment results in complete regression of established tumors. Our findings demonstrate that Val-boroPro has antitumor activity and a novel mechanism of action that involves more robust DC trafficking with earlier priming of T cells. Finally, we show that Val-boroPro has potent adjuvant properties resulting in an effective therapeutic vaccine. PMID:23554941

  13. Radiofrequency Ablation of Renal Tumors with an Expandable Multitined Electrode: Results, Complications, and Pilot Evaluation of Cooled Pyeloperfusion for Collecting System Protection

    SciTech Connect

    Rouviere, Olivier Badet, Lionel; Murat, Francois Joseph; Marechal, Jean Marie; Colombel, Marc; Martin, Xavier; Lyonnet, Denis; Gelet, Albert

    2008-05-15

    The objective of this study was to retrospectively evaluate the results of radiofrequency ablation (RFA) of renal tumors with an impedance-based system using an expandable multitined electrode. Twenty-two patients (30 tumors) were treated with RFA over a 7-year period, percutaneously (16 tumors) or intraoperatively (14 tumors). Follow-up imaging was performed at 1-3, 6, and 12 months and yearly thereafter. Twenty-seven of 30 tumors (19/22 patients) showed no residual tumor on the first imaging control. Two residual tumors were successfully ablated by a second RFA procedure. Our mean follow-up period was 35 months (range, 3-84 months). Two tumors that had been completely ablated based on imaging criteria recurred 11 and 48 months after RFA. One was treated by partial nephrectomy. The other one was not treated because the patient developed bone metastases. One patient had nephrectomy because of an RFA-induced ureteropelvic junction stricture. Nine patients (11 sessions) had a pyeloperfusion of cooled saline during RFA. None developed symptomatic complications, even though in three patients the ablation zone extended to the closest calyx (3-5 mm from the tumor). We conclude that RFA of renal tumors is promising, but serious complications to the collecting system must be taken into consideration. Prophylactic per-procedural cooling of the collecting system is feasible but needs further assessment.

  14. Anterior callosal section is useful for the removal of large tumors invading the dorsal part of the anterior third ventricle: operative technique and results.

    PubMed

    Shiramizu, Hideki; Hori, Tomokatsu; Matsuo, Seigo; Niimura, Kaku; Yoshimoto, Haruko; Ishida, Atsushi; Asakuno, Keizoh; Yuzawa, Miki; Moriyama, Takashi

    2013-07-01

    Large tumors invading the dorsal part of the anterior third ventricle are difficult to manage. The anterior transcallosal approach is usually used to manage these tumors. In our clinic, anterior callosal section was combined with the anterior interhemispheric (AIH) translamina terminalis approach for these tumors with excellent results. The AIH approach is useful for removing tumors in and around the anterior part of the third ventricle. However, AIH alone is insufficient for large tumors invading the dorsal part of the anterior third ventricle. In such situations, simple anterior callosal section enables the neurosurgeon to extirpate the caudal part of the tumors deeply hidden from operative field, sparing the foramen of Monro, fornix, etc. We treated four large tumors (malignant teratoma, recurrent chordoid glioma, recurrent papillary tumor of pineal region occupying the third ventricle, and paraventricular meningioma) without major complications. The malignant teratoma case exhibited no recurrence with >10 years follow-up. The chordoid glioma and papillary tumor of pineal region were totally removed. The meningioma was subtotally removed except only a small tumor around the bilateral anterior cerebral artery. This simple technique is a new way to manage difficult large lesions in and around the third ventricle. PMID:23568695

  15. Multidisciplinary Oncoplastic Approach Reduces Infection in Chest Wall Resection and Reconstruction for Malignant Chest Wall Tumors

    PubMed Central

    Malahias, Marco N.; Balasubramanian, Balapathiran; Djearaman, Madava G.; Naidu, Babu; Grainger, Melvin F.; Kalkat, Maninder

    2016-01-01

    Background: Management of complex thoracic defects post tumor extipiration is challenging because of the nature of pathology, the radical approach, and the insertion of prosthetic material required for biomechanical stability. Wound complications pose a significant problem that can have detrimental effect on patient outcome. The authors outline an institutional experience of a multidisciplinary thoracic oncoplastic approach to improve outcomes. Methods: Prospectively collected data from 71 consecutive patients treated with chest wall resection and reconstruction were analyzed (2009–2015). The demographic data, comorbidities, operative details, and outcomes with special focus on wound infection were recorded. All patients were managed in a multidisciplinary approach to optimize perioperative surgical planning. Results: Pathology included sarcoma (78%), locally advanced breast cancer (15%), and desmoids (6%), with age ranging from 17 to 82 years (median, 42 years) and preponderance of female patients (n = 44). Chest wall defects were located anterior and anterolateral (77.5%), posterior (8.4%), and apical axillary (10%) with skeletal defect size ranging from 56 to 600 cm2 (mean, 154 cm2). Bony reconstruction was performed using polyprolene mesh, methyl methacrylate prosthesis, and titanium plates. Soft tissue reconstructions depended on size, location, and flap availability and were achieved using regional, distant, and free tissue flaps. The postoperative follow-up ranged from 5 to 70 months (median, 32 months). All flaps survived with good functional and aesthetic outcome, whereas 2 patients experienced surgical site infection (2.8%). Conclusions: Multidisciplinary thoracic oncoplastic maximizes outcome for patients with large resection of chest wall tumors with reduction in surgical site infection and wound complications particularly in association with rigid skeletal chest wall reconstruction. PMID:27536488

  16. MTHFR C677T Polymorphism is Associated with Tumor Response to Preoperative Chemoradiotherapy: A Result Based on Previous Reports

    PubMed Central

    Zhao, Yue; Li, Xingde; Kong, Xiangjun

    2015-01-01

    Background Preoperative chemoradiotherapy (pRCT) followed by surgery has been widely practiced in locally advanced rectal cancer, esophageal cancer, gastric cancer and other cancers. However, the therapy also exerts some severe adverse effects and some of the patients show poor or no response. It is very important to develop biomarkers (e.g., gene polymorphisms) to identify patients who have a higher likelihood of responding to pRCT. Recently, a series of reports have investigated the association of the genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and epidermal growth factor receptor (EGFR) genes with the tumor response to pRCT; however, the results were inconsistent and inconclusive. Material/Methods A systematic review and meta-analysis was performed by searching relevant studies about the association of MTHFR and EGFR polymorphisms with the tumor regression grade (TRG) in response to pRCT in databases of PubMed, EMBAS, Web of science, Chinese National Knowledge Infrastructure, and Wanfang database up to March 30, 2015. The pooled odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were calculated to assess the strength of the association under 5 genetic models. Results A total of 11 eligible articles were included in the present meta-analysis, of which 8 studies were performed in rectal cancer and 3 studies were performed in esophageal cancer. We finally included 8 included studies containing 839 cases for MTHFR C677T, 5 studies involving 634 cases for MTHFR A1298C, 3 studies containing 340 cases for EGFR G497A, and 4 studies containing 396 cases for EGFR CA repeat. The pooled analysis results indicated that MTHFR C677T might be correlated with the tumor response to pRCT under the recessive model (CC vs. CTTT) in overall analysis (OR=1.426(1.074–1.894), P=0.014), rectal cancer (OR=1.483(1.102–1.996), P=0.009), and TRG 1–2 vs. 3–5 group (OR=1.423(1.046–1.936), P=0.025), while other polymorphism including MTHFR

  17. A Plan to Improve Melanoma Tumor Depth Data Quality in the Surveillance, Epidemiology, and End Results Program.

    PubMed

    Lam, Clara; Dickie, Lois; Adamo, Peggy; Penberthy, Lynne

    2016-01-01

    In light of the recent assessment done for ProstateSpecific Antigen values in the Surveillance, Epidemiology, and End Results (SEER) Program, it is possible that coding procedures for melanoma tumor depth may have similar quality issues. Potential errors that have been initially identified are implied decimal errors, transcription errors, and incomplete information. Because of the SEER Program's commitment to high data quality standards, various studies are being planned to review and adjudicate incorrect lab values for several different data items in the SEER data collection. PMID:27556846

  18. KRAS mutation leads to decreased expression of regulator of calcineurin 2, resulting in tumor proliferation in colorectal cancer

    PubMed Central

    Niitsu, H; Hinoi, T; Kawaguchi, Y; Sentani, K; Yuge, R; Kitadai, Y; Sotomaru, Y; Adachi, T; Saito, Y; Miguchi, M; Kochi, M; Sada, H; Shimomura, M; Oue, N; Yasui, W; Ohdan, H

    2016-01-01

    KRAS mutations occur in 30–40% of all cases of human colorectal cancer (CRC). However, to date, specific therapeutic agents against KRAS-mutated CRC have not been developed. We previously described the generation of mouse models of colon cancer with and without Kras mutations (CDX2P-G22Cre;Apcflox/flox; LSL-KrasG12D and CDX2P-G22Cre;Apcflox/flox mice, respectively). Here, the two mouse models were compared to identify candidate genes, which may represent novel therapeutic targets or predictive biomarkers. Differentially expressed genes in tumors from the two mouse models were identified using microarray analysis, and their expression was compared by quantitative reverse transcription–PCR (qRT–PCR) and immunohistochemical analyses in mouse tumors and surgical specimens of human CRC, with or without KRAS mutations, respectively. Furthermore, the functions of candidate genes were studied using human CRC cell lines. Microarray analysis of 34 000 transcripts resulted in the identification of 19 candidate genes. qRT–PCR analysis data showed that four of these candidate genes (Clps, Irx5, Bex1 and Rcan2) exhibited decreased expression in the Kras-mutated mouse model. The expression of the regulator of calcineurin 2 (RCAN2) was also observed to be lower in KRAS-mutated human CRC. Moreover, inhibitory function for cancer cell proliferation dependent on calcineurin was indicated with overexpression and short hairpin RNA knockdown of RCAN2 in human CRC cell lines. KRAS mutations in CRC lead to a decrease in RCAN2 expression, resulting in tumor proliferation due to derepression of calcineurin–nuclear factor of activated T cells (NFAT) signaling. Our findings suggest that calcineurin–NFAT signal may represent a novel molecular target for the treatment of KRAS-mutated CRC. PMID:27526107

  19. How parents cope with their child's diagnosis and treatment of an embryonal tumor: results of a prospective and longitudinal study.

    PubMed

    Palmer, Shawna L; Lesh, Shawn; Wallace, Dana; Bonner, Melanie J; Swain, Michelle; Chapieski, Lynn; Janzen, Laura; Mabbott, Donald; Knight, Sarah; Boyle, Robyn; Armstrong, Carol L; Gajjar, Amar

    2011-11-01

    The current study reports longitudinal coping responses among parents of children diagnosed with an embryonal brain tumor. Patients (n = 219) were enrolled on a treatment protocol for a pediatric embryonal brain tumor. Their parents (n = 251) completed the Coping Response Inventory at time of their child's diagnosis and yearly thereafter, resulting in 502 observations. Outcomes were examined with patient and parent age at diagnosis, patient risk, parent gender and education as covariates. At the time of diagnosis, the highest observed coping method was seeking guidance with well above average scores (T = 61.6). Over time, younger parents were found to seek guidance at a significantly higher rate than older parents (P = .016) and the use of acceptance resignation and seeking alternative results by all parents significantly increased (P = .011 and P < .0001 respectively). The use of emotional discharge was also observed above average at time of diagnosis (T = 55.4) with younger fathers being more likely to exhibit emotional discharge than older fathers (P = .002). Differences in coping according to age of the patient and parent education level are also discussed. Results show a high need for guidance, and above average emotional discharge, especially among younger parents. It is imperative for the healthcare team to lead with accurate information so that these parents may make informed decisions about the care of their child. This need remains high years after diagnosis. Therefore it is critical to continue a consistent level of effective communication and support, even following treatment. PMID:21499990

  20. Targeting breast cancer stem cells by dendritic cell vaccination in humanized mice with breast tumor: preliminary results

    PubMed Central

    Pham, Phuc Van; Le, Hanh Thi; Vu, Binh Thanh; Pham, Viet Quoc; Le, Phong Minh; Phan, Nhan Lu-Chinh; Trinh, Ngu Van; Nguyen, Huyen Thi-Lam; Nguyen, Sinh Truong; Nguyen, Toan Linh; Phan, Ngoc Kim

    2016-01-01

    Background Breast cancer (BC) is one of the leading cancers in women. Recent progress has enabled BC to be cured with high efficiency. However, late detection or metastatic disease often renders the disease untreatable. Additionally, relapse is the main cause of death in BC patients. Breast cancer stem cells (BCSCs) are considered to cause the development of BC and are thought to be responsible for metastasis and relapse. This study aimed to target BCSCs using dendritic cells (DCs) to treat tumor-bearing humanized mice models. Materials and methods NOD/SCID mice were used to produce the humanized mice by transplantation of human hematopoietic stem cells. Human BCSCs were injected into the mammary fat pad to produce BC humanized mice. Both hematopoietic stem cells and DCs were isolated from the human umbilical cord blood, and immature DCs were produced from cultured mononuclear cells. DCs were matured by BCSC-derived antigen incubation for 48 hours. Mature DCs were vaccinated to BC humanized mice with a dose of 106 cells/mice, and the survival percentage was monitored in both treated and untreated groups. Results The results showed that DC vaccination could target BCSCs and reduce the tumor size and prolong survival. Conclusion These results suggested that targeting BCSCs with DCs is a promising therapy for BC. PMID:27499638

  1. Does Local Recurrence of Prostate Cancer After Radiation Therapy Occur at the Site of Primary Tumor? Results of a Longitudinal MRI and MRSI Study

    SciTech Connect

    Arrayeh, Elnasif; Westphalen, Antonio C.; Kurhanewicz, John; Roach, Mack; Jung, Adam J.; Carroll, Peter R.; Coakley, Fergus V.

    2012-04-01

    Purpose: To determine if local recurrence of prostate cancer after radiation therapy occurs at the same site as the primary tumor before treatment, using longitudinal magnetic resonance (MR) imaging and MR spectroscopic imaging to assess dominant tumor location. Methods and Materials: This retrospective study was HIPAA compliant and approved by our Committee on Human Research. We identified all patients in our institutional prostate cancer database (1996 onward) who underwent endorectal MR imaging and MR spectroscopic imaging before radiotherapy for biopsy-proven prostate cancer and again at least 2 years after radiotherapy (n = 124). Two radiologists recorded the presence, location, and size of unequivocal dominant tumor on pre- and postradiotherapy scans. Recurrent tumor was considered to be at the same location as the baseline tumor if at least 50% of the tumor location overlapped. Clinical and biopsy data were collected from all patients. Results: Nine patients had unequivocal dominant tumor on both pre- and postradiotherapy imaging, with mean pre- and postradiotherapy dominant tumor diameters of 1.8 cm (range, 1-2.2) and 1.9 cm (range, 1.4-2.6), respectively. The median follow-up interval was 7.3 years (range, 2.7-10.8). Dominant recurrent tumor was at the same location as dominant baseline tumor in 8 of 9 patients (89%). Conclusions: Local recurrence of prostate cancer after radiation usually occurs at the same site as the dominant primary tumor at baseline, suggesting supplementary focal therapy aimed at enhancing local tumor control would be a rational addition to management.

  2. Functional results of endoscopic laser surgery in advanced head and neck tumors

    NASA Astrophysics Data System (ADS)

    Sadick, Haneen; Baker-Schreyer, Antonio; Bergler, Wolfgang; Maurer, Joachim; Hoermann, Karl

    1998-01-01

    Functional results following lasersurgery of minor laryngeal carcinomas were very encouraging. The indication for lasersurgical intervention was then extended to larger carcinomas of the larynx and hypopharynx. The purpose of this study was to assess vocal function and swallowing ability after endoscopic lasersurgery and to compare the results with conventional surgical procedures. From January 1994 to December 1996, 72 patients with advanced squamous cell carcinoma of the larynx and hypopharynx were examined prospectively. The patients underwent endoscopic lasersurgery instead of laryngopharyngectomy. The voice quality was evaluated pre- and postoperatively by subjective assessment, registration of voice parameters and sonegraphic classification. The swallowing ability was judged according to individual scores. The necessity of tracheostomy and nasogastric tube were registered and the duration of hospitalization was documented. The results showed that laryngeal phonation and swallowing ability were significantly better 12 months after lasersurgery compared to the preoperative findings whereas the recurrence rate was similar or even better after conventional pharyngolaryngectomy. Lasersurgery as an alternative surgical procedure to laryngectomy enables patients to retain a sufficient voice function and swallowing ability.

  3. Tumor Shrinkage With Lanreotide Autogel 120 mg as Primary Therapy in Acromegaly: Results of a Prospective Multicenter Clinical Trial

    PubMed Central

    Bevan, John S.; Petersenn, Stephan; Flanagan, Daniel; Tabarin, Antoine; Prévost, Gaëtan; Maisonobe, Pascal; Clermont, Antoine

    2014-01-01

    Context: Methodological shortcomings often compromise investigations into the effects of primary somatostatin-analog treatment on tumor size in acromegaly. There are also limited data for the long-acting lanreotide formulation. Objective: The aim of the study was to better characterize the effects of primary lanreotide Autogel treatment on tumor size in patients with GH-secreting macroadenomas. Design: PRIMARYS was a 48-week, multicenter, open-label, single-arm study. Setting: The study was conducted at specialist endocrine centers. Patients: Treatment-naïve acromegalic patients with GH-secreting macroadenomas participated in the study. Intervention: Lanreotide Autogel 120 mg was administered sc every 28 days (without dose titration). Outcome Measures: The primary endpoint was the proportion of patients with clinically significant (≥20%) tumor volume reduction (TVR) at week 48/last post-baseline value available using central assessments from three readers. The null hypothesis (H0) for the primary endpoint was that the proportion with TVR was ≤55%. Secondary endpoints included: TVR at other time points, GH and IGF-1, acromegalic symptoms, quality of life (QoL), and safety. Results: Sixty-four of 90 (71.1%) patients completed the study. Clinically significant TVR at 48 weeks/last post-baseline value available was achieved by 62.9% (95% confidence interval, 52.0, 72.9) of 89 patients in the primary analysis (intention-to-treat population; H0 not rejected) and 71.9–75.3% in sensitivity (n = 89) and secondary analyses (n = 63) (H0 rejected). At 12 weeks, 54.1% had clinically significant TVR. Early and sustained improvements also occurred in GH and IGF-1, acromegalic symptoms, and QoL. No patients withdrew due to gastrointestinal intolerance. Conclusions: Primary treatment with lanreotide Autogel, administered at 120 mg (highest available dose) without dose titration, in patients with GH-secreting macroadenomas provides early and sustained reductions in tumor

  4. Necrosis After Craniospinal Irradiation: Results From a Prospective Series of Children With Central Nervous System Embryonal Tumors

    SciTech Connect

    Murphy, Erin S.; Merchant, Thomas E.; Wu Shengjie; Xiong Xiaoping; Lukose, Renin; Wright, Karen D.; Qaddoumi, Ibrahim; Armstrong, Gregory T.; Broniscer, Alberto; Gajjar, Amar

    2012-08-01

    Purpose: Necrosis of the central nervous system (CNS) is a known complication of craniospinal irradiation (CSI) in children with medulloblastoma and similar tumors. We reviewed the incidence of necrosis in our prospective treatment series. Patients and Methods: Between 1996 and 2009, 236 children with medulloblastoma (n = 185) or other CNS embryonal tumors (n = 51) received postoperative CSI followed by dose-intense cyclophosphamide, vincristine, and cisplatin. Average risk cases (n = 148) received 23.4 Gy CSI, 36 Gy to the posterior fossa, and 55.8 Gy to the primary; after 2003, the treatment was 23.4 Gy CSI and 55.8 Gy to the primary. All high-risk cases (n = 88) received 36-39.6 Gy CSI and 55.8 Gy primary. The primary site clinical target volume margin was 2 cm (pre-2003) or 1 cm (post-2003). With competing risk of death by any cause, we determined the cumulative incidence of necrosis. Results: With a median follow-up of 52 months (range, 4-163 months), eight cases of necrosis were documented. One death was attributed. The median time to the imaging evidence was 4.8 months and to symptoms 6.0 months. The cumulative incidence at 5 years was 3.7% {+-} 1.3% (n = 236) for the entire cohort and 4.4% {+-} 1.5% (n = 196) for infratentorial tumor location. The mean relative volume of infratentorial brain receiving high-dose irradiation was significantly greater for patients with necrosis than for those without: {>=}50 Gy (92.12% {+-} 4.58% vs 72.89% {+-} 1.96%; P=.0337), {>=}52 Gy (88.95% {+-} 5.50% vs 69.16% {+-} 1.97%; P=.0275), and {>=}54 Gy (82.28% {+-} 7.06% vs 63.37% {+-} 1.96%; P=.0488), respectively. Conclusions: Necrosis in patients with CNS embryonal tumors is uncommon. When competing risks are considered, the incidence is 3.7% at 5 years. The volume of infratentorial brain receiving greater than 50, 52, and 54 Gy, respectively, is predictive for necrosis.

  5. [Results of cryosurgery for the treatment of vascular nevi and tumors (author's transl)].

    PubMed

    Scholz, A; Sebastian, G; Baerthold, W; Matthäus, W; Pässler, L

    1980-01-01

    Report on experiences of the application of cryotherapy in 187 patients with 200 vascular nevi and angiomas. The fit form of therapy for angiomas is contact-freezing because of simultaneous compression. The cryotherapy of cavernous angiomas in skin and oral mucosa, especially in difficult locations, produces excellent results. In those cases the cryotherapy is the method of choice. In founded indications capillary angiomas of infants could be successfully treated. Port-wine nevi in part are suitable for the application of low temperatures. PMID:7224821

  6. [Bladder tumor lethality. Results in the autonomous community of Rioja between 1975-1991].

    PubMed

    Fernández Fernández, A; Gil Fabra, J; Fernández Ruíz, M; Angulo Castellanos, M G; Blanco Martín, E; Otero Mauricio, G

    1998-01-01

    Between 1975-1991, a total of 557 cases of bladder carcinoma were identified in the Autonomous Community of La Rioja (CAR) which were followed up to December 1994. The overall lethality was 21.9%. 492 cases with 22.35% lethality were identified in males. In females, however, there was 65 cases with 18.46% lethality. The comparison of males and females lethality resulted in p = 0.525. Lethality between cases diagnosed within each 5-year period analyzed is: 1975-1981: 177 cases, lethality 23.72%. 1982-1986: 168 cases, lethality 30.95%. 1987-1991: 212 cases, lethality 13.20%. Between the first and the second 5-year periods, p = 0.132; between the first and third 5-year periods p = 0.007 and between the second and third 5-year periods p < 0.000. Bladder tumours accounts in CAR for a 22.35% lethality. Lethality is higher in males that in females but the difference is not statistically significant. In the last 5-year period assessed, 1987-1991, a reduction of lethality from bladder neoplasms has been documented. PMID:9807870

  7. [Melanoma research in Hungary: promising results in a previously orphan tumor].

    PubMed

    Balázs, Margit; Vízkeleti, Laura; Ecsedi, Szilvia; Ádány, Róza; Rásó, Erzsébet; Hegedûs, Balázs; Ladányi, Andrea; Tóvári, József; Tímár, József

    2015-12-01

    Melanoma research has a two decade history in Hungary and is based on three groups located at the National Institute of Oncology (NIO), the University of Debrecen (DU) and Semmelweis University (SU). Previously we have summarized the achievements of the NIO group in this Journal, now this paper summarizes the recent results of their collaborations. The research group of DU revealed several novel genetic alterations in the melanoma genome which might have clinical relevance as prognosticators or predictors in light of the novel target therapies. Data indicating unique, perhaps melanoma-specific epigenetic changes during progression might be even more important, identifying novel genes otherwise not detected as genetically altered ones. The research group in Budapest extensively used experimental human melanoma models and demonstrated the host sex as a key factor in progression due to the specific function of NK cells. Identification of functional glucocorticoid receptor in human melanoma might lead to therapeutic exploitation similar to certain leukemias. Studies on extracellular matrix revealed collagen XVII and CD44 splice variants as progression associated factors of melanoma. Since the double wild type genotype of melanoma is lacking effective therapy, data on the use of FGFR2, c-met or cannabinoid receptor as target can be important. On the other hand, experimental data on the antitumoral effects of heparin derivatives or bisphosphonate in melanoma models can also be encouraging. PMID:26665186

  8. Time-domain optical mammography Softscan: initial results on detection and characterization of breast tumors

    NASA Astrophysics Data System (ADS)

    Intes, Xavier; Djeziri, Salim; Ichalalene, Zahia; Mincu, Niculae; Wang, Yong; St.-Jean, Philippe; Lesage, Frédéric; Hall, David; Boas, David A.; Polyzos, Margaret

    2004-10-01

    Near-infrared (NIR) technology appears promising as a non-invasive clinical technique for breast cancer screening and diagnosis. The technology capitalizes on the relative transparency of human tissue in this spectral range and its sensitivity to the main components of the breast:; water, lipid and hemoglobin. In this work we present initial results obtained using the SoftScan® breast-imaging system developed by ART, Advanced Research Technologies inc., Montreal. This platform consists of a 4-wavelength time-resolved scanning system used to quantify non-invasively the local functional state of breast tissue. The different aspects of the system used to retrieve 3D optical contrast will be presented. Furthermore, preliminary data obtained from a prospective study conducted at The Royal Victoria Hospital of the McGill University Health Center in Montreal will be discussed. Analysis of the data gathered by SoftScan® demonstrated the potential of the technology in discriminating between healthy and diseased tissue.

  9. Disruption of protein kinase Ceta results in impairment of wound healing and enhancement of tumor formation in mouse skin carcinogenesis.

    PubMed

    Chida, Kazuhiro; Hara, Takeshi; Hirai, Takaaki; Konishi, Chieko; Nakamura, Kenji; Nakao, Kazuki; Aiba, Atsu; Katsuki, Motoya; Kuroki, Toshio

    2003-05-15

    We have generated a mouse strain lacking protein kinase C (PKC) eta to evaluate its significance in epithelial organization and tumor formation. The PKCeta-deficient mice exhibited increased susceptibility to tumor formation in two-stage skin carcinogenesis by single application of 7,12-dimethylbenz(a)anthracene (DMBA) for tumor initiation and repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA) for tumor promotion. The tumor formation was not enhanced by DMBA or TPA treatment alone, suggesting that PKCeta suppresses tumor promotion. Epidermal hyperplasia induced by topical TPA treatment was prolonged in the mutant mice. The enhanced tumor formation may be closely associated with the prolonged hyperplasia induced by topical TPA treatment. In the mutant mice, after inflicting injury by punch biopsy, wound healing on the dorsal skin, particularly reepithelialization, was significantly delayed and impaired in structure. Impairment of epithelial regeneration in wound healing indicates a possibility that PKCeta plays a role in maintenance of epithelial architecture. Homeostasis in epithelial tissues mediated by PKCeta is important for tumor formation in vivo. We propose that PKCeta is involved in tumor formation modulated by regulation of proliferation and remodeling of epithelial cells in vivo. PMID:12750259

  10. [Correlation of clinical effect, pathological response of tumor cells and the end results of combined treatment of locally advanced breast cancer].

    PubMed

    Kharchenko, V P; Voznyĭ, E K; Galil-Ogly, G A; Gurov, S N; Dobrovol'skaia, N I; Alinchenko, L A; Bol'shakova, S A

    2000-01-01

    A correlation was established between the end-results of neoadjuvant chemotherapy for locally-advanced breast cancer and pathological response of tumor cells. Also, the end-results correlated with CR or PR and pathological response. Only a small proportion of patients with tumor progression were registered as stage III or IV of pathological response (0.6 and 0.8%, respectively). PMID:11219951

  11. Combination of vatalanib and a 20-HETE synthesis inhibitor results in decreased tumor growth in an animal model of human glioma

    PubMed Central

    Shankar, Adarsh; Borin, Thaiz F; Iskander, Asm; Varma, Nadimpalli RS; Achyut, Bhagelu R; Jain, Meenu; Mikkelsen, Tom; Guo, Austin M; Chwang, Wilson B; Ewing, James R; Bagher-Ebadian, Hassan; Arbab, Ali S

    2016-01-01

    Background Due to the hypervascular nature of glioblastoma (GBM), antiangiogenic treatments, such as vatalanib, have been added as an adjuvant to control angiogenesis and tumor growth. However, evidence of progressive tumor growth and resistance to antiangiogenic treatment has been observed. To counter the unwanted effect of vatalanib on GBM growth, we have added a new agent known as N-hydroxy-N′-(4-butyl-2 methylphenyl)formamidine (HET0016), which is a selective inhibitor of 20-hydroxyeicosatetraenoic acid (20-HETE) synthesis. The aims of the studies were to determine 1) whether the addition of HET0016 can attenuate the unwanted effect of vatalanib on tumor growth and 2) whether the treatment schedule would have a crucial impact on controlling GBM. Methods U251 human glioma cells (4×105) were implanted orthotopically. Two different treatment schedules were investigated. Treatment starting on day 8 (8–21 days treatment) of the tumor implantation was to mimic treatment following detection of tumor, where tumor would have hypoxic microenvironment and well-developed neovascularization. Drug treatment starting on the same day of tumor implantation (0–21 days treatment) was to mimic cases following radiation therapy or surgery. There were four different treatment groups: vehicle, vatalanib (oral treatment 50 mg/kg/d), HET0016 (intraperitoneal treatment 10 mg/kg/d), and combined (vatalanib and HET0016). Following scheduled treatments, all animals underwent magnetic resonance imaging on day 22, followed by euthanasia. Brain specimens were equally divided for immunohistochemistry and protein array analysis. Results Our results demonstrated a trend that HET0016, alone or in combination with vatalanib, is capable of controlling the tumor growth compared with that of vatalanib alone, indicating attenuation of the unwanted effect of vatalanib. When both vatalanib and HET0016 were administered together on the day of the tumor implantation (0–21 days treatment), tumor

  12. Is Antibiotic Prophylaxis for Percutaneous Radiofrequency Ablation (RFA) of Primary Liver Tumors Necessary? Results From a Single-Center Experience

    SciTech Connect

    Bhatia, Shivank S.; Echenique, Ana Froud, Tatiana Suthar, Rekha Lawson, Ivy Dalal, Ravi; Yrizarry, Jose Narayanan, Govindarajan

    2015-08-15

    PurposeThe purpose of this study was to evaluate need for antibiotic prophylaxis for radiofrequency ablation (RFA) of liver tumors in patients with no significant co-existing risk factors for infection.Materials and MethodsFrom January 2004 to September 2013, 83 patients underwent 123 percutaneous RFA procedures for total of 152 hepatocellular carcinoma (HCC) lesions. None of the patients had pre-existing biliary enteric anastomosis (BEA) or any biliary tract abnormality predisposing to ascending biliary infection or uncontrolled diabetes mellitus. No pre- or post-procedure antibiotic prophylaxis was provided for 121 procedures. Data for potential risk factors were reviewed retrospectively and analyzed for the frequency of infectious complications, including abscess formation.ResultsOne patient (1/121 (0.8 %) RFA sessions) developed a large segment 5 liver abscess/infected biloma communicating with the gallbladder 7 weeks after the procedure, successfully treated over 10 weeks with IV and PO antibiotic therapy and percutaneous catheter drainage. This patient did not receive any antibiotics prior to RFA. During the procedure, there was inadvertent placement of RFA probe tines into the gallbladder. No other infectious complications were documented.ConclusionThese data suggest that the routine use of prophylactic antibiotics for liver RFA is not necessary in majority of the patients undergoing liver ablation for HCC and could be limited to patients with high-risk factors such as the presence of BEA or other biliary abnormalities, uncontrolled diabetes mellitus, and large centrally located tumors in close proximity to central bile ducts. Larger randomized studies are needed to confirm this hypothesis.

  13. Recurrent angio-fibroma of breast masquerading as phyllodes tumor.

    PubMed

    Chaurasia, Jai K; Alam, Feroz; Shadan, Mariam; Naim, Mohammed

    2015-01-01

    A young Indian female presented with a recurring tumor in the right breast masquerading as phyllodes tumor. Patient had history of five times excision and recurrences of the tumor, diagnosed as fibrous phyllodes of the breast. Presently, a well-circumscribed tumor of about 10 cm size, comprising of benign fibrous-angiomatous tissue with evidence of foci of pyogenic vasculitis was observed. Immuno-histochemical markers for the myo-epithelial and epithelial elements excluded the possibility of fibrous phyllodes, inflammatory myofibroblastic tumor, desmoid fibromatosis, and metaplastic carcinoma. The present findings were diagnostic of an inflammatory angio-fibroma of the right breast, not reported in the earlier literature. The observations indicated that the female breast may be susceptible to spontaneous productive and common-antibiotic-resistant focal septic vascular inflammation giving rise to angio-fibromatous proliferation producing a well-defined tumor mass in the breast, distinguishable from the other breast lesions by the connective tissue stains and immuno-histochemical markers. PMID:26458623

  14. Combination of gold nanoparticle-conjugated TNF-α and radiation therapy results in a synergistic anti-tumor response in murine carcinoma models

    PubMed Central

    Koonce, Nathan A.; Quick, Matthew C.; Hardee, Matthew E.; Jamshidi-Parsian, Azemat; Dent, Judith A.; Paciotti, Giulio F.; Nedosekin, Dmitry; Dings, Ruud P.M.; Griffin, Robert J.

    2016-01-01

    Introduction Although remarkable preclinical antitumor effects have been shown for tumor necrosis factor-α (TNF) alone and in combination with radiation, clinical use is hindered by systemic dose-limiting toxicities. Here, we investigated the physiological and anti-tumor effects of radiotherapy combined with the novel nanomedicine CYT-6091, a 27-nm average diameter polyethylene glycol-TNF coated gold nanoparticle which passed through Phase I trials recently. Methods Physiological and anti-tumor effects of single and fractionated radiation in combination with CYT-6091 were studied in the murine 4T1 breast carcinoma and SCCVII head and neck tumor squamous cell carcinoma models. Results In the 4T1 murine breast tumor model we observed a significant reduction in tumor interstitial fluid pressure (IFP) 24h after CYT-6091 alone and combined with a radiation dose of 12 Gy (p<0.05 vs control), whereas radiation alone (12Gy) had negligible effect on IFP. In the SCCVII head and neck tumor model, the baseline IFP was not markedly elevated and there was little additional change in IFP post single dose radiation or combined therapy (p>0.05 vs control) despite extensive observed vascular damage. The IFP reduction in the 4T1 model was also associated with marked vascular damage and extravasation of red blood cells into the tumor interstitium. A sustained reduction in tumor cell density was observed in the combined therapy group compared to all other groups (p<0.05). Finally, we observed a >2-fold delay in tumor growth when CYT-6091 was combined with a single 20 Gy irradiation- notably irrespective of treatment sequence. Moreover, when hypofractionated radiation (12 Gy × 3) was applied in combination with CYT-6091 treatment, a >5-fold growth delay was observed in the combined treatment group of both tumor models and determined to be synergistic. Conclusions Our results demonstrate that gold-labeled TNF nanoparticles in combination with single or fractionated high-dose radiation

  15. Epidermal Platelet-activating Factor Receptor Activation and Ultraviolet B Radiation Result in Synergistic Tumor Necrosis Factor-alpha Production

    PubMed Central

    Wolverton, Jay E.; Al-Hassani, Mohammed; Yao, Yongxue; Zhang, Qiwei; Travers, Jeffrey B.

    2010-01-01

    Ultraviolet B radiation (UVB) is a potent stimulator of epidermal cytokine production which has been implicated in photoaggravated dermatoses. In addition to cytokines such as tumor necrosis factor-α (TNF-α), UVB generates bioactive lipids including platelet-activating factor (PAF). Our previous studies have demonstrated that UVB-mediated production of keratinocyte TNF-α is in part due to PAF. The current studies use a human PAF-receptor (PAF-R) negative epithelial cell line transduced with PAF-Rs and PAF–R-deficient mice to demonstrate that activation of the epidermal PAF-R along with UVB irradiation results in a synergistic production of TNF-α. It should be noted that PAF-R effects are mimicked by the protein kinase C (PKC) agonist phorbol myristic acetate, and are inhibited by pharmacological antagonists of the PKC gamma isoenzyme. These studies suggest that concomitant PAF-R activation and UVB irradiation results in a synergistic production of the cytokine TNF-α which is mediated in part via PKC. These studies provide a novel potential mechanism for photosensitivity responses. PMID:19769579

  16. Solid tumors of the peritoneum, omentum, and mesentery in children: radiologic-pathologic correlation: from the radiologic pathology archives.

    PubMed

    Chung, Ellen M; Biko, David M; Arzamendi, Aaron M; Meldrum, Jaren T; Stocker, J Thomas

    2015-01-01

    Intraperitoneal solid tumors are far less common in children than in adults, and the histologic spectrum of neoplasms of the peritoneum and its specialized folds in young patients differs from that in older patients. Localized masses may be caused by inflammatory myofibroblastic tumor, Castleman disease, mesenteric fibromatosis, or other mesenchymal masses. Inflammatory myofibroblastic tumor is a mesenchymal tumor of borderline biologic potential that appears as a solitary circumscribed mass, possibly with central calcification. Castleman disease is an idiopathic lymphoproliferative disorder that appears as a circumscribed, intensely enhancing mass in the mesentery. Mesenteric fibromatosis, or intra-abdominal desmoid tumor, is a benign tumor of mesenchymal origin associated with familial adenomatous polyposis. Mesenteric fibromatosis appears as a mildly enhancing, circumscribed solitary mass without metastases. Diffuse peritoneal disease may be due to desmoplastic small round cell tumor (DSRCT), non-Hodgkin lymphoma, or rhabdomyosarcoma. DSRCT is a rare member of the small round blue cell tumor family that causes diffuse peritoneal masses without a visible primary tumor. A dominant mass is typically found in the retrovesical space. Burkitt lymphoma is a pediatric tumor that manifests with extensive disease because of its short doubling time. The bowel and adjacent mesentery are commonly involved. Rhabdomyosarcoma may arise as a primary tumor of the omentum or may spread from a primary tumor in the bladder, prostate, or scrotum. Knowledge of this spectrum of disease allows the radiologist to provide an appropriate differential diagnosis and suggest proper patient management. PMID:25763737

  17. A Multi-Institutional Study of Feasibility, Implementation, and Early Clinical Results With Noninvasive Breast Brachytherapy for Tumor Bed Boost

    SciTech Connect

    Hamid, Subarna; Rocchio, Kathy; Arthur, Douglas; Vera, Robyn; Sha, Sandra; Jolly, Michele; Cavanaugh, Sean; Wooten, Eric; Benda, Rashmi; Greenfield, Brad; Prestidge, Bradley; Ackerman, Scot; Kuske, Robert; Quiet, Coral; Snyder, Margaret; Wazer, David E.

    2012-08-01

    Purpose: To evaluate the feasibility, implementation, and early results of noninvasive breast brachytherapy (NIBB) for tumor bed boost with whole breast radiation therapy (WBRT). Methods and Materials: NIBB is a commercially available (AccuBoost, Billerica, MA) mammography-based, brachytherapy system in which the treatment applicators are centered on the planning target volume (PTV) to direct {sup 192}Ir emissions along orthogonal axes. A privacy-encrypted online data registry collected information from 8 independent academic and community-based institutions. Data were from 146 consecutive women with early-stage breast cancer after lumpectomy and WBRT receiving boost with NIBB between July 2007 and March 2010. Toxicity and cosmesis were graded according to the Common Toxicity Criteria (v. 3.0) and the Harvard scale. Median follow-up was 6 months (1-39 months). Results: Grade 1-2 skin toxicity was observed in 64%, 48%, and 21% during the acute (1-3 weeks), intermediate (4-26 weeks), and late-intermediate (>26 weeks) periods. There was no Grade 4 toxicity. At 6 months, for the entire cohort, cosmesis was excellent/good in 62%/38%. The subset receiving NIBB before WBRT had cosmetic scores of 32% and 63%, whereas during WBRT, 58% and 37% were rated as excellent and good, respectively. Breast compression was scored as 'uncomfortable' in 12%, 29%, and 59% when NIBB was delivered before, during, or after WBRT. For each patient, the fraction-to-fraction variability in PTV was low. Skin flash was associated with a higher proportion of excellent cosmesis (58% vs. 42%) relative to having the applicator all within breast tissue. Conclusions: These data indicate that NIBB is feasible and can be consistently implemented in a broad array of practice settings. Preliminary evaluation suggests that NIBB is associated with acceptably mild normal tissue toxicity and favorable early cosmesis. The application of NIBB before WBRT may be associated with better patient tolerance at the

  18. Real-Time US-CT/MRI Image Fusion for Guidance of Thermal Ablation of Liver Tumors Undetectable with US: Results in 295 Cases

    SciTech Connect

    Mauri, Giovanni Cova, Luca; Beni, Stefano De; Ierace, Tiziana Tondolo, Tania Cerri, Anna; Goldberg, S. Nahum; Solbiati, Luigi

    2015-02-15

    PurposeThis study was designed to assess feasibility of US-CT/MRI fusion-guided ablation in liver tumors undetectable with US.MethodsFrom 2002 to 2012, 295 tumors (162 HCCs and 133 metastases; mean diameter 1.3 ± 0.6 cm, range 0.5–2.5 cm) detectable on contrast-enhanced CT/MRI, but completely undetectable with unenhanced US and either totally undetectable or incompletely conspicuous with contrast-enhanced US (CEUS), were treated in 215 sessions using either internally cooled radiofrequency or microwave with standard ablation protocols, guided by an image fusion system (Virtual Navigation System, Esaote S.p.A., Genova, Italy) that combines US with CT/ MRI images. Correct targeting and successful ablation of tumor were verified after 24 hours with CT or MRI.ResultsA total of 282 of 295 (95.6 %) tumors were correctly targeted with successful ablation achieved in 266 of 295 (90.2 %). Sixteen of 295 (5.4 %) tumors were correctly targeted, but unsuccessfully ablated, and 13 of 295 (4.4 %) tumors were unsuccessfully ablated due to inaccurate targeting. There were no perioperative deaths. Major complications were observed in 2 of the 215 treatments sessions (0.9 %).ConclusionsReal-time virtual navigation system with US-CT/MRI fusion imaging is precise for targeting and achieving successful ablation of target tumors undetectable with US alone. Therefore, a larger population could benefit from ultrasound guided ablation procedures.

  19. Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of cancer stem cell-like characteristics and a reduced tumor burden

    PubMed Central

    2014-01-01

    Background Current treatment of ovarian cancer patients with chemotherapy leaves behind a residual tumor which results in recurrent ovarian cancer within a short time frame. We have previously demonstrated that a single short-term treatment of ovarian cancer cells with chemotherapy in vitro resulted in a cancer stem cell (CSC)-like enriched residual population which generated significantly greater tumor burden compared to the tumor burden generated by control untreated cells. In this report we looked at the mechanisms of the enrichment of CSC-like residual cells in response to paclitaxel treatment. Methods The mechanism of survival of paclitaxel-treated residual cells at a growth inhibitory concentration of 50% (GI50) was determined on isolated tumor cells from the ascites of recurrent ovarian cancer patients and HEY ovarian cancer cell line by in vitro assays and in a mouse xenograft model. Results Treatment of isolated tumor cells from the ascites of ovarian cancer patients and HEY ovarian cancer cell line with paclitaxel resulted in a CSC-like residual population which coincided with the activation of Janus activated kinase 2 (JAK2) and signal transducer and activation of transcription 3 (STAT3) pathway in paclitaxel surviving cells. Both paclitaxel-induced JAK2/STAT3 activation and CSC-like characteristics were inhibited by a low dose JAK2-specific small molecule inhibitor CYT387 (1 μM) in vitro. Subsequent, in vivo transplantation of paclitaxel and CYT387-treated HEY cells in mice resulted in a significantly reduced tumor burden compared to that seen with paclitaxel only-treated transplanted cells. In vitro analysis of tumor xenografts at protein and mRNA levels demonstrated a loss of CSC-like markers and CA125 expression in paclitaxel and CYT387-treated cell-derived xenografts, compared to paclitaxel only-treated cell-derived xenografts. These results were consistent with significantly reduced activation of JAK2 and STAT3 in paclitaxel and CYT387-treated

  20. SU-C-210-06: Quantitative Evaluation of Dosimetric Effects Resulting From Positional Variations of Pancreatic Tumor Volumes

    SciTech Connect

    Yu, S; Sehgal, V; Wei, R; Lawrenson, L; Kuo, J; Hanna, N; Ramsinghani, N; Daroui, P; Al-Ghazi, M

    2015-06-15

    Purpose: The aim of this study is to quantify dosimetric effects resulting from variation in pancreatic tumor position assessed by bony anatomy and implanted fiducial markers Methods: Twelve pancreatic cancer patients were retrospectively analyzed for this study. All patients received modulated arc therapy (VMAT) treatment using fiducial-based Image Guided Radiation Therapy (IGRT) to the intact pancreas. Using daily orthogonal kV and/or Cone beam CT images, the shift needed to co-register the daily pre-treatment images to reference CT from fiducial to bone (Fid-Bone) were recorded as Left-Right (LR), Anterior-Posterior (AP) and Superior-Inferior (SI). The original VMAT plan iso-center was shifted based on KV bone matching positions at 5 evenly spaced fractions. Dose coverage of the planning target volumes (PTVs) (V100%), mean dose to liver, kidney and stomach/duodenum were assessed in the modified plans. Results: A total of 306 fractions were analyzed. The absolute fiducial-bone positional shifts were greatest in the SI direction, (AP = 2.7 ± 3.0, LR = 2.8 ± 2.8, and SI 6.3 ± 7.9 mm, mean ± SD). The V100% was significantly reduced by 13.5%, (Fid-Bone = 95.3 ± 2.0 vs. 82.3 ± 11.8%, p=0.02). This varied widely among patients (Fid-Bone V100% Range = 2–60%), where 33% of patients had a reduction in V100% of more than 10%. The impact on OARs was greatest to the liver (Fid-Bone= 14.6 vs. 16.1 Gy, 10%), and stomach, (Fid-Bone = 23.9 vx. 25.5 Gy, 7%), however was not statistically significant (p=0.10 both). Conclusion: Compared to matching by fiducial markers, matching by bony anatomy would have substantially reduced the PTV coverage by 13.5%. This reinforces the importance of online position verification based on fiducial markers. Hence, implantation of fiducial markers is strongly recommended for pancreatic cancer patients undergoing intensity modulated radiation therapy treatments.

  1. Inducible loss of one Apc allele in Lrig1-expressing progenitor cells results in multiple distal colonic tumors with features of familial adenomatous polyposis

    PubMed Central

    Powell, Anne E.; Vlacich, Gregory; Zhao, Zhen-Yang; McKinley, Eliot T.; Washington, M. Kay; Manning, H. Charles

    2014-01-01

    Individuals with familial adenomatous polyposis (FAP) harbor a germline mutation in adenomatous polyposis coli (APC). The major clinical manifestation is development of multiple colonic tumors at a young age due to stochastic loss of the remaining APC allele. Extracolonic features, including periampullary tumors, gastric abnormalities, and congenital hypertrophy of the retinal pigment epithelium, may occur. The objective of this study was to develop a mouse model that simulates these features of FAP. We combined our Lrig1-CreERT2/+ mice with Apcfl/+ mice, eliminated one copy of Apc in leucine-rich repeats and immunoglobulin-like domains protein 1 (Lrig1)-positive (Lrig1+) progenitor cells with tamoxifen injection, and monitored tumor formation in the colon by colonoscopy and PET. Initial loss of one Apc allele in Lrig1+ cells results in a predictable pattern of preneoplastic changes, culminating in multiple distal colonic tumors within 50 days of induction, as well as the extracolonic manifestations of FAP mentioned above. We show that tumor formation can be monitored by noninvasive PET imaging. This inducible stem cell-driven model recapitulates features of FAP and offers a tractable platform on which therapeutic interventions can be monitored over time by colonoscopy and noninvasive imaging. PMID:24833705

  2. GATA-4 and FOG-2 Expression in Pediatric Ovarian Sex Cord-Stromal Tumors Replicates Embryonal Gonadal Phenotype: Results from the TREP Project

    PubMed Central

    Virgone, Calogero; Cecchetto, Giovanni; Ferrari, Andrea; Bisogno, Gianni; Donofrio, Vittoria; Boldrini, Renata; Collini, Paola; Dall’Igna, Patrizia; Alaggio, Rita

    2012-01-01

    Aim GATA proteins are a family of zinc finger transcription factors regulating gene expression, differentiation and proliferation in various tissues. The expression of GATA-4 and FOG-2, one of its modulators, was studied in pediatric Sex Cord-Stromal tumors of the ovary, in order to evaluate their potential role as diagnostic markers and prognostic factors. Materials and Methods Clinical and histological data of 15 patients, enrolled into the TREP Project since 2000 were evaluated. When available, immunostaines for FOG-2, GATA-4, α-Inhibin, Vimentin and Pancytokeratin were also analyzed. Results In our series there were 6 Juvenile Granulosa Cell Tumors (JGCT), 6 Sertoli-Leydig Cell Tumors (SLCT), 1 Cellular Fibroma, 1 Theca Cell Tumor and 1 Stromal Sclerosing Tumor (SST). Thirteen patients obtained a complete remission (CR), 1 reached a second CR after the removal of a metachronous tumor and 1 died of disease. Inhibin was detectable in 11/15, Vimentin in 13/15, Pancytokeratin in 6/15, GATA-4 in 5/13 and FOG-2 in 11/15. FOG-2 was highly expressed in 5/6 JGCT, while GATA-4 was weakly detectable only in 1 of the cases. SLCT expressed diffusely FOG-2 (4/6) and GATA-4 (3/5). GATA-4 and FOG-2 were detected in fibroma and thecoma but not in the SST. Conclusions Pediatric granulosa tumors appear to express a FOG-2/GATA-4 phenotype in keeping with primordial ovarian follicles. High expression of GATA-4 does not correlate with aggressive behaviour as seen in adults, but it is probably involved in cell proliferation its absence can be associated with the better outcome of JGCT. SLCTs replicate the phenotype of Sertoli cells during embryogenesis in normal testis. In this group, the lack of expression of FOG-2 in tumors in advanced stages might reveal a hypothetical role in inhibiting GATA-4 cell proliferation pathway. In fibroma/thecoma group GATA-4 and FOG-2 point out the abnormal activation of GATA pathway and might be involved in the onset of these tumors. PMID:23029311

  3. Loss of tumor suppressor Merlin results in aberrant activation of Wnt/β-catenin signaling in cancer

    PubMed Central

    Meng, Erhong; Menezes, Mitchell E.; Bailey, Sarah K.; Metge, Brandon J.; Buchsbaum, Donald J.; Samant, Rajeev S.; Shevde, Lalita A.

    2016-01-01

    The expression of the tumor suppressor Merlin is compromised in nervous system malignancies due to genomic aberrations. We demonstrated for the first time, that in breast cancer, Merlin protein expression is lost due to proteasome-mediated elimination. Immunohistochemical analysis of tumor tissues from patients with metastatic breast cancer revealed characteristically reduced Merlin expression. Importantly, we identified a functional role for Merlin in impeding breast tumor xenograft growth and reducing invasive characteristics. We sought to determine a possible mechanism by which Merlin accomplishes this reduction in malignant activity. We observed that breast and pancreatic cancer cells with loss of Merlin show an aberrant increase in the activity of β-catenin concomitant with nuclear localization of β-catenin. We discovered that Merlin physically interacts with β-catenin, alters the sub-cellular localization of β-catenin, and significantly reduces the protein levels of β-catenin by targeting it for degradation through the upregulation of Axin1. Consequently, restoration of Merlin inhibited β-catenin-mediated transcriptional activity in breast and pancreatic cancer cells. We also present evidence that loss of Merlin sensitizes tumor cells to inhibition by compounds that target β-catenin-mediated activity. Thus, this study provides compelling evidence that Merlin reduces the malignant activity of pancreatic and breast cancer, in part by suppressing the Wnt/β-catenin pathway. Given the potent role of Wnt/β-catenin signaling in breast and pancreatic cancer and the flurry of activity to test β-catenin inhibitors in the clinic, our findings are opportune and provide evidence for Merlin in restraining aberrant activation of Wnt/β-catenin signaling. PMID:26908451

  4. Radiotherapy in Ewing tumors of the vertebrae: Treatment results and local relapse analysis of the Chess 81/86 and EICESS 92 trials

    SciTech Connect

    Schuck, Andreas . E-mail: schuck@uni-muenster.de; Ahrens, Susanne; Schorlemer, Ines von; Kuhlen, Michaela; Paulussen, Michael; Hunold, Andrea; Gosheger, Georg; Winkelmann, Winfried; Dunst, Juergen; Willich, Normann; Juergens, Heribert

    2005-12-01

    Purpose: Treatment results in patients with Ewing tumors of the vertebrae enrolled in the Cooperative Ewing's Sarcoma Study (CESS) 81, 86, and the European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) 92 trials were analyzed with special emphasis on radiation-associated factors. Patients and Methods: A retrospective analysis was performed on 116 patients with primary tumors of the cervical, thoracic, or lumbar vertebrae treated between 1981 and 1999. Furthermore, a relapse analysis was done on those patients who underwent radiotherapy and subsequently had a local recurrence. Results: A total of 64.6% of the patients received definitive radiotherapy; 27.5% of patients had surgery and radiotherapy. Only 4 patients (3.4%) underwent definitive surgery. Twenty-seven patients presented with metastases at diagnosis. 22.4% of the total group developed a local relapse. Among the subgroup with definitive radiotherapy, local recurrence was seen in 17 of 75 patients (22.6%). Event-free survival and survival at 5 years were 47% and 58%, respectively. Of the 14 evaluable patients with a local relapse after radiotherapy, 13 were in-field. No correlation between radiation dose and local control could be found. Conclusion: Surgery with wide resection margins is rarely possible. The results after definitive radiotherapy in vertebral tumors are comparable to those of other tumor sites when definitive radiotherapy is given. Nearly all local relapses after radiotherapy are in-field.

  5. Metabolic Tumor Volume as a Prognostic Imaging-Based Biomarker for Head and Neck Cancer—Pilot Results from RTOG 0522

    PubMed Central

    Schwartz, David L.; Harris, Jonathan; Yao, Min; Rosenthal, David I.; Opanowski, Adam; Levering, Anthony; (R)(CT)(MR), RT; Ang, K. Kian; Trotti, Andy M.; Garden, Adam S.; Jones, Christopher U.; Harari, Paul; Foote, Robert; Holland, John; Zhang, Qiang; Le, Quynh-Thu

    2014-01-01

    Purpose To evaluate candidate FDG-PET/CT imaging biomarkers for head and neck chemoradiotherapy outcomes in the cooperative group trial setting. Methods RTOG 0522 patients consenting to a secondary FDG-PET/CT sub-study were serially imaged at baseline and 8 weeks following radiation. Maximum standardized uptake value (SUVmax), SUV peak (mean SUV within a 1 cm sphere centered on SUVmax), and metabolic tumor volume (MTV) using 40% of SUVmax as threshold were obtained from primary tumor and involved nodes. Results Out of 940 patients entered onto RTOG 0522, 74 were analyzable for this sub-study. Neither high baseline SUVmax nor SUVpeak from primary or nodal disease were associated with poor treatment outcomes. However, primary tumor MTV above the cohort median was associated with worse LRC (HR 4.01, 95% CI [1.28, 12.52], p = 0.02) and PFS (HR 2.34, 95% CI [1.02, 5.37], p = 0.05). Although MTV and T stage appeared to correlate (mean MTV 6.4, 13.2, 26.8 for T2, T3, and T4 tumors, respectively), MTV remained a strong independent prognostic factor for PFS in bivariate analysis that included T stage. Primary MTV remained prognostic in p16-associated oropharyngeal cancer cases, although sample size was limited. Conclusion High baseline primary tumor MTV was associated with worse treatment outcomes in this limited patient subset of RTOG 0522. Additional confirmatory work will be required to validate primary tumor MTV as a prognostic imaging biomarker for patient stratification in future trials. PMID:25752384

  6. Metabolic Tumor Volume as a Prognostic Imaging-Based Biomarker for Head-and-Neck Cancer: Pilot Results From Radiation Therapy Oncology Group Protocol 0522

    SciTech Connect

    Schwartz, David L.; Harris, Jonathan; Yao, Min; Rosenthal, David I.; Opanowski, Adam; Levering, Anthony; Ang, K. Kian; Trotti, Andy M.; Garden, Adam S.; Jones, Christopher U.; Harari, Paul; Foote, Robert; Holland, John; Zhang, Qiang; Le, Quynh-Thu

    2015-03-15

    Purpose: To evaluate candidate fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging biomarkers for head-and-neck chemoradiotherapy outcomes in the cooperative group trial setting. Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 0522 patients consenting to a secondary FDG-PET/CT substudy were serially imaged at baseline and 8 weeks after radiation. Maximum standardized uptake value (SUVmax), SUV peak (mean SUV within a 1-cm sphere centered on SUVmax), and metabolic tumor volume (MTV) using 40% of SUVmax as threshold were obtained from primary tumor and involved nodes. Results: Of 940 patients entered onto RTOG 0522, 74 were analyzable for this substudy. Neither high baseline SUVmax nor SUVpeak from primary or nodal disease were associated with poor treatment outcomes. However, primary tumor MTV above the cohort median was associated with worse local-regional control (hazard ratio 4.01, 95% confidence interval 1.28-12.52, P=.02) and progression-free survival (hazard ratio 2.34, 95% confidence interval 1.02-5.37, P=.05). Although MTV and T stage seemed to correlate (mean MTV 6.4, 13.2, and 26.8 for T2, T3, and T4 tumors, respectively), MTV remained a strong independent prognostic factor for progression-free survival in bivariate analysis that included T stage. Primary MTV remained prognostic in p16-associated oropharyngeal cancer cases, although sample size was limited. Conclusion: High baseline primary tumor MTV was associated with worse treatment outcomes in this limited patient subset of RTOG 0522. Additional confirmatory work will be required to validate primary tumor MTV as a prognostic imaging biomarker for patient stratification in future trials.

  7. Early perfusion changes in patients with recurrent high-grade brain tumor treated with Bevacizumab: preliminary results by a quantitative evaluation

    PubMed Central

    2012-01-01

    Background To determine whether early monitoring of the effects of bevacizumab in patients with recurrent high-grade gliomas, by a Perfusion Computed Tomography (PCT), may be a predictor of the response to treatment assessed through conventional MRI follow-up. Methods Sixteen patients were enrolled in the present study. For each patient, two PCT examinations, before and after the first dose of bevacizumab, were acquired. Areas of abnormal Cerebral Blood Volume (CBV) were manually defined on the CBV maps, using co-registered T1- weighted images, acquired before treatment, as a guide to the tumor location. Different perfusion metrics were derived from the histogram analysis of the normalized CBV (nCBV) maps; both hyper and hypo-perfused sub-volumes were quantified in the lesion, including tumor necrosis. A two-tailed Wilcoxon test was used to establish the significance of changes in the different perfusion metrics, observed at baseline and during treatment. The relationships between changes in perfusion and morphological MRI modifications at first follow-up were investigated. Results Significant reductions in mean and median nCBV were detected throughout the entire patient population, after only a single dose of bevacizumab. The nCBV histogram modifications indicated the normalization effect of bevacizumab on the tumor abnormal vasculature. An improvement in hypoxia after a single dose of bevacizumab was predictive of a greater reduction in T1-weighted contrast-enhanced volumes at first follow-up. Conclusions These preliminary results show that a quantification of changes in necrotic intra-tumoral regions could be proposed as a potential imaging biomarker of tumor response to anti-VEGF therapies. PMID:22494770

  8. Familial adenomatous patients with desmoid tumours show increased expression of miR-34a in serum and high levels in tumours

    PubMed Central

    Walton, Sarah-Jane; Lewis, Amy; Jeffery, Rosemary; Thompson, Hannah; Feakins, Roger; Giannoulatou, Eleni; Yau, Christopher; Lindsay, James O.; Clark, Susan K.; Silver, Andrew

    2016-01-01

    Familial adenomatous polyposis (FAP) is rare affecting 1 in 10,000 people and a subset (10%) are at risk of myofibroblastic desmoid tumours (DTs) after colectomy to prevent cancer. DTs are a major cause of morbidity and mortality. The absence of markers to monitor progression and a lack of treatment options are significant limitations to clinical management. We investigated microRNAs (miRNA) levels in DTs and serum using expression array analysis on two independent cohorts of FAP patients (total, n=24). Each comprised equal numbers of patients who had formed DTs (cases) and those who had not (controls). All controls had absence of DTs confirmed by clinical and radiological assessment over at least three years post- colectomy. Technical qPCR validation was performed using an expanded cohort (29 FAP patients; 16 cases and 13 controls). The most significant elevated serum miRNA marker of DTs was miR-34a-5p and in-situ hybridisation (ISH) showed most DTs analysed (5/6) expressed miRNA-34a-5p. Exome sequencing of tumour and matched germline DNA did not detect mutations within the miR-34a-5p transcript sites or 3′-UTR of target genes that would alter functional miRNA activity. In conclusion, miR-34a-5p is a potential circulatory marker and therapy target. A large prospective world-wide multi-centre study is now warranted. PMID:27489864

  9. Sporadic desmoid-type fibromatosis: a stepwise approach to a non-metastasising neoplasm—a position paper from the Italian and the French Sarcoma Group

    PubMed Central

    Gronchi, A.; Colombo, C.; Le Péchoux, C.; Dei Tos, A. P.; Le Cesne, A.; Marrari, A.; Penel, N.; Grignani, G.; Blay, J. Y.; Casali, P. G.; Stoeckle, E.; Gherlinzoni, F.; Meeus, P.; Mussi, C.; Gouin, F.; Duffaud, F.; Fiore, M.; Bonvalot, S.

    2014-01-01

    Desmoid-type fibromatosis (DF) is a rare locally aggressive monoclonal proliferation of myofibroblasts lacking metastatic capacity. It may be observed in nearly every part of the body. Considering the variable clinical presentations, anatomic locations, and biologic behaviors, an individualized treatment approach is required. The pathogenesis of DF is not completely understood even if a high prevalence (∼85%) of CTNNB1 mutations discovered in sporadic DF underlies the importance of the Wnt/β-catenin pathway. No established and evidence-based approach for the treatment of this neoplasm is available as of today. Considering the unpredictable behavior and the heterogeneity of this disease, we propose a treatment algorithm approved by the French and the Italian Sarcoma Group, based on a front-line wait and see approach and subsequent therapy in the case of progression. A careful counseling at a referral center is mandatory and should be offered to all patients affected by sporadic DF from the time of their diagnosis. PMID:24325833

  10. Familial adenomatous patients with desmoid tumours show increased expression of miR-34a in serum and high levels in tumours.

    PubMed

    Walton, Sarah-Jane; Lewis, Amy; Jeffery, Rosemary; Thompson, Hannah; Feakins, Roger; Giannoulatou, Eleni; Yau, Christopher; Lindsay, James O; Clark, Susan K; Silver, Andrew

    2016-01-01

    Familial adenomatous polyposis (FAP) is rare affecting 1 in 10,000 people and a subset (10%) are at risk of myofibroblastic desmoid tumours (DTs) after colectomy to prevent cancer. DTs are a major cause of morbidity and mortality. The absence of markers to monitor progression and a lack of treatment options are significant limitations to clinical management. We investigated microRNAs (miRNA) levels in DTs and serum using expression array analysis on two independent cohorts of FAP patients (total, n=24). Each comprised equal numbers of patients who had formed DTs (cases) and those who had not (controls). All controls had absence of DTs confirmed by clinical and radiological assessment over at least three years post- colectomy. Technical qPCR validation was performed using an expanded cohort (29 FAP patients; 16 cases and 13 controls). The most significant elevated serum miRNA marker of DTs was miR-34a-5p and in-situ hybridisation (ISH) showed most DTs analysed (5/6) expressed miRNA-34a-5p. Exome sequencing of tumour and matched germline DNA did not detect mutations within the miR-34a-5p transcript sites or 3'-UTR of target genes that would alter functional miRNA activity. In conclusion, miR-34a-5p is a potential circulatory marker and therapy target. A large prospective world-wide multi-centre study is now warranted. PMID:27489864

  11. Ligand stimulation of ErbB4 and a constitutively-active ErbB4 mutant result in different biological responses in human pancreatic tumor cell lines

    SciTech Connect

    Mill, Christopher P.; Gettinger, Kathleen L.; Riese, David J.

    2011-02-15

    Pancreatic cancer is the fourth leading cause of cancer death in the United States. Indeed, it has been estimated that 37,000 Americans will die from this disease in 2010. Late diagnosis, chemoresistance, and radioresistance of these tumors are major reasons for poor patient outcome, spurring the search for pancreatic cancer early diagnostic and therapeutic targets. ErbB4 (HER4) is a member of the ErbB family of receptor tyrosine kinases (RTKs), a family that also includes the Epidermal Growth Factor Receptor (EGFR/ErbB1/HER1), Neu/ErbB2/HER2, and ErbB3/HER3. These RTKs play central roles in many human malignancies by regulating cell proliferation, survival, differentiation, invasiveness, motility, and apoptosis. In this report we demonstrate that human pancreatic tumor cell lines exhibit minimal ErbB4 expression; in contrast, these cell lines exhibit varied and in some cases abundant expression and basal tyrosine phosphorylation of EGFR, ErbB2, and ErbB3. Expression of a constitutively-dimerized and -active ErbB4 mutant inhibits clonogenic proliferation of CaPan-1, HPAC, MIA PaCa-2, and PANC-1 pancreatic tumor cell lines. In contrast, expression of wild-type ErbB4 in pancreatic tumor cell lines potentiates stimulation of anchorage-independent colony formation by the ErbB4 ligand Neuregulin 1{beta}. These results illustrate the multiple roles that ErbB4 may be playing in pancreatic tumorigenesis and tumor progression.

  12. Development of venous thromboembolism (VTE) in patients undergoing surgery for brain tumors: results from a single center over a 10 year period.

    PubMed

    Smith, Timothy R; Nanney, Allan D; Lall, Rishi R; Graham, Randall B; McClendon, Jamal; Lall, Rohan R; Adel, Joseph G; Zakarija, Anaadriana; Cote, David J; Chandler, James P

    2015-03-01

    Patients who undergo craniotomy for brain neoplasms have a high risk of developing venous thromboembolism (VTE), including deep vein thromboses (DVT) and pulmonary emboli (PE). The reasons for this correlation are not fully understood. This retrospective, single-center review aimed to determine the risk factors for VTE in patients who underwent neurosurgical resection of brain tumors at Northwestern University from 1999 to 2010. Our cohort included 1148 patients, 158 (13.7%) of whom were diagnosed with DVT and 38 (3.3%) of whom were diagnosed with PE. A variety of clinical factors were studied to determine predictors of VTE, including sex, ethnicity, medical co-morbidities, surgical positioning, length of hospital stay, tumor location, and tumor histology. Use of post-operative anticoagulants and hemorrhagic complications were also investigated. A prior history of VTE was found to be highly predictive of post-operative DVT (odds ratio [OR]=7.6, p=0.01), as was the patient's sex (OR=14.2, p<0.001), ethnicity (OR=0.5, p=0.04), post-operative intensive care unit days (OR=0.2, p=0.003), and tumor histology (OR=-0.16, p=0.01). Contrary to reports in the literature, the data collected did not indicate that the administration of post-operative medical prophylaxis for VTE was significant in preventing their formation (OR=-0.14, p=0.76). Hemorrhagic complications were low (2.2%) and resultant neurologic deficit was lower still (0.7%). The study indicates that patients with high-grade primary brain tumors and metastatic lesions should receive aggressive preventative measures in the post-operative period. PMID:25533212

  13. Imaging Tumor Perfusion and Oxidative Metabolism in Patients With Head-and-Neck Cancer Using 1- [{sup 11}C]-Acetate PET During Radiotherapy: Preliminary Results

    SciTech Connect

    Sun Aijun; Johansson, Silvia; Turesson, Ingela; Dasu, Alexandru; Soerensen, Jens

    2012-02-01

    Background: A growing body of in vitro evidence links alterations of the intermediary metabolism in cancer to treatment outcome. This study aimed to characterize tumor oxidative metabolism and perfusion in vivo using dynamic positron emission tomography (PET) with 1- [{sup 11}C]-acetate (ACE) during radiotherapy. Methods and Materials: Nine patients with head-and-neck cancer were studied. Oxidative metabolic rate (k{sub mono}) and perfusion (rF) of the primary tumors were assessed by dynamic ACE-PET at baseline and after 15, 30, and 55 Gy was delivered. Tumor glucose uptake (Tglu) was evaluated with [{sup 18}F]-fluorodeoxyglucose PET at baseline. Patients were grouped into complete (CR, n = 6) and partial responders (PR, n = 3) to radiotherapy. Results: The 3 PR patients died within a median follow-up period of 33 months. Baseline k{sub mono} was almost twice as high in CR as in PR (p = 0.02) and Tglu was lower in CR than in PR (p = 0.04). k{sub mono} increased during radiotherapy in PR (p = 0.004) but remained unchanged in CR. There were no differences in rF between CR and PR at any dosage. k{sub mono} and rF were coupled in CR (p = 0.001), but not in PR. Conclusions: This study shows that radiosensitive tumors might rely predominantly on oxidative metabolism for their bioenergetic needs. The impairment of oxidative metabolism in radioresistant tumors is potentially reversible, suggesting that therapies targeting the intermediary metabolism might improve treatment outcome.

  14. Five-chlorodeoxycytidine and biomodulators of its metabolism result in fifty to eighty percent cures of advanced EMT-6 tumors when used with fractionated radiation

    SciTech Connect

    Greer, S.; Schwade, J.; Marion, H.S.

    1995-07-15

    The purpose of this investigation was to extend our findings in previous radiation and biochemical studies with five rodent tumors, in which we used one and occasionally two or three irradiations. The extent of control of the EMT-6 mammary adenocarcinoma was determined using fractionated radiation (12 irradiations) over a 3-week period using the radiosensitizer 5-chloro-2{prime}-deoxycytidine (CldC) and biomodulators of its metabolism. Drug and radiation treatments overlapped for 3 weeks. Fifty to 80% cures (usually 70%) were obtained with no apparent morbidity and the same moderate weight loss that occurs with radiation alone. An apparent threefold dose increase effect was obtained with the end point: {open_quotes}days to reach 4 times initial tumor volume.{close_quotes} Increasing the radiation dose threefold (without drugs) resulted in four out of five deaths; increasing the dose twofold (without drugs) resulted in extensive weight loss and hair loss in the entire ventral area and no cures. Increasing the dose of drugs or radiation 1.5-fold, in the complete protocol, did not result in increased morbidity. Comparative studies with Iododeoxyuridine demonstrate the heightened efficacy of CldC. One cannot achieve the same results obtained with CldC and the modulators by merely increasing the dose of radiation. There is a significant window of safety in this approach. The evidence we have obtained with EMT-6, the fifth rodent tumor we have studied with CldC, as well as the demonstrated and proposed reasons for its superior efficacy over 5-Iododeoxyuridine (and 5-Bromodeoxyuridine), drugs in current use, indicate that CldC will allow more aggressive treatment of human tumors with radiation than is now feasible. 50 refs., 2 figs., 4 tabs.

  15. The strong in vivo anti-tumor effect of the UIC2 monoclonal antibody is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity.

    PubMed

    Szalóki, Gábor; Krasznai, Zoárd T; Tóth, Ágnes; Vízkeleti, Laura; Szöllősi, Attila G; Trencsényi, György; Lajtos, Imre; Juhász, István; Krasznai, Zoltán; Márián, Teréz; Balázs, Margit; Szabó, Gábor; Goda, Katalin

    2014-01-01

    P-glycoprotein (Pgp) extrudes a large variety of chemotherapeutic drugs from the cells, causing multidrug resistance (MDR). The UIC2 monoclonal antibody recognizes human Pgp and inhibits its drug transport activity. However, this inhibition is partial, since UIC2 binds only to 10-40% of cell surface Pgps, while the rest becomes accessible to this antibody only in the presence of certain substrates or modulators (e.g. cyclosporine A (CsA)). The combined addition of UIC2 and 10 times lower concentrations of CsA than what is necessary for Pgp inhibition when the modulator is applied alone, decreased the EC50 of doxorubicin (DOX) in KB-V1 (Pgp+) cells in vitro almost to the level of KB-3-1 (Pgp-) cells. At the same time, UIC2 alone did not affect the EC50 value of DOX significantly. In xenotransplanted severe combined immunodeficient (SCID) mice co-treated with DOX, UIC2 and CsA, the average weight of Pgp+ tumors was only ∼10% of the untreated control and in 52% of these animals we could not detect tumors at all, while DOX treatment alone did not decrease the weight of Pgp+ tumors. These data were confirmed by visualizing the tumors in vivo by positron emission tomography (PET) based on their increased 18FDG accumulation. Unexpectedly, UIC2+DOX treatment also decreased the size of tumors compared to the DOX only treated animals, as opposed to the results of our in vitro cytotoxicity assays, suggesting that immunological factors are also involved in the antitumor effect of in vivo UIC2 treatment. Since UIC2 binding itself did not affect the viability of Pgp expressing cells, but it triggered in vitro cell killing by peripheral blood mononuclear cells (PBMCs), it is concluded that the impressive in vivo anti-tumor effect of the DOX-UIC2-CsA treatment is the combined result of Pgp inhibition and antibody dependent cell-mediated cytotoxicity (ADCC). PMID:25238617

  16. Microwave tumor ablation: cooperative academic-industry development of a high-power gas-cooled system with early clinical results

    NASA Astrophysics Data System (ADS)

    Brace, Christopher L.; Ziemlewicz, Timothy J.; Schefelker, Rick; Hinshaw, J. L.; Lubner, Meghan G.; Lee, Fred T.

    2013-02-01

    Microwave tumor ablation continues to evolve into a viable treatment option for many cancers. Current systems are poised to supplant radiofrequency ablation as the dominant percutaneous thermal therapy. Here is provided an overview of technical details and early clinical results with a high-powered, gas-cooled microwave ablation system. The system was developed with academic-industry collaboration using federal and private funding. The generator comprises three synchronous channels that each produce up to 140W at 2.45GHz. A mountable power distribution module facilitates CT imaging guidance and monitoring and reduces clutter in the sterile field. Cryogenic carbon-dioxide cools the coaxial applicator, permitting a thin applicator profile (~1.5 mm diameter) and high power delivery. A total of 106 liver tumors were treated (96 malignant, 10 benign) from December 2010 to June 2012 at a single academic institution. Mean tumor size +/- standard deviation was 2.5+/-1.3cm (range 0.5-13.9cm). Treatment time was 5.4+/-3.3min (range 1-20min). Median follow-up was 6 months (range 1-16 months). Technical success was reported in 100% of cases. Local tumor progression was noted in 4/96 (4.3%) of malignancies. The only major complication was a pleural effusion that was treated with thoracentesis. Microwave ablation with this system is an effective treatment for liver cancer. Compared to previous data from the same institution, these results suggest an increased efficacy and equivalent safety to RF ablation. Additional data from the lung and kidney support this conclusion.

  17. Alternative splicing of Wilms tumor suppressor 1 (Wt1) exon 4 results in protein isoforms with different functions.

    PubMed

    Schnerwitzki, Danny; Perner, Birgit; Hoppe, Beate; Pietsch, Stefan; Mehringer, Rebecca; Hänel, Frank; Englert, Christoph

    2014-09-01

    The Wilms tumor suppressor gene Wt1 encodes a zinc finger transcription factor that is essential for development of multiple organs including kidneys, gonads, spleen and heart. In mammals Wt1 comprises 10 exons with two characteristic splicing events: inclusion or skipping of exon 5 and alternative usage of two splice donor sites between exons 9 and 10. Most fish including zebrafish and medaka possess two wt1 paralogs, wt1a and wt1b, both lacking exon 5. Here we have characterized wt1 in guppy, platyfish and the short-lived African killifish Nothobranchius furzeri. All fish except zebrafish show alternative splicing of exon 4 of wt1a but not of wt1b with the wt1a(-exon 4) isoform being the predominant splice variant. With regard to function, Wt1a(+exon 4) showed less dimerization but stimulated transcription more effectively than the Wt1a(-exon 4) isoform. A specific knockdown of wt1a exon 4 in zebrafish was associated with anomalies in kidney development demonstrating a physiological function for Wt1a exon 4. Interestingly, alternative splicing of exon 4 seems to be an early evolutionary event as it is observed in the single wt1 gene of the sturgeon, a species that has not gone through teleost-specific genome duplication. PMID:25014653

  18. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation

    PubMed Central

    Fokas, E; Prevo, R; Pollard, J R; Reaper, P M; Charlton, P A; Cornelissen, B; Vallis, K A; Hammond, E M; Olcina, M M; Gillies McKenna, W; Muschel, R J; Brunner, T B

    2012-01-01

    Combined radiochemotherapy is the currently used therapy for locally advanced pancreatic ductal adenocarcinoma (PDAC), but normal tissue toxicity limits its application. Here we test the hypothesis that inhibition of ATR (ATM-Rad3-related) could increase the sensitivity of the cancer cells to radiation or chemotherapy without affecting normal cells. We tested VE-822, an ATR inhibitor, for in vitro and in vivo radiosensitization. Chk1 phosphorylation was used to indicate ATR activity, γH2AX and 53BP1 foci as evidence of DNA damage and Rad51 foci for homologous recombination activity. Sensitivity to radiation (XRT) and gemcitabine was measured with clonogenic assays in vitro and tumor growth delay in vivo. Murine intestinal damage was evaluated after abdominal XRT. VE-822 inhibited ATR in vitro and in vivo. VE-822 decreased maintenance of cell-cycle checkpoints, increased persistent DNA damage and decreased homologous recombination in irradiated cancer cells. VE-822 decreased survival of pancreatic cancer cells but not normal cells in response to XRT or gemcitabine. VE-822 markedly prolonged growth delay of pancreatic cancer xenografts after XRT and gemcitabine-based chemoradiation without augmenting normal cell or tissue toxicity. These findings support ATR inhibition as a promising new approach to improve the therapeutic ration of radiochemotherapy for patients with PDAC. PMID:23222511

  19. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation.

    PubMed

    Fokas, E; Prevo, R; Pollard, J R; Reaper, P M; Charlton, P A; Cornelissen, B; Vallis, K A; Hammond, E M; Olcina, M M; Gillies McKenna, W; Muschel, R J; Brunner, T B

    2012-01-01

    Combined radiochemotherapy is the currently used therapy for locally advanced pancreatic ductal adenocarcinoma (PDAC), but normal tissue toxicity limits its application. Here we test the hypothesis that inhibition of ATR (ATM-Rad3-related) could increase the sensitivity of the cancer cells to radiation or chemotherapy without affecting normal cells. We tested VE-822, an ATR inhibitor, for in vitro and in vivo radiosensitization. Chk1 phosphorylation was used to indicate ATR activity, γH2AX and 53BP1 foci as evidence of DNA damage and Rad51 foci for homologous recombination activity. Sensitivity to radiation (XRT) and gemcitabine was measured with clonogenic assays in vitro and tumor growth delay in vivo. Murine intestinal damage was evaluated after abdominal XRT. VE-822 inhibited ATR in vitro and in vivo. VE-822 decreased maintenance of cell-cycle checkpoints, increased persistent DNA damage and decreased homologous recombination in irradiated cancer cells. VE-822 decreased survival of pancreatic cancer cells but not normal cells in response to XRT or gemcitabine. VE-822 markedly prolonged growth delay of pancreatic cancer xenografts after XRT and gemcitabine-based chemoradiation without augmenting normal cell or tissue toxicity. These findings support ATR inhibition as a promising new approach to improve the therapeutic ration of radiochemotherapy for patients with PDAC. PMID:23222511

  20. AB058. Intravenous chemotherapy combined with intravesical chemotherapy to treat T1G3 bladder urothelial carcinoma after transurethral resection of bladder tumor: results of a retrospective study

    PubMed Central

    Zhang, Yu; Hu, Hailong; Tian, Dawei; Wu, Changli

    2016-01-01

    Objective The management of stage 1 and grade 3 (T1G3) bladder cancer continues to be controversial. Although the transurethral resection of bladder tumor (TURBT) followed by intravesical chemotherapy is a conservative strategy for treatment of T1G3 bladder cancer, a relatively high risk of tumor recurrence and progression remains regarding the therapy. This study aimed to compare the efficacy of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder cancer after TURBT surgery. Methods We retrospectively reviewed the cases of 457 patients who were newly diagnosed with T1G3 bladder urothelial carcinoma between January 2009 and March 2014. After TURBT, 281 patients received intravesical chemotherapy alone, whereas 176 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. Tumor recurrence and progression were monitored periodically by urine cytology and cystoscopy in follow-up. Recurrence-free survival and progression-free survival of the two chemotherapy strategies following TURBT were analyzed. Univariable and multivariable Cox hazards analyses were performed to predict the prognostic factors for tumor recurrence and progression. Results The tumor recurrence rate was 36.7% for patients who received intravesical chemotherapy alone after TURBT, compared with 19.9% for patients who received intravenous chemotherapy combined with intravesical chemotherapy after TURBT (P<0.001). The progression rate was 10.6% for patients who underwent intravesical chemotherapy alone and 2.3% for patients who underwent the combined chemotherapies (P=0.003). Kaplan-Meier curves showed significant differences in recurrence-free survival and progression-free survival between the two treatment strategies, with a log-rank P value of <0.001 and 0.003, respectively. Multivariable analyses revealed that intravenous chemotherapy was the independent prognostic factor for tumor recurrence and

  1. Intravenous chemotherapy combined with intravesical chemotherapy to treat T1G3 bladder urothelial carcinoma after transurethral resection of bladder tumor: results of a retrospective study

    PubMed Central

    Zhang, Yu; Xie, Linguo; Chen, Tao; Xie, Wanqin; Wu, Zhouliang; Xu, Hao; Xing, Chen; Sha, Nan; Shen, Zhonghua; Qie, Yunkai; Liu, Xiaoteng; Hu, Hailong; Wu, Changli

    2016-01-01

    Objective The management of stage 1 and grade 3 (T1G3) bladder cancer continues to be controversial. Although the transurethral resection of bladder tumor (TURBT) followed by intravesical chemotherapy is a conservative strategy for treatment of T1G3 bladder cancer, a relatively high risk of tumor recurrence and progression remains regarding the therapy. This study aimed to compare the efficacy of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder cancer after TURBT surgery. Methods We retrospectively reviewed the cases of 457 patients who were newly diagnosed with T1G3 bladder urothelial carcinoma between January 2009 and March 2014. After TURBT, 281 patients received intravesical chemotherapy alone, whereas 176 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. Tumor recurrence and progression were monitored periodically by urine cytology and cystoscopy in follow-up. Recurrence-free survival and progression-free survival of the two chemotherapy strategies following TURBT were analyzed. Univariable and multivariable Cox hazards analyses were performed to predict the prognostic factors for tumor recurrence and progression. Results The tumor recurrence rate was 36.7% for patients who received intravesical chemotherapy alone after TURBT, compared with 19.9% for patients who received intravenous chemotherapy combined with intravesical chemotherapy after TURBT (P<0.001). The progression rate was 10.6% for patients who underwent intravesical chemotherapy alone and 2.3% for patients who underwent the combined chemotherapies (P=0.003). Kaplan–Meier curves showed significant differences in recurrence-free survival and progression-free survival between the two treatment strategies, with a log-rank P-value of <0.001 and 0.003, respectively. Multivariable analyses revealed that intravenous chemotherapy was the independent prognostic factor for tumor recurrence and

  2. Results.

    ERIC Educational Resources Information Center

    Zemsky, Robert; Shaman, Susan; Shapiro, Daniel B.

    2001-01-01

    Describes the Collegiate Results Instrument (CRI), which measures a range of collegiate outcomes for alumni 6 years after graduation. The CRI was designed to target alumni from institutions across market segments and assess their values, abilities, work skills, occupations, and pursuit of lifelong learning. (EV)

  3. Development of a single vial kit formulation of [99mTc]-labeled doxorubicin for tumor imaging and treatment response assessment-preclinical evaluation and preliminary human results.

    PubMed

    Kumar, Pardeep; Singh, Baljinder; Ghai, Anchal; Hazari, Puja P; Mittal, B R; Mishra, Anil K

    2015-05-30

    The present study describes the successful radiolabeling of [99mTcO(-) 4 ] with doxorubicin, and the resultant product was formulated in to a ready-to-label lyophilized single vial kit preparation for convenient use in a routine clinical setting. The radiolabeled preparation of [99mTc]-doxorubicin exhibited a high radiolabeling efficiency of more than 95.0%, serum stability for up to 24 h, and shelf-life of lyophilized cold kits was more than 6 months. Animal imaging data in tumor-bearing mice demonstrated that [99mTc]-doxorubicin accumulated in the tumor site with high target (tumor) to non-target (contra-lateral thigh) ratio (3.2 ± 0.5). The ratio decreased to 1.2 ± 0.6 indicating a good response on follow up imaging performed after 2 weeks of doxorubicin treatment. [99mTc]-doxorubicin scintigraphic data in human volunteers supported the hepato-renal excretion of the radiotracer as reflected by the increased accumulation of the radiotracer as a function of time in intestine, kidneys, and urinary bladder. Further, imaging in patients (very limited number) indicated that the technique may be useful in the detection of active sarcoma and post treatment (surgery/chemotherapy) remission or absence of the disease. The technique, however, needs validation through further preclinical evaluation and imaging in a larger number of patients. PMID:25968484

  4. Long-term results of adjuvant imatinib mesylate in localized, high-risk, primary gastrointestinal stromal tumor (GIST): ACOSOG Z9000 (Alliance) intergroup phase 2 trial

    PubMed Central

    DeMatteo, Ronald P.; Ballman, Karla V.; Antonescu, Cristina R.; Corless, Christopher; Kolesnikova, Violetta; von Mehren, Margaret; McCarter, Martin D.; Norton, Jeffrey; Maki, Robert G.; Pisters, Peter W.T.; Demetri, George D.; Brennan, Murray F.; Owzar, Kouros

    2014-01-01

    Objective To conduct the first adjuvant trial of imatinib mesylate for treatment of gastrointestinal stromal tumor (GIST). Summary Background Data GIST is the most common sarcoma. While surgical resection has been the mainstay of therapy for localized, primary GIST, postoperative tumor recurrence is common. The KIT proto-oncogene or, less frequently, platelet-derived growth factor receptor alpha (PDGFRA) is mutated in GIST; the gene products of both are inhibited by imatinib mesylate. Methods This was a phase II, intergroup trial led by the American College of Surgeons Oncology Group (ACOSOG), registered at ClinicalTrials.gov as NCT00025246. From 09/2001 to 09/2003, we accrued 106 patients who had undergone complete gross tumor removal but were deemed at high risk for recurrence. Patients were prescribed imatinib 400 mg/day for 1 year and followed with serial radiologic evaluation. The primary endpoint was overall survival (OS). Results After a median follow-up of 7.7 years, the 1-, 3-, and 5-year OS rate was 99, 97, and 83%, which compared favorably with a historical 5 year OS rate of 35%. The 1-, 3-, and 5-year RFS rate was 96, 60, and 40%. On univariable analysis, age and mitotic rate were associated with OS. On multivariable analysis, the RFS rate was lower with increasing tumor size, small bowel site, KIT exon 9 mutation, high mitotic rate, and older age. Conclusion Adjuvant imatinib in patients with primary GIST who are at high risk of recurrence prolongs OS compared to that of historical controls. Optimal duration of adjuvant therapy remains undefined. (NCT00025246) PMID:23860199

  5. Prognostic and predictive value of tumor vascular endothelial growth factor gene amplification in metastatic breast cancer treated with paclitaxel with and without bevacizumab; results from ECOG 2100 trial

    PubMed Central

    Schneider, Bryan P.; Gray, Robert J.; Radovich, Milan; Shen, Fei; Vance, Gail; Li, Lang; Jiang, Guanglong; Miller, Kathy D.; Gralow, Julie R.; Dickler, Maura N.; Cobleigh, Melody A.; Perez, Edith A.; Shenkier, Tamara N.; Nielsen, Kirsten Vang; Müller, Sven; Thor, Ann; Sledge, George W.; Sparano, Joseph A.; Davidson, Nancy E.; Badve, Sunil S.

    2013-01-01

    Purpose Clinically validated biomarkers for anti-angiogenesis agents are not available. We have previously reported associations between candidate VEGFA SNPs and overall survival (OS) in E2100. The associations between tumor VEGFA amplification and outcome are evaluated here. Patients and Methods E2100 was a phase III trial comparing paclitaxel with or without bevacizumab for patients with metastatic breast cancer. Fluorescence in situ hybridization to assess gene amplification status for VEGFA was performed on paraffin embedded tumors from 363 patients in E2100. Evaluation for association between amplification status and outcomes was performed. Results ER+ or PR+ tumors were less likely to have VEGFA amplification compared with ER/PR-tumors (p=0.020). VEGFA amplification was associated with worse OS (20.2 vs. 25.3 months; p=0.013) in univariate analysis with a trend for worse OS in multivariate analysis (p=0.08). There was a significant interaction between VEGFA amplification, hormone-receptor status, and study arm. Patients with VEGFA amplification and triple negative breast cancers (TNBCs) or HER2 amplification had inferior OS (p=0.047); amplification did not affect OS for those who were ER+ or PR+ and HER2-. Those who received bevacizumab with VEGFA amplification had inferior PFS (p=0.010) and OS (p=0.042); no association was seen in the control arm. Test for interaction between study arm and VEGFA amplification with OS was not significant. Conclusion VEGFA amplification in univariate analysis was associated with poor outcomes; this was particularly prominent in HER2+ or TNBCs. Additional studies are necessary to confirm the trend for poor OS seen on multivariate analysis for patients treated with bevacizumab. PMID:23340303

  6. Retargeting of natural killer-cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction.

    PubMed

    Uherek, Christoph; Tonn, Torsten; Uherek, Barbara; Becker, Sven; Schnierle, Barbara; Klingemann, Hans-Georg; Wels, Winfried

    2002-08-15

    The continuously growing natural killer (NK) cell line NK-92 is highly cytotoxic against malignant cells of various origins without affecting normal human cells. Based on this selectivity, the potential of NK-92 cells for adoptive therapy is currently being investigated in phase I clinical studies. To further enhance the antitumoral activity of NK-92 cells and expand the range of tumor entities suitable for NK-92-based therapies, here by transduction with a retroviral vector we have generated genetically modified NK-92 cells expressing a chimeric antigen receptor specific for the tumor-associated ErbB2 (HER2/neu) antigen, which is overexpressed by many tumors of epithelial origin. The chimeric antigen receptor consists of the ErbB2-specific scFv(FRP5) antibody fragment, a flexible hinge region derived from CD8, and transmembrane and intracellular regions of the CD3 zeta chain. Transduced NK-92-scFv(FRP5)-zeta cells express high levels of the fusion protein on the cell surface as determined by fluorescence-activated cell-scanning (FACS) analysis. In europium release assays, no difference in cytotoxic activity of NK-92 and NK-92-scFv(FRP5)-zeta cells toward ErbB2-negative targets was found. However, even at low effector-to-target ratios, NK-92-scFv(FRP5)-zeta cells specifically and efficiently lysed established and primary ErbB2-expressing tumor cells that were completely resistant to cytolytic activity of parental NK-92 cells. These results demonstrate that efficient retargeting of NK-92 cytotoxicity can be achieved and might allow the generation of potent cell-based therapeutics for the treatment of ErbB2-expressing malignancies. PMID:12149207

  7. First clinical results of a personalized immunotherapeutic vaccine against recurrent, incompletely resected, treatment-resistant glioblastoma multiforme (GBM) tumors, based on combined allo- and auto-immune tumor reactivity.

    PubMed

    Schijns, Virgil E J C; Pretto, Chrystel; Devillers, Laurent; Pierre, Denis; Hofman, Florence M; Chen, Thomas C; Mespouille, Pascal; Hantos, Peter; Glorieux, Philippe; Bota, Daniela A; Stathopoulos, Apostolos

    2015-05-28

    Glioblastoma multiforme (GBM) patients have a poor prognosis. After tumor recurrence statistics suggest an imminent death within 1-4.5 months. Supportive preclinical data, from a rat model, provided the rational for a prototype clinical vaccine preparation, named Gliovac (or ERC 1671) composed of autologous antigens, derived from the patient's surgically removed tumor tissue, which is administered together with allogeneic antigens from glioma tissue resected from other GBM patients. We now report the first results of the Gliovac treatment for treatment-resistant GBM patients. Nine (9) recurrent GBM patients, after standard of care treatment, including surgery radio- and chemotherapy temozolomide, and for US patients, also bevacizumab (Avastin™), were treated under a compassionate use/hospital exemption protocol. Gliovac was given intradermally, together with human GM-CSF (Leukine(®)), and preceded by a regimen of regulatory T cell-depleting, low-dose cyclophosphamide. Gliovac administration in patients that have failed standard of care therapies showed minimal toxicity and enhanced overall survival (OS). Six-month (26 weeks) survival for the nine Gliovac patients was 100% versus 33% in control group. At week 40, the published overall survival was 10% if recurrent, reoperated patients were not treated. In the Gliovac treated group, the survival at 40 weeks was 77%. Our data suggest that Gliovac has low toxicity and a promising efficacy. A phase II trial has recently been initiated in recurrent, bevacizumab naïve GBM patients (NCT01903330). PMID:25865468

  8. Whole-Body MR Imaging for Staging of Malignant Tumors in Pediatric Patients: Results of the American College of Radiology Imaging Network 6660 Trial

    PubMed Central

    Acharyya, Suddhasatta; Hoffer, Frederic A.; Wyly, J. Brad; Friedmann, Alison M.; Snyder, Bradley S.; Babyn, Paul S.; Khanna, Geetika; Siegel, Barry A.

    2013-01-01

    Purpose: To compare whole-body magnetic resonance (MR) imaging with conventional imaging for detection of distant metastases in pediatric patients with common malignant tumors. Materials and Methods: This institutional review board–approved, HIPAA-compliant, multicenter prospective cohort study included 188 patients (109 male, 79 female; mean age, 10.2 years; range, < 1 to 21 years) with newly diagnosed lymphoma, neuroblastoma, or soft-tissue sarcoma. Informed consent was obtained and all patients underwent noncontrast material–enhanced whole-body MR imaging and standard-practice conventional imaging. All images were reviewed centrally by 10 pairs of readers. An independent panel verified the presence or absence of distant metastases. Detection of metastasis with whole-body MR and conventional imaging was quantified by using the area under the receiver operating characteristic curve (AUC). The effects of tumor subtype, patient age, and distant skeletal and pulmonary disease on diagnostic accuracy were also analyzed. Results: Of the 134 eligible patients, 66 (33 positive and 33 negative for metastasis) were selected for image review and analysis. Whole-body MR imaging did not meet the noninferiority criterion for accuracy when compared with conventional imaging for detection of metastasis (difference between average AUCs was −0.03 [95% confidence interval: −0.10, 0.04]); however, the average AUC for solid tumors was significantly higher than that for lymphomas (P = .006). More skeletal metastases were detected by using whole-body MR imaging than by using conventional imaging (P = .03), but fewer lung metastases were detected (P < .001). Patient age did not affect accuracy. Conclusion: The noninferior accuracy for diagnosis of distant metastasis in patients with common pediatric tumors was not established for the use of whole-body MR imaging compared with conventional methods. However, improved accuracy was seen with whole-body MR imaging in patients with

  9. Sinus Tumors

    MedlinePlus

    ... Tumors Nasal Deformities Choanal Atresia Epiphora (Excessive Tearing) Disclosure Statement Printer Friendly Sinus Tumors Abtin Tabaee, MD Introduction Tumors of the nose and paranasal sinuses are rare, accounting for fewer than 1% of all tumors. These ...

  10. Bone tumor

    MedlinePlus

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  11. [Craniosinusonasal tumors].

    PubMed

    Blagoveshchenskaia, N S; Egorova, V K

    1997-01-01

    Tumors extending into the nasal cavity, cranium, and paranasal sinuses have a number of distinctive features to take into consideration. Among them are the communication with an open air, high incidence of associated intracranial infections, specific complications (i.e. suppurative sinusitis, polyps, mucocele, pneumocephalus, nasal CSF leak). The features mentioned make these lesions unique. 50 consecutive patients underwent treatment in Burdenko Neurosurgical Institute. The diagnosis was confirmed either by CT, MRI, or at operation. Rhinological and otoneurological signs were also subjected to analysis. Most frequently these tumors (the majority of which were meningiomas (n = 34) extended into the nasal cavity (40 patients) and paranasal sinuses (n = 50). It was noted that the clinical signs vary depending on the histological type of tumor, its location and direction of growth (i.e. medial or lateral). Medially growing tumors usually involved 2-4 sinuses, while laterally growing tumors involved only one sinus. Among the symptoms, disturbances of smell, conductive hearing impairment, deformation of both the soft and hard palate, slowing of the experimental nystagmus due to disturbed extraocular movements. Some light is shed on the differential diagnosis, indications for various surgical approaches (transcranial, transnasal, and facial). The results of surgical treatment and postoperative complications are presented in the paper. The diagnosis and treatment of such patients require an interdisciplinary approach while would involve a team of a neurosurgeon, neuroradiologist, otoneurologist, and a neuro-ophthalmologist. PMID:9424946

  12. Atypical teratoid rhabdoid tumors: a population-based clinical outcomes study involving 174 patients from the Surveillance, Epidemiology, and End Results database (1973–2010)

    PubMed Central

    Lau, Christine SM; Mahendraraj, Krishnaraj; Chamberlain, Ronald S

    2015-01-01

    Introduction Atypical teratoid rhabdoid tumors (ATRTs) are rare, highly malignant embryonal tumors of the central nervous system (CNS) accounting for 20% of CNS tumors in children under the age of 3. This study examines a large cohort of ATRT patients to determine demographic, clinical, and pathologic factors which impact prognosis and survival. Methods Demographic and clinical data were abstracted on 174 ATRT patients (171 pediatric patients age <20 and 3 adult patients age ≥20) from the Surveillance, Epidemiology, and End Results database (1973–2010). Standard statistical methodology was used. Results A total of 174 ATRT cases (mean age of 2.84 years) were identified. ATRT had a higher incidence in males (56.3%), Caucasians (59.1%), and children <3 years of age (80.5%), P<0.001. The most common primary sites were the cerebellum (17.8%), ventricles (16.1%), and frontal lobe (12.6%). Mean overall survival was 3.2±0.4 years, while overall and cancer-specific mortality were 63.2% and 56.3%, respectively, P=0.005. Most ATRT cases were treated with surgery alone (58.0%), followed by a combination of surgery and radiation (34.3%), no treatment (6.5%), and radiation alone (1.2%). The use of combination therapy has increased significantly (16.1%) since 2005 (P<0.001), while primary surgical resection and radiation therapy rates remain relatively unchanged. The longest survival was observed among ATRT patients receiving combination therapy (5.9±0.7 years), followed by radiation alone (2.8±1.2 years), and surgery alone (1.9±0.4 years), P<0.001. Multivariable analysis identified only distant metastases (OR =4.6) as independently associated with increased mortality, whereas combination therapy (OR =0.4) was associated with reduced mortality, P<0.005. Conclusion ATRT is a rare and highly aggressive embryonal malignancy of the CNS that presents more often as locoregional tumors >4 cm in male Caucasian children of age <3 years, involving the cerebellum, ventricles, or

  13. [Thymic tumors].

    PubMed

    Le Péchoux, C; Mahé, M; Bretel, J-J; Roberti, E; Ruffié, P

    2005-11-01

    Thymomas and thymic carcinomas are rare and slow-growing tumors, which develop within the anterior mediastinum. Thymomas are often associated with autoimmune disorders and most particularly myasthenia gravis. The treatment of choice remains a complete surgical resection. Postoperative radiotherapy is often combined in case of invasive thymoma invading into adjacent organs. Postoperative radiotherapy in stage II with invasion into capsule has been more controversial lately. In inoperable locally advanced, or metastatic thymic tumors, neoadjuvant cisplatin-based followed by surgery and radiotherapy has given interesting results in the past years. PMID:16168694

  14. Quantitative Sodium MR Imaging at 7 T: Initial Results and Comparison with Diffusion-weighted Imaging in Patients with Breast Tumors.

    PubMed

    Zaric, Olgica; Pinker, Katja; Zbyn, Stefan; Strasser, Bernhard; Robinson, Simon; Minarikova, Lenka; Gruber, Stephan; Farr, Alex; Singer, Christian; Helbich, Thomas H; Trattnig, Siegfried; Bogner, Wolfgang

    2016-07-01

    Purpose To investigate the clinical feasibility of a quantitative sodium 23 ((23)Na) magnetic resonance (MR) imaging protocol developed for breast tumor assessment and to compare it with 7-T diffusion-weighted imaging (DWI). Materials and Methods Written informed consent in this institutional review board-approved study was obtained from eight healthy volunteers and 17 patients with 20 breast tumors (five benign, 15 malignant). To achieve the best image quality and reproducibility, the (23)Na sequence was optimized and tested on phantoms and healthy volunteers. For in vivo quantification of absolute tissue sodium concentration (TSC), an external phantom was used. Static magnetic field, or B0, and combined transmit and receive radiofrequency field, or B1, maps were acquired, and image quality, measurement reproducibility, and accuracy testing were performed. Bilateral (23)Na and DWI sequences were performed before contrast material-enhanced MR imaging in patients with breast tumors. TSC and apparent diffusion coefficient (ADC) were calculated and correlated for healthy glandular tissue and benign and malignant lesions. Results The (23)Na MR imaging protocol is feasible, with 1.5-mm in-plane resolution and 16-minute imaging time. Good image quality was achieved, with high reproducibility (mean TSC values ± standard deviation for the test, 36 mmol per kilogram of wet weight ± 2 [range, 34-37 mmol/kg]; for the retest, 37 mmol/kg ± 1 [range, 35-39 mmol/kg]; P = .610) and accuracy (r = 0.998, P < .001). TSC values in normal glandular and adipose breast tissue were 35 mmol/kg ± 3 and 18 mmol/kg ± 3, respectively. In malignant lesions (mean size, 31 mm ± 24; range, 6-92 mm), the TSC of 69 mmol/kg ± 10 was, on average, 49% higher than that in benign lesions (mean size, 14 mm ± 12; range, 6-35 mm), with a TSC of 47 mmol/kg ± 8 (P = .002). There were similar ADC differences between benign ([1.78 ± 0.23] × 10(-3) mm(2)/sec) and malignant ([1.03 ± 0.23] × 10(-3) mm

  15. The S229L Colon Tumor-associated Variant of DNA Polymerase β Induces Cellular Transformation as a Result of Decreased Polymerization Efficiency*

    PubMed Central

    Nemec, Antonia A.; Murphy, Drew L.; Donigan, Katherine A.; Sweasy, Joann B.

    2014-01-01

    DNA polymerase β (Pol β) plays a key role in base excision repair (BER) by filling in small gaps that are generated after base adducts are excised from the DNA. Pol β is mutated in a large number of colorectal tumors, and these mutations may drive carcinogenesis. In the present study, we wished to determine whether the S229L somatic Pol β variant identified in a stage 3 colorectal tumor is a driver of carcinogenesis. We show that S229L does not possess any defects in binding to either DNA or nucleotides compared with the WT enzyme, but exhibits a significant loss of polymerization efficiency, largely due to an 8-fold decrease in the polymerization rate. S229L participates in BER, but due to its lower catalytic rate, does so more slowly than WT. Expression of S229L in mammalian cells induces the accumulation of BER intermediate substrates, chromosomal aberrations, and cellular transformation. Our results are consistent with the interpretation that S229L is a driver of carcinogenesis, likely as a consequence of its slow polymerization activity during BER in vivo. PMID:24668809

  16. Premature termination of SMARCB1 translation may be followed by reinitiation in schwannomatosis-associated schwannomas, but results in absence of SMARCB1 expression in rhabdoid tumors.

    PubMed

    Hulsebos, Theo J M; Kenter, Susan; Verhagen, Wim I M; Baas, Frank; Flucke, Uta; Wesseling, Pieter

    2014-09-01

    In schwannomatosis, germline SMARCB1 mutations predispose to the development of multiple schwannomas, but not vestibular schwannomas. Many of these are missense or splice-site mutations or in-frame deletions, which are presumed to result in the synthesis of altered SMARCB1 proteins. However, also nonsense and frameshift mutations, which are characteristic for rhabdoid tumors and are predicted to result in the absence of SMARCB1 protein via nonsense-mediated mRNA decay, have been reported in schwannomatosis patients. We investigated the consequences of four of the latter mutations, i.e. c.30delC, c.34C>T, c.38delA, and c.46A>T, all in SMARCB1-exon 1. We could demonstrate for the c.30delC and c.34C>T mutations that the respective mRNAs were still present in the schwannomas of the patients. We hypothesized that these were prevented from degradation by translation reinitiation at the AUG codon encoding methionine at position 27 of the SMARCB1 protein. To test this, we expressed the mutations in MON cells, rhabdoid cells without endogenous SMARCB1 protein, and found that all four resulted in synthesis of the N-terminally truncated protein. Mutation of the reinitiation methionine codon into a valine codon prevented synthesis of the truncated protein, thereby confirming its identity. Immunohistochemistry with a SMARCB1 antibody revealed a mosaic staining pattern in schwannomas of the patients with the c.30delC and c.34C>T mutations. Our findings support the concept that, in contrast to the complete absence of SMARCB1 expression in rhabdoid tumors, altered SMARCB1 proteins with modified activity and reduced (mosaic) expression are formed in the schwannomas of schwannomatosis patients with a germline SMARCB1 mutation. PMID:24740647

  17. Predicting tumor sizes of ductal carcinoma in situ from immunohistochemical images using a novel approach of mathematical pathology: preliminary results, potentials and challenges ahead

    NASA Astrophysics Data System (ADS)

    Chuang, Yao-Li; Edgerton, Mary; Macklin, Paul; Yang, Wei; Bearer, Elaine; Cristini, Vittorio

    2012-02-01

    Differential equation models have recently drawn increasing attentions as a useful tool to help advance the knowledge in cancer research. However, challenges remain for applying such models to clinical practices on a patient-specific basis to assist surgical decisions. Clinical diagnoses essentially at a single time point are often insufficient to fully constrain the time-dependent differential equations. Here we present a novel mathematical pathology approach, identifying robust indicators for time-invariant predictions of the model that can be used for surgical planning. We demonstrate this approach by predicting the sizes of ductal carcinoma in situ by calibrating model parameters from immunohistochemical images. Our preliminary studies of 17 excised tumor cases resulted in a better agreement with the actual measured sizes than the other estimates available to us, showing the potential of our approach for patient-specific cancer diagnosis. Conversely, our studies also revealed challenges to overcome before we can take this approach to the next level.

  18. Tumor angiogenesis--characteristics of tumor endothelial cells.

    PubMed

    Hida, Kyoko; Maishi, Nako; Torii, Chisaho; Hida, Yasuhiro

    2016-04-01

    Tumor blood vessels provide nutrition and oxygen to the tumor, resulting in tumor progression. They also act as gatekeepers, inducing tumor metastasis. Thus, targeting tumor blood vessels is an important strategy in cancer therapy. Tumor endothelial cells (TECs), which line the inner layer of blood vessels of the tumor stromal tissue, are the main targets of anti-angiogenic therapy. Because new tumor blood vessels generally sprout from pre-existing vasculature, they have been considered to be the same as normal blood vessels. However, tumor blood vessels demonstrate a markedly abnormal phenotype that includes several important morphological changes. The degree of angiogenesis is determined by the balance between the angiogenic stimulators and inhibitors released by the tumor and host cells. Recent studies have revealed that TECs also exhibit altered characteristics which depend on the tumor microenvironment. Here, we review recent studies on TEC abnormalities and heterogeneity with respect to tumor progression and consider their therapeutic implications. PMID:26879652

  19. Spinal tumor

    MedlinePlus

    Tumor - spinal cord ... spinal tumors occur in the nerves of the spinal cord itself. Most often these are ependymomas and other ... gene mutations. Spinal tumors can occur: Inside the spinal cord (intramedullary) In the membranes (meninges) covering the spinal ...

  20. Trastuzumab improves tumor perfusion and vascular delivery of cytotoxic therapy in a murine model of HER2+ breast cancer: preliminary results.

    PubMed

    Sorace, Anna G; Quarles, C Chad; Whisenant, Jennifer G; Hanker, Ariella B; McIntyre, J Oliver; Sanchez, Violeta M; Yankeelov, Thomas E

    2016-01-01

    To employ in vivo imaging and histological techniques to identify and quantify vascular changes early in the course of treatment with trastuzumab in a murine model of HER2+ breast cancer. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to quantitatively characterize vessel perfusion/permeability (via the parameter K (trans) ) and the extravascular extracellular volume fraction (v e ) in the BT474 mouse model of HER2+ breast cancer (N = 20) at baseline, day one, and day four following trastuzumab treatment (10 mg/kg). Additional cohorts of mice were used to quantify proliferation (Ki67), microvessel density (CD31), pericyte coverage (α-SMA) by immunohistochemistry (N = 44), and to quantify human VEGF-A expression (N = 29) throughout the course of therapy. Longitudinal assessment of combination doxorubicin ± trastuzumab (N = 42) tested the hypothesis that prior treatment with trastuzumab will increase the efficacy of subsequent doxorubicin therapy. Compared to control tumors, trastuzumab-treated tumors exhibited a significant increase in K (trans) (P = 0.035) on day four, indicating increased perfusion and/or vessel permeability and a simultaneous significant increase in v e (P = 0.01), indicating increased cell death. Immunohistochemical and ELISA analyses revealed that by day four the trastuzumab-treated tumors had a significant increase in vessel maturation index (i.e., the ratio of α-SMA to CD31 staining) compared to controls (P < 0.001) and a significant decrease in VEGF-A (P = 0.03). Additionally, trastuzumab dosing prior to doxorubicin improved the overall effectiveness of the therapies (P < 0.001). This study identifies and validates improved perfusion characteristics following trastuzumab therapy, resulting in an improvement in trastuzumab-doxorubicin combination therapy in a murine model of HER2+ breast cancer. This data suggests properties of vessel maturation. In particular, the use of DCE-MRI, a clinically

  1. THE TUMOR MACROENVIRONMENT: CANCER-PROMOTING NETWORKS BEYOND TUMOR BEDS

    PubMed Central

    Rutkowski, Melanie R.; Svoronos, Nikolaos; Puchalt, Alfredo Perales; Conejo-Garcia, Jose R.

    2015-01-01

    During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota residing within mucosal surfaces, and myeloid cells and even the bone marrow impact the systemic immune system, tumor growth, and metastatic spread. Understanding the reciprocal interactions between the cells and soluble factors within the macroenvironment and the primary tumor will enable the design of specific therapies that have the potential to prevent dissemination and metastatic spread. This chapter will summarize recent findings detailing how the primary tumor and systemic tumor macroenvironment coordinate malignant progression. PMID:26216635

  2. Structural fragility of blood vessels and peritoneum in calponin h1-deficient mice, resulting in an increase in hematogenous metastasis and peritoneal dissemination of malignant tumor cells.

    PubMed

    Taniguchi, S; Takeoka, M; Ehara, T; Hashimoto, S; Shibuki, H; Yoshimura, N; Shigematsu, H; Takahashi, K; Katsuki, M

    2001-10-15

    We have observed weak expression of calponin h1, which stabilizes the actin filament system, in blood vessels within human malignant tumors. This observation suggested that because of a deficiency in stabilization by calponin h1, the structure of blood vessels in malignant tumors is fragile compared with blood vessels in normal tissues. We therefore generated calponin h1-deficient (CN(-/-)) mice to examine the effect of calponin h1 on the integrity of the barrier system in blood vessels against cancer metastasis. The CN(-/-) mice exhibited morphological fragility of the tissues, including the uterus and blood vessels. In particular, we frequently observed bleeding into the surrounding tissue from blood vessels of the ocular fundus in CN(-/-) mice. In addition, mesothelial cells, which usually express calponin h1 in normal (CN(+/+)) mice, were retracted in the CN(-/-) mice. When fluorescein was injected i.v. into mice, the CN(-/-) mice exhibited a greater and more rapid leakage of fluorescein from the blood vessels of the ocular fundus compared with the CN(+/+) mice. In the CN(-/-) mice receiving i.v. inoculations of B16 melanoma cells, significantly more metastatic nodules were formed in the lung than in the CN(+/+) mice. When B16 melanoma cells were injected i.p., the severity of peritonitis carcinomatosa was greater in CN(-/-) than in CN(+/+) mice. These results indicate that calponin h1 plays an important role in the regulation of the integrity of the blood vessels and peritoneum, which in turn is an important factor influencing the frequency of cancer metastasis. The CN(-/-) mice, which exhibit fragile blood vessels and peritoneum, could serve as sensitive and useful host models to investigate cancer metastasis. PMID:11606404

  3. Somatic mutation of GRIN2A in malignant melanoma results in loss of tumor suppressor activity via aberrant NMDAR complex formation.

    PubMed

    Prickett, Todd D; Zerlanko, Brad J; Hill, Victoria K; Gartner, Jared J; Qutob, Nouar; Jiang, Jiji; Simaan, May; Wunderlich, John; Gutkind, J Silvio; Rosenberg, Steven A; Samuels, Yardena

    2014-09-01

    The ionotropic glutamate receptors (N-methyl-D-aspartate receptors (NMDARs)) are composed of large complexes of multi-protein subunits creating ion channels in the cell plasma membranes that allow for influx or efflux of mono- or divalent cations (e.g., Ca(2+)) important for synaptic transmissions, cellular migration, and survival. Recently, we discovered the high prevalence of somatic mutations within one of the ionotropic glutamate receptors, GRIN2A, in malignant melanoma. Functional characterization of a subset of GRIN2A mutants demonstrated a loss of NMDAR complex formation between GRIN1 and GRIN2A, increased anchorage-independent growth in soft agar, and increased migration. Somatic mutation of GRIN2A results in a dominant negative effect inhibiting the tumor-suppressive phenotype of wild-type (WT) GRIN2A in melanoma. Depletion of endogenous GRIN2A in melanoma cells expressing WT GRIN2A resulted in increased proliferation compared with control. In contrast, short-hairpin RNA depletion of GRIN2A in mutant cell lines slightly reduced proliferation. Our data show that somatic mutation of GRIN2A results in increased survival, and we demonstrate the functional importance of GRIN2A mutations in melanoma and the significance that ionotropic glutamate receptor signaling has in malignant melanoma. PMID:24739903

  4. Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer1

    PubMed Central

    Caruso, Denise A.; Orme, Lisa M.; Neale, Alana M.; Radcliff, Fiona J.; Amor, Gerlinda M.; Maixner, Wirginia; Downie, Peter; Hassall, Timothy E.; Tang, Mimi L.K.; Ashley, David M.

    2004-01-01

    We conducted a phase 1 study of 9 pediatric patients with recurrent brain tumors using monocyte-derived dendritic cells pulsed with tumor RNA to produce antitumor vaccine (DCRNA) preparations. The objectives of this study included (1) establishing safety and feasibility and (2) measuring changes in general, antigen-specific, and tumor-specific immune responses after DCRNA. Dendritic cells were derived from freshly isolated monocytes after 7 days of culture with IL-4 and granulocyte-macrophage colony–stimulating factor, pulsed with autologous tumor RNA, and then cryopreserved. Patients received at least 3 vaccines, each consisting of an intravenous and an intra-dermal administration at biweekly intervals. The study showed that this method for producing and administering DCRNA from a single leukapheresis product was both feasible and safe in this pediatric brain tumor population. Immune function at the time of enrollment into the study was impaired in all patients tested. While humoral responses to recall antigens (diphtheria and tetanus) were intact in all patients, cellular responses to mitogen and recall antigens were below normal. Following DCRNA vaccine, 2 of 7 patients showed stable clinical disease and 1 of 7 showed a partial response. Two of 7 patients who were tested showed a tumor-specific immune response to DCRNA. This study showed that DCRNA vaccines are both safe and feasible in children with tumors of the central nervous system with a single leukapheresis. PMID:15279716

  5. RGD peptide conjugation results in enhanced antitumor activity of PD0325901 against glioblastoma by both tumor-targeting delivery and combination therapy.

    PubMed

    Hou, Jianjun; Diao, Yiping; Li, Wei; Yang, Zhenjun; Zhang, Lihe; Chen, Zili; Wu, Yun

    2016-05-30

    Glioblastoma (GBM) is the most aggressive tumor type in the central nervous system. Both tumor-targeting drug delivery and combination therapy of multiple therapeutic agents with distinct mechanisms are important for GBM treatment. We combined these two strategies and developed a new platform of peptide-drug conjugate (RGD-PEG-Suc-PD0325901, W22) for tumor-targeting delivery using a combination of PD0325901 (a MEK1/2 inhibitor) and RGD peptide. In the present study, the combination of PD0325901 and RGD peptide strongly inhibited U87MG model in vitro and in vivo. This inhibition contributed to synergistic suppression of cell proliferation by blocking ERK pathway activity and cell migration. Modified by conjugation strategy, their conjugate W22 enhanced PD0325901 delivery to GBM cells by receptor mediated cellular internalization. W22 showed great superiority in targeting to U87MG xenografted tumors and strong anti-tumor efficacy based on ERK pathway inhibition and tumor-targeted delivery in vitro and in vivo. Moreover, W22 was stable in serum and able to release PD0325901 in the enzymatic environment. These data indicated that the RGD-PEG-Suc-PD0325901 conjugate provided a strategy for effective delivery of PD0325901 and RGD peptide into the GBM cells and inhibition of tumor growth in a synergistic manner. PMID:27085642

  6. Fibromatosis of the Sigmoid Colon With CTNNB1 (β-Catenin) Gene Mutation, Arising at the Site of Ileocolic Anastomosis for Resection of Gastrointestinal Stromal Tumor.

    PubMed

    Thway, Khin; Abou Sherif, Sara; Riddell, Angela M; Mudan, Satvinder

    2016-05-01

    We describe a case of intra-abdominal fibromatosis, which occurred in a 44-year-old woman who had a previous history of gastrointestinal stromal tumor (GIST) of the sigmoid mesocolon, which was treated with imatinib and resection. A mass was detected at the site of ileocolic anastomosis of the previous small bowel resection and sigmoid colectomy, nearly 3 years later. Clinically, this was suspected to represent recurrent GIST and was excised, but histology and mutational analysis showed desmoid-type fibromatosis with a mutation in codon 41 of exon 3 of the CTNNB1 (β-catenin) gene. The occurrence of fibromatosis at the site of excision of GIST is very rare, but its recognition is important as the treatment of the two neoplasms differs significantly. As imaging cannot reliably distinguish between these 2 entities, histological diagnosis is crucial for correct clinical management. PMID:26721303

  7. Neuroimaging of Spinal Tumors.

    PubMed

    Merhemic, Zulejha; Stosic-Opincal, Tatjana; Thurnher, Majda M

    2016-08-01

    Intradural tumors are relatively rare neoplasms; however, when unrecognized in a timely manner, they can result in serious deficits and disability. These tumors lack obvious clinical symptoms until compression of the cord or neurologic deficits occur. The most common intramedullary lesions are ependymomas, astrocytomas, and hemangioblastomas. Meningiomas and nerve sheath tumors (schwannomas and neurofibromas) comprise most intradural-extramedullary tumors. Less common tumors are hemangiopericytoma, paraganglioma, melanocytoma, melanoma, metastases, and lymphoma. MR imaging is the imaging method of choice, helpful for localization and characterization of these lesions before treatment and for follow-up after treatment. PMID:27417401

  8. Non-surgical organ preservation strategies for locally advanced laryngeal tumors: what is the Italian attitude? Results of a national survey on behalf of AIRO and AIOM.

    PubMed

    Alterio, D; Franco, P; Numico, G; Licitra, L; Cossu Rocca, M; Ferrari, A; Pinto, C; Russi, E G; Ricardi, U; Jereczek Fossa, B A

    2016-07-01

    Chemoradiotherapy is the treatment mostly used as organ preservation (OP) strategy worldwide in advanced laryngo-hypopharyngeal cancer. Due to the not homogeneous results of the literature data regarding the pre-treatment assessment and treatment schedule in this setting of patients, the Italian societies of radiation oncology and medical oncology surveyed (by an online survey) their memberships regarding the Italian attitude on larynx preservation in clinical practice. The survey outline addressed different items such as: demographics (11 items), pre-treatment evaluation (12 items), treatment schedules (10 items) and outcomes (3 items). The survey was filled in by 116 clinical oncologists (64 % radiation and 36 % medical oncologists). Results highlighted that pretreatment evaluation was not homogeneous among the respondents. The treatment of choice for the OP program resulted the concurrent chemoradiotherapy (66 %). Induction chemotherapy was proposed mostly in case of aggressive tumors such as advanced stage (T4 or N3) and/or unfavorable primary sites (hypopharynx). Moreover, after induction chemotherapy, for responders patients most participants (46 %) proposed concurrent chemoradiotherapy, while 18 and 19 % proposed radiotherapy alone or radiotherapy and cetuximab, respectively. For patients with stable disease after induction chemotherapy, the respondents declared to suggest surgery, radiotherapy and cetuximab or radiotherapy alone in 38, 32 and 15 % of cases, respectively. Results of the present survey highlighted the variability of therapeutic approaches offered in clinical practice for patients candidate to a larynx OP program. Analysis of abovementioned results may give the chance to modify some clinical attitudes and create the background for future clinical investigation in this field. PMID:27290695

  9. Lack of Proinflammatory Cytokine Interleukin-6 or Tumor Necrosis Factor Receptor-1 Results in a Failure of the Innate Immune Response after Bacterial Meningitis

    PubMed Central

    Albrecht, Lea-Jessica; Tauber, Simone C.; Merres, Julika; Kress, Eugenia; Stope, Matthias B.; Jansen, Sandra; Pufe, Thomas; Brandenburg, Lars-Ove

    2016-01-01

    The most frequent pathogen that causes bacterial meningitis is the Gram-positive bacterium Streptococcus pneumoniae. By entering the brain, host cells will be activated and proinflammatory cytokines like interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are released. The goal of the current study was to examine the interaction between IL-6 and TNFR1 as receptor for TNF-α and the innate immune response in vivo in a model of Streptococcus pneumoniae-induced meningitis. For the experiments IL-6−/−, TNFR1−/−, and TNFR1-IL-6−/− KO mice were used. Our results revealed higher mortality rates and bacterial burden after infection in TNFR1−/−, IL-6−/−, and TNFR1-IL-6−/− mice and a decreased immune response including lower neutrophil infiltration in the meninges of TNFR1−/− and TNFR1-IL-6−/− mice in contrast to IL-6−/− and wild type mice. Furthermore, the increased mortality of TNFR1−/− and TNFR1-IL-6−/− mice correlated with decreased glial cell activation compared to IL-6−/− or wild type mice after pneumococcal meningitis. Altogether, the results show the importance of TNFR1 and IL-6 in the regulation of the innate immune response. The lack of TNFR1 and IL-6 results in higher mortality by weakened immune defence, whereas the lack of TNFR1 results in more severe impairment of the innate immune response than the lack of IL-6 alone. PMID:27057100

  10. Experimental pain ratings and reactivity of cortisol and soluble tumor necrosis factor-α receptor II following a trial of hypnosis: Results of a randomized controlled pilot study

    PubMed Central

    Goodin, Burel R.; Quinn, Noel B.; Kronfli, Tarek; King, Christopher D.; Page, Gayle G.; Haythornthwaite, Jennifer A.; Edwards, Robert R.; Stapleton, Laura M.; McGuire, Lynanne

    2011-01-01

    Objective Current evidence supports the efficacy of hypnosis for reducing the pain associated with experimental stimulation and various acute and chronic conditions; however, the mechanisms explaining how hypnosis exerts its effects remain less clear. The hypothalamic-pituitary-adrenal (HPA) axis and pro-inflammatory cytokines represent potential targets for investigation given their purported roles in the perpetuation of painful conditions; yet, no clinical trials have thus far examined the influence of hypnosis on these mechanisms. Design Healthy participants, highly susceptible to the effects of hypnosis, were randomized to either a hypnosis intervention or a no-intervention control. Using a cold pressor task, assessments of pain intensity and pain unpleasantness were collected prior to the intervention (Pre) and following the intervention (Post) along with pain-provoked changes in salivary cortisol and the soluble receptor of tumor necrosis factor-α (sTNFαRII). Results Compared to the no-intervention control, data analyses revealed that hypnosis significantly reduced pain intensity and pain unpleasantness. Hypnosis was not significantly associated with suppression of cortisol or sTNFαRII reactivity to acute pain from Pre to Post; however, the effect sizes for these associations were medium-sized. Conclusions Overall, the findings from this randomized controlled pilot study support the importance of a future large-scale study on the effects of hypnosis for modulating pain-related changes of the HPA axis and pro-inflammatory cytokines. PMID:22233394

  11. Adenovirus-mediated gene transfer of endostatin in vivo results in high level of transgene expression and inhibition of tumor growth and metastases

    NASA Astrophysics Data System (ADS)

    Sauter, Bernhard V.; Martinet, Olivier; Zhang, Wei-Jian; Mandeli, John; Woo, Savio L. C.

    2000-04-01

    Inhibition of angiogenesis has been shown to be an effective strategy in cancer therapy in mice. However, its widespread application has been hampered by difficulties in the large-scale production of the antiangiogenic proteins. This limitation may be resolved by in vivo delivery and expression of the antiangiogenic genes. We have constructed a recombinant adenovirus that expresses murine endostatin that is biologically active both in vitro, as determined in endothelial cell proliferation assays, and in vivo, by suppression of angiogenesis induced by vascular endothelial growth factor 165. Persistent high serum levels of endostatin (605-1740 ng/ml; mean, 936 ng/ml) were achieved after systemic administration of the vector to nude mice, which resulted in significant reduction of the growth rates and the volumes of JC breast carcinoma and Lewis lung carcinoma (P < 0.001 and P < 0.05, respectively). In addition, the endostatin vector treatment completely prevented the formation of pulmonary micrometastases in Lewis lung carcinoma (P = 0.0001). Immunohistochemical staining of the tumors demonstrated a decreased number of blood vessels in the treatment group versus the controls. In conclusion, the present study clearly demonstrates the potential of vector-mediated antiangiogenic gene therapy as a component in cancer therapy.

  12. Nonepithelial Neoplasms of the Pancreas: Radiologic-Pathologic Correlation, Part 1--Benign Tumors: From the Radiologic Pathology Archives.

    PubMed

    Manning, Maria A; Srivastava, Amogh; Paal, Edina E; Gould, Charles F; Mortele, Koenraad J

    2016-01-01

    Solid and cystic pancreatic neoplasms are being recognized more frequently with increasing utilization and spatial resolution of modern imaging techniques. In addition to the more common primary pancreatic solid (ductal adenocarcinoma) and cystic neoplasms of epithelial origin, nonepithelial neoplasms of the pancreas may appear as well-defined solid or cystic neoplasms. Most of these lesions have characteristic imaging features, such as a well-defined border, which allows differentiation from ductal adenocarcinoma. Solid masses include neurofibroma, ganglioneuroma, leiomyoma, lipoma, and perivascular epithelioid cell tumor (PEComa). Schwannomas and desmoid tumors can be solid or cystic. Cystic tumors include mature cystic teratoma and lymphangioma. Lipoma, PEComa, and mature cystic teratoma can contain fat, and ganglioneuroma and mature cystic teratoma may contain calcification. Although these unusual benign neoplasms are rare, the radiologist should at least consider them in the differential diagnosis of well-defined lesions of the pancreas. The goal of this comprehensive review is to improve understanding of these rare primary pancreatic mesenchymal tumors. PMID:26761535

  13. Brain tumors.

    PubMed Central

    Black, K. L.; Mazziotta, J. C.; Becker, D. P.

    1991-01-01

    Recent advances in experimental tumor biology are being applied to critical clinical problems of primary brain tumors. The expression of peripheral benzodiazepine receptors, which are sparse in normal brain, is increased as much as 20-fold in brain tumors. Experimental studies show promise in using labeled ligands to these receptors to identify the outer margins of malignant brain tumors. Whereas positron emission tomography has improved the dynamic understanding of tumors, the labeled selective tumor receptors with positron emitters will enhance the ability to specifically diagnose and greatly aid in the pretreatment planning for tumors. Modulation of these receptors will also affect tumor growth and metabolism. Novel methods to deliver antitumor agents to the brain and new approaches using biologic response modifiers also hold promise to further improve the management of brain tumors. Images PMID:1848735

  14. Tumors of the spine

    PubMed Central

    Ciftdemir, Mert; Kaya, Murat; Selcuk, Esref; Yalniz, Erol

    2016-01-01

    Spine tumors comprise a small percentage of reasons for back pain and other symptoms originating in the spine. The majority of the tumors involving the spinal column are metastases of visceral organ cancers which are mostly seen in older patients. Primary musculoskeletal system sarcomas involving the spinal column are rare. Benign tumors and tumor-like lesions of the musculoskeletal system are mostly seen in young patients and often cause instability and canal compromise. Optimal diagnosis and treatment of spine tumors require a multidisciplinary approach and thorough knowledge of both spine surgery and musculoskeletal tumor surgery. Either primary or metastatic tumors involving the spine are demanding problems in terms of diagnosis and treatment. Spinal instability and neurological compromise are the main and critical problems in patients with tumors of the spinal column. In the past, only a few treatment options aiming short-term control were available for treatment of primary and metastatic spine tumors. Spine surgeons adapted their approach for spine tumors according to orthopaedic oncologic principles in the last 20 years. Advances in imaging, surgical techniques and implant technology resulted in better diagnosis and surgical treatment options, especially for primary tumors. Also, modern chemotherapy drugs and regimens with new radiotherapy and radiosurgery options caused moderate to long-term local and systemic control for even primary sarcomas involving the spinal column. PMID:26925382

  15. Dosimetric results in treatments of neuroblastoma and neuroendocrine tumors with {sup 131}I-metaiodobenzylguanidine with implications for the activity to administer

    SciTech Connect

    Mínguez, Pablo; Genollá, José; Guayambuco, Sonía; Delgado, Alejandro; Fombellida, José Cruz

    2015-07-15

    Purpose: The aim was to investigate whole-body and red marrow absorbed doses in treatments of neuroblastoma (NB) and adult neuroendocrine tumors (NETs) with {sup 131}I-metaiodobenzylguanidine and to propose a simple method for determining the activity to administer when dosimetric data for the individual patient are not available. Methods: Nine NB patients and six NET patients were included, giving in total 19 treatments as four patients were treated twice. Whole-body absorbed doses were determined from dose-rate measurements and planar gamma-camera imaging. For six NB and five NET treatments, red marrow absorbed doses were also determined using the blood-based method. Results: Dosimetric data from repeated administrations in the same patient were consistent. In groups of NB and NET patients, similar whole-body residence times were obtained, implying that whole-body absorbed dose per unit of administered activity could be reasonably well described as a power function of the patient mass. For NB, this functional form was found to be consistent with dosimetric data from previously published studies. The whole-body to red marrow absorbed dose ratio was similar among patients, with values of 1.4 ± 0.6–1.7 ± 0.7 (1 standard deviation) in NB treatments and between 1.5 ± 0.6 and 1.7 ± 0.7 (1 standard deviation) in NET treatments. Conclusions: The consistency of dosimetric results between administrations for the same patient supports prescription of the activity based on dosimetry performed in pretreatment studies, or during the first administration in a fractionated schedule. The expressions obtained for whole-body absorbed doses per unit of administered activity as a function of patient mass for NB and NET treatments are believed to be a useful tool to estimate the activity to administer at the stage when the individual patient biokinetics has not yet been measured.

  16. Simvastatin Hydroxy Acid Fails to Attain Sufficient Central Nervous System Tumor Exposure to Achieve a Cytotoxic Effect: Results of a Preclinical Cerebral Microdialysis Study.

    PubMed

    Patel, Yogesh T; Jacus, Megan O; Davis, Abigail D; Boulos, Nidal; Turner, David C; Vuppala, Pradeep K; Freeman, Burgess B; Gilbertson, Richard J; Stewart, Clinton F

    2016-04-01

    3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors were potent hits against a mouse ependymoma cell line, but their effectiveness against central nervous system tumors will depend on their ability to cross the blood-brain barrier and attain a sufficient exposure at the tumor. Among 3-hydroxy-3-methylglutaryl coenzyme A inhibitors that had activity in vitro, we prioritized simvastatin (SV) as the lead compound for preclinical pharmacokinetic studies based on its potential for central nervous system penetration as determined from in silico models. Furthermore, we performed systemic plasma disposition and cerebral microdialysis studies of SV (100 mg/kg, p.o.) in a murine model of ependymoma to characterize plasma and tumor extracellular fluid (tECF) pharmacokinetic properties. The murine dosage of SV (100 mg/kg, p.o.) was equivalent to the maximum tolerated dose in patients (7.5 mg/kg, p.o.) based on equivalent plasma exposure of simvastatin acid (SVA) between the two species. SV is rapidly metabolized in murine plasma with 15 times lower exposure compared with human plasma. SVA exposure in tECF was <33.8 ± 11.9 µg/l per hour, whereas the tumor to plasma partition coefficient of SVA was <0.084 ± 0.008. Compared with in vitro washout IC50 values, we did not achieve sufficient exposure of SVA in tECF to suggest tumor growth inhibition; therefore, SV was not carried forward in subsequent preclinical efficacy studies. PMID:26802130

  17. SPECT studies of brain tumors with L-3-( sup 123 I) iodo-alpha-methyl tyrosine: Comparison with PET, 124IMT and first clinical results

    SciTech Connect

    Langen, K.J.; Coenen, H.H.; Roosen, N.; Kling, P.; Muzik, O.; Herzog, H.; Kuwert, T.; Stoecklin, G.F.; Feinendegen, L.E. )

    1990-03-01

    L-3-({sup 123}I)iodo-alpha-methyltyrosine ({sup 123}IMT) like tyrosine has been reported previously to have a high affinity for a transport system in the blood-brain-barrier (BBB). We examined the kinetic behavior of {sup 124}IMT in brain and plasma in two patients with glioblastoma using dynamic positron emission tomography (PET). {sup 124}IMT accumulated in brain and tumor tissue, reaching a maximum after 15 min, with a washout of 20% to 35% at 60 min postinjection. Animal experiments confirmed the accumulation of the intact tracer in murine brain, but there was no incorporation into proteins. SPECT studies with {sup 123}IMT in patients with different types of brain tumors showed increased uptake in 26 of 32 tumors. Although nonspecific uptake in tumors must be considered, the accumulation of IMT in normal brain and in some tumors with intact BBB suggests a specific uptake of IMT. As transport is the main determinant of initial amino acid uptake, {sup 123}IMT appears to be a suitable SPECT tracer of amino acid uptake although it is not incorporated into protein.

  18. Evaluation of Response to Preoperative Chemotherapy Versus Surgery Alone in Gastroesophageal Cancer: Tumor Resectability, Pathologic Results and Post-Operative Complications.

    PubMed

    Kashefi Marandi, Aref; Shojaiefard, Abolfazl; Soroush, Ahmadreza; Ghorbani Abdegah, Ali; Jafari, Mehdi; Khodadost, Mahmoud; Mahmoudzade, Hossein

    2016-01-01

    Gastroesophageal cancer is one of the most common types of cancer worldwide. Despite significant developments in management, 5-year survival in the developing world is less than 20 percent. Due to restricted research about the impact of preoperative chemotherapy (POC) on tumor resection, pathological response and postoperative complications in Iran, we designed and implemented ‎the present retrospective cross- sectional study on 156 patients with gastroesophageal cancer (GEc) between 2013 and 2015 at Shariati Hospital of Tehran. Two groups were included, the first group had previously received preoperative chemotherapy and the second group had only undergone surgery. All patients were followed for at least one year after the operation in terms of tumor recurrence, relapse free survival and one-year survival. The two groups were eventually compared regarding tumor resection, pathological response, postoperative complications, recurrence rate and survival. The mean age was 66.5± 7.3 years and 78 percent were male. The tumor resectability, pathological response and postoperative complications in the group which received POC were 93.5%, 21.8% and 12.8%, respectively, and in the surgery alone group figures for tumor resection and postoperative complications were 76% and 29.5%, respectively. Also based on our study the 5-year survival in the POC group was better (79.5% vs. 66.5%). Using standard neoadjuvant regimens (preoperative chemotherapy/ chemoradiotherapy) beforesurgery could increase tumor resectability, pathological response, and improve the general status of the patients. Therefore using POC may be recommended over surgery alone. PMID:27165231

  19. Chemoradiation for Advanced Head and Neck Cancer: Potential for Improving Results to Match Those of Current Treatment Modalities for Early-Stage Tumors-Long-Term Results of Hyperfractionated Chemoradiation With Carbogen Breathing and Anemia Correction With Erythropoietin

    SciTech Connect

    Villar, Alfonso Martinez, Jose Carlos; Serdio, Jose Luis de

    2008-04-01

    Purpose: To attempt to improve results of chemoradiation for head and neck cancer. Methods and Materials: From March 1996 to April 2007, 98 patients with head and neck cancer (15 Stage III and 83 Stage IV) were treated with a twice-daily hyperfractionated schedule. Eleven patients presented with N0, 11 with N1, 13 with N2A, 17 with N2B, 24 with N2C, and 22 with N3. Each fraction of treatment consisted of 5 mg/m{sup 2} of carboplatin plus 115 cGy with carbogen breathing. Treatment was given 5 days per week up to total doses of 350 mg/m{sup 2} of carboplatin plus 8050 cGy in 7 weeks. Anemia was corrected with erythropoietin. Results: Ninety-six patients tolerated the treatment as scheduled. All patients tolerated the planned radiation dose. Local toxicity remained at the level expected with irradiation alone. Chemotherapy toxicity was moderate. Ninety-seven complete responses were achieved. After 11 years of follow-up (median, 81 months), actuarial locoregional control, cause-specific survival, overall survival, and nodal control rates at 5 and 10 years were, respectively, 83% and 83%, 68% and 68%, 57% and 55%, and 100% and 100%. Median follow-up of disease-free survivors was 80 months. No significant differences in survival were observed between the different subsites or between the pretreatment node status groups (N0 vs. N+, N0 vs. N1, N0 vs. N2A, N0 vs. N2B, N0 vs. N2C, and N0 vs. N3). Conclusions: Improving results of chemoradiation for advanced head and neck cancer up to the level obtained with current treatments for early-stage tumors is a potentially reachable goal.

  20. Antibody specific to muscle actins in the diagnosis and classification of soft tissue tumors.

    PubMed Central

    Miettinen, M.

    1988-01-01

    A series of soft tissue tumors, melanomas, carcinomas, and lymphomas were studied immunohistochemically for the presence of muscle actins (MA) with the monoclonal antibody HHF-35, and for the presence of desmin for comparison. In nonneoplastic tissues, MA immunoreactivity was present in skeletal and smooth muscle cells, in the pericytes of small vessels, and in the myoepithelial cells. Desmin immunoreactivity had a similar distribution, except that the pericytes of small vessels and myoepithelial cells were negative. All 17 rhabdomyosarcomas were positive for both MA and desmin. Of leiomyosarcomas, 31/32 were positive for MA, and 29/32 for desmin. In pleomorphic undifferentiated sarcomas (malignant fibrous histiocytomas) MA and desmin-positive cells were present in 9/35 and 5/35 cases, respectively. Three of five pleomorphic liposarcomas showed MA-positive tumor cells, which were also desmin-positive in one case. Desmoid tumors often showed a moderate number of both desmin- and MA-positive cells. Hemangiopericytoma, Kaposi's sarcoma, and endometrial stromal sarcoma showed MA-positive staining only in the pericytes and not in the neoplastic cells. In various types of carcinomas, melanomas, and lymphomas, MA- or desmin-positive neoplastic cells were not identified. MA, but not desmin, was present in the desmoplastic stroma in many carcinomas. Both MA and desmin are good markers for muscle differentiation and especially serve to identify rhabdomyosarcomas and leiomyosarcomas. These markers are also present in some sarcomas currently regarded as nonmuscle tumors. This may suggest that some of these tumors have differentiation properties related to true myosarcomas. The absence of muscle actin, a pericytic marker, in hemangiopericytoma does not confirm the concept of pericytic nature of this tumor. Images Figure 2 Figure 1 Figure 3 Figure 4 Figure 5 Figure 6 PMID:3276210

  1. Tumor Types

    MedlinePlus

    ... acoustic neuroma is also known as a schwannoma, vestibular schwannoma, or neurilemmoma. Characteristics Arises from cells that ... multiple CNS tumors, including neurofibromas, multiple meningiomas, bilateral vestibular schwannomas, optic nerve gliomas, and spinal cord tumors. ...

  2. Vismodegib Exerts Targeted Efficacy Against Recurrent Sonic Hedgehog–Subgroup Medulloblastoma: Results From Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032

    PubMed Central

    Robinson, Giles W.; Orr, Brent A.; Wu, Gang; Gururangan, Sridharan; Lin, Tong; Qaddoumi, Ibrahim; Packer, Roger J.; Goldman, Stewart; Prados, Michael D.; Desjardins, Annick; Chintagumpala, Murali; Takebe, Naoko; Kaste, Sue C.; Rusch, Michael; Allen, Sariah J.; Onar-Thomas, Arzu; Stewart, Clinton F.; Fouladi, Maryam; Boyett, James M.; Gilbertson, Richard J.; Curran, Tom; Ellison, David W.; Gajjar, Amar

    2015-01-01

    Purpose Two phase II studies assessed the efficacy of vismodegib, a sonic hedgehog (SHH) pathway inhibitor that binds smoothened (SMO), in pediatric and adult recurrent medulloblastoma (MB). Patients and Methods Adult patients enrolled onto PBTC-025B and pediatric patients enrolled onto PBTC-032 were treated with vismodegib (150 to 300 mg/d). Protocol-defined response, which had to be sustained for 8 weeks, was confirmed by central neuroimaging review. Molecular tests to identify patterns of response and insensitivity were performed when tissue was available. Results A total of 31 patients were enrolled onto PBTC-025B, and 12 were enrolled onto PBTC-032. Three patients in PBTC-025B and one in PBTC-032, all with SHH-subgroup MB (SHH-MB), exhibited protocol-defined responses. Progression-free survival (PFS) was longer in those with SHH-MB than in those with non-SHH–MB, and prolonged disease stabilization occurred in 41% of patient cases of SHH-MB. Among those with SHH-MB, loss of heterozygosity of PTCH1 was associated with prolonged PFS, and diffuse staining of P53 was associated with reduced PFS. Whole-exome sequencing identified mutations in SHH genes downstream from SMO in four of four tissue samples from nonresponders and upstream of SMO in two of four patients with favorable responses. Conclusion Vismodegib exhibits activity against adult recurrent SHH-MB but not against recurrent non-SHH–MB. Inadequate accrual of pediatric patients precluded conclusions in this population. Molecular analyses support the hypothesis that SMO inhibitor activity depends on the genomic aberrations within the tumor. Such inhibitors should be advanced in SHH-MB studies; however, molecular and genomic work remains imperative to identify target populations that will truly benefit. PMID:26169613

  3. Hepatitis B virus (HBV) receptors: Deficiency in tumor results in scant HBV infection and overexpression in peritumor leads to higher recurrence risk

    PubMed Central

    Ye, Fei; Fan, Qing-Min; Yu, Guo-Feng; Yu, Dan-Dan; Gao, Lu; Sun, Kai; Han, Zhi-Peng; Li, Rong; Yang, Yang; Zhao, Qiu-Dong; Wu, Meng-Chao; Wang, Hong-Yang; Wei, Li-Xin

    2015-01-01

    Hepatitis B virus (HBV) infection is a risk factor for hepatocarcinogenesis and recurrence. Here, we sought to characterize intratumoral and peritumoral expression of HBsAg and its specific receptors in HBsAg-positive hepatocellular carcinoma (HCC) patients and further examined their correlation with the recurrence-free survival (RFS). HCC tissue and adjacent normal tissue specimens were acquired from HBsAg-positive patients. The presence of HBsAg and receptors, as well as hepatic progenitor cells (HPCs) were detected by tissue microassay and immunohistochemistry. Necroinflammatory activity was evaluated by HE staining. The mean IOD of HBsAg and HBV DNA in the intratumoral tissues was markedly lower than that in the peritumoral tissues (P < 0.001). Pearson correlation analysis further showed a significant correlation between the expression of HBsAg and NTCP (r = 0.461, P < 0.001) or ASGPR (r = 0.506, P < 0.001) in peritumoral tissues. And the peritumoral HBsAg and receptors presented a positive association with necroinflammatory activity (P < 0.05). Inflammation induced by HBV infection presented a positive association with HPCs activation (P < 0.05). Additionally, due to lack of HBV receptors, HPCs was not preferentially infected with HBV, but activated HPCs had a significant correlation with HBsAg expression in peritumoral tissues, and the peritumoral HPCs activation was associated with RFS of HCC patients, therefore, the overexpression of HBsAg and receptors in peritumor were also with higher recurrence risk (P < 0.05). In conclusion, lack of HBV receptors resulted in scant HBV infection in tumor cells, and overexpression of HBsAg and receptors in peritumor was strongly associated with higher recurrence risk in HCC patients. PMID:26515593

  4. Brain Tumors

    MedlinePlus

    A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

  5. Urogenital tumors

    SciTech Connect

    Weller, R.E.

    1994-03-01

    An overview is provided for veterinary care of urogenital tumors in companion animals, especially the dog. Neoplasms discussed include tumors of the kidney, urinary bladder, prostate, testis, ovary, vagina, vulva and the canine transmissible venereal tumor. Topics addressed include description, diagnosis and treatment.

  6. Disparate results between proliferation rates of surgically excised prostate tumors and an in vitro bioassay using sera from a positive randomized controlled trial.

    PubMed

    Azrad, M; Vollmer, R T; Madden, J; Polascik, T J; Snyder, D C; Ruffin, M T; Moul, J W; Brenner, D; He, X; Demark-Wahnefried, W

    2015-04-01

    In vitro bioassay has been used extensively to test the effects of culturing cancer cells in sera from humans participating in dietary interventions, i.e, studies of modified intake of nutrients for the purpose of reducing cancer risk or progression. It has been hypothesized that cell proliferation rates determined by the in vitro bioassay indicate whether modification of dietary intake could decrease cancer cell growth in vivo. It has been suggested, however, that the in vitro bioassay may not correlate with tumor cell proliferation rates in prostate cancer. We investigated the concordance of cell proliferation rates from surgically excised prostate tumor tissue with the in vitro bioassay using sera from matched patients. We used samples from an earlier randomized clinical trial that showed that supplementation with flaxseed significantly inhibited prostate cancer cell proliferation rates in vivo as indicated by Ki67 staining in tumor specimens. Proliferation rates of LNCaP, DU145 and PC3 cell lines cultured in 10% human sera from participants in the flaxseed trial were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Spearman's Rho correlation coefficients (ρ) indicated no association between Ki67 staining in prostate tumors and the in vitro bioassay for the three cell lines. These disparate findings suggest that the in vitro bioassay may not provide an accurate assessment of the environment in vivo. PMID:25434394

  7. Secondary EWSR1 gene abnormalities in SMARCB1-deficient tumors with 22q11-12 regional deletions: Potential pitfalls in interpreting EWSR1 FISH results.

    PubMed

    Huang, Shih-Chiang; Zhang, Lei; Sung, Yun-Shao; Chen, Chun-Liang; Kao, Yu-Chien; Agaram, Narasimhan P; Antonescu, Cristina R

    2016-10-01

    SMARCB1 inactivation occurs in a variety of tumors, being caused by various genetic mechanisms. Since SMARCB1 and EWSR1 genes are located close to each other on chromosome 22, larger SMARCB1 deletions may encompass the EWSR1 locus. Herein, we report four cases with SMARCB1-deletions showing concurrent EWSR1 gene abnormalities by FISH, which lead initially to misinterpretations as EWSR1-rearranged tumors. Our study group included various morphologies: a poorly differentiated chordoma, an extrarenal rhabdoid tumor, a myoepithelial carcinoma, and a proximal-type epithelioid sarcoma. All cases showed loss of SMARCB1 (INI1) by immunohistochemistry (IHC) and displayed characteristic histologic features for the diagnoses. The SMARCB1 FISH revealed homozygous or heterozygous deletions in three and one case, respectively. The co-hybridized EWSR1 probes demonstrated either unbalanced split signals or heterozygous deletion in two cases each. The former suggested bona fide rearrangement, while the latter resembled an unbalanced translocation. However, all the FISH patterns were quite complex and distinct from the simple and uniform split signals seen in typical EWSR1 rearrangements. We conclude that in the context of 22q11-12 regional alterations present in SMARCB1-deleted tumors, simultaneous EWSR1 involvement may be misinterpreted as equivalent to EWSR1 rearrangement. A detailed clinicopathologic correlation and supplementing the EWSR1 FISH assay with complementary methodology is mandatory for correct diagnosis. © 2016 Wiley Periodicals, Inc. PMID:27218413

  8. Disparate results between proliferation rates of surgically excised prostate tumors and an in vitro bioassay using sera from a positive randomized controlled trial

    PubMed Central

    Azrad, M; Vollmer, RT; Madden, J; Polascik, TJ; Snyder, DC; Ruffin, MT; Moul, JW; Brenner, D; He, X; Demark-Wahnefried, W

    2014-01-01

    In vitro bioassay has been used extensively to test the effects of culturing cancer cells in sera from humans participating in dietary interventions, i.e, studies of modified intake of nutrients for the purpose of reducing cancer risk or progression. It has been hypothesized that cell proliferation rates determined by the in vitro bioassay indicate whether modification of dietary intake could decrease cancer cell growth in vivo. It has been suggested, however, that the in vitro bioassay may not correlate with tumor cell proliferation rates in prostate cancer. We investigated the concordance of cell proliferation rates from surgically excised prostate tumor tissue with the in vitro bioassay using sera from matched patients. We used samples from an earlier randomized clinical trial that showed that supplementation with flaxseed significantly inhibited prostate cancer cell proliferation rates in vivo as indicated by Ki67 staining in tumor specimens. Proliferation rates of LNCaP, DU145 and PC3 cell lines cultured in 10% human sera from participants in the flaxseed trial were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Spearman’s Rho correlation coefficients (ρ) indicated no association between Ki67 staining in prostate tumors and the in vitro bioassay for the three cell lines. These disparate findings suggest that the in vitro bioassay may not provide an accurate assessment of the environment in vivo. PMID:25434394

  9. Validation of the Concept of a Common Typical Time of Disease Duration for Hepatocellular Carcinoma Patients Using the Fisher Information Processing of Tumor Imaging Results Combined With Network Phenotyping Strategy Quantification of Individual Patient Clinical Profile Patterns.

    PubMed

    Pančoška, Petr; Skála, Lubomír; Nešetřil, Jaroslav; Carr, Brian I

    2015-08-01

    A primary goal of current clinical cancer research is the identification of prognostic tumor subtypes. It is increasingly clear that tumor growth depends on both internal tumor factors, and factors that are external to the tumor, such as microenvironment. We recently showed that parameter values alone are less important than the patterns of all patient parameters together for the identification of prognostic subtypes and have identified a network phenotyping strategy method to quantitatively describe the dependency of the tumor on the environment, to characterize hepatocellular carcinoma (HCC) subtypes. We have also shown that information about tumor mass together with patterns of other prognostic factors is related to survival. We now use a different patient cohort to validate this prognostic approach. A main finding is our identification of a common time of total disease duration (TDD) for every HCC patient. Clinical prognosis at the time of baseline patient evaluation is then calculable as the difference between TDD and the time from disease onset to diagnosis (T(onset)). We show that the total pattern of all parameter values and the differences in the relationships between this pattern and a reference pattern that, together with the tumor mass, best reflects the patient's prognosis at baseline. Our approach led us to identify 15 different composite HCC subtypes. Our results highlight the nearly identical TDD in all patients, which must therefore be a characteristic of the HCC disease, as opposed to the variable quantity of T(onset), which is impacted by multiple macro- and micro-environmental factors. PMID:26320070

  10. Can brain thallium 201 SPECT substitute for F-18-FDG PET in detecting recurrent brain tumor in the presence of radiation necrosis; correlation with biopsy/surgery results

    SciTech Connect

    Antar, M.A.; Barnett, G.H.; McIntyre, W.J.

    1994-05-01

    F-18-FDG PET man has been largely successful in differentiating between radiation necrosis and recurrent brain tumors. Because of the expense and unavailability of PET scanners in most clinical centers, Tl-201 SPECT scan may offer an alternative. Therefore, we have evaluated both techniques in 18 patients (13 men and 5 women) whose ages range from 28 to 74 year old. Eleven patients had glioblastoma multiformi and 4 patients high grade astrocytoma and 3 patient meningiosarcoma. All patients received radiation therapy (5500-6000 Rad) and 13 patients received also chemotherapy. PET scan was performed 40-60 min. after 5-10 mCi of F-18 FDG (i.v.) and SPECT 30 min. after 4.6 mCi of Tl-201 chloride (i.v.). Severe FDG hypometabolism was evident in the irradiated regions, in all patients. Evidence of tumor recurrence was seen in 15 patients by both FDG PET and Thallium 201 SPECT. The ratio of peak pixel uptake of suspected tumor to that of normal cortex for FDG ranged from 0.67 to 1.5 with a mean of 1.02. The ratio of peak pixel uptake of thallium 201 in the suspected lesion to that of the contralateral scalp area ranges from 0.8 to 1.9 with mean of 1.1. There was concordance between the findings of PET and SPECT in 16/18 patients. However, the volume of involvement differs in these patients; most likely secondary to different mechanisms of uptake and both studies may complement each other. Subsequent biopsy/surgery in 11 patients confirmed tumor recurrence in 10 out of 11 patients. The findings suggest that thallium 201 brain SPECT scan can provide similar (but not identical) information regarding brain tumor recurrence in these patients.