Complete resection of contrast-enhancing tumor volume is associated with improved survival in recurrent glioblastoma—results from the DIRECTOR trial

PubMed Central

Suchorska, Bogdana; Weller, Michael; Tabatabai, Ghazaleh; Senft, Christian; Hau, Peter; Sabel, Michael C.; Herrlinger, Ulrich; Ketter, Ralf; Schlegel, Uwe; Marosi, Christine; Reifenberger, Guido; Wick, Wolfgang; Tonn, Jörg C.; Wirsching, Hans-Georg

2016-01-01

Background The role of reoperation for recurrent glioblastoma (GBM) remains unclear. Prospective studies are lacking. Here, we studied the association of clinical outcome with extent of resection upon surgery for recurrent GBM in the patient cohort of DIRECTOR, a prospective randomized multicenter trial comparing 2 dose-intensified temozolomide regimens at recurrence of GBM. Methods We analyzed prospectively collected clinical and imaging data from the DIRECTOR cohort (N = 105). Volumetric analysis was performed on gadolinium contrast-enhanced MRI as well as fluid attenuated inversion recovery/T2 MRI and correlated with PFS after initial progression (PFS2) and post-recurrence survival (PRS). Quality of life was monitored by the EORTC QLQ-C30 and QLQ-BN20 questionnaires at 8-week intervals. Results Seventy-one patients received surgery at first recurrence. Prognostic factors, including age, MGMT promoter methylation, and Karnofsky performance score, were balanced between patients with and without reoperation. Outcome in patients with versus without surgery at recurrence was similar for PFS2 (2.0 mo vs 1.9 mo, P = .360) and PRS (11.4 mo vs 9.8 mo, P = .633). Among reoperated patients, post-surgery imaging was available in 59 cases. In these patients, complete resection of contrast-enhancing tumor (N = 40) versus residual detection of contrast enhancement (N = 19) was associated with improved PRS (12.9 mo [95% CI: 11.5–18.2] vs 6.5 mo [95% CI: 3.6–9.9], P < .001) and better quality of life. Incomplete tumor resection was associated with inferior PRS compared with patients who did not undergo surgery (6.5 vs 9.8 mo, P = .052). Quality of life was similar in these 2 groups. Conclusion Surgery at first recurrence of GBM improves outcome if complete resection of contrast-enhancing tumor is achieved. PMID:26823503

Toward real-time tumor margin identification in image-guided robotic brain tumor resection

NASA Astrophysics Data System (ADS)

Hu, Danying; Jiang, Yang; Belykh, Evgenii; Gong, Yuanzheng; Preul, Mark C.; Hannaford, Blake; Seibel, Eric J.

2017-03-01

For patients with malignant brain tumors (glioblastomas), a safe maximal resection of tumor is critical for an increased survival rate. However, complete resection of the cancer is hard to achieve due to the invasive nature of these tumors, where the margins of the tumors become blurred from frank tumor to more normal brain tissue, but in which single cells or clusters of malignant cells may have invaded. Recent developments in fluorescence imaging techniques have shown great potential for improved surgical outcomes by providing surgeons intraoperative contrast-enhanced visual information of tumor in neurosurgery. The current near-infrared (NIR) fluorophores, such as indocyanine green (ICG), cyanine5.5 (Cy5.5), 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX), are showing clinical potential to be useful in targeting and guiding resections of such tumors. Real-time tumor margin identification in NIR imaging could be helpful to both surgeons and patients by reducing the operation time and space required by other imaging modalities such as intraoperative MRI, and has the potential to integrate with robotically assisted surgery. In this paper, a segmentation method based on the Chan-Vese model was developed for identifying the tumor boundaries in an ex-vivo mouse brain from relatively noisy fluorescence images acquired by a multimodal scanning fiber endoscope (mmSFE). Tumor contours were achieved iteratively by minimizing an energy function formed by a level set function and the segmentation model. Quantitative segmentation metrics based on tumor-to-background (T/B) ratio were evaluated. Results demonstrated feasibility in detecting the brain tumor margins at quasi-real-time and has the potential to yield improved precision brain tumor resection techniques or even robotic interventions in the future.

Sustained complete response of hepatocellular carcinoma with portal vein tumor thrombus following discontinuation of sorafenib: A case report

PubMed Central

SHIOZAWA, KAZUE; WATANABE, MANABU; IKEHARA, TAKASHI; MATSUKIYO, YASUSHI; KOGAME, MICHIO; KANAYAMA, MASAHIRO; MATSUI, TEPPEI; KIKUCHI, YOSHINORI; ISHII, KOJI; IGARASHI, YOSHINORI; SUMINO, YASUKIYO

2014-01-01

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-associated mortality worldwide. No effective treatment has been established for unresectable advanced HCC, and the prognosis is poor. Sorafenib is an oral multi-targeted tyrosine kinase inhibitor for unresectable advanced HCC that significantly improves progression-free and overall survival. However, in the two large phase III clinical trials (the SHARP and Asia-Pacific trials), no cases of complete response (CR) were reported. The present study reports the case of a 68-year-old male with hepatitis C virus-related cirrhosis and multiple recurrent HCCs, with a tumor thrombus of the third portal vein following resection. The patient received 400 mg once daily (half the standard dose) of sorafenib for two years and achieved a CR. At the most recent follow-up examination at one year after the cessation of treatment, the patient was observed to be in remission without clinical or imaging evidence of disease recurrence. PMID:24348819

Short-term tumor control and acute toxicity after stereotactic radiosurgery for glomus jugulare tumors.

PubMed

Poznanovic, Sheri A; Cass, Stephen P; Kavanagh, Brian D

2006-03-01

Glomus jugulare tumors (GJT) have traditionally been treated by surgery or fractionated external beam radiation therapy (XRT). This study evaluates acute toxicity and short-term efficacy of single-fraction stereotactic radiosurgery (SRS) for the treatment of GJT. Eight patients (age range 28-74) with GJT underwent SRS (Brainlab linear accelerator) as primary treatment. A nominal dose of 15-16 Gy was prescribed. After undergoing SRS, 7 of 8 patients (87.5%) reported complete resolution of presenting symptoms. Follow-up MRIs showed tumor stabilization in 100% of patients. Transient vertigo occurred in one patient. One patient suffered acute GI upset and transient lower cranial neuropathy. Stereotactic radiosurgery is an effective alternative for patients with GJT in achieving tumor control and resolution of symptoms. C-4.

Endovascular Approach to Glomus Jugulare Tumors.

PubMed

Kocur, Damian; Ślusarczyk, Wojciech; Przybyłko, Nikodem; Hofman, Mariusz; Jamróz, Tomasz; Suszyński, Krzysztof; Baron, Jan; Kwiek, Stanisław

2017-01-01

Paragangliomas are benign neuroendocrine tumors derived from the glomus cells of the vegetative nervous system. Typically, they are located in the region of the jugular bulb and middle ear. The optimal management is controversial and can include surgical excision, stereotactic radiosurgery and embolization. We report the endovascular approach to three patients harboring glomus jugulare paragangliomas. In all cases incomplete occlusion of the lesions was achieved and recanalization in the follow-up period was revealed. Two patients presented no clinical improvement and the remaining one experienced a transient withdrawal of tinnitus. It is technically difficult to achieve complete obliteration of glomus jugulare tumors with the use of embolization and the subtotal occlusion poses a high risk of revascularization and is not beneficial in terms of alleviating clinical symptoms.

Utility of MRI versus tumor markers for post-treatment surveillance of marker-positive CNS germ cell tumors.

PubMed

Cheung, Victoria; Segal, Devorah; Gardner, Sharon L; Zagzag, David; Wisoff, Jeffrey H; Allen, Jeffrey C; Karajannis, Matthias A

2016-09-01

Patients with marker-positive central nervous system (CNS) germ cell tumors are typically monitored for tumor recurrence with both tumor markers (AFP and b-hCG) and MRI. We hypothesize that the recurrence of these tumors will always be accompanied by an elevation in tumor markers, and that surveillance MRI may not be necessary. We retrospectively identified 28 patients with CNS germ cell tumors treated at our institution that presented with an elevated serum or cerebrospinal fluid (CSF) tumor marker at the time of diagnosis. We then identified those who had a tumor recurrence after having been in remission and whether each recurrence was detected via MRI changes, elevated tumor markers, or both. Four patients suffered a tumor recurrence. Only one patient had simultaneously elevated tumor markers and MRI evidence of recurrence. Two patients had evidence of recurrence on MRI without corresponding elevations in serum or CSF tumor markers. One patient had abnormal tumor markers with no evidence of recurrence on MRI until 6 months later. We conclude that in patients with marker-positive CNS germ cell tumors who achieve complete remission, continued surveillance imaging in addition to measurement of tumor markers is indicated to detect recurrences.

Late recurrence of nonseminomatous germ cell tumor successfully treated with intensity-modulated radiation therapy.

PubMed

Kita, Yuki; Imamura, Masaaki; Mizowaki, Takashi; Norihisa, Yoshiki; Yoshimura, Koji; Hiraoka, Masahiro; Ogawa, Osamu

2013-08-01

We report the case of a 41-year-old man with a late recurrence of nonseminomatous germ cell tumor, which was successfully treated with intensity-modulated radiation therapy. For the residual retrocrural tumor invading the 11th and 12th thoracic vertebrae with an abnormal level of tumor marker (α-fetoprotein: 23.2 ng/ml) after salvage chemotherapy, chemotherapy could not be continued due to its neurotoxicity, and surgery could not be performed due to the location. In this situation, intensity-modulated radiation therapy achieved a complete response of tumor marker. The patient remained in complete clinical remission after 3 years. The efficacy of radiotherapy, especially intensity-modulated radiation therapy, for a nonseminomatous germ cell tumor is discussed.

[Supratentorial primitive neuroectodermal tumor: a single center experience and comparison with the literature].

PubMed

Schmid, I; Stachel, D; Graubner, U B; Elsner, R; Schulze, S; Pöllinger, B; Goetz, C; Haas, R J

2005-01-01

Supratentorial primitive neuroectodermal tumors (stPNETs) are malignant tumors. We saw within three years six children with stPNETs. In four of the six children radical resection could be achieved. All had craniospinal irradiation and chemotherapy according to the HIT-91 protocol. The two children with incomplete resection died due to tumor progression after 7 and 10 months. Two of the 4 children with complete tumor resection had local relapses 8 months after diagnosis and died after 14 and 18 months. One child had a diffuse meningeal relapse 12 months after diagnosis. Despite (high-dose) systemic chemotherapy and intraventricular mafosfamide, he died 21 months after diagnosis due to tumor although remission could be achieved. Only one child is still in remission 86 months after diagnosis.

Endovascular Approach to Glomus Jugulare Tumors

PubMed Central

Kocur, Damian; Ślusarczyk, Wojciech; Przybyłko, Nikodem; Hofman, Mariusz; Jamróz, Tomasz; Suszyński, Krzysztof; Baron, Jan; Kwiek, Stanisław

2017-01-01

Summary Background Paragangliomas are benign neuroendocrine tumors derived from the glomus cells of the vegetative nervous system. Typically, they are located in the region of the jugular bulb and middle ear. The optimal management is controversial and can include surgical excision, stereotactic radiosurgery and embolization. Case Report We report the endovascular approach to three patients harboring glomus jugulare paragangliomas. In all cases incomplete occlusion of the lesions was achieved and recanalization in the follow-up period was revealed. Two patients presented no clinical improvement and the remaining one experienced a transient withdrawal of tinnitus. Conclusions It is technically difficult to achieve complete obliteration of glomus jugulare tumors with the use of embolization and the subtotal occlusion poses a high risk of revascularization and is not beneficial in terms of alleviating clinical symptoms. PMID:28685005

Risk interrelationship among multiple primary tumors

PubMed Central

Safi, Mohammed; Sun, Xiuhua; Wang, Lifen; Zhang, Xinwei; Song, Jicheng; Ameen, Mohammed

2018-01-01

Abstract Rationale: Along with advanced management in oncology, great progress has been recently achieved in the studies of multiple primary tumors. Several reports have studied the coexistence between lymphoma and either renal cell carcinoma (RCC) or Warthin tumor. However, the level of coexistence between these cases remains unclear due to the absence of a distinct link between them. Patient concerns: We present a unique case of multiple primary tumors (lymphoma, RCC, and Warthin tumor) in an 80-year-old man and a review of the literature on the coexistence of RCC with lymphoma and lymphoma with Warthin tumor. Diagnosis: With a history of RCC, the patient had a freely movable lump under his left ear, and the pathological report indicated Hodgkin lymphoma and Warthin tumor. Intervention: RCC and Warthin tumor of the patient were surgically treated, followed by 2 cycles (14 days per cycle) of Epirubicin 40 mg day 1, Bleomycin 8 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1. The chemotherapy protocol was then changed to Epirubicin 40 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1 for 7 cycles. Outcomes: After the last day of chemotherapy, the patient showed a complete response. Lessons: To the best of our knowledge, this paper is the first to report a case of multiple primary tumors with a complete response. For their early detection, favorable prognosis, and correlation identification, we suggest a transitive relation between these coexisting tumors. Therefore, similar studies should be conducted. PMID:29642151

Adjuvant therapy sparing in rectal cancer achieving complete response after chemoradiation

PubMed Central

García-Albéniz, Xabier; Gallego, Rosa; Hofheinz, Ralf Dieter; Fernández-Esparrach, Gloria; Ayuso-Colella, Juan Ramón; Bombí, Josep Antoni; Conill, Carles; Cuatrecasas, Miriam; Delgado, Salvadora; Ginés, Angels; Miquel, Rosa; Pagés, Mario; Pineda, Estela; Pereira, Verónica; Sosa, Aarón; Reig, Oscar; Victoria, Iván; Feliz, Luis; María de Lacy, Antonio; Castells, Antoni; Burkholder, Iris; Hochhaus, Andreas; Maurel, Joan

2014-01-01

AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team. PMID:25400468

Development of Advanced Technologies for Complete Genomic and Proteomic Characterization of Quantized Human Tumor Cells

DTIC Science & Technology

2014-07-01

13. SUPPLEMENTARY NOTES 14. ABSTRACT With the establishment of Glioblastoma ( GBM ) cell lines from GBM patient’s tumor samples and quantized cell...populations of each of the parental GBM cell lines, we have completed most of our major aims of this project. We will continue in our efforts in the...signatures. Whole genome sequencing from two families of GBM patients are now well established and from the basis of the molecular characterization of

Novel theranostic nanoplatform for complete mice tumor elimination via MR imaging-guided acid-enhanced photothermo-/chemo-therapy.

PubMed

Li, Bei; Tang, Jie; Chen, Weiyu; Hao, Guanyu; Kurniawan, Nyoman; Gu, Zi; Xu, Zhi Ping

2018-05-31

Non-invasive imaging-guided tumor therapy requires new-generation bio-nanomaterials to sensitively respond to the unique tumor microenvironment for precise diagnosis and efficient treatment. Here, we report such a theranostic nanoplatform by engineering defect-rich multifunctional Cu-doped layered double hydroxide (Cu-LDH) nanoparticles, which integrates pH-sensitive T 1 -magnetic resonance imaging (MRI), acid-enhanced photothermal therapy and heat-facilitated chemotherapy. As characterized with EXAFS and XPS, smaller Cu-LDH nanoparticles possess a considerable amount of defects around Cu cations, an advantageous microstructure that enables a high photothermal conversion of 808 nm NIR laser (53.1%). The exposure of CuOH octahedra on the LDH surface makes the photothermal conversion significantly acid-enhanced (53.1% at pH 7.0 vs. 81.9% at pH 5.0). This Cu peculiar microstructure also makes T 1 -MRI very pH-sensitive, a desirable guide for subsequent tumor photothermal therapy. Combined photothermal therapy and chemotherapy lead to nearly complete elimination of tumor tissues in vivo with a low injection dose of agents. Therefore, this novel defect-rich Cu-LDH nanoplatform is one of promising tumor-specific nanotheranostic agents for non-invasive imaging-guided combinational therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Three-dimensional fluoroscopic navigation-assisted surgery for tumors in patients with tumor-induced osteomalacia in the bones.

PubMed

Kobayashi, Hiroshi; Akiyama, Toru; Okuma, Tomotake; Shinoda, Yusuke; Oka, Hiroyuki; Ito, Nobuaki; Fukumoto, Seiji; Tanaka, Sakae; Kawano, Hirotaka

2017-12-01

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome usually caused by phosphaturic mesenchymal tumors. Segmental resection has been recommended for these tumors in the bones because curettage was found to be associated with a high local recurrence rate. Navigation-assisted surgery provides radiological information to guide the surgeon during surgery. No previous study has reported on the efficacy of navigation-assisted surgery for tumors in patients with TIO. Therefore, the present study aimed to evaluate the efficacy of navigation-assisted surgery for tumors in patients with TIO. The study included seven patients with TIO who were treated between January 2003 and December 2014 at our hospital. All patients underwent surgical treatment with or without the use of a 3-dimensional (3D) fluoroscopy-based navigation system. The laboratory data and oncological outcomes were evaluated. The follow-up period was 8-128 months. The tumors were located at the femur (n = 4), ischium, spine and ilium (n = 1). Of the seven patients, five underwent navigation-assisted surgery and two underwent surgery without navigation assistance. In the two patients who underwent surgery without navigation assistance, a complete cure was not obtained and osteomalacia did not resolve. One of these two patients and the other five patients who underwent navigation-assisted surgery, one patient had incomplete resection due to massive invasion of the tumor into the spinal canal, but five patients achieved complete excision and recovered from osteomalacia. Navigation-assisted surgery using a 3D fluoroscopy-based navigation system is effective for tumors in patients with TIO.

Transoral robotic surgery for parapharyngeal space tumors.

PubMed

O'Malley, Bert W; Quon, Harry; Leonhardt, Fernando D; Chalian, Ara A; Weinstein, Gregory S

2010-01-01

To evaluate the outcomes of patients with parapharyngeal space (PPS) tumors treated with a transoral robotic surgery (TORS) approach. We prospectively enrolled well-defined benign PPS tumors accessible from the oropharynx with no carotid encasement or bone erosion. We designated outcome measures that included technical feasibility of the approach, local tumor control and complication rates. Descriptive statistics were used to summarize the outcome data. With a mean follow-up of 29.9 months (range 12-40 months), a total of 10 patients have been enrolled. TORS was completed in 9 of 10 patients with acceptable operative time and blood loss and no significant complications including hemorrhage, infection, trismus or tumor spillage. Local control has been 100% for 7 patients with pleomorphic adenomas. We confirm the safety and feasibility of the TORS approach for PPS tumors that achieves a high local control and low surgical complication rate. TORS is a viable approach for removing benign tumors and lesions of the PPS. Copyright © 2010 S. Karger AG, Basel.

Is complete resection of high-risk stage IV neuroblastoma associated with better survival?

PubMed

Yeung, Fanny; Chung, Patrick Ho Yu; Tam, Paul Kwong Hang; Wong, Kenneth Kak Yuen

2015-12-01

The role of surgery in the management of stage IV neuroblastoma is controversial. In this study, we attempted to study if complete tumor resection had any impact on event-free survival (EFS) and overall survival (OS). A retrospective analysis of patients with stage IV neuroblastoma between November 2000 and July 2014 in a tertiary referral center was performed. Demographics data, extent of surgical resection, and outcomes were analyzed. A total of 34 patients with stage IV neuroblastoma according to International Neuroblastoma Staging System (INSS) were identified. The median age at diagnosis and operation was 3.5 (±1.9) years and 3.8 (±2.0) years, respectively. Complete gross tumor resection (CTR) was achieved in twenty-four patients (70.1%), in which one of the patients had nephrectomy and another had distal pancreatectomy. Gross total resection (GTR) with removal of >95% of tumor was performed in six patients (17.6%) and subtotal tumor resection (STR) with removal of >50%, but <95% of tumor was performed in four patients (11.8%). There was no statistical significance in terms of 5-year EFS and OS among the 3 groups. There was no surgery-related mortality or morbidity. From our center's experience, as there was no substantial survival benefit in stage IV neuroblastoma patients undergoing complete tumor resection, organ preservation and minimalization of morbidity should also be taken into consideration. Copyright © 2015. Published by Elsevier Inc.

Low-dose dacarbazine-doxorubicin therapy against intra-abdominal desmoid tumors.

PubMed

Yamamoto, Hirofumi; Oshiro, Ryota; Nishimura, Junichi; Uemura, Mamoru; Haraguchi, Naotsugu; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Sekimoto, Mitsugu; Doki, Yuichiro; Mori, Masaki

2013-05-01

Intra-abdominal desmoid tumor is a life-threatening disease. Studies have shown that dacarbazine (DTIC)-doxorubicin (DOX) (D-D) therapy is the most effective treatment. However, myelosuppression is a major problem, and cardiac muscle disorders due to DOX limit the number of administration cycles, whereas it usually requires a long time to achieve tumor shrinkage. To resolve these issues, we introduced low-dose D-D therapy to 3 patients employing 50 mg/m² DOX and 600-700 mg/m² DTIC per cycle, which permits repeated administration cycles up to 10-11 times. Case 1 was a 23-year-old female with a sporadic recurrent mesenterium desmoid tumor located in the pelvis (maximum diameter, 8 cm). Cases 2 and 3 were a 33-year-old female and a 36-year-old male. Both patients had intra-abdominal mesenterium desmoid tumors (maximum diameter 9.6 and 9.0 cm, respectively) that were generated after proctocolectomy due to familial adenomatous polyposis. No severe adverse events occurred during the therapy. With the aid of sulindac and tamoxifen after low-dose D-D therapy, the first two patients achieved a complete response, and the third patient achieved a partial response and awaits further tumor shrinkage. Our experience indicates that low-dose DT-D therapy is a safe and effective regimen for patients with intra-abdominal desmoid tumors.

A Tumor-stroma Targeted Oncolytic Adenovirus Replicated in Human Ovary Cancer Samples and Inhibited Growth of Disseminated Solid Tumors in Mice

PubMed Central

Lopez, M Veronica; Rivera, Angel A; Viale, Diego L; Benedetti, Lorena; Cuneo, Nicasio; Kimball, Kristopher J; Wang, Minghui; Douglas, Joanne T; Zhu, Zeng B; Bravo, Alicia I; Gidekel, Manuel; Alvarez, Ronald D; Curiel, David T; Podhajcer, Osvaldo L

2012-01-01

Targeting the tumor stroma in addition to the malignant cell compartment is of paramount importance to achieve complete tumor regression. In this work, we modified a previously designed tumor stroma-targeted conditionally replicative adenovirus (CRAd) based on the SPARC promoter by introducing a mutated E1A unable to bind pRB and pseudotyped with a chimeric Ad5/3 fiber (Ad F512v1), and assessed its replication/lytic capacity in ovary cancer in vitro and in vivo. AdF512v1 was able to replicate in fresh samples obtained from patients: (i) with primary human ovary cancer; (ii) that underwent neoadjuvant treatment; (iii) with metastatic disease. In addition, we show that four intraperitoneal (i.p.) injections of 5 × 1010 v.p. eliminated 50% of xenografted human ovary tumors disseminated in nude mice. Moreover, AdF512v1 replication in tumor models was enhanced 15–40-fold when the tumor contained a mix of malignant and SPARC-expressing stromal cells (fibroblasts and endothelial cells). Contrary to the wild-type virus, AdF512v1 was unable to replicate in normal human ovary samples while the wild-type virus can replicate. This study provides evidence on the lytic capacity of this CRAd and highlights the importance of targeting the stromal tissue in addition to the malignant cell compartment to achieve tumor regression. PMID:22948673

Multimodality Treatment of Desmoplastic small round cell tumor: Chemotherapy and Complete Cytoreductive Surgery Improve Patient Survival.

PubMed

Subbiah, Vivek; Lamhamedi-Cherradi, Salah-Eddine; Cuglievan, Branko; Menegaz, Brian A; Camacho, Pamela; Huh, Winston W; Ramamoorthy, Vandhana; Anderson, Peter M; Pollock, Raphael E; Lev, Dina; Qiao, Wei; McAleer, Mary Frances; Benjamin, Robert S; Patel, Shreyaskumar; Herzog, Cynthia E; Daw, Najat C; Feig, Barry W; Lazar, Alexander J; Hayes-Jordan, Andrea; Ludwig, Joseph A

2018-06-05

Purpose Desmoplastic small round cell tumor (DSRCT), which harbors EWSR1-WT1 t(11;22)(p13:q12) chromosomal translocation, is an aggressive malignancy that typically presents as intra-abdominal sarcomatosis in young males. Given its rarity, optimal treatment has not been defined. Experimental Design We conducted a retrospective study of 187 DSRCT patients treated at MD Anderson Cancer Center over two decades. Univariate and multivariate regression analyses were performed. We determined whether chemotherapy, complete cytoreductive surgery (CCS), hyperthermic intraperitoneal cisplatin (HIPEC), and/or whole abdominal radiation (WART) improve overall survival in DSRCT patients. Critically, since our institutional practice limits HIPEC and WART to patients with less extensive, potentially resectable disease that had benefited from neoadjuvant chemotherapy, a time-variant analysis was performed to evaluate those adjunct treatment modalities. CONCLUSIONS Improved 3- and 5-year overall survival were observed following multidisciplinary treatment that includes ES-based chemotherapy and complete tumor cytoreductive surgery, but few if any patients are cured. Prospective randomized studies will be required to prove whether HIPEC or WART are important. In the meantime, chemotherapy and CCS remain the cornerstone of treatment and provide a solid foundation to evaluate new biologically targeted therapies. Copyright ©2018, American Association for Cancer Research.

Reconstruction of segmental bone defect of long bones after tumor resection by devitalized tumor-bearing bone.

PubMed

Qu, Huayi; Guo, Wei; Yang, Rongli; Li, Dasen; Tang, Shun; Yang, Yi; Dong, Sen; Zang, Jie

2015-09-24

The reconstruction of an intercalary bone defect after a tumor resection of a long bone remains a challenge to orthopedic surgeons. Though several methods have been adopted to enhance the union of long segmental allografts or retrieved segmental autografts to the host bones, still more progresses are required to achieve a better union rate. Several methods have been adopted to devitalize tumor bone for recycling usage, and the results varied. We describe our experiences of using devitalized tumor-bearing bones for the repairing of segmental defects after tumor resection. Twenty-seven eligible patients treated from February 2004 to May 2012 were included. The segmental tumor bone (mean length, 14 cm) was resected, and then devitalized in 20% sterile saline at 65 °C for 30 min after the tumor tissue was removed. The devitalized bone was implanted back into the defect by using nails or plates. Complete healing of 50 osteotomy ends was achieved at a median time of 11 months (interquartile range (IQR) 9-13 months). Major complications included bone nonunion in four bone junctions (7.4%), devitalized bone fracture in one patient (3.7%), deep infection in three patients (11.1%), and fixation failure in two patients (7.4%). The bone union rates at 1 and 2 years were 74.1 and 92.6%, respectively. The average functional score according to the Musculoskeletal Tumor Society (MSTS) 93 scoring system was 93 % (IQR 80-96.7%). Incubation in 20% sterile saline at 65 °C for 30 min is an effective method of devitalization of tumor-bearing bone. The retrieved bone graft may provide as a less expensive alternative for limb salvage. The structural bone and the preserved osteoinductivity of protein may improve bone union.

Glioma Surgery: Technological Advances to Achieve a Maximal Safe Resection.

PubMed

Altieri, Roberto; Zenga, Francesco; Fontanella, Marco Maria; Cofano, Fabio; Agnoletti, Alessandro; Spena, Giannantonio; Crobeddu, Emanuela; Fornaro, Riccardo; Ducati, Alessandro; Garbossa, Diego

2015-11-01

Glioblastoma multiforme (GBM) is the most frequent primary central nervous system (CNS) tumor. Despite the best treatment and advances in therapy, prognosis remains poor. One of the mainstays of therapy in GBM is surgical excision. Several studies have confirmed that the extent of resection (EOR) positively influences overall survival (OS) in patients with high-grade gliomas (HGGs). A literature search was performed using PubMed to assess the useful neurosurgical tools to achieve the best neurosurgical performance. In order to achieve the major extent of resection, preserving neurological function, many tools are now available, especially neuronavigation, intraoperative fluorescence, intraoperative ultrasound, and neuromonitoring. In addition to the maximal excision of tumor, the neurosurgeon can use photodynamic therapy (PTD) and local drug delivery (LDD) to improve the local control and bridge conventional radio and chemotherapy. EOR improves OS in patients with HGGs. There are technological possibilities for achieving a complete resection preserving neurological function, and it is not acceptable to perform only biopsy of these lesions.

Tumor infiltrating BRAFV600E-specific CD4 T cells correlated with complete clinical response in melanoma. | Office of Cancer Genomics

Cancer.gov

T cells specific for neoantigens encoded by mutated genes in cancers are increasingly recognized as mediators of tumor destruction after immune checkpoint inhibitor therapy or adoptive cell transfer. Unfortunately, most neoantigens result from random mutations and are patient specific, and some cancers contain few mutations to serve as potential antigens. We describe a patient with stage IV acral melanoma who obtained a complete response following adoptive transfer of tumor infiltrating lymphocytes (TIL).

Complete responses of relapsed lymphoma following genetic modification of tumor-antigen presenting cells and T-lymphocyte transfer.

PubMed

Bollard, Catherine M; Gottschalk, Stephen; Leen, Ann M; Weiss, Heidi; Straathof, Karin C; Carrum, George; Khalil, Mariam; Wu, Meng-fen; Huls, M Helen; Chang, Chung-Che; Gresik, M Victoria; Gee, Adrian P; Brenner, Malcolm K; Rooney, Cliona M; Heslop, Helen E

2007-10-15

Epstein-Barr virus (EBV)-associated tumors developing in immunocompetent individuals present a challenge to immunotherapy, since they lack expression of immunodominant viral antigens. However, the tumors consistently express viral proteins including LMP2, which are immunologically "weak" but may nonetheless be targets for immune T cells. We previously showed that a majority of cytotoxic T lymphocytes (CTLs) reactivated using EBV-transformed B-lymphoblastoid cells lines (LCLs) contained minor populations of LMP2-specific T cells and homed to tumor sites. However, they did not produce remissions in patients with bulky disease. We have now used gene transfer into antigen-presenting cells (APCs) to augment the expression and immunogenicity of LMP2. These modified APCs increased the frequency of LMP2-specific CTLs by up to 100-fold compared with unmodified LCL-APCs. The LMP2-specific population expanded and persisted in vivo without adverse effects. Nine of 10 patients treated in remission of high-risk disease remain in remission, and 5 of 6 patients with active relapsed disease had a tumor response, which was complete in 4 and sustained for more than 9 months. It is therefore possible to generate immune responses to weak tumor antigens by ex vivo genetic modification of APCs and the CTLs so produced can have substantial antitumor activity. This study is registered at http://www.cancer.gov/clinicaltrials (protocol IDs: BCM-H-9936, NCT00062868, NCT00070226).

The release of Doxorubicin from liposomes monitored by MRI and triggered by a combination of US stimuli led to a complete tumor regression in a breast cancer mouse model.

PubMed

Rizzitelli, S; Giustetto, P; Faletto, D; Delli Castelli, D; Aime, S; Terreno, E

2016-05-28

The work aimed at developing a novel MRI-based theranostic protocol for improving the anticancer efficacy of a Doxil-like liposomal formulation. The goal was achieved stimulating the intratumor release of the drug from the nanocarrier and favoring its diffusion in the lesion by the sequential application of low-intensity pulsed ultrasound. The protocol was tested on mice bearing a syngeneic breast cancer model. The combination of acoustic waves with different characteristics allowed for: i) the release of the drug and the co-encapsulated MRI agent (Gadoteridol) from the liposomes in the vessels of the tumor region, and ii) the extravasation of the released material, as well as intact liposomes, in the tumor stroma. The MR-T1 contrast enhancement measured in the tumor reported on the delivery and US-triggered release of Doxorubicin. The developed protocol resulted in a marked increase in the intratumor drug concentration that, in turn, led to the complete regression of the lesion. The protocol has a good clinical translatability because all the components of the theranostic agent (Doxorubicin, liposomes, Gadoteridol) are approved for human use. Copyright © 2016 Elsevier B.V. All rights reserved.

WE-E-17A-06: Assessing the Scale of Tumor Heterogeneity by Complete Hierarchical Segmentation On MRI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gensheimer, M; Trister, A; Ermoian, R

2014-06-15

Purpose: In many cancers, intratumoral heterogeneity exists in vascular and genetic structure. We developed an algorithm which uses clinical imaging to interrogate different scales of heterogeneity. We hypothesize that heterogeneity of perfusion at large distance scales may correlate with propensity for disease recurrence. We applied the algorithm to initial diagnosis MRI of rhabdomyosarcoma patients to predict recurrence. Methods: The Spatial Heterogeneity Analysis by Recursive Partitioning (SHARP) algorithm recursively segments the tumor image. The tumor is repeatedly subdivided, with each dividing line chosen to maximize signal intensity difference between the two subregions. This process continues to the voxel level, producing segmentsmore » at multiple scales. Heterogeneity is measured by comparing signal intensity histograms between each segmented region and the adjacent region. We measured the scales of contrast enhancement heterogeneity of the primary tumor in 18 rhabdomyosarcoma patients. Using Cox proportional hazards regression, we explored the influence of heterogeneity parameters on relapse-free survival (RFS). To compare with existing methods, fractal and Haralick texture features were also calculated. Results: The complete segmentation produced by SHARP allows extraction of diverse features, including the amount of heterogeneity at various distance scales, the area of the tumor with the most heterogeneity at each scale, and for a given point in the tumor, the heterogeneity at different scales. 10/18 rhabdomyosarcoma patients suffered disease recurrence. On contrast-enhanced MRI, larger scale of maximum signal intensity heterogeneity, relative to tumor diameter, predicted for shorter RFS (p=0.05). Fractal dimension, fractal fit, and three Haralick features did not predict RFS (p=0.09-0.90). Conclusion: SHARP produces an automatic segmentation of tumor regions and reports the amount of heterogeneity at various distance scales. In rhabdomyosarcoma

Targeting and destroying tumor vasculature with a near-infrared laser-activated "nanobomb" for efficient tumor ablation.

PubMed

Gao, Wen; Li, Shuangshuang; Liu, Zhenhua; Sun, Yuhui; Cao, Wenhua; Tong, Lili; Cui, Guanwei; Tang, Bo

2017-09-01

Attacking the supportive vasculature network of a tumor offers an important new avenue for cancer therapy. Herein, a near-infrared (NIR) laser-activated "nanobomb" was developed as a noninvasive and targeted physical therapeutic strategy to effectively disrupt tumor neovasculature in an accurate and expeditious manner. This "nanobomb" was rationally fabricated via the encapsulation of vinyl azide (VA) into c(RGDfE) peptide-functionalized, hollow copper sulfide (HCuS) nanoparticles. The resulting RGD@HCuS(VA) was selectively internalized into integrin α v β 3 -expressing tumor vasculature endothelial cells and dramatically increased the photoacoustic signals from the tumor neovasculature, achieving a maximum signal-to-noise ratio at 4 h post-injection. Upon NIR irradiation, the local temperature increase triggered VA to release N 2 bubbles rapidly. Subsequently, these N 2 bubbles could instantly explode to destroy the neovasculature and further induce necrosis of the surrounding tumor cells. A single-dose injection of RGD@HCuS(VA) led to complete tumor regression after laser irradiation, with no tumor regrowth for 30 days. More importantly, high-resolution photoacoustic angiography, combined with excellent biodegradability, facilitated the precise destruction of tumor neovasculature by RGD@HCuS(VA) without damaging normal tissues. These results demonstrate the great potential of this "nanobomb" for clinical translation to treat cancer patients with NIR laser-accessible orthotopic tumors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pancreatic neuroendocrine tumor with complete replacement of the pancreas by serous cystic neoplasms in a patient with von Hippel-Lindau disease: a case report.

PubMed

Maeda, Shimpei; Motoi, Fuyuhiko; Oana, Shuhei; Ariake, Kyohei; Mizuma, Masamichi; Morikawa, Takanori; Hayashi, Hiroki; Nakagawa, Kei; Kamei, Takashi; Naitoh, Takeshi; Unno, Michiaki

2017-09-25

von Hippel-Lindau disease is a dominantly inherited multi-system syndrome with neoplastic hallmarks. Pancreatic lesions associated with von Hippel-Lindau include serous cystic neoplasms, simple cysts, and neuroendocrine tumors. The combination of pancreatic neuroendocrine tumors and serous cystic neoplasms is relatively rare, and the surgical treatment of these lesions must consider both preservation of pancreatic function and oncological clearance. We report a patient with von Hippel-Lindau disease successfully treated with pancreas-sparing resection of a pancreatic neuroendocrine tumor where the pancreas had been completely replaced by serous cystic neoplasms, in which pancreatic function was preserved. A 39-year-old female with von Hippel-Lindau disease was referred to our institution for treatment of a pancreatic neuroendocrine tumor. Abdominal computed tomography demonstrated a well-enhanced mass, 4 cm in diameter in the tail of the pancreas, and two multilocular tumors with several calcifications, 5 cm in diameter, in the head of the pancreas. There was complete replacement of the pancreas by multiple cystic lesions with diameters ranging from 1 to 3 cm. Magnetic resonance cholangiopancreatography showed innumerable cystic lesions on the whole pancreas and no detectable main pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration of the mass in the pancreatic tail showed characteristic features of a neuroendocrine tumor. A diagnosis of pancreatic neuroendocrine tumor in the tail of the pancreas and mixed-type serous cystic neoplasms replacing the whole pancreas was made and she underwent distal pancreatectomy while avoiding total pancreatectomy. The stump of the pancreas was sutured as firm as possible using a fish-mouth closure. The patient made a good recovery and was discharged on postoperative day 9. She is currently alive and well with no symptoms of endocrine or exocrine pancreatic insufficiency 8 months after surgery. A pancreas

Direct Tumor Embolization of Sinonasal Unclassified Spindle Cell Sarcoma with Onyx.

PubMed

Kansal, Ankit; Srinet, Prateek; Manes, Richard Peter

2016-07-01

To evaluate the use of a new tumor embolization agent, Onyx (Covidien, Dublin, Ireland), for the use of intraoperative embolization of a sinonasal unclassified spindle cell sarcoma. A 45-year-old female patient presented to the rhinology clinic with a nasal mass. A biopsy revealed a highly vascular mass consistent with a sinonasal unclassified spindle cell sarcoma. Secondary to its extensive vascularity, the patient underwent preoperative transarterial embolization (TAE) before definitive resection. Due to complex vascular anatomy including feeding vessels emanating from intracranial circulation, incomplete embolization was achieved. Subsequently, intraoperative embolization with Onyx at the time of resection was performed. Intraoperative Onyx use resulted in almost complete devascularization of the tumor with decreased risk of intracranial embolization. Intraoperative embolization with Onyx after an incomplete TAE can be a safe and effective method of achieving near-total embolization of sinonasal tumors.

MRI and Diffusion-weighted MRI Volumetry for Identification of Complete Tumor Responders After Preoperative Chemoradiotherapy in Patients With Rectal Cancer: A Bi-institutional Validation Study.

PubMed

Lambregts, Doenja M J; Rao, Sheng-Xiang; Sassen, Sander; Martens, Milou H; Heijnen, Luc A; Buijsen, Jeroen; Sosef, Meindert; Beets, Geerard L; Vliegen, Roy A; Beets-Tan, Regina G H

2015-12-01

Retrospective single-center studies have shown that diffusion-weighted magnetic resonance imaging (DWI) is promising for identification of patients with rectal cancer with a complete tumor response after neoadjuvant chemoradiotherapy (CRT), using certain volumetric thresholds. This study aims to validate the diagnostic value of these volume thresholds in a larger, independent, and bi-institutional patient cohort. A total of 112 patients with locally advanced rectal cancer (2 centers) treated with a long course of CRT were enrolled. Patients underwent standard T2W-magnetic resonance imaging and DWI, both pre- and post-CRT. Two experienced readers independently determined pre-CRT and post-CRT tumor volumes (cm) on T2W-magnetic resonance image and diffusion-weighted magnetic resonance image by means of freehand tumor delineation. Tumor volume reduction rates (Δvolume) were calculated. Previously determined T2W and DWI threshold values for prevolume, postvolume, and Δvolume were tested to "prospectively" assess their respective diagnostic value in discriminating patients with a complete tumor response from patients with residual tumor. Twenty patients had a complete response. Using the average measurements between the 2 readers, areas under the curve for the pre-/post-/Δvolumes was 0.73/0.82/0.78 for T2W-magnetic resonance imaging and 0.77/0.92/0.86 for DWI, respectively. For T2W-volumetry, sensitivity and specificity using the predefined volume thresholds were 55% and 74% for pre-, 60% and 89% for post-, and 60% and 86% for Δvolume. For DWI volumetry, sensitivity and specificity were 65% and 76% for pre-, 70% and 98% for post-, and 70% and 93% for Δvolume. Previously established DWI volume thresholds can be reproduced with good results. Post-CRT DWI volumetry offers the best results for the detection of patients with a complete response after CRT with an area under the curve of 0.92, sensitivity of 70%, and specificity of 98%.

Endoscopic resection of subepithelial tumors

PubMed Central

Schmidt, Arthur; Bauder, Markus; Riecken, Bettina; Caca, Karel

2014-01-01

Management of subepithelial tumors (SETs) remains challenging. Endoscopic ultrasound (EUS) has improved differential diagnosis of these tumors but a definitive diagnosis on EUS findings alone can be achieved in the minority of cases. Complete endoscopic resection may provide a reasonable approach for tissue acquisition and may also be therapeutic in case of malignant lesions. Small SET restricted to the submucosa can be removed with established basic resection techniques. However, resection of SET arising from deeper layers of the gastrointestinal wall requires advanced endoscopic methods and harbours the risk of perforation. Innovative techniques such as submucosal tunneling and full thickness resection have expanded the frontiers of endoscopic therapy in the past years. This review will give an overview about endoscopic resection techniques of SET with a focus on novel methods. PMID:25512768

Endoscopic resection of subepithelial tumors.

PubMed

Schmidt, Arthur; Bauder, Markus; Riecken, Bettina; Caca, Karel

2014-12-16

Management of subepithelial tumors (SETs) remains challenging. Endoscopic ultrasound (EUS) has improved differential diagnosis of these tumors but a definitive diagnosis on EUS findings alone can be achieved in the minority of cases. Complete endoscopic resection may provide a reasonable approach for tissue acquisition and may also be therapeutic in case of malignant lesions. Small SET restricted to the submucosa can be removed with established basic resection techniques. However, resection of SET arising from deeper layers of the gastrointestinal wall requires advanced endoscopic methods and harbours the risk of perforation. Innovative techniques such as submucosal tunneling and full thickness resection have expanded the frontiers of endoscopic therapy in the past years. This review will give an overview about endoscopic resection techniques of SET with a focus on novel methods.

Use of a Quality Improvement Initiative to Achieve Consistent Reporting of Level of Suspicion for Tumor on Multiparametric Prostate MRI.

PubMed

Rosenkrantz, Andrew B; Pujara, Akshat C; Taneja, Samir S

2016-05-01

The purpose of this article is to evaluate the utility of a quality improvement (QI) initiative in achieving long-term adherence to an evolving structured format for reporting the level of suspicion for tumor on prostate MRI examinations. The original QI initiative occurred over a 4-month period in 2010, before which prostate MRI was reported using free text. The initiative consisted of development of a section-wide macro, an initial group training session, ordering physician input regarding the structured report's value, subsequent weekly sessions for ongoing review, and timely individualized feedback in instances of nonuse. The initial structured report included pick lists for describing the level of suspicion for tumor as negative, low, medium, or high. Pick lists were modified in 2011 to incorporate a 5-point Likert scale and again in 2015 to incorporate Prostate Imaging Data and Reporting System (PI-RADS) version 2. These refinements were implemented after accelerated training periods. The frequency of reports providing an MRI-based suspicion level during these periods was assessed. Fifty-five percent of reports provided an MRI-based level of suspicion for tumor before the initiative. For various cohorts evaluated after the initiative (using structured reports based on the low, medium, or high scheme; a numeric Likert scale; or PI-RADS), this frequency improved to 95-100% (p < 0.001). Among reports without a suspicion level, potential confounding factors included marked artifact from hip prosthesis and overt diffuse tumor. The QI initiative achieved excellent adherence in reporting a suspicion level for tumor on prostate MRI examinations. The described components of the initiative were useful for maintaining long-term adherence that persisted after serial modifications to the report lexicon.

Transoral robotic resection of selected parapharyngeal space tumors.

PubMed

Arshad, Hassan; Durmus, Kasim; Ozer, Enver

2013-05-01

Currently, transoral robotic surgery (TORS) with the daVinci robot is mainly used for squamous cell carcinoma of the oropharynx and supraglottic larynx. The safety, efficacy, and functional outcomes regarding this approach have previously been described. In addition to transoral resection of squamous cell carcinoma, we have found use for this technique in removing selected tumors of the parapharyngeal space. Three patients with benign or malignant tumors of the parapharyngeal space who underwent successful transoral resection using the daVinci robot were included in the study. In all three cases, complete tumor excision was achieved without any complication. None required conversion to an open procedure. Mean TORS operative time and intraoperative blood loss were 16.3 min and 4.7 mL, respectively. Inadequate oral exposure, involvement of the internal carotid artery, limited cervical spine mobility and large tumor size are the main limitations of this approach. Result indicates that magnified view, 3D visualization with the combination of the transoral robotic experience, allow en bloc resection of selected parapharyngeal space tumors located medial to the carotid sheath.

A Percutaneous Transtubular Middle Fossa Approach for Intracanalicular Tumors.

PubMed

Bernardo, Antonio; Evins, Alexander I; Tsiouris, Apostolos J; Stieg, Philip E

2015-07-01

In cases of small intracanalicular tumors (≤ 1.5 cm), the middle fossa approach (MFA) provides the ability for adequate tumor removal with preservation of existing auditory function. Application of a minimally invasive tubular retractor in this approach may help mitigate the risk of postoperative seizures, aphasia, and venous complications by minimizing intraoperative retraction of the temporal lobe. We propose a minimally invasive microscopic and/or endoscopic percutaneous transtubular MFA for the management of intracanalicular tumors. Subtemporal keyhole craniectomies were performed on 5 preserved cadaveric heads (10 sides), with 6 sides previously injected with a synthetic tumor model. A ViewSite Brain Access System tubular retractor (Vycor Medical, Inc., Boca Raton, Florida, USA) was used to provide minimal temporal retraction and protection of the surrounding anatomy. An extradural dissection of the internal auditory canal was performed under microscopic and endoscopic visualization with a minimally invasive surgical drill and tube shaft instruments, the intracanalicular tumors were removed, and degree of resection was assessed. All 10 approaches were completed successfully through the tubular retractor with minimal retraction of the temporal lobe. Excellent visualization of the structures within the internal auditory canal was achieved with both the microscope and 3-dimensional endoscope. On the 6 synthetic intracanalicular tumors resected, 5 gross total (Grade I) and 1 near total (Grade II) resections were achieved. A percutaneous transtubular MFA is a feasible minimally invasive option for resection of small intracanalicular tumors with potential preservation of auditory function, reduced temporal retraction, and enhanced protection of surrounding structures. Copyright © 2015 Elsevier Inc. All rights reserved.

Can Navigation-assisted Surgery Help Achieve Negative Margins in Resection of Pelvic and Sacral Tumors?

PubMed

Abraham, John A; Kenneally, Barry; Amer, Kamil; Geller, David S

2018-03-01

Navigation-assisted resection has been proposed as a useful adjunct to resection of malignant tumors in difficult anatomic sites such as the pelvis and sacrum where it is difficult to achieve tumor-free margins. Most of these studies are case reports or small case series, but these reports have been extremely promising. Very few reports, however, have documented benefits of navigation-assisted resection in series of pelvic and sacral primary tumors. Because this technology may add time and expense to the surgical procedure, it is important to determine whether navigation provides any such benefits or simply adds cost and time to an already complex procedure. (1) What proportion of pelvic and sacral bone sarcoma resections utilizing a computer-assisted resection technique achieves negative margins? (2) What are the oncologic outcomes associated with computer-assisted resection of pelvic and sacral bone sarcomas? (3) What complications are associated with navigation-assisted resection? Between 2009 and 2015 we performed 24 navigation-assisted resections of primary tumors of the pelvis or sacrum. Of those, four were lost to followup after the 2-year postoperative visit. In one patient, however, there was a failure of navigation as a result of inadequate imaging, so nonnavigated resection was performed; the remaining 23 were accounted for and were studied here at a mean of 27 months after surgery (range, 12-52 months). During this period, we performed navigation-assisted resections in all patients presenting with a pelvis or sacral tumor; there was no selection process. No patients were treated for primary tumors in these locations without navigation during this time with the exception of the single patient in whom the navigation system failed. We retrospectively evaluated the records of these 23 patients and evaluated the margin status of these resections. We calculated the proportion of patients with local recurrence, development of metastases, and overall survival

Role of stereotactic radiosurgery with a linear accelerator in treatment of intracranial arteriovenous malformations and tumors in children.

PubMed

Loeffler, J S; Rossitch, E; Siddon, R; Moore, M R; Rockoff, M A; Alexander, E

1990-05-01

Between 1986 and 1988, 16 children were treated for 10 arteriovenous malformations and 6 recurrent intracranial tumors with stereotactic radiation therapy using a modified Clinac 6/100 linear accelerator. The median age of our patients was 10.5 years. For the group with arteriovenous malformation, follow-up ranged from 6 months to 37 months (median was 20 months). No patient bled during the follow-up period. Five of eight patients with follow-up longer than 12 months have achieved complete obliteration of their arteriovenous malformation by angiogram. The four remaining patients who have not achieved a complete obliteration are awaiting their 2-year posttreatment angiogram. The other patient has been treated within the year and have not yet been studied. Five of the six recurrent tumor patients are alive with a median follow-up of 8 months. The remaining patient was controlled locally, but he died of recurrent disease outside the area treated with radiosurgery. The radiographic responses of these patients have included three complete responses, two substantial reductions in tumor volume (greater than 50%) and one stabilization. Despite previous radiotherapy, there have been no significant complications in these patients. We conclude that stereotactic radiation therapy using a standard linear accelerator is an effective and safe technique in the treatment of selected intracranial arteriovenous malformations and tumors in children. In addition, stereotactic radiosurgery may have unique applications in the treatment of localized primary and recurrent pediatric brain tumors.

Application of anaerobic ammonium-oxidizing consortium to achieve completely autotrophic ammonium and sulfate removal.

PubMed

Liu, Sitong; Yang, Fenglin; Gong, Zheng; Meng, Fangang; Chen, Huihui; Xue, Yuan; Furukawa, Kenji

2008-10-01

The simultaneous ammonium and sulfate removal was detected in an anammox reactor, consisted of ammonium oxidization with sulfate deoxidization, and subsequently traditional anammox process, in via of middle medium nitrite with solid sulfur and N2 as the terminal products. The pure anammox bacteria offered a great biotechnological potential for the completely autotrophic reaction indicated by batch tests. Denaturing gradient gel electrophoresis (DGGE) analysis further revealed that a new organism belonging to Planctomycetales was strongly enriched in the defined niche: the redox of ammonium and sulfate. The new species "Anammoxoglobussulfate" was so considered as holding a critical role in the ammonium oxidization with sulfate deoxidization to nitrite. Afterwards, the Planctomyces existing in the bacteria community performed the anammox process together to achieve the complete nitrogen and sulfate removal. The potential use of sulfate as electron acceptor for ammonium oxidizing widens the usage of anammox bacteria.

Tumor Metabolism and Blood Flow as Assessed by PET Varies by Tumor Subtype in Locally Advanced Breast Cancer

PubMed Central

Specht, Jennifer M.; Kurland, Brenda F.; Montgomery, Susan K.; Dunnwald, Lisa K.; Doot, Robert K.; Gralow, Julie R.; Ellis, Georgina K.; Linden, Hannah M.; Livingston, Robert B.; Allison, Kimberly H.; Schubert, Erin K.; Mankoff, David A.

2010-01-01

Purpose Dynamic PET imaging can identify patterns of breast cancer metabolism and perfusion in patients receiving neoadjuvant chemotherapy (NC) that are predictive of response. This analysis examines tumor metabolism and perfusion by tumor subtype. Experimental Design Tumor subtype was defined by immunohistochemistry (IHC) in 71 patients with LABC undergoing NC. Subtype was defined as luminal (ER/PR positive), triple-negative (TN; ER/PR negative, HER2 negative) and HER2 (ER/PR negative, HER2 over-expressing). Metabolic rate (MRFDG) and blood flow (BF) were calculated from PET imaging prior to NC. Pathologic complete response (pCR) to NC was classified as pCR versus other. Results Twenty-five (35%) of 71 patients had TN tumors, 6 (8%) were HER2 and 40 (56%) were luminal. MRFDG for TN tumors was on average 67% greater than for luminal tumors (95% CI 9% – 156%), and average MRFDG/BF ratio was 53% greater in TN compared to luminal tumors (95% CI 9% – 114%) (p < 0.05 for both). Average blood flow levels did not differ by subtype (p = 0.73). Most luminal tumors showed relatively low MRFDG and BF (and did not achieve pCR); high MRFDG was generally matched with high BF in luminal tumors, and predicted pCR. This was not true in TN tumors. Conclusions The relationship between breast tumor metabolism and perfusion differed by subtype. The high MRFDG/BF ratio that predicts poor response to NC was more common in TN tumors. Metabolism and perfusion measures may identify subsets of tumors susceptible and resistant to NC and may help direct targeted therapy. PMID:20460489

[Establishment and Management of Multicentral Collection Bio-sample Banks of Malignant Tumors from Digestive System].

PubMed

Shen, Si; Shen, Junwei; Zhu, Liang; Wu, Chaoqun; Li, Dongliang; Yu, Hongyu; Qiu, Yuanyuan; Zhou, Yi

2015-11-01

To establish and manage of multicentral collection bio-sample banks of malignant tumors from digestive system, the paper designed a multicentral management system, established the standard operation procedures (SOPs) and leaded ten hospitals nationwide to collect tumor samples. The biobank has been established for half a year, and has collected 695 samples from patients with digestive system malignant tumor. The clinical data is full and complete, labeled in a unified way and classified to be managed. The clinical and molecular biology researches were based on the biobank, and obtained achievements. The biobank provides a research platform for malignant tumor of digestive system from different regions and of different types.

Incidental finding of upper lip Warthin tumor.

PubMed

Petrocelli, Marzia; Sbordone, Carolina; Salzano, Giovanni; Orabona, Giovanni Dell'Aversana; Cassandro, Francesco Maria; Fusetti, Stefano; Califano, Luigi; Cassandro, Ettore

2017-11-14

This report shows an incidental finding of Warthin tumor in upper lip mucosa during hospitalization for a biting lesion of cheek mucosa MATERIALS AND METHODS: A 32-year-old male affected by a biting lesion of cheek mucosa was presented at Maxillo- Facial Unit of Federico II University. Clinical examination showed as an incidental finding a solid mass in the superficial layer of upper lip mucosa. We performed mini-invasive surgical treatment to obtain a radical excision of the cheek lesion at the same time as excision of Warthin tumor. a follow up of 12 months was performed. The complete healing of the two wounds was achieved, with no recurrence of any of the pathologies. The location of this Warthin tumor of minor salivary glands is very unusual. The role of imaging in diagnosis of Warthin tumor of minor salivary glands is to define localization, shape and dimension, contour, malignant features, nodal involvement. The role of fine needle aspiration cytology (FNAC) is critical in the diagnosis and therapy of minor salivary gland tumors. The surgical treatment in patients affected by Warthin tumour of minor salivary glands is local excision with a wide tumor free margin to prevent potential recurrence. Warthin tumor of minor salivary glands is a rare disease. We report a singular case of Warthin tumor localized in the upper lip mucosa, found as an incidental finding during a recovery for a biting lesion of cheek mucosa. Incidental finding, Minor salivary glands, Warthin tumor.

Complete Recovery of Visual Disorder Following Surgical Resection of Adenoid Cystic Carcinoma Arising in the Pterygopalatine Fossa

PubMed Central

Du, Wei; Cui, Meng; Li, Peng; Wang, Jiheng; Luo, Ruihua; Qi, Jinxing; Zhao, Ming; Lou, Weihua

2015-01-01

Abstract Adenoid cystic carcinoma (ACC) arising in the pterygopalatine fossa was rare, only 3 cases have been reported. In previous literature, few authors reported whether the visual deficit could be resolved following the resection of the tumor. One patient with visual dysfunction induced by ACC arising in the pterygopalatine fossa was reported. Complete visual recovery was achieved following the operation. And the patient was satisfied with the appearance and the functional results in the follow-up. Visual loss contributed by the tumor in the pterygopalatine fossa could recover in selected patients. PMID:26039119

The Achievement of Intersubjectivity through Embodied Completions: A Study of Interactions between First and Second Language Speakers

ERIC Educational Resources Information Center

Mori, Junko; Hayashi, Makoto

2006-01-01

This study examines casual interactions between first language (L1) and second language (L2) speakers of Japanese, paying special attention to the coordination of vocal and non-vocal resources that are brought to bear on the achievement of intersubjectivity. More specifically, this study investigates a practice of "embodied completion" (Olsher…

Wilms' tumor with vena caval, atrial, and middle hepatic vein tumor thrombus.

PubMed

Sripathi, V; Muralidharan, K V; Ramesh, S; Muralinath, S

2000-01-01

A 3-year-old male with a right-sided Wilms' tumor presented with tender hepatomegaly and bilateral lower-limb edema. Ultrasound and echocardiography showed a massive tumor thrombus completely occluding the inferior vena cava, right atrial cavity, and extending retrogradely into the middle hepatic vein. Two courses of preoperative chemotherapy (vincristine, actinomycin D, adriamycin) caused minimal shrinkage of the thrombus. The tumor and thrombus were successfully removed with the patient under cardiopulmonary bypass and deep hypothermic circulatory arrest followed by multiagent chemotherapy (vincristine, actinomycin D, adriamycin, cyclophosphamide). The child is alive and well with no evidence of disease 15 months later. Occlusion of the hepatic vein by a tumor thrombus in Wilms' tumor is a very rare event. It was completely removed by the right atrial route under direct vision in this child.

Factors determining antibody distribution in tumors.

PubMed

Thurber, Greg M; Schmidt, Michael M; Wittrup, K Dane

2008-02-01

The development of antibody therapies for cancer is increasing rapidly, primarily owing to their specificity. Antibody distribution in tumors is often extremely uneven, however, leading to some malignant cells being exposed to saturating concentrations of antibody, whereas others are completely untargeted. This is detrimental because large regions of cells escape therapy, whereas other regions might be exposed to suboptimal concentrations that promote a selection of resistant mutants. The distribution of antibody depends on a variety of factors, including dose, affinity, antigens per cell and molecular size. Because these parameters are often known or easily estimated, a quick calculation based on simple modeling considerations can predict the uniformity of targeting within a tumor. Such analyses should enable experimental researchers to identify in a straightforward way the limitations in achieving evenly distributed antibody, and design and test improved antibody therapeutics more rationally.

Factors determining antibody distribution in tumors

PubMed Central

Thurber, Greg M.; Schmidt, Michael M.; Wittrup, K. Dane

2009-01-01

The development of antibody therapies for cancer is increasing rapidly, primarily owing to their specificity. Antibody distribution in tumors is often extremely uneven, however, leading to some malignant cells being exposed to saturating concentrations of antibody, whereas others are completely untargeted. This is detrimental because large regions of cells escape therapy, whereas other regions might be exposed to suboptimal concentrations that promote a selection of resistant mutants. The distribution of antibody depends on a variety of factors, including dose, affinity, antigens per cell and molecular size. Because these parameters are often known or easily estimated, a quick calculation based on simple modeling considerations can predict the uniformity of targeting within a tumor. Such analyses should enable experimental researchers to identify in a straightforward way the limitations in achieving evenly distributed antibody, and design and test improved antibody therapeutics more rationally. PMID:18179828

Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy.

PubMed

Parissenti, Amadeo M; Guo, Baoqing; Pritzker, Laura B; Pritzker, Kenneth P H; Wang, Xiaohui; Zhu, Mu; Shepherd, Lois E; Trudeau, Maureen E

2015-08-01

In a prior substudy of the CAN-NCIC-MA.22 clinical trial (ClinicalTrials.gov identifier NCT00066443), we observed that neoadjuvant chemotherapy reduced tumor RNA integrity in breast cancer patients, a phenomenon we term "RNA disruption." The purpose of the current study was to assess in the full patient cohort the relationship between mid-treatment tumor RNA disruption and both pCR post-treatment and, subsequently, disease-free survival (DFS) up to 108 months post-treatment. To meet these objectives, we developed the RNA disruption assay (RDA) to quantify RNA disruption and stratify it into 3 response zones of clinical importance. Zone 1 is a level of RNA disruption inadequate for pathologic complete response (pCR); Zone 2 is an intermediate level, while Zone 3 has high RNA disruption. The same RNA disruption cut points developed for pCR response were then utilized for DFS. Tumor RDA identified >fourfold more chemotherapy non-responders than did clinical response by calipers. pCR responders were clustered in RDA Zone 3, irrespective of tumor subtype. DFS was about 2-fold greater for patients with tumors in Zone 3 compared to Zone 1 patients. Kaplan-Meier survival curves corroborated these findings that high tumor RNA disruption was associated with increased DFS. DFS values for patients in zone 3 that did not achieve a pCR were similar to that of pCR recipients across tumor subtypes, including patients with hormone receptor positive tumors that seldom achieve a pCR. RDA appears superior to pCR as a chemotherapy response biomarker, supporting the prospect of its use in response-guided chemotherapy.

[Complete hormonal and metabolic response after iodine-131 metaiodobenzylguanidine treatment in a patient diagnosed of malignant pheochromocytoma].

PubMed

García Alonso, M P; Balsa Bretón, M A; Paniagua Correa, C; Castillejos Rodríguez, L; Rodríguez Pelayo, E; Mendoza Paulini, A; Ortega Valle, A; Penín González, J

2013-01-01

Radiolabeled metaiodobenzylguanidine is an analogue of norepinephrine used to localize tumors that express the neurohormone transporters, specifically those derived from the neural crest having a neuroendocrine origin. It is also used to treat non-surgical metastases derived from them. A review of the literature revealed symptomatic improvements associated to a decrease in hormone levels in a significant percentage of patients after (131)I-MIBG treatment. However, complete tumor remission has been described only in very few cases and hardly ever when bone metastases exist. We present a case of a patient diagnosed of malignant pheochromocytoma who achieved complete hormonal and metabolic response after (131)I-MIBG treatment (600 mCi) in spite of the presence of bone metastases. Copyright © 2012 Elsevier España, S.L. and SEMNIM. All rights reserved.

Hemostasis of the liver, spleen, and bone achieved by electrocautery greased with lidocaine gel.

PubMed

Petroianu, Andy

2011-02-01

Despite advances in surgical techniques, achieving hemostasis of the liver, spleen, and bone during major surgery, especially after trauma, is still difficult. I describe a new procedure my colleagues and I devised to achieve parenchymatous hemostasis using electrocautery greased with lidocaine gel. After achieving good results in experimental studies and obtaining approval from our ethics committee, we used electrocautery greased with lidocaine gel for hemostasis in the following 36 procedures: multisegmental hepatectomy to remove hepatic tumors (n = 6); partial hepatectomy to allow hepatojejunostomy for intrahepatic biliary obstruction (n = 10); laparoscopic liver biopsy (n = 4); subtotal splenectomy (n = 8; for portal hypertension in 5 patients, splenic ischemia in 2, and Gaucher's disease in 1); laparoscopic splenic biopsy (n = 1); and bone resection (n = 7; as pelvic-femoral resection in 6 patients and to remove a rectal tumor invading the coccyx in 1). This procedure was easy to perform and achieved complete hemostasis of the minor blood vessels in all patients. No postoperative bleeding occurred and the follow-up course was satisfactory. Electrocautery greased with lidocaine gel is an inexpensive, readily available, and efficient method to achieve hemostasis of minor vessels in hepatic, splenic, and bone operations.

Clinical characteristics, surgical and neuropsychological outcomes in drug resistant tumoral temporal lobe epilepsy.

PubMed

Ravat, Sangeeta; Iyer, Vivek; Muzumdar, Dattatraya; Shah, Urvashi; Pradhan, Pranjali; Jain, Neeraj; Godge, Yogesh

2016-12-01

Glioneuronal tumors are found in nearly one third patients who undergo surgery for pharmacoresistant epilepsy with temporal lobe being the most common location. Few studies, however have concentrated on the neurological and neuropsychological outcomes after surgery, hitherto none from India. We studied 34 patients with temporal lobe tumors and drug resistant epilepsy. These patients underwent anterior temporal lobectomy or lesionectomy based on the involvement of the hippocampus and mesial temporal structures. The clinical history, EEG, neuropsychology profile and MRI were compared. Seizure outcome was categorized using Engel's classification. At a mean follow up of 62 months, 85.29% of the patients were seizure free (Engel's Class I). All 8 patients with intraoperative electrocorticography (ECoG) guided resection were seizure free. Presence of a residual lesion was significantly associated with persistence of seizures post surgery (p = 0.002). Group analysis revealed no significant shifts in IQ and memory scores postoperatively. There was a significant improvement in the quality of life scores (total and across all subdomains) in all patients (p < 0.001). Postoperative EEG abnormalities predicted unfavorable ​seizure outcome. Surgery for temporal lobe tumors and refractory epilepsy offers complete seizure freedom in majority. Complete surgical excision of the epileptogenic zone is of paramount importance in achieving seizure freedom. Intraoperative electrocorticography (EcoG) is a useful adjunct to ensure complete removal of epileptogenic zone, thus achieving optimal seizure freedom. There is a significant improvement in the quality of life scores (p < 0.001) with no negative impact of surgery on memory and intelligence. Even the patients who are not seizure free can achieve worthwhile improvement post surgery. Copyright © 2015 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

Management of tracheal chondrosarcoma almost completely obstructing the airway: a case report.

PubMed

Andolfi, Marco; Vaccarili, Maurizio; Crisci, Roberto; Puma, Francesco

2016-07-11

Primary malignant tracheal tumors account for only 0.2 % of all malignancies of the respiratory tract. Tracheal chondrosarcoma is a rare condition and only 17 cases have been described in the literature from 1965 to date. Herein we report the very unusual case of a patient with a tracheal chondrosarcoma, electively treated by curative surgery despite the virtually complete obstruction of the airway. We present the case of a 79-year old Caucasian man with long-lasting wheezing misdiagnosed as asthma and affected by a tracheal chondrosarcoma almost completely obstructing the airway. Videobronchoscopy and imaging investigations revealed a well-circumscribed mass arising from the cartilaginous rings of the cervical trachea with a posterior residual respiratory space of about 1 mm. Because of the mobility and flaccidity of the uninvolved pars membranacea, the tiny respiratory space slightly expanded during inspiration and expiration allowing the patient to be treated without an essential emergency procedure. Standard tracheal intubation was impossible. Rigid bronchoscopy enabled placement of a small tracheal tube distally to the tumor. Successful cervical tracheal resection and reconstruction was then performed, achieving complete tumor excision. Histologically, the mass was characterized as a low-grade tracheal chondrosarcoma. Videobronchoscopy performed 9 months after surgery showed a wide, well healed tracheal anastomosis. Ten months after surgery, the patient is alive and disease free. Complete surgical resection is the treatment of choice for tracheal chondrosarcoma. Rigid bronchoscopy is an essential tool for diagnostic and therapeutic purposes. It allows the palliative maneuvers for obstruction relief but also, in resectable patients, the intraoperative safe and straightforward management of the obstructed airway.

Pure transcatheter arterial chemoembolization therapy for intrahepatic tumors causes a shrink in pulmonary metastases of hepatocellular carcinoma.

PubMed

Wu, Huiyong; Zhao, Wei; Liu, Shuguang; Zheng, Jinsong; Ji, Guanglei; Xie, Yinfa

2015-01-01

Pulmonary metastasis of hepatocellular carcinoma (HCC) could be defined as advanced HCC and systematic treatment is the main therapeutic modality. However, local therapy of intrahepatic tumor, which is significantly associated with the prognosis of HCC, remains important for advanced HCC. Twenty-six HCC patients with pulmonary metastasis underwent intrahepatic transcatheter arterial chemoembolization (TACE). We investigated the progression of lung metastastic tumors, overall survival and risk factors related to survival of these patients. Of the 26 patients who underwent TACE for one to four times, 10 patients achieved complete remission (CR) of intrahepatic tumors and among these 10 patients, 4 patients successfully received hepatic artery-venous shunt embolization combined with TACE. The lung metastasis lesions also achieved CR and the survival time was significantly longer than the other 22 patients. The lung metastastic lesions of the other 6 patients of intrahepatic tumors achieved stable disease (SD). Six patients acquired partial remission (PR) of intrahepatic tumors after TACE, while the lung metastastic lesions showed SD or progress disease (PD). Patients who showed CR and PR of intrahepatic tumors had longer survival time than patients with SD and PD. Portal vein tumor thrombus and size of the lung metastastic lesions were significant prognostic factors in these advanced HCC patients. With respect to HCC patients with lung metastasis, TACE was an effective and important therapeutic tool to control pulmonary metastatic tumor growth, and prolong the survival of advanced HCC patients, especially patients with hepatic artery-venous shunt.

Living donor liver transplantation for hepatocellular carcinoma achieves better outcomes.

PubMed

Lin, Chih-Che; Chen, Chao-Long

2016-10-01

Liver transplantation (LT) for hepatocellular carcinoma (HCC) at Kaohsiung Chang Gung Memorial Hospital mainly relies on live donor LT (LDLT). Owing to taking the risk of LD, we are obligated to adopt strict selection criteria for HCC patients and optimize the pre-transplant conditions to ensure a high disease-free survival similar to those without HCC, even better than deceased donor LT (DDLT). Better outcomes are attributed to excellent surgical results and optimal patient selection. The hospital mortality of primary and salvage LDLT are lower than 2% in our center. Although Taiwan Health Insurance Policy extended the Milan to University of California, San Francisco (UCSF) criteria in 2006, selection criteria will not be consolidated to take into account only by the morphologic size/number of tumors but also by their biology. The criteria are divided into modifiable image morphology, alpha fetoprotein (AFP), and positron emission tomography (PET) scan with standard uptake value (SUV) and unmodifiable unfavorable pathology such as HCC combined with cholangiocarcinoma (CC), sarcomatoid type, and poor differentiation. Downstaging therapy is necessary for HCC patients beyond criteria to fit all modifiable standards. The upper limit of downstaging treatment seems to be extended by more effective drug eluting transarterial chemoembolization in cases without absolute contraindications. In contrast, the pitfall of unmodifiable tumor pathology should be excluded by the findings of pretransplant core biopsy/resection if possible. More recently, achieving complete tumor necrosis in explanted liver could almost predict no recurrence after transplant. Necrotizing therapy is advised if possible before transplant even the tumor status within criteria to minimize the possibility of tumor recurrence. LDLT with low surgical mortality in experienced centers provides the opportunities of optimizing the pre-transplant tumor conditions and timing of transplant to achieve better

Assessing the scale of tumor heterogeneity by complete hierarchical segmentation of MRI.

PubMed

Gensheimer, Michael F; Hawkins, Douglas S; Ermoian, Ralph P; Trister, Andrew D

2015-02-07

In many cancers, intratumoral heterogeneity has been found in histology, genetic variation and vascular structure. We developed an algorithm to interrogate different scales of heterogeneity using clinical imaging. We hypothesize that heterogeneity of perfusion at coarse scale may correlate with treatment resistance and propensity for disease recurrence. The algorithm recursively segments the tumor image into increasingly smaller regions. Each dividing line is chosen so as to maximize signal intensity difference between the two regions. This process continues until the tumor has been divided into single voxels, resulting in segments at multiple scales. For each scale, heterogeneity is measured by comparing each segmented region to the adjacent region and calculating the difference in signal intensity histograms. Using digital phantom images, we showed that the algorithm is robust to image artifacts and various tumor shapes. We then measured the primary tumor scales of contrast enhancement heterogeneity in MRI of 18 rhabdomyosarcoma patients. Using Cox proportional hazards regression, we explored the influence of heterogeneity parameters on relapse-free survival. Coarser scale of maximum signal intensity heterogeneity was prognostic of shorter survival (p = 0.05). By contrast, two fractal parameters and three Haralick texture features were not prognostic. In summary, our algorithm produces a biologically motivated segmentation of tumor regions and reports the amount of heterogeneity at various distance scales. If validated on a larger dataset, this prognostic imaging biomarker could be useful to identify patients at higher risk for recurrence and candidates for alternative treatment.

Mutated PPP1R3B is recognized by T cells used to treat a melanoma patient who experienced a durable complete tumor regression

PubMed Central

Lu, Yong-Chen; Yao, Xin; Li, Yong F.; El-Gamil, Mona; Dudley, Mark E.; Yang, James C.; Almeida, Jorge R.; Douek, Daniel C.; Samuels, Yardena; Rosenberg, Steven A.; Robbins, Paul F.

2013-01-01

Adoptive cell therapy with tumor infiltrating lymphocytes (TILs) represents an effective treatment for patients with metastatic melanoma. However, most of the antigen targets recognized by effective melanoma reactive TILs remain elusive. In this study, patient 2369 experienced a complete response, including regressions of bulky liver tumor masses ongoing beyond seven years following adoptive TILs transfer. The screening of a cDNA library generated from the autologous melanoma cell line resulted in the isolation of a mutated PPP1R3B (protein phosphatase 1, regulatory (inhibitor) subunit 3B) gene product. The mutated PPP1R3B peptide represents the immunodominant epitope recognized by tumor reactive T cells in TIL 2369. Five years following adoptive transfer, peripheral blood T lymphocytes obtained from patient 2369 recognized the mutated PPP1R3B epitope. These results demonstrate that adoptive T cell therapy targeting a tumor-specific antigen can mediate long-term survival for a patient with metastatic melanoma. This study also provides an impetus to develop personalized immunotherapy targeting tumor-specific, mutated antigens. PMID:23690473

Complete resection of locally advanced ovarian carcinoma fixed to the pelvic sidewall and involving external and internal iliac vessels.

PubMed

Nishikimi, Kyoko; Tate, Shinichi; Matsuoka, Ayumu; Shozu, Makio

2017-08-01

Locally advanced ovarian carcinomas may be fixed to the pelvic sidewall, and although these often involve the internal iliac vessels, they rarely involve the external iliac vessels. Such tumors are mostly considered inoperable. We present a surgical technique for complete resection of locally advanced ovarian carcinoma fixed to the pelvic sidewall and involving external and internal iliac vessels. A 69-year-old woman presented with ovarian carcinoma fixed to the right pelvic sidewall, which involved the right external and internal iliac arteries and veins and the right lower ureter, rectum, and vagina. We cut the external iliac artery and vein at the bifurcation and at the inguinal ligament to resect the external artery and vein. Then, we reconstructed the arterial and venous supplies of the right external artery and vein with grafts. After creating a wide space immediately inside of the sacral plexus to allow the tumor fixed to pelvic sidewall with the internal iliac vessels to move medially, we performed total internal iliac vessel resection. We achieved complete en bloc tumor resection with the right external and internal artery and vein, right ureter, vagina, and rectum adhering to the tumor. There were no intra- or postoperative complications, such as bleeding, graft occlusion, infection, or limb edema. Exfoliation from the sacral plexus and total resection with external and internal iliac vessels enables complete resection of the tumor fixed to the pelvic sidewall. Copyright © 2017 Elsevier Inc. All rights reserved.

Management of craniofacial chondroid tumors.

PubMed

Cherekaev, Vasily A; Golbin, Denis A; Gasparyan, Tigran G; Shishkina, Lyudmila V; Tsukanova, Tatiana V

2015-01-01

Craniofacial chondroid tumors (CFCTs) constitute less than 1% of all intracranial mass lesions. No protocol for evaluation and management of CFCTs is developed at the moment. We analyzed 51 patients with CFCTs operated on in Burdenko Neurosurgical Institute from 1980 until 2012, which included chondroma (15), chondroblastoma (3), chondromyxoid fibroma (11), and chondrosarcoma (22). Age varied from 2 to 76 years (mean, 40 y); the series included 23 women and 28 men. All tumors were divided into 4 groups: midline unilateral (8),midline bilateral (21), anterolateral (19), and lateral (3). This division was based on differences in surgical approaches (P = 0.009). All patients underwent surgical treatment. Complete removal was achieved in 20; subtotal, in 21; and partial, in 10. Two patients died, and early complications were observed in 10 cases. Early outcomes correlated with the benign nature of the tumors (P = 0.002). Follow-up data were available in 22 patients. Fifteen of 51 patients were reoperated on because of recurrence (a total of 43 reoperations were performed). The mean recurrence-free period was 45 months. In 3 patients, the tumor metastasized, and malignant transformation was observed in 3 cases. Sixteen patients received postoperative radiation therapy. Delayed sequelae occurred in 5 observations, and 5 patients died during long-term follow-up. Three-year survival in benign and malignant tumors was 87.5% and 55.6%, respectively, and 5-year survival was 83.3% and 40.0%, respectively. Surgical resection is the mainstay in treatment of both benign and malignant craniofacial tumors, and adjuvant radiation therapy is mandatory in malignant lesions; however, it should be avoided in benign lesions.

Efficacy of Precut Endoscopic Mucosal Resection for Treatment of Rectal Neuroendocrine Tumors

PubMed Central

So, Hoonsub; Yoo, Su Hyun; Han, Seungbong; Kim, Gwang-un; Seo, Myeongsook; Hwang, Sung Wook; Yang, Dong-Hoon; Byeon, Jeong-Sik

2017-01-01

Background/Aims Endoscopic resection is the first-line treatment for rectal neuroendocrine tumors (NETs) measuring <1 cm and those between 1 and 2 cm in size. However, conventional endoscopic resection cannot achieve complete resection in all cases. We aimed to analyze clinical outcomes of precut endoscopic mucosal resection (EMR-P) used for the management of rectal NET. Methods EMR-P was used to treat rectal NET in 72 patients at a single tertiary center between 2011 and 2015. Both, circumferential precutting and EMR were performed with the same snare device in all patients. Demographics, procedural details, and histopathological features were reviewed for all cases. Results Mean size of the tumor measured endoscopically was 6.8±2.8 mm. En bloc and complete resection was achieved in 71 (98.6%) and 67 patients (93.1%), respectively. The mean time required for resection was 9.0±5.6 min. Immediate and delayed bleeding developed in six (8.3%) and 4 patients (5.6%), respectively. Immediate bleeding observed during EMR-P was associated with the risk of delayed bleeding. Conclusions Both, the en bloc and complete resection rates of EMR-P in the treatment of rectal NETs using the same snare for precutting and EMR were noted to be high. The procedure was short and safe. EMR-P may be a good treatment choice for the management of rectal NETs. PMID:29020763

Characterization of the Tumor Secretome from Tumor Interstitial Fluid (TIF).

PubMed

Gromov, Pavel; Gromova, Irina

2016-01-01

Tumor interstitial fluid (TIF) surrounds and perfuses bodily tumorigenic tissues and cells, and can accumulate by-products of tumors and stromal cells in a relatively local space. Interstitial fluid offers several important advantages for biomarker and therapeutic target discovery, especially for cancer. Here, we describe the most currently accepted method for recovering TIF from tumor and nonmalignant tissues that was initially performed using breast cancer tissue. TIF recovery is achieved by passive extraction of fluid from small, surgically dissected tissue specimens in phosphate-buffered saline. We also present protocols for hematoxylin and eosin (H&E) staining of snap-frozen and formalin-fixed, paraffin-embedded (FFPE) tumor sections and for proteomic profiling of TIF and matched tumor samples by high-resolution two-dimensional gel electrophoresis (2D-PAGE) to enable comparative analysis of tumor secretome and paired tumor tissue.

Neoadjuvant chemoradiation therapy and pathological complete response in rectal cancer

PubMed Central

Ferrari, Linda; Fichera, Alessandro

2015-01-01

The management of rectal cancer has evolved significantly in the last few decades. Significant improvements in local disease control were achieved in the 1990s, with the introduction of total mesorectal excision and neoadjuvant radiotherapy. Level 1 evidence has shown that, with neoadjuvant chemoradiation therapy (CRT) the rates of local recurrence can be lower than 6% and, as a result, neoadjuvant CRT currently represents the accepted standard of care. This approach has led to reliable tumor down-staging, with 15–27% patients with a pathological complete response (pCR)—defined as no residual cancer found on histological examination of the specimen. Patients who achieve pCR after CRT have better long-term outcomes, less risk of developing local or distal recurrence and improved survival. For all these reasons, sphincter-preserving procedures or organ-preserving options have been suggested, such as local excision of residual tumor or the omission of surgery altogether. Although local recurrence rate has been stable at 5–6% with this multidisciplinary management method, distal recurrence rates for locally-advanced rectal cancers remain in excess of 25% and represent the main cause of death in these patients. For this reason, more recent trials have been looking at the administration of full-dose systemic chemotherapy in the neoadjuvant setting (in order to offer early treatment of disseminated micrometastases, thus improving control of systemic disease) and selective use of radiotherapy only in non-responders or for low rectal tumors smaller than 5 cm. PMID:26290512

Lateral skull base approaches in the management of benign parapharyngeal space tumors.

PubMed

Prasad, Sampath Chandra; Piccirillo, Enrico; Chovanec, Martin; La Melia, Claudio; De Donato, Giuseppe; Sanna, Mario

2015-06-01

To evaluate the role of lateral skull base approaches in the management of benign parapharyngeal space tumors and to propose an algorithm for their surgical approach. Retrospective study of patients with benign parapharyngeal space tumors. The clinical features, radiology and preoperative management of skull base neurovasculature, the surgical approaches and overall results were recorded. 46 patients presented with 48 tumors. 12 were prestyloid and 36 poststyloid. 19 (39.6%) tumors were paragangliomas, 15 (31.25%) were schwannomas and 11 (23%) were pleomorphic adenomas. Preoperative embolization was performed in 19, stenting of the internal carotid artery in 4 and permanent balloon occlusion in 2 patients. 19 tumors were approached by the transcervical, 13 by transcervical-transparotid, 5 by transcervical-transmastoid, 6, 1 and 2 tumors by the infratemporal fossa approach types A, B and D, respectively. Total radical tumor removal was achieved in 46 (96%) of the cases. Lateral skull base approaches have an advantage over other approaches in the management of benign tumors of the parapharyngeal space due to the fact that they provide excellent exposure with less morbidity. The use of microscope combined with bipolar cautery reduces morbidity. Stenting of internal carotid artery gives a chance for complete tumor removal with arterial preservation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Complete segmental resection of the spine, including the spinal cord, for telangiectatic osteosarcoma: a report of 2 cases.

PubMed

Murakami, Hideki; Tomita, Katsuro; Kawahara, Norio; Oda, Makoto; Yahata, Tetsutaro; Yamaguchi, Takehiko

2006-02-15

Two case reports of telangiectatic osteosarcoma treated with complete segmental resection of the spine, including the spinal cord. To report the en bloc tumor excision, including the spinal cord, for telangiectatic osteosarcoma, and discuss the indication of cord transection and influence after cutting the spinal cord. To our knowledge, there are no previous reports describing telangiectatic osteosarcoma of the spine and the subsequent en bloc excision of the spine, including the spinal cord. The clinical and radiographic presentations of 2 cases with telangiectatic osteosarcoma are presented. Because these 2 cases already had complete paralysis for at least 1 month, it was suspected that there was no possibility of recovering spinal cord function. Complete segmental spinal resection (total en bloc spondylectomy) was performed. At that level, the spinal cord was also cut and resected. En bloc excision of the tumor with a wide margin was achieved in both cases. In the resected specimen, the nerve cells in the spinal cord had lapsed into degenerative necrosis. The pathologic findings showed that there was no hope for recovery of spinal cord function. En bloc spinal resection, including the spinal cord, is an operation allowed when there is no hope for recovery of spinal cord function. This surgery should be accepted as an option in spine tumor surgeries.

L-asparaginase induced complete remission in Epstein-Barr virus positive, multidrug resistant, cutaneous T-cell lymphoma.

PubMed

Obama, K; Tara, M; Niina, K

1999-06-01

A 30-year-old man was admitted to our hospital with subcutaneous tumors and a high fever. Based on biomicroscopic findings of the tumor, the patient was diagnosed as having diffuse, medium, well-differentiated malignant lymphoma. Immunochemical analysis showed that CD3, CD4, CD25, and TCR beta were positive, and in situ hybridization revealed Epstein-Barr virus-encoded small RNAs in the nuclei of the lymphoma cells. Despite the patient's resistance to multidrug therapy, complete remission was achieved using L-asparaginase. This case is unique because of its peculiar clinical course and a possible association with the Epstein-Barr virus. L-asparaginase may be an important treatment in other patients who exhibit some of these characteristics.

Profiling Learners' Achievement Goals when Completing Academic Essays

ERIC Educational Resources Information Center

Ng, Chi-Hung Clarence

2009-01-01

This study explored adult learners' goal profiles in relation to the completion of a compulsory academic essay. Based on learners' scores on items assessing mastery, performance-approach, and work-avoidance goals, cluster analyses produced three distinct categories of learners: performance-focused, work-avoidant, and multiple-goal learners. These…

A simple technique to achieve bloodless excision of carotid body tumors.

PubMed

Spinelli, Francesco; Massara, Mafalda; La Spada, Michele; Stilo, Francesco; Barillà, David; De Caridi, Giovanni

2014-05-01

We describe a technique for Shamblin II-III carotid body tumor (CBT) resection to reduce bleeding and neurologic complications during surgery. The technique was based on the fact that CBTs are supplied almost exclusively from the external carotid artery. Therefore, we carefully isolated the origin of the external carotid artery and its distal branches outside the tumor and temporarily clamped all of these vessels after heparin administration. This allowed a safe and bloodless resection as the tumor was dissected from the internal carotid artery in the usual subadventitial plane. The internal carotid artery was never clamped, and respect of peripheral nerves was warranted in the clean and bloodless field. From 2007 to 2010, we treated 11 patients with a CBT: six had a Shamblin II and five had a Shamblin III lesion. Neither perioperative neurologic events nor recurrences occurred after a mean follow-up of 42 months. Copyright © 2014 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Detection limits of intraoperative near infrared imaging for tumor resection.

PubMed

Thurber, Greg M; Figueiredo, Jose-Luiz; Weissleder, Ralph

2010-12-01

The application of fluorescent molecular imaging to surgical oncology is a developing field with the potential to reduce morbidity and mortality. However, the detection thresholds and other requirements for successful intervention remain poorly understood. Here we modeled and experimentally validated depth and size of detection of tumor deposits, trade-offs in coverage and resolution of areas of interest, and required pharmacokinetics of probes based on differing levels of tumor target presentation. Three orthotopic tumor models were imaged by widefield epifluorescence and confocal microscopes, and the experimental results were compared with pharmacokinetic models and light scattering simulations to determine detection thresholds. Widefield epifluorescence imaging can provide sufficient contrast to visualize tumor margins and detect tumor deposits 3-5  mm deep based on labeled monoclonal antibodies at low objective magnification. At higher magnification, surface tumor deposits at cellular resolution are detectable at TBR ratios achieved with highly expressed antigens. A widefield illumination system with the capability for macroscopic surveying and microscopic imaging provides the greatest utility for varying surgical goals. These results have implications for system and agent designs, which ultimately should aid complete resection in most surgical beds and provide real-time feedback to obtain clean margins. © 2010 Wiley-Liss, Inc.

Complete surgical resection improves outcome in INRG high-risk patients with localized neuroblastoma older than 18 months.

PubMed

Fischer, Janina; Pohl, Alexandra; Volland, Ruth; Hero, Barbara; Dübbers, Martin; Cernaianu, Grigore; Berthold, Frank; von Schweinitz, Dietrich; Simon, Thorsten

2017-08-04

Although several studies have been conducted on the role of surgery in localized neuroblastoma, the impact of surgical timing and extent of primary tumor resection on outcome in high-risk patients remains controversial. Patients from the German neuroblastoma trial NB97 with localized neuroblastoma INSS stage 1-3 age > 18 months were included for retrospective analysis. Imaging reports were reviewed by two independent physicians for Image Defined Risk Factors (IDRF). Operation notes and corresponding imaging reports were analyzed for surgical radicality. The extent of tumor resection was classified as complete resection (95-100%), gross total resection (90-95%), incomplete resection (50-90%), and biopsy (<50%) and correlated with local control rate and outcome. Patients were stratified according to the International Neuroblastoma Risk Group (INRG) staging system. Survival curves were estimated according to the method of Kaplan and Meier and compared by the log-rank test. A total of 179 patients were included in this study. 77 patients underwent more than one primary tumor operation. After best surgery, 68.7% of patients achieved complete resection of the primary tumor, 16.8% gross total resection, 14.0% incomplete surgery, and 0.5% biopsy only. The cumulative complication rate was 20.3% and the surgery associated mortality rate was 1.1%. Image defined risk factors (IDRF) predicted the extent of resection. Patients with complete resection had a better local-progression-free survival (LPFS), event-free survival (EFS) and OS (overall survival) than the other groups. Subgroup analyses showed better EFS, LPFS and OS for patients with complete resection in INRG high-risk patients. Multivariable analyses revealed resection (complete vs. other), and MYCN (non-amplified vs. amplified) as independent prognostic factors for EFS, LPFS and OS. In patients with localized neuroblastoma age 18 months or older, especially in INRG high-risk patients harboring MYCN amplification

Educational achievement, employment, smoking, marital, and insurance statuses in long-term survivors of childhood malignant solid tumors.

PubMed

Yağci-Küpeli, Begül; Yalçin, Bilgehan; Küpeli, Serhan; Varan, Ali; Akyüz, Canan; Kutluk, Tezer; Büyükpamukçu, Münevver

2013-03-01

Survivors of childhood cancer experience many social adaptation problems. We aimed to identify social, educational, and occupational issues of this growing population. Survivors treated for childhood malignant solid tumors who were older than 18 years and in remission for at least 3 years were surveyed. The educational achievement, employment, type of habitation, marital status, parenthood, social insurance, and smoking status of the patients were inquired and recorded. Two hundred one patients (126 male patients/75 female patients) were included in the study between 2007 and 2009. The median ages at the time of diagnosis and at the time of study were 10 years (range, 0 to 19 y) and 23 years (range, 18 to 39 y), respectively. The median follow-up duration was 13.5 years (range, 3 to 31 y). Nearly half of the participants were lymphoma survivors. One hundred eleven (55.5%) survivors were high school graduates and 47 (23%) were university graduates. Unemployment rate was 36.8%. Public social insurance rate was 90.5%. Fifty-three (26.4%) survivors had independent habitation. Thirty percent of survivors were married and 7.5% had at least 1 child. Marriage rates were significantly higher in survivors who were older than 23 years, had a follow-up duration of >13 years, had a job, and lived independently (for each parameter P=0.001). University degree was significantly lower in survivors who were treated for central nervous system tumors. Our results have drawn a more marked picture with lower educational achievement and marital rates when compared with the results of large survivorship studies conducted in developed countries. However, they can be interpreted as intriguing when limited resources are taken into account.

[Regression and therapy-resistance of primary liver tumors and liver metastases after regional chemotherapy and local tumor ablation].

PubMed

Fischer, H-P

2005-05-01

High dosage regional chemotherapy, chemoembolization and other methods of regional treatment are commonly used to treat unresectable primary liver malignancies and liver metastases. In liver malignancies of childhood neoadjuvant chemotherapy is successfully combined with surgical treatment. Chemotherapy and local tumor ablation lead to characteristic histomorphologic changes: Complete destruction of the tumor tissue and its vascular bed is followed by encapsulated necroses. After selective eradication of the tumor cells under preservation of the fibrovasular bed the tumor is replaced by hypocellular edematous and fibrotic tissue. If completely damaged tumor tissue is absorbed quickly, the tumor area is replaced by regenerating liver tissue. Obliterating fibrohyalinosis of tumor vessels, and perivascular edema or necrosis indicate tissue damage along the vascular bed. Degenerative pleomorphism of tumor cells, steatosis, hydropic swelling and Malloryhyalin in HCC can represent cytologic findings of cytotoxic cellular damage. Macroscopic type of HCC influences significantly the response to treatment. Multinodular HCC often contain viable tumor nodules close to destroyed nodules after treatment. Encapsulated uninodular tumors undergo complete necrosis much easier. Large size and a tumor capsule limitate the effect of percutaneous injection of ethanol into HCC. In carcinomas with an infiltrating border, especially in metastases of adenocarcinomas and hepatic cholangiocarcinoma cytostatic treatment damages the tumor tissue mainly in the periphery. Nevertheless the infiltrating rim, portal veins, lymphatic spaces and bile ducts as well as the angle between liver capsule, tumor nodule and bordering parenchyma are the main refugees of viable tumor tissue even after high dosage regional chemotherapy. This local resistance is caused by special local conditions of vascularization and perfusion. These residues are the source of local tumor progression and distant metastases

Role of intraoperative ultrasound in achieving complete resection of intra-axial solid brain tumours.

PubMed

Mari, Abdul Razaque; Shah, Irfanullah; Imran, Muhammed; Ashraf, Junaid

2014-12-01

To determine the frequency of completeness of resection for intra-axial solid brain tumours with the help of intra-operative ultrasound to detect residual brain tumour. The cross-sectional study was conducted at the Department of Neurosurgery, Dow University of Health Sciences and Civil Hospital Karachi, from September 2009 to June 2010 and comprised patients with intra-axial solid brain lesion. During operation following standard craniotomy, multi-plane sonographic examination was performed using intra-operative ultrasound for tumour localisation and calculation of dimension, followed by tumour resection in the standard fashion. At the end of tumour resection ultrasound was again used for the detection of any residual tumour. Results of intra-operative ultrasound were compared with post-operative contrast magnetic resonance imaging. Of the 39 cases in which intra-operative ultrasound was performed, 32(82.1%) were males and 7(17.9%) were females, with an overall mean age of 42.6±19.7 years. Intra-operative ultrasonography was able to localise and delineate the tumour in all 39 (100%) cases. It showed no residual tumour in 36 (92.3%) cases, but in 3(7.7%) cases residual tumour was detected. Post-operative contrast enhancing magnetic resonance imaging showed no residual tumour in 35(89.7%) cases and in 4(10.3%) cases residual tumour was detected. The frequency of completely resected intra-axial solid brain tumour was 35(89.7%), while in 4(10.3%) cases incomplete resection was observed. The study concluded that intra-operative ultrasonography has an important role in achieving increased frequency of completely resected intra-axial solid brain tumours.

Bursts of Bipolar Microsecond Pulses Inhibit Tumor Growth

NASA Astrophysics Data System (ADS)

Sano, Michael B.; Arena, Christopher B.; Bittleman, Katelyn R.; Dewitt, Matthew R.; Cho, Hyung J.; Szot, Christopher S.; Saur, Dieter; Cissell, James M.; Robertson, John; Lee, Yong W.; Davalos, Rafael V.

2015-10-01

Irreversible electroporation (IRE) is an emerging focal therapy which is demonstrating utility in the treatment of unresectable tumors where thermal ablation techniques are contraindicated. IRE uses ultra-short duration, high-intensity monopolar pulsed electric fields to permanently disrupt cell membranes within a well-defined volume. Though preliminary clinical results for IRE are promising, implementing IRE can be challenging due to the heterogeneous nature of tumor tissue and the unintended induction of muscle contractions. High-frequency IRE (H-FIRE), a new treatment modality which replaces the monopolar IRE pulses with a burst of bipolar pulses, has the potential to resolve these clinical challenges. We explored the pulse-duration space between 250 ns and 100 μs and determined the lethal electric field intensity for specific H-FIRE protocols using a 3D tumor mimic. Murine tumors were exposed to 120 bursts, each energized for 100 μs, containing individual pulses 1, 2, or 5 μs in duration. Tumor growth was significantly inhibited and all protocols were able to achieve complete regressions. The H-FIRE protocol substantially reduces muscle contractions and the therapy can be delivered without the need for a neuromuscular blockade. This work shows the potential for H-FIRE to be used as a focal therapy and merits its investigation in larger pre-clinical models.

Clinical outcomes of gastrointestinal stromal tumor in southern Thailand

PubMed Central

Pornsuksiri, Kittima; Chewatanakornkul, Siripong; Kanngurn, Samornmas; Maneechay, Wanwisa; Chaiyapan, Walawee; Sangkhathat, Surasak

2012-01-01

AIM: To review a single institutional experience in clinical management of gastrointestinal stromal tumors (GIST) and analyze for factors determining treatment outcome. METHODS: Clinicopathological data of patients with a diagnosis of GIST who were treated at our institute during November 2004 to September 2009 were retrospectively reviewed. RESULTS: Ninety-nine cases were included in the analysis. Primary tumor sites were at the stomach in and small bowel in 44% and 33%, respectively. Thirty-one cases already had metastasis at presentation and the most common metastatic site was the liver. Sixty-four cases (65%) were in the high-risk category. Surgical treatment was performed in 77 cases (78%), 3 of whom received upfront targeted therapy. Complete resection was achieved in 56 cases (73% of operative cases) and of whom 27 developed local recurrence or distant metastasis at a median duration of 2 years. Imatinib was given as a primary therapy in unresectable cases (25 cases) and as an adjuvant in cases with residual tumor (21 cases). Targeted therapy gave partial response in 7 cases (15%), stable disease in 27 cases (57%) and progressive disease in 13 cases (28%). Four-year overall survival was 74% (95% CI: 61%-83%). Univariate survival analysis found that low-risk tumor, gastric site, complete resection and response to imatinib were associated with better survival. CONCLUSION: The overall outcomes of GIST can be predicted by risk-categorization. Surgery alone may not be a curative treatment for GIST. Response to targeted therapy is a crucial survival determinant in these patients. PMID:23444235

[A case of bilateral testicular tumors showing remarkable regression of huge metastatic tumors after VAB-6 combined chemotherapy].

PubMed

Nakashima, T; Nakajima, K; Yokoyama, O; Sugata, T; Tokunaga, S; Nitta, M; Hisazumi, H

1988-10-01

A case of bilateral testicular seminomas with abdominal huge metastatic tumors is presented. The patient is a 23-year-old male. An abdominal huge mass was found incidentally by a physician. CT scan and ultrasonography revealed the presence of the tumor in the left retroperitoneal space and biopsy specimen of the abdominal tumor was diagnosed as seminoma. On March 7, 1985, he was referred to our clinic. Bilateral testicular tumors were detected on palpation and ultrasonography. Bilateral orchiectomy was performed. Histological diagnosis was pure seminoma. After four sessions of VAB-6 combined chemotherapy, the abdominal tumor, 14.1 x 12.3 cm in size, decreased to 5.7 x 4.4 cm ( a regression rate of 85.5%). Retroperitoneal lymph-node dissection was undertaken, but the abdominal tumor could not be resected completely. Histological examination of the resected tumor revealed complete necrosis of the tumor tissue. After the operation, one session of the chemotherapy and irradiation were added. A total of 109 cases of bilateral testicular germ cell tumors in Japan was reviewed.

Bilateral Wilms' tumor with anaplasia: lessons from the National Wilms' Tumor Study.

PubMed

Hamilton, Thomas E; Green, Daniel M; Perlman, Elizabeth J; Argani, Pedram; Grundy, Paul; Ritchey, Michael L; Shamberger, Robert C

2006-10-01

The purpose of this study was to evaluate whether initial diagnostic technique influenced the ability to identify anaplastic histology, to determine the time interval to diagnosis of anaplasia, and to delineate the incidence of discordant pathology in bilateral Wilms' tumor. We hypothesized that delay in diagnosis of anaplasia could affect time to appropriate surgery and intensive multimodality therapy. One hundred eight-nine children were enrolled in the fourth National Wilms' Tumor Study with synchronous bilateral tumors, 27 of whom were eventually shown to have anaplastic histology. Initial diagnostic technique, time interval to diagnosis of anaplasia, and the incidence of discordant pathology were determined. Anaplasia was identified in 0 of 7 tumors by core needle biopsy, 3 of 9 tumors by open wedge biopsy, and in 7 of 9 cases by partial or complete nephrectomy. The mean duration of first chemotherapy regimen (DD or EE) was 20, 39, and 36 weeks, respectively, before anaplasia was identified at second surgery. Discordant pathology between bilateral tumors was identified on final tissue diagnosis in 20 patients. Only 4 patients had anaplastic tumors in both kidneys. Core needle biopsy did not identify anaplasia in 7 of 7 children. Open biopsy or partial/complete nephrectomy identified anaplasia at initial diagnostic procedure in 10 of 18 children. Twenty of 24 patients at final tissue diagnosis had discordant pathology between the 2 kidneys. Earlier interval incisional biopsy or resection may identify anaplastic histology and limit the duration of chemotherapy targeted to favorable histology for children with bilateral Wilms' tumor and anaplasia.

Endoscopic Approach to Remove Intra-extracranial Tumors in Various Skull Base Regions: 10-year Experience of a Single Center

PubMed Central

Zhang, Qiu-Hang; Wang, Zhen-Lin; Guo, Hong-Chuan; Kong, Feng; Yan, Bo; Li, Ming-Chu; Chen, Ge; Liang, Jian-Tao; Bao, Yu-Hai; Ling, Feng

2017-01-01

Background: Some problems have been found in the usually adopted combined approach for the removal of intra-extracranial tumors in skull base. Herein, we described a pure endoscopic transnasal or transoral approach (ETA) for the removal of intra-extracranial tumors in various skull base regions. Methods: Retrospectively, clinical data, major surgical complications, pre- and postoperative images, and follow-up information of a series of 85 patients with intra-extracranial tumors in various skull base regions who were treated by surgery via ETA in our skull base center during the past 10 years were reviewed and analyzed. Results: Gross total tumor removal was achieved in 80/85 cases (94.1%) in this study. All 37 cases with tumors in anterior skull base and all 14 cases with tumors in jugular foramen received total tumor removal. Thirteen and three cases with tumors in clivus received total and subtotal tumor removal, respectively. Total and subtotal tumor removal was performed for 16 cases and 2 cases in lateral skull base, respectively. The complications in this study included: cerebrospinal fluid leakage (n = 3), meningitis (n = 3), and new cranial nerve deficits (n = 3; recovered in 3 months after surgery). In the follow-up period of 40–151 months (median: 77 months), seven patients (8.8%) out of the 80 cases of total tumor removal experienced recurrence. Conclusions: Complete resection of intra-extracranial growing tumors in various skull base regions can be achieved via the pure ETA in one stage in selected cases. Surgical procedure for radical removal of tumors is feasible and safe. PMID:29237926

Intramedullary Solitary Fibrous Tumor--A Benign Form of Hemangiopericytoma? Case Report and Review of the Literature.

PubMed

Bruder, Markus; Tews, Dominique; Mittelbronn, Michel; Capper, David; Seifert, Volker; Marquardt, Gerhard

2015-07-01

Solitary fibrous tumors (SFTs) are benign tumors of the soft tissue occurring anywhere in the human body but arise predominantly in the visceral pleura. SFTs of the central nervous system are rare, especially when they occur within the spinal cord. We present a case of an 83-year-old female patient presenting with acute spastic paralysis of the lower extremities after a history of progressive weakness and incontinence. Magnetic resonance imaging (MRI) findings were typical for meningioma, but an intradural, mainly intramedullary tumor was found at the first operation. A second operation was performed under neurophysiological monitoring, and complete removal of the tumor was achieved. Neurological conditions improved after the procedure, but the patient remained paraparetic. Histological and immunohistochemical findings revealed an SFT. There is evidence that SFTs and hemangiopericytomas (HPCs) are not different entities but should be considered as different graduations of a common spectrum. The extent of resection is a prognostic factor for recurrence-free survival in SFT; therefore we recommend surgery with complete resection whenever possible depending on the results of mandatory intraoperative neurophysiological monitoring in these cases. Copyright © 2015 Elsevier Inc. All rights reserved.

Development of Advanced Technologies for Complete Genomic and Proteomic Characterization of Quantized Human Tumor Cells

DTIC Science & Technology

2014-07-01

establishment of Glioblastoma ( GBM ) cell lines from GBM patient’s tumor samples and quantized cell populations of each of the parental GBM cell lines, we... GBM patients are now well established and from the basis of the molecular characterization of the tumor development and signatures presented by these...analysis of these quantized cell sub populations and have begun to assemble the protein signatures of GBM tumors underpinned by the comprehensive

Multimodality Molecular Imaging-Guided Tumor Border Delineation and Photothermal Therapy Analysis Based on Graphene Oxide-Conjugated Gold Nanoparticles Chelated with Gd.

PubMed

Ma, Xibo; Jin, Yushen; Wang, Yi; Zhang, Shuai; Peng, Dong; Yang, Xin; Wei, Shoushui; Chai, Wei; Li, Xuejun; Tian, Jie

2018-01-01

Tumor cell complete extinction is a crucial measure to evaluate antitumor efficacy. The difficulties in defining tumor margins and finding satellite metastases are the reason for tumor recurrence. A synergistic method based on multimodality molecular imaging needs to be developed so as to achieve the complete extinction of the tumor cells. In this study, graphene oxide conjugated with gold nanostars and chelated with Gd through 1,4,7,10-tetraazacyclododecane-N,N',N,N'-tetraacetic acid (DOTA) (GO-AuNS-DOTA-Gd) were prepared to target HCC-LM3-fLuc cells and used for therapy. For subcutaneous tumor, multimodality molecular imaging including photoacoustic imaging (PAI) and magnetic resonance imaging (MRI) and the related processing techniques were used to monitor the pharmacokinetics process of GO-AuNS-DOTA-Gd in order to determine the optimal time for treatment. For orthotopic tumor, MRI was used to delineate the tumor location and margin in vivo before treatment. Then handheld photoacoustic imaging system was used to determine the tumor location during the surgery and guided the photothermal therapy. The experiment result based on orthotopic tumor demonstrated that this synergistic method could effectively reduce tumor residual and satellite metastases by 85.71% compared with the routine photothermal method without handheld PAI guidance. These results indicate that this multimodality molecular imaging-guided photothermal therapy method is promising with a good prospect in clinical application.

Intraoperative 3 tesla magnetic resonance imaging: our experience in tumors.

PubMed

García-Baizán, A; Tomás-Biosca, A; Bartolomé Leal, P; Domínguez, P D; García de Eulate Ruiz, R; Tejada, S; Zubieta, J L

To report our experience in the use of 3 tesla intraoperative magnetic resonance imaging (MRI) in neurosurgical procedures for tumors, and to evaluate the criteria for increasing the extension of resection. This retrospective study included all consecutive intraoperative MRI studies done for neuro-oncologic disease in the first 13 months after the implementation of the technique. We registered possible immediate complications, the presence of tumor remnants, and whether the results of the intraoperative MRI study changed the surgical management. We recorded the duration of surgery in all cases. The most common tumor was recurrent glioblastoma, followed by primary glioblastoma and metastases. Complete resection was achieved in 28%, and tumor remnants remained in 72%. Intraoperative MRI enabled neurosurgeons to improve the extent of the resection in 85% of cases. The mean duration of surgery was 390±122minutes. Intraoperative MRI using a strong magnetic field (3 teslas) is a valid new technique that enables precise study of the tumor resection to determine whether the resection can be extended without damaging eloquent zones. Although the use of MRI increases the duration of surgery, the time required decreases as the team becomes more familiar with the technique. Copyright © 2018 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Translational progress on tumor biomarkers

PubMed Central

Guo, Hongwei; Zhou, Xiaolin; Lu, Yi; Xie, Liye; Chen, Qian; Keller, Evan T; Liu, Qian; Zhou, Qinghua; Zhang, Jian

2015-01-01

There is an urgent need to apply basic research achievements to the clinic. In particular, mechanistic studies should be developed by bench researchers, depending upon clinical demands, in order to improve the survival and quality of life of cancer patients. To date, translational medicine has been addressed in cancer biology, particularly in the identification and characterization of novel tumor biomarkers. This review focuses on the recent achievements and clinical application prospects in tumor biomarkers based on translational medicine. PMID:26557902

Educational achievement in Swiss childhood cancer survivors compared with the general population.

PubMed

Kuehni, Claudia E; Strippoli, Marie-Pierre F; Rueegg, Corina S; Rebholz, Cornelia E; Bergstraesser, Eva; Grotzer, Michael; von der Weid, Nicolas X; Michel, Gisela

2012-03-01

The objective of this study was to describe educational achievements of childhood cancer survivors in Switzerland compared with the general population. In particular, the authors investigated educational problems during childhood, final educational achievement in adulthood, and its predictors. Childhood cancer survivors who were aged <16 years at diagnosis from 1976 to 2003 who had survived for ≥5 years and were currently ages 20 to 40 years received a postal questionnaire during 2007 to 2009. Controls were respondents of the Swiss Health Survey ages 20 to 40 years. Educational achievement included compulsory schooling, vocational training, upper secondary schooling, and university degree. The analysis was weighted to optimize comparability of the populations. The authors analyzed the association between demographic and clinical predictors and educational achievement using multivariable logistic regression. Subgroup analyses focused on survivors aged ≥27 years. One-third of survivors encountered educational problems during schooling (30% repeated 1 year, and 35% received supportive tutoring). In the total sample, more survivors than controls achieved compulsory schooling only (8.7% vs 5.2%) and fewer acquired a university degree (7.3% vs 11%), but more survivors than controls achieved an upper secondary education (36.1 vs 24.1%). In those aged ≥27 years, differences in compulsory schooling and university education largely disappeared. In survivors and controls, sex, nationality, language region, and migration background were strong predictors of achievement. Survivors of central nervous system tumors or those who had a relapse had poorer outcomes (P < .05). Childhood cancer survivors encountered problems during schooling and completed professional education with some delay. However, with the exception of patients who had central nervous system tumors and those who experienced a relapse, the final educational achievement in survivors of child cancer was

Vanishing tumor in pregnancy

PubMed Central

Vimal, M. V.; Budyal, Sweta; Kasliwal, Rajeev; Jagtap, Varsha S.; Lila, Anurag R.; Bandgar, Tushar; Menon, Padmavathy; Shah, Nalini S.

2012-01-01

A patient with microprolactinoma, who had two successful pregnancies, is described for management issues. First pregnancy was uneventful. During the second pregnancy, the tumor enlarged to macroprolactinoma with headache and blurring of vision which was managed successfully with bromocriptine. Post delivery, complete disappearance of the tumor was documented. PMID:23226664

Effects of tumor necrosis factor-related apoptosis-inducing ligand alone and in combination with chemotherapeutic agents on patients' colon tumors grown in SCID mice.

PubMed

Naka, Takuji; Sugamura, Kenji; Hylander, Bonnie L; Widmer, Michael B; Rustum, Youcef M; Repasky, Elizabeth A

2002-10-15

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to induce apoptosis in a variety of malignant cell lines, but it shows little or no toxicity in most normal cells. We examined the response of three human colon tumors to TRAIL alone and in combination with chemotherapy, using SCID mice engrafted with intact patient surgical specimens. These tumors, taken from fresh surgical specimens, contained the heterogeneous tumor cell population characteristic of patient tumors and showed differential sensitivity to TRAIL alone. We also investigated the effect of TRAIL in combination with chemotherapy, using one tumor that showed moderate sensitivity to TRAIL alone. Combining TRAIL with either 5-fluorouracil (5-FU) or CPT-11 (irinotecan hydrochloride) produced a greatly enhanced antitumor effect over that of either agent alone, with 50% of the animals achieving complete tumor regression with a combination of TRAIL and CPT-11. By histological analysis, tumors treated with TRAIL plus either 5-FU or CPT-11 were seen to consist mainly of connective tissue and fibrotic areas with only a few scattered tumor cells encapsulated in the connective tissue. Several markers were assessed to investigate the basis for the observed therapeutic effect, and significant induction of apoptosis was observed in tumors treated with curative combinations. Cytoplasmic and cell surface expression of the TRAIL receptors DR4 and DR5 was observed in this patient's tumor by immunohistochemistry. Tumors treated with CPT-11 showed increased membrane expression of DR5, suggesting that CPT-11 may increase sensitivity to TRAIL by up-regulation of DR5. These results obtained in a relevant preclinical model support the idea that the use of TRAIL in combination with either 5-FU or CPT-11 may be an effective strategy in controlling human colon cancer.

Hemangiopericytoma/solitary fibrous tumor of pectoralis major muscle mimicking a breast mass

PubMed Central

Dragoumis, Dimitrios; Desiris, Klearchos; Kyropoulou, Aikaterini; Malandri, Maria; Assimaki, Anthoula; Tsiftsoglou, Aris

2013-01-01

INTRODUCTION Hemangiopericytoma (HPC)/solitary fibrous tumor (SFT) is a very uncommon tumor of uncertain malignant behavior. In 1942, Stout and Murray first characterized these neoplasms as “vascular tumors arising from Zimmerman's pericytes” and till now hemangiopericytomas and solitary fibrous tumors of the soft tissues are regarded as features of the same entity in the soft tissue fascicle. PRESENTATION OF CASE We present a case of hemangiopericytoma/solitary fibrous tumor of the pectoralis major muscle in a 33-year-old female. She first noticed a painless mass in her right breast. Ultrasound of the breast revealed a large heterogeneously hypoechoic lesion within the pectoralis major muscle. Fine needle aspiration of the tumor did not produce any meaningful result. The lesion was completely removed by surgical resection. Histologically, the tumor had staghorn-like vasculature and immunohistochemistry for CD34 was positive, whereas desmin, smooth-muscle actin, S-100 protein, cytokeratins (AE1/AE3) and epithelial membrane antigen (EMA) were all negative. A diagnosis of hemangiopericytoma/solitary fibrous tumor was rendered. DISCUSSION Tumors comprising the HPC/SFT spectrum represent a small subset of soft tissue sarcomas and are found virtually at any site in the body. Wide surgical resection can achieve favorable long-term survival. CONCLUSION Due to the rarity and unpredictable biological potential of these tumors, long-term follow-up is mandatory even after radical resection, because recurrence or development of metastasis may be delayed many years. PMID:23416503

An automatic brain tumor segmentation tool.

PubMed

Diaz, Idanis; Boulanger, Pierre; Greiner, Russell; Hoehn, Bret; Rowe, Lindsay; Murtha, Albert

2013-01-01

This paper introduces an automatic brain tumor segmentation method (ABTS) for segmenting multiple components of brain tumor using four magnetic resonance image modalities. ABTS's four stages involve automatic histogram multi-thresholding and morphological operations including geodesic dilation. Our empirical results, on 16 real tumors, show that ABTS works very effectively, achieving a Dice accuracy compared to expert segmentation of 81% in segmenting edema and 85% in segmenting gross tumor volume (GTV).

Complete Resolution of a Recurrent Canine Anal Sac Squamous Cell Carcinoma with Palliative Radiotherapy and Carboplatin Chemotherapy

PubMed Central

Giuliano, Antonio; Dobson, Jane; Mason, Sarah

2017-01-01

Anal sac squamous cell carcinoma (SCC) is a rare tumor in dogs. Only eight cases have been described in the literature, and previous reports of treatment only describe surgery or palliative treatment with non-steroidal anti-inflammatory drugs. We report a case of a 12-year-old female neutered Labrador with locally advanced anal sac SCC. The dog was treated with four cycles of carboplatin 300 mg/m2 and four weekly fractions of 8.5 Gy radiation. The dog achieved a complete response, and one year later the dog is still alive and well with no evidence of tumor recurrence. Radiotherapy in combination with carboplatin chemotherapy was effective in the long-term control of this rare disease. PMID:29056703

Adult Wilms tumor with inferior vena cava thrombus and distal deep vein thrombosis - a case report and literature review.

PubMed

Ratajczyk, Krzysztof; Czekaj, Adrian; Rogala, Joanna; Kowal, Pawel

2018-02-23

Adult Wilms tumor (WT, nephroblastoma) is a rare, but well-described renal neoplasm. Although inferior vena cava tumor thrombosis is present in up to 10% of Wilms tumors in childhood, only few cases of this clinical manifestation in adults have been reported. To the best of our knowledge, this is the first case of adult WT infiltrating into inferior vena cava (IVC) with concomitant distal deep vein thrombosis. A 28-year-old male patient with gross hematuria and right flank pain was diagnosed with right kidney tumor penetrating to IVC. Preoperatively, acute distal thrombosis in inferior vena cava and lower extremities veins occurred. Right radical nephrectomy with tumor thrombectomy via cavotomy was performed. In order to prevent pulmonary embolism, IVC was ligated below left renal vein level. Histopathological examination revealed a triphasic nephroblastoma without anaplastic features. Postoperatively, patient was diagnosed with metastatic liver disease, which was treated with two lines of chemotherapy followed by radiotherapy with achievement of complete response. Adult WT occurs usually in young patients, under 40 years of age. Neoadjuvant chemotherapy proved to be effective in children, resulting with tumor shrinkage and venous tumor thrombus regression. Therefore, percutaneous biopsy should be always considered in young patients presenting with renal tumor invading venous system. IVC ligation is a safe treatment option in the event of complete inferior vena cava occlusion due to distal thrombosis concomitant to tumor thrombus, provided collateral venous pathways are well-developed.

Cryoablation of Bone Metastases from Renal Cell Carcinoma for Local Tumor Control.

PubMed

Gardner, Carly S; Ensor, Joe E; Ahrar, Kamran; Huang, Steven Y; Sabir, Sharjeel H; Tannir, Nizar M; Lewis, Valerae O; Tam, Alda L

2017-11-15

Patients with bone metastases from renal cell carcinoma often are not surgical candidates and have a poor prognosis. There are limited data on the use of cryoablation as a locoregional therapy for bone metastases. Our objective was to assess the local tumor-control rate following cryoablation of bone metastases in the setting of renal cell carcinoma. We retrospectively reviewed the medical records of patients with metastatic renal cell carcinoma who underwent cryoablation for bone metastases between 2007 and 2014. We excluded patients if the intent of treatment was for pain palliation only, if cryoablation was performed without an attempt for complete tumor control (cytoreduction), or if the patient had no further follow-up beyond the cryoablation procedure. We recorded patient demographics, procedural variables, and complications. Cross-sectional imaging and clinical follow-up were reviewed to determine disease recurrence. The median overall survival and recurrence-free survival were determined using the Kaplan-Meier method. Forty patients (30 male and 10 female) with 50 bone metastases were included for analysis. The mean patient age was 62 years (range, 47 to 82 years). The median follow-up was 35 months (95% confidence interval [CI], 22.7 to 74.4 months). Twenty-five (62.5%) of the 40 patients had oligometastatic disease, defined as ≤5 metastases at the time of ablation. The mean tumor size was 3.4 ± 1.5 cm. Metastases in the pelvic region represented 68% of the treated tumors (34 of 50). The overall local tumor-control rate per lesion was 82% (41 of 50). Patients with oligometastatic disease experienced better local tumor control (96% [24 of 25]) compared with patients who had >5 metastases (53.3% [8 of 15]) (p = 0.001). The local tumor-control rate was better for lesions for which a larger mean difference between maximum ice-ball diameter and maximum lesion diameter was achieved (2.2 ± 0.9 cm for those without recurrence versus 1.35 ± 1.2 cm for those

Endoscopic full-thickness resection of gastric subepithelial tumors: a single-center series.

PubMed

Schmidt, Arthur; Bauder, Markus; Riecken, Bettina; von Renteln, Daniel; Muehleisen, Helmut; Caca, Karel

2015-02-01

Endoscopic full-thickness resection of gastric subepithelial tumors with a full-thickness suturing device has been described as feasible in two small case series. The aim of this study was to evaluate the efficacy, safety, and clinical outcome of this resection technique. After 31 patients underwent endoscopic full-thickness resection, the data were analyzed retrospectively. Before snare resection, 1 to 3 full-thickness sutures were placed underneath each tumor with a device originally designed for endoscopic anti-reflux therapy. All tumors were resected successfully. Bleeding occurred in 12 patients (38.7 %); endoscopic hemostasis could be achieved in all cases. Perforation occurred in 3 patients (9.6 %), and all perforations could be managed endoscopically. Complete resection was histologically confirmed in 28 of 31 patients (90.3 %). Mean follow-up was 213 days (range, 1 - 1737), and no tumor recurrences were observed. Endoscopic full-thickness resection of gastric subepithelial tumors with the suturing technique described above is feasible and effective. After the resection of gastrointestinal stromal tumors (GISTs), we did not observe any recurrences during follow-up, indicating that endoscopic full-thickness resection may be an alternative to surgical resection for selected patients. © Georg Thieme Verlag KG Stuttgart · New York.

Endoscopic ultrasound-guided radiofrequency ablation for management of benign solid pancreatic tumors.

PubMed

Choi, Jun-Ho; Seo, Dong-Wan; Song, Tae Jun; Park, Do Hyun; Lee, Sang Soo; Lee, Sung Koo; Kim, Myung-Hwan

2018-05-04

 Radiofrequency ablation (RFA) has been increasingly employed in experimental and clinical settings for the management of pancreatic lesions. This study aimed to assess the safety and efficacy of endoscopic ultrasound (EUS)-guided RFA for benign solid pancreatic tumors.  In a single-center, prospective study, 10 patients with benign solid pancreatic tumors underwent EUS-RFA. After the RFA electrode had been inserted into the pancreatic mass, the radiofrequency generator was activated to deliver 50 W of ablation power.  Among the 10 patients, 16 sessions of EUS-RFA were successfully performed. Diagnoses included nonfunctioning neuroendocrine tumor (n = 7), solid pseudopapillary neoplasm (n = 2), and insulinoma (n = 1); the median largest diameter of the tumors was 20 mm (range 8 - 28 mm). During follow-up (median 13 months), radiologic complete response was achieved in seven patients. Two adverse events (12.4 %; 1 moderate and 1 mild) occurred.  EUS-RFA may be a safe and potentially effective treatment option in selected patients with benign solid pancreatic tumors. Multiple sessions may be required if there is a remnant tumor, and adverse events must be carefully monitored. © Georg Thieme Verlag KG Stuttgart · New York.

Radiosurgery of Glomus Jugulare Tumors: A Meta-Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guss, Zachary D.; Batra, Sachin; Limb, Charles J.

2011-11-15

Purpose: During the past two decades, radiosurgery has arisen as a promising approach to the management of glomus jugulare. In the present study, we report on a systematic review and meta-analysis of the available published data on the radiosurgical management of glomus jugulare tumors. Methods and Materials: To identify eligible studies, systematic searches of all glomus jugulare tumors treated with radiosurgery were conducted in major scientific publication databases. The data search yielded 19 studies, which were included in the meta-analysis. The data from 335 glomus jugulare patients were extracted. The fixed effects pooled proportions were calculated from the data whenmore » Cochrane's statistic was statistically insignificant and the inconsistency among studies was <25%. Bias was assessed using the Egger funnel plot test. Results: Across all studies, 97% of patients achieved tumor control, and 95% of patients achieved clinical control. Eight studies reported a mean or median follow-up time of >36 months. In these studies, 95% of patients achieved clinical control and 96% achieved tumor control. The gamma knife, linear accelerator, and CyberKnife technologies all exhibited high rates of tumor and clinical control. Conclusions: The present study reports the results of a meta-analysis for the radiosurgical management of glomus jugulare. Because of its high effectiveness, we suggest considering radiosurgery for the primary management of glomus jugulare tumors.« less

Reirradiation of tumors in cats and dogs.

PubMed

Turrel, J M; Théon, A P

1988-08-15

Fifty-one cats and dogs with tumor recurrence after irradiation were treated with a second course of radiotherapy, using either teletherapy or brachytherapy. Eighty-six percent of the tumors had partial or complete response at 2 months after reirradiation. Tumor response was significantly (P = 0.041) affected when the interval between the 2 courses of irradiation was greater than 5 months. The estimated local tumor control rate was 38% at 1 year after reirradiation. Of all the factors examined, complete response at 2 months, reirradiation field size less than or equal to 10 cm2, and reirradiation dose greater than 40 gray emerged as predictors of local tumor control. The estimated overall survival rate was 47% at 2 years. Tumor location had a significant (P = 0.001) influence on overall survival; animals with cutaneous tumors had the longest survival times, and those with oral tumors had the shortest survival times. The other significant (P = 0.001) factor affecting overall survival time was the field size of the reirradiated site. Estimated survival time after reirradiation was 41% at 1 year. Favorable prognostic indicators were complete response at 2 months and location of tumor; animals with skin tumors had a favorable prognosis. The acute effects of reirradiation on normal tissues were acceptable, but 12% of the animals had severe delayed complications. Significant risk of complications after reirradiation was associated with squamous cell carcinoma (P = 0.015) and reirradiated field size greater than 30 cm2 (P = 0.056). When the interval between irradiations was greater than 5 months, the risk of complications was significantly (P = 0.022) lower.(ABSTRACT TRUNCATED AT 250 WORDS)

Race is associated with completion of neoadjuvant chemotherapy for breast cancer.

PubMed

Knisely, Anne T; Michaels, Alex D; Mehaffey, J Hunter; Hassinger, Taryn E; Krebs, Elizabeth D; Brenin, David R; Schroen, Anneke T; Showalter, Shayna L

2018-05-03

Completion of prescribed neoadjuvant chemotherapy for breast cancer is paramount to patients obtaining full benefit from the treatment; however, factors affecting neoadjuvant chemotherapy completion are not known. We hypothesized that race is a predictor of completion of neoadjuvant chemotherapy in patients with breast cancer. All patients with breast cancer treated with neoadjuvant chemotherapy 2009-2016 at a single institution were stratified by completion of neoadjuvant chemotherapy and by race. Univariate analysis and multivariable logistic regression were used to identify patient and tumor characteristics that affected the rate of neoadjuvant chemotherapy completion. A total of 92 (74%) of 124 patients completed their prescribed neoadjuvant chemotherapy. On univariate analysis, white patients were more likely to complete neoadjuvant chemotherapy than non-white patients (76% vs 50%, P = .006). Non-white patients were more likely to have government insurance and larger prechemotherapy tumors (both, P < .05), but these factors were not associated with rates of neoadjuvant chemotherapy completion. After controlling for age, insurance status, tumor size, and estrogen receptor status, whites remained associated with completion of neoadjuvant chemotherapy (OR 3.65, P = .014). At our institution, white patients with breast cancer were more likely than non-white patients to complete neoadjuvant chemotherapy. Further investigation into the underlying factors impacting this disparity is needed. Copyright © 2018 Elsevier Inc. All rights reserved.

Non-exposed endoscopic wall-inversion surgery for gastrointestinal stromal tumor

PubMed Central

Mitsui, Takashi; Aikou, Susumu; Niimi, Keiko; Fujishiro, Mitsuhiro; Seto, Yasuyuki

2018-01-01

Laparoscopic and endoscopic cooperative surgery (LECS) is an accepted method of laparoscopic wedge resection, which is minimally invasive, for gastrointestinal stromal tumors (GISTs). We established a type of LECS achieving a full-thickness resection, non-exposed endoscopic wall-inversion surgery (NEWS), in an effort to prevent exposure of the peritoneal cavity to gastric intraluminal contents. We employed this surgical technique in 28 gastric GIST patients. We failed to complete NEWS in the initial two patients and in one patient with a large tumor (40 mm × 35 mm), but otherwise carried out the procedure successfully. Although a learning effect is speculated to occur, based on a decreasing trend in the operation time, the median operation time was 184 minutes showing that NEWS is still a time-consuming method. No significant differences were recognized in tumor size or location, except near the esophagogastric junction (EGJ), nor in the cross-sectional circumference. NEWS is feasible and appears to be a good option, especially for small GISTs with mucosal ulceration rendering full-thickness enucleation by opening of the gastric wall unfeasible. PMID:29682624

Tumor cell apoptosis induces tumor-specific immunity in a CC chemokine receptor 1- and 5-dependent manner in mice.

PubMed

Iida, Noriho; Nakamoto, Yasunari; Baba, Tomohisa; Kakinoki, Kaheita; Li, Ying-Yi; Wu, Yu; Matsushima, Kouji; Kaneko, Shuichi; Mukaida, Naofumi

2008-10-01

The first step in the generation of tumor immunity is the migration of dendritic cells (DCs) to the apoptotic tumor, which is presumed to be mediated by various chemokines. To clarify the roles of chemokines, we induced apoptosis using suicide gene therapy and investigated the immune responses following tumor apoptosis. We injected mice with a murine hepatoma cell line, BNL 1ME A.7R.1 (BNL), transfected with HSV-thymidine kinase (tk) gene and then treated the animals with ganciclovir (GCV). GCV treatment induced massive tumor cell apoptosis accompanied with intratumoral DC infiltration. Tumor-infiltrating DCs expressed chemokine receptors CCR1 and CCR5, and T cells and macrophages expressed CCL3, a ligand for CCR1 and CCR5. Moreover, tumor apoptosis increased the numbers of DCs migrating into the draining lymph nodes and eventually generated a specific cytotoxic cell population against BNL cells. Although GCV completely eradicated HSV-tk-transfected BNL cells in CCR1-, CCR5-, or CCL3-deficient mice, intratumoral and intranodal DC infiltration and the subsequent cytotoxicity generation were attenuated in these mice. When parental cells were injected again after complete eradication of primary tumors by GCV treatment, the wild-type mice completely rejected the rechallenged cells, but the deficient mice exhibited impairment in rejection. Thus, we provide definitive evidence indicating that CCR1 and CCR5 and their ligand CCL3 play a crucial role in the regulation of intratumoral DC accumulation and the subsequent establishment of tumor immunity following induction of tumor apoptosis by suicide genes.

Tumor necrosis factor-alpha induced enhancement of cryosurgery

NASA Astrophysics Data System (ADS)

Goel, Raghav; Paciotti, Guilio F.; Bischof, John C.

2008-02-01

Local recurrence of cancer after cryosurgery is related to the inability to monitor and predict destruction of cancer (temperatures > -40°C) within an iceball. We previously reported that a cytokine adjuvant TNF-α could be used to achieve complete cancer destruction at the periphery of an iceball (0 to -40°C). This study is a further development of that work in which cryosurgery was performed using cryoprobes operating at temperatures > -40°C. LNCaP Pro 5 tumor grown in a dorsal skin fold chamber (DSFC) was frozen at -6°C after TNF-α incubation for 4 or 24 hours. Tumors grown in the hind limb were frozen with a probe tip temperature of -40°C, 4 or 24 hours after systemic injection with TNF-α. Both cryosurgery alone or TNF-α treatment alone caused only a minimal damage to the tumor tissue at the conditions used in the study. The combination of TNF-α and cryosurgery produced a significant damage to the tumor tissue in both the DSFC and the hind limb model system. This augmentation in cryoinjury was found to be time-dependent with 4-hour time period between the two treatments being more effective than 24-hour. These results suggests the possibility of cryotreatment at temperatures > -40°C with the administration of TNF-α.

Hypoxia-activated cytotoxic agent tirapazamine enhances hepatic artery ligation-induced killing of liver tumor in HBx transgenic mice

PubMed Central

Lin, Wei-Hsiang; Yeh, Shiou-Hwei; Yeh, Kun-Huei; Chen, Kai-Wei; Cheng, Ya-Wen; Su, Tung-Hung; Jao, Ping; Ni, Lin-Chun; Chen, Pei-Jer; Chen, Ding-Shinn

2016-01-01

Transarterial chemoembolization (TACE) is the main treatment for intermediate stage hepatocellular carcinoma (HCC) with Barcelona Clinic Liver Cancer classification because of its exclusive arterial blood supply. Although TACE achieves substantial necrosis of the tumor, complete tumor necrosis is uncommon, and the residual tumor generally rapidly recurs. We combined tirapazamine (TPZ), a hypoxia-activated cytotoxic agent, with hepatic artery ligation (HAL), which recapitulates transarterial embolization in mouse models, to enhance the efficacy of TACE. The effectiveness of this combination treatment was examined in HCC that spontaneously developed in hepatitis B virus X protein (HBx) transgenic mice. We proved that the tumor blood flow in this model was exclusively supplied by the hepatic artery, in contrast to conventional orthotopic HCC xenografts that receive both arterial and venous blood supplies. At levels below the threshold oxygen levels created by HAL, TPZ was activated and killed the hypoxic cells, but spared the normoxic cells. This combination treatment clearly limited the toxicity of TPZ to HCC, which caused the rapid and near-complete necrosis of HCC. In conclusion, the combination of TPZ and HAL showed a synergistic tumor killing activity that was specific for HCC in HBx transgenic mice. This preclinical study forms the basis for the ongoing clinical program for the TPZ-TACE regimen in HCC treatment. PMID:27702890

The treatment of tumors by the induction of anemia and irradiation in hyperbaric oxygen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sealy, R.; Jacobs, P.; Wood, L.

1989-08-01

Because increased effects have been achieved when murine tumors are irradiated after a period of hypoxia and because of anecdotal clinical experiences of an improved result after irradiation of previously anemic patients in hyperbaric oxygen, the relationship between irradiation and increased survival was investigated in seventy-two patients with advanced head and neck or cervical cancer. Anemia was achieved by means of a two-stage isovolemic venesection maintained for seventy-two hours, hemoglobin was returned to a normal level, and treatment in hyperbaric oxygen was started. Marked tumor shrinkage after the induction of anemia and before radiotherapy was seen and was probably disease,more » site, and hemoglobin level related. As a result, a possible new approach to cancer therapy is suggested. After completion of therapy, the 1-year disease-free survival for patients with head and neck and cervical cancer was not improved, but the 21-month survival for cervical cancer was improved. Further studies are strongly urged.« less

Complete remission of a case of hepatocellular carcinoma with tumor invasion in inferior vena cava and with pulmonary metastasis successfully treated with repeated arterial infusion chemotherapy.

PubMed

Kogure, Takayuki; Iwasaki, Takao; Ueno, Yoshiyuki; Kanno, Noriatsu; Fukushima, Koji; Yamagiwa, Yoko; Nagasaki, Futoshi; Kakazu, Eiji; Matsuda, Yasunori; Kido, Osamu; Nakagome, Yu; Ninomiya, Masashi; Shimosegawa, Tooru

2007-01-01

We report the case of a patient having hepatocellular carcinoma with tumor invasion to the inferior vena cava and with multiple pulmonary metastases who was treated with repeated one-shot administration of epirubicin, cisplatin, and mitomycin C by hepatic artery and bronchial artery, which led to complete remission. A 72-year-old woman was diagnosed with infiltrative hepatocellular carcinoma with Vv3, multiple intrahepatic metastases, and multiple pulmonary metastases associated with compensated liver cirrhosis. One-shot infusion of epirubicin, cisplatin, and mitomycin C was performed through proper hepatic artery and bronchial artery for twice at eight weeks of intervals. Pulmonary metastases disappeared and intrahepatic lesions indicated marked shrinkage leaving a scar-like lesion with decreases in tumor markers. After six months and 20 months, tumor markers indicated increasing tendency but no evident recurrence was found by computed tomography or hepatic arteriography. One-shot infusion of the same regimens through proper hepatic artery was performed and tumor markers decreased to normal levels. After 14 months of the last therapy, no evidence of recurrence has been found on image analysis or in tumor markers. This arterial infusion therapy is well tolerated for the patients with compensated liver cirrhosis and might be promising for the effective treatment of advanced hepatocellular carcinoma with pulmonary metastases.

Endoscopic-modified medial maxillectomy and its limitation for a solitary fibrous tumor of the lacrimal sac and nasolacrimal duct.

PubMed

Moriyama, Munehito; Kodama, Satoru; Hirano, Takashi; Suzuki, Masashi

2017-06-01

Solitary fibrous tumor (SFT) is an uncommon neoplasm that usually arises from the pleura. Recently, SFTs have been reported in the head and neck region located in subsites such as the orbit. SFTs of the lacrimal sac are extremely rare, with only six cases reported in the English literature. We describe a SFT arising from the right lacrimal sac and extending along the nasolacrimal duct into the nasal cavity. Although, the tumor could not be removed by endoscopic-modified medial maxillectomy (EMMM) alone, combined approach with EMMM and a small external incision achieved the complete removal of the tumor. The patient has remained disease-free 24 months after surgery. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Minimally invasive resection of large dumbbell tumors of the lumbar spine: Advantages and pitfalls.

PubMed

Zairi, Fahed; Troux, Camille; Sunna, Tarek; Karnoub, Mélodie-Anne; Boubez, Ghassan; Shedid, Daniel

2018-05-01

The surgical management of dumbbell tumors of the lumbar spine remains controversial, because of their large volume and complex location, involving both the spinal canal and the retro peritoneum. While sporadically reported, our study aims to confirm the value of minimally invasive posterior access for the complete resection of large lumbar dumbbell tumors. In this prospective study, we included all consecutive patients who underwent the resection of a voluminous dumbbell tumor at the lumbar spine through a minimally invasive approach, between March 2015 and August 2017. There were 4 men and 4 women, with a mean age at diagnosis of 40.6 years (range 29-58 years). The resection was performed through a trans muscular tubular retractor by the same surgical team. Operative parameters and initial postoperative course were systematically reported. Clinical and radiological monitoring was scheduled at 3 months, 1 year and 2 years. The mean operative time was 144 min (range 58-300 minutes) and the mean estimated blood loss was 250 ml (range 100-500 ml). Gross total resection was achieved in all patients. No major complication was reported. The mean length of hospital stay was 3.1 days (range 2 to 6 days). Histological analysis confirmed the diagnosis of grade 1 schwannoma in all patients. The mean follow up period was 14.9 months (range 6 to 26 months), and 5 patients completed at least 1-year follow-up. At 6 months the Macnab was excellent in 6 patients, good in one patient and fair in one patient because of residual neuropathic pain requiring the maintenance of a long-term treatment. No tumor recurrence was noted to date. Lumbar dumbbell tumors can be safely and completely resected using a single-stage minimally invasive procedure, in a trained team. Copyright © 2018 Elsevier B.V. All rights reserved.

Tumor Expression of CD200 Inhibits IL-10 Production by Tumor-Associated Myeloid Cells and Prevents Tumor Immune Evasion of CTL Therapy

PubMed Central

Wang, Lixin; Liu, Jin-Qing; Talebian, Fatemeh; El-Omrani, Hani Y.; Khattabi, Mazin; Yu, Li; Bai, Xue-Feng

2010-01-01

CD200 is a cell-surface glycoprotein that functions through interaction with the CD200 receptor (CD200R) on myeloid lineage cells to regulate myeloid cell functions. Expression of CD200 has been implicated in multiple types of human cancer, however the impact of tumor expression of CD200 on tumor immunity remains poorly understood. To evaluate this issue, we generated CD200-positive mouse plasmacytoma J558 and mastocytoma P815 cells. We found that established CD200-positive tumors were often completely rejected by adoptively transferred CTL without tumor recurrence; in contrast, CD200-negative tumors were initially rejected by adoptively transferred CTL but the majority of tumors recurred. Tumor expression of CD200 significantly inhibited suppressive activity and IL-10 production by tumor-associated myeloid cells (TAMC), and as a result, more CTL accumulated in the tumor and exhibited a greater capacity to produce IFN-γ in CD200-positive tumors than in CD200-negative tumors. Neutralization of IL-10 significantly inhibited the suppressor activity of TAMC, and IL-10-deficiency allowed TAMC to kill cancer cells and their antigenic variants, which prevented tumor recurrence during CTL therapy. Thus, tumor expression of CD200 prevents tumor recurrence via inhibiting IL-10 production by TAMC. PMID:20662098

Oncologic results of laparoscopic liver resection for malignant liver tumors.

PubMed

Akyuz, Muhammet; Yazici, Pinar; Yigitbas, Hakan; Dural, Cem; Okoh, Alexis; Aliyev, Shamil; Aucejo, Federico; Quintini, Cristiano; Fung, John; Berber, Eren

2016-02-01

There are scant data regarding oncologic outcomes of laparoscopic liver resection (LLR). The aim of this study is to analyze the oncologic outcomes of LLR for malignant liver tumors (MLT). This was a prospective IRB-approved study of 123 patients with MLT undergoing LLR. Kaplan-Meier disease-free (DFS) and overall survival (OS) was calculated. Tumor type was colorectal in 61%, hepatocellular cancer in 21%, neuroendocrine in 5% and others in 13%. Mean tumor size was 3.2 ± 1.9 cm and number of tumors 1.6 ± 1.2. A wedge resection or segmentectomy was performed in 63.4%, bisegmentectomy in 24.4%, and hemihepatectomy in 12.2%. Procedures were totally laparoscopic in 67% and hand-assisted in 33%. Operative time was 235.2 ± 94.3 min, and conversion rate 7.3%. An R0 resection was achieved in 90% of patients and 94% of tumors. Median hospital stay was 3 days. Morbidity was 22% and mortality 0.8%. For patients with colorectal liver metastasis, DFS and OS at 2 years was 47% and 88%, respectively. This study shows that LLR is a safe and efficacious treatment for selected patients with MLT. Complete resection and margin recurrence rate are comparable to open series in the literature. © 2015 Wiley Periodicals, Inc.

Preclinical validation of the utility of BLZ-100 in providing fluorescence contrast for imaging canine spontaneous solid tumors

PubMed Central

Fidel, Janean; Kennedy, Katie C.; Dernell, William S.; Hansen, Stacey; Wiss, Valorie; Stroud, Mark R.; Molho, Joshua I.; Knoblaugh, Sue E.; Meganck, Jeffrey; Olson, James M.; Rice, Brad; Parrish-Novak, Julia

2015-01-01

There is a need in surgical oncology for contrast agents that can enable real-time intraoperative visualization of solid tumors that can enable complete resections while sparing normal surrounding tissues. The Tumor Paint™ agent BLZ-100 is a peptide-fluorophore conjugate that can specifically bind solid tumors and fluoresce in the near-infrared range, minimizing light scatter and signal attenuation. In this study, we provide a preclinical proof of concept for use of this imaging contrast agent as administered before surgery to dogs with a variety of naturally occurring spontaneous tumors. Imaging was performed on excised tissues as well as intraoperatively in a subset of cases. Actionable contrast was achieved between tumor tissue and surrounding normal tissues in adenocarcinomas, squamous cell carcinomas, mast cell tumors and soft tissue sarcomas. Subcutaneous soft tissue sarcomas were labeled with the highest fluorescence intensity and greatest tumor-to-background signal ratio. Our results establish a foundation that rationalizes clinical studies in humans with soft tissue sarcoma, an indication with a notably high unmet need. PMID:26471914

Intraperitoneal Administration of a Tumor-Associated Antigen SART3, CD40L, and GM-CSF Gene-Loaded Polyplex Micelle Elicits a Vaccine Effect in Mouse Tumor Models

PubMed Central

Furugaki, Kouichi; Cui, Lin; Kunisawa, Yumi; Osada, Kensuke; Shinkai, Kentaro; Tanaka, Masao; Kataoka, Kazunori; Nakano, Kenji

2014-01-01

Polyplex micelles have demonstrated biocompatibility and achieve efficient gene transfection in vivo. Here, we investigated a polyplex micelle encapsulating genes encoding the tumor-associated antigen squamous cell carcinoma antigen recognized by T cells-3 (SART3), adjuvant CD40L, and granulocyte macrophage colony-stimulating factor (GM-CSF) as a DNA vaccine platform in mouse tumor models with different types of major histocompatibility antigen complex (MHC). Intraperitoneally administrated polyplex micelles were predominantly found in the lymph nodes, spleen, and liver. Compared with mock controls, the triple gene vaccine significantly prolonged the survival of mice harboring peritoneal dissemination of CT26 colorectal cancer cells, of which long-term surviving mice showed complete rejection when re-challenged with CT26 tumors. Moreover, the DNA vaccine inhibited the growth and metastasis of subcutaneous CT26 and Lewis lung tumors in BALB/c and C57BL/6 mice, respectively, which represent different MHC haplotypes. The DNA vaccine highly stimulated both cytotoxic T lymphocyte and natural killer cell activities, and increased the infiltration of CD11c+ DCs and CD4+/CD8a+ T cells into tumors. Depletion of CD4+ or CD8a+ T cells by neutralizing antibodies deteriorated the anti-tumor efficacy of the DNA vaccine. In conclusion, a SART3/CD40L+GM-CSF gene-loaded polyplex micelle can be applied as a novel vaccine platform to elicit tumor rejection immunity regardless of the recipient MHC haplotype. PMID:25013909

Improved brain tumor segmentation by utilizing tumor growth model in longitudinal brain MRI

NASA Astrophysics Data System (ADS)

Pei, Linmin; Reza, Syed M. S.; Li, Wei; Davatzikos, Christos; Iftekharuddin, Khan M.

2017-03-01

In this work, we propose a novel method to improve texture based tumor segmentation by fusing cell density patterns that are generated from tumor growth modeling. To model tumor growth, we solve the reaction-diffusion equation by using Lattice-Boltzmann method (LBM). Computational tumor growth modeling obtains the cell density distribution that potentially indicates the predicted tissue locations in the brain over time. The density patterns is then considered as novel features along with other texture (such as fractal, and multifractal Brownian motion (mBm)), and intensity features in MRI for improved brain tumor segmentation. We evaluate the proposed method with about one hundred longitudinal MRI scans from five patients obtained from public BRATS 2015 data set, validated by the ground truth. The result shows significant improvement of complete tumor segmentation using ANOVA analysis for five patients in longitudinal MR images.

Improved brain tumor segmentation by utilizing tumor growth model in longitudinal brain MRI.

PubMed

Pei, Linmin; Reza, Syed M S; Li, Wei; Davatzikos, Christos; Iftekharuddin, Khan M

2017-02-11

In this work, we propose a novel method to improve texture based tumor segmentation by fusing cell density patterns that are generated from tumor growth modeling. In order to model tumor growth, we solve the reaction-diffusion equation by using Lattice-Boltzmann method (LBM). Computational tumor growth modeling obtains the cell density distribution that potentially indicates the predicted tissue locations in the brain over time. The density patterns is then considered as novel features along with other texture (such as fractal, and multifractal Brownian motion (mBm)), and intensity features in MRI for improved brain tumor segmentation. We evaluate the proposed method with about one hundred longitudinal MRI scans from five patients obtained from public BRATS 2015 data set, validated by the ground truth. The result shows significant improvement of complete tumor segmentation using ANOVA analysis for five patients in longitudinal MR images.

The learning curve to achieve satisfactory completion rates in upper GI endoscopy: an analysis of a national training database.

PubMed

Ward, S T; Hancox, A; Mohammed, M A; Ismail, T; Griffiths, E A; Valori, R; Dunckley, P

2017-06-01

The aim of this study was to determine the number of OGDs (oesophago-gastro-duodenoscopies) trainees need to perform to acquire competency in terms of successful unassisted completion to the second part of the duodenum 95% of the time. OGD data were retrieved from the trainee e-portfolio developed by the Joint Advisory Group on GI Endoscopy (JAG) in the UK. All trainees were included unless they were known to have a baseline experience of >20 procedures or had submitted data for <20 procedures. The primary outcome measure was OGD completion, defined as passage of the endoscope to the second part of the duodenum without physical assistance. The number of OGDs required to achieve a 95% completion rate was calculated by the moving average method and learning curve cumulative summation (LC-Cusum) analysis. To determine which factors were independently associated with OGD completion, a mixed effects logistic regression model was constructed with OGD completion as the outcome variable. Data were analysed for 1255 trainees over 288 centres, representing 243 555 OGDs. By moving average method, trainees attained a 95% completion rate at 187 procedures. By LC-Cusum analysis, after 200 procedures, >90% trainees had attained a 95% completion rate. Total number of OGDs performed, trainee age and experience in lower GI endoscopy were factors independently associated with OGD completion. There are limited published data on the OGD learning curve. This is the largest study to date analysing the learning curve for competency acquisition. The JAG competency requirement for 200 procedures appears appropriate. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Treatment efficacy with electrochemotherapy: A multi-institutional prospective observational study on 376 patients with superficial tumors.

PubMed

Campana, L G; Testori, A; Curatolo, P; Quaglino, P; Mocellin, S; Framarini, M; Borgognoni, L; Ascierto, P A; Mozzillo, N; Guida, M; Bucher, S; Rotunno, R; Marenco, F; De Salvo, G L; De Paoli, A; Rossi, C R; Bonadies, A

2016-12-01

Cutaneous metastases represent a therapeutic challenge. An increasing body of experience suggests that electrochemotherapy (ECT) provides effective tumor control, although its evidence basis should be strengthened. This prospective, multicenter, observational study enrolled patients with superficial metastases, who underwent ECT at 10 centers between 2008 and 2013. Outcomes included adherence to European Standard Operating Procedures of ECT (ESOPE), tumor response, local progression-free survival (LPFS), toxicity and patient-reported outcomes (PROs, EORTC QLQ-C30 plus an 8-item questionnaire). We enrolled 376 eligible patients. Tumor histotype distribution was as follows: melanoma, 56%; squamous cell carcinoma, 11%; Kaposi sarcoma, 11%; breast carcinoma, 8%; basal cell carcinoma, 6%; soft tissue sarcomas, 3%; others, 5%. We registered 1304 target tumors (median size 1 cm). Treatment adhered to ESOPE in 88% of patients as to the route of drug administration, and in 70% as to electrode application. The procedure was mainly performed under sedation (64.6%) and by using intravenous chemotherapy (93.4%). Tumor response rate at 60 days was 88% (complete, 50%). Small tumor size predicted complete response achievement (OR 2.24, p = 0.003), higher LPFS (HR 0.68, p = 0.004) and improved PROs (Global Health Status, p < 0.001; wound bleeding, p < 0.001; healing, p = 0.002; and aesthetics, p < 0.001). Skin toxicity (grade ≥3, 7.8%) was lower in patients with tumors <2 cm (p≤0.001). One-year LPFS was 73.7% (95%CI 68.4-78.3). ECT represents a valuable skin-directed therapy across a range of malignancies. The most frequently applied treatment modality is intravenous chemotherapy under sedation. Small tumor size predicts durable tumor control, fewer side-effects and better PROs. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mechanism and Natural Course of Tumor Involution in Hepatocellular Carcinoma Following Transarterial Ethanol Ablation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Simon Chun Ho, E-mail: simonyu@cuhk.edu.hk; Lau, Tiffany Wing Wa; Tang, Peggy

PurposeTo evaluate the microvascular distribution of lipiodol–ethanol, the histological change of the tumor lesion, and the status of tumor involution over time in hepatocellular carcinoma (HCC) following transarterial ethanol ablation (TEA), in lesions that showed CT evidence of complete tumor response.Materials and methodsPatients with unresectable HCC were treated (183 patients, 242 lesions) with TEA using lipiodol–ethanol mixture (LEM) mixed in 2:1 ratio by volume and followed with CT at 3-month intervals for a median of 14.1 months. Liver tumors (n = 131) that showed CT evidence of complete tumor response, defined as the absence of any enhancing tumor throughout the follow-up period, weremore » included. The surgical specimens of five patients who subsequently received partial hepatectomy were available for histological assessment. The microvascular distribution of LEM and the degree of tumor necrosis were analyzed. Tumor involution over time was assessed with CT in lesions that showed complete response.ResultsLipid stain revealed lipiodol infiltration throughout arterioles, intratumoral sinusoidal spaces, tumor capsule, and peritumoral portal venules. Complete tumor necrosis (100 %) occurred in all 5 surgical specimens. The median (IQR) percentage tumor volume compared to baseline volumes at 12, 36, and 60 months was 32 % (23.5–52.5 %), 22 % (8–31 %), and 13.5 % (6–21.5 %), respectively.ConclusionIntrahepatic HCC lesion that showed CT evidence of complete tumor response following TEA is associated with histological evidence of LEM infiltration throughout the intratumoral and peritumoral vasculature and complete tumor necrosis, as well as sustained reduction in tumor volume over time.« less

Therapeutic cure against human tumor xenografts in nude mice by a microtubule stabilization agent, fludelone, via parenteral or oral route.

PubMed

Chou, Ting-Chao; Dong, Huajin; Zhang, Xiuguo; Tong, William P; Danishefsky, Samuel J

2005-10-15

Epothilones, 16-membered macrolides isolated from a myxobacterium in soil, exert their antitumor effect, like Taxol, by induction of microtubule polymerization and microtubule stabilization. They are effective against tumor cells that are resistant to Taxol or vinblastine. We recently designed, via molecular editing and total synthesis, a new class of epothilones represented by 26-trifluoro-(E)-9,10-dehydro-12,13-desoxy-epothilone B (Fludelone), which has emerged as a lead candidate for clinical development. Treatment of nude mice bearing MX-1 human mammary carcinoma xenografts (as large as 3.4% body weight) with Fludelone (6-hour i.v. infusion, 25 mg/kg, q3d x 5, q3d x 4) led to complete disappearance and de facto "cure" (i.e., remission without a relapse for over 15% of the average life span of 2 years). The toxicities induced by bolus i.v. injection could be avoided through prolonged i.v. infusion, which allowed for a 10-fold increase in maximal tolerated dose. Complete remission of MX-1 xenografts was achieved with only one third of this maximal tolerated dose. Parallel studies with Taxol and Fludelone [20 mg/kg, 6-hour i.v. infusion (q2d x 4) x3] against HCT-116 human colon carcinoma xenografts revealed that both drugs achieved tumor remission; however, all Taxol-treated mice relapsed in approximately 1.3 months, whereas the Fludelone-treated mice were cured without any relapse for over 7 months. Furthermore, tumor remission was achieved by Fludelone against SK-OV-3 (ovary), PC-3 (prostate), and the Taxol-resistant CCRF-CEM/Taxol (leukemia) xenograft tumors. Most remarkably, p.o. administration of Fludelone (30 mg/kg, q2d x 7, q2d x 9, q2d x 5) against MX-1 xenografts achieved a nonrelapsing cure for as long as 8.4 months. The above results indicate that Fludelone is a highly promising compound for cancer chemotherapeutics.

Detection of human brain tumor infiltration with multimodal multiscale optical analysis

NASA Astrophysics Data System (ADS)

Poulon, Fanny; Metais, Camille; Jamme, Frederic; Zanello, Marc; Varlet, Pascale; Devaux, Bertrand; Refregiers, Matthieu; Abi Haidar, Darine

2017-02-01

Brain tumor surgeries are facing major challenges to improve patients' quality of life. The extent of resection while preserving surrounding eloquent brain areas is necessary to equilibrate the onco-functional. A tool able to increase the accuracy of tissue analysis and to deliver an immediate diagnostic on tumor, could drastically improve actual surgeries and patient survival rates. To achieve such performances a complete optical study, ranging from ultraviolet to infrared, of biopsies has been started by our group. Four different contrasts were used: 1) spectral analysis covering the DUV to IR range, 2) two photon fluorescence lifetime imaging and one photon time domain measurement, 3) second harmonic generation imaging and 4) fluorescence imaging using DUV to IR, one and two photon excitation. All these measurements were done on the endogenous fluorescence of tissues to avoid any bias and further clinical complication due to the introduction of external markers. The different modalities are then crossed to build a matrix of criteria to discriminate tumorous tissues. The results of multimodal optical analysis on human biopsies were compared to the gold standard histopathology.

Clinical development of BLZ-100 for real-time optical imaging of tumors during resection

NASA Astrophysics Data System (ADS)

Franklin, Heather L.; Miller, Dennis M.; Hedges, Teresa; Perry, Jeff; Parrish-Novak, Julia

2016-03-01

Complete initial resection can give cancer patients the best opportunity for long-term survival. There is unmet need in surgical oncology for optical imaging that enables simple and precise visualization of tumors and consistent contrast with surrounding normal tissues. Near-infrared (NIR) contrast agents and camera systems that can detect them represent an area of active research and development. The investigational Tumor Paint agent BLZ-100 is a conjugate of a chlorotoxin peptide and the NIR dye indocyanine green (ICG) that has been shown to specifically bind to a broad range of solid tumors. Clinical efficacy studies with BLZ-100 are in progress, a necessary step in bringing the product into clinical practice. To ensure a product that will be useful for and accepted by surgeons, the early clinical development of BLZ- 100 incorporates multiple tumor types and imaging devices so that surgeon feedback covers the range of anticipated clinical uses. Key contrast agent characteristics include safety, specificity, flexibility in timing between dose and surgery, and breadth of tumor types recognized. Imaging devices should use wavelengths that are optimal for the contrast agent, be sensitive enough that contrast agent dosing can be adjusted for optimal contrast, include real-time video display of fluorescence and white light image, and be simple for surgeons to use with minimal disruption of surgical flow. Rapid entry into clinical studies provides the best opportunity for early surgeon feedback, enabling development of agents and devices that will gain broad acceptance and provide information that helps surgeons achieve more complete and precise resections.

Antibody recognition of a unique tumor-specific glycopeptide antigen

PubMed Central

Brooks, Cory L.; Schietinger, Andrea; Borisova, Svetlana N.; Kufer, Peter; Okon, Mark; Hirama, Tomoko; MacKenzie, C. Roger; Wang, Lai-Xi; Schreiber, Hans; Evans, Stephen V.

2010-01-01

Aberrant glycosylation and the overexpression of certain carbohydrate moieties is a consistent feature of cancers, and tumor-associated oligosaccharides are actively investigated as targets for immunotherapy. One of the most common aberrations in glycosylation patterns is the presentation of a single O-linked N-acetylgalactosamine on a threonine or serine residue known as the “Tn antigen.” Whereas the ubiquitous nature of Tn antigens on cancers has made them a natural focus of vaccine research, such carbohydrate moieties are not always tumor-specific and have been observed on embryonic and nonmalignant adult tissue. Here we report the structural basis of binding of a complex of a monoclonal antibody (237mAb) with a truly tumor-specific glycopeptide containing the Tn antigen. In contrast to glycopeptide-specific antibodies in complex with simple peptides, 237mAb does not recognize a conformational epitope induced in the peptide by sugar substitution. Instead, 237mAb uses a pocket coded by germ-line genes to completely envelope the carbohydrate moiety itself while interacting with the peptide moiety in a shallow groove. Thus, 237mAb achieves its striking tumor specificity, with no observed physiological cross-reactivity to the unglycosylated peptide or the free glycan, by a combination of multiple weak but specific interactions to both the peptide and to the glycan portions of the antigen. PMID:20479270

Retrorectal Tumors

PubMed Central

Neale, Jeffrey A.

2011-01-01

Tumors that arise in the retrorectal (presacral) space are uncommon lesions that present with nonspecific signs and symptoms, which lead to difficult diagnoses. For complete evaluation of the lesion, cross-sectional imaging is required to determine the extent of resection and the appropriate surgical approach. Surgical removal leads to favorable outcomes for patients with benign purely cystic retrorectal tumors. Preoperative tissue diagnosis with transperineal and transsacral biopsies of solid or heterogeneous cystic lesions, are essential to determine the necessity of neoadjuvant therapy, which may decrease local recurrence after surgery and avoid an unnecessary delay in systemic therapy. PMID:22942797

Tumor regression achieved by encapsulating a moderately soluble drug into a polymeric thermogel

PubMed Central

Ci, Tianyuan; Chen, Liang; Yu, Lin; Ding, Jiandong

2014-01-01

For cancer chemotherapy, a tumor regression without any surgical resection and severe side effects is greatly preferred to merely slowing down the growth of tumors. Here, we report a formulation composed of irinotecan (IRN) and poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA). IRN is a clinically used antitumor drug with active and inactive chemical forms in equilibrium, and the major form at physiological conditions is inactive but still has side effects. The aqueous solution of the PLGA-PEG-PLGA is a sol at room temperature and physically gels at body temperature, forming a thermogel. We successfully mixed this moderately soluble drug into the amphiphilic copolymer aqueous solution for the first time. The mixture was subcutaneously injected into nude mice with xenografted SW620 human colon tumors. Excellent in vivo antitumor efficacy was observed in the group that received the IRN-loaded thermogel. The tumor was significantly regressed after being treated with the IRN/thermogel, and the side effects (blood toxicity and body weight decrease) were very mild. These results might be attributed to the ideal sustained release profile and period of release of the drug from the thermogel and to the significant enhancement of the fraction of the active form of the drug by the thermogel. PMID:24980734

Tumor regression achieved by encapsulating a moderately soluble drug into a polymeric thermogel

NASA Astrophysics Data System (ADS)

Ci, Tianyuan; Chen, Liang; Yu, Lin; Ding, Jiandong

2014-07-01

For cancer chemotherapy, a tumor regression without any surgical resection and severe side effects is greatly preferred to merely slowing down the growth of tumors. Here, we report a formulation composed of irinotecan (IRN) and poly(D,L-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(D,L-lactide-co-glycolide) (PLGA-PEG-PLGA). IRN is a clinically used antitumor drug with active and inactive chemical forms in equilibrium, and the major form at physiological conditions is inactive but still has side effects. The aqueous solution of the PLGA-PEG-PLGA is a sol at room temperature and physically gels at body temperature, forming a thermogel. We successfully mixed this moderately soluble drug into the amphiphilic copolymer aqueous solution for the first time. The mixture was subcutaneously injected into nude mice with xenografted SW620 human colon tumors. Excellent in vivo antitumor efficacy was observed in the group that received the IRN-loaded thermogel. The tumor was significantly regressed after being treated with the IRN/thermogel, and the side effects (blood toxicity and body weight decrease) were very mild. These results might be attributed to the ideal sustained release profile and period of release of the drug from the thermogel and to the significant enhancement of the fraction of the active form of the drug by the thermogel.

In Vitro and In Vivo Tumor Targeted Photothermal Cancer Therapy Using Functionalized Graphene Nanoparticles.

PubMed

Kim, Sung Han; Lee, Jung Eun; Sharker, Shazid Md; Jeong, Ji Hoon; In, Insik; Park, Sung Young

2015-11-09

Despite the tremendous progress that photothermal therapy (PTT) has recently achieved, it still has a long way to go to gain the effective targeted photothermal ablation of tumor cells. Driven by this need, we describe a new class of targeted photothermal therapeutic agents for cancer cells with pH responsive bioimaging using near-infrared dye (NIR) IR825, conjugated poly(ethylene glycol)-g-poly(dimethylaminoethyl methacrylate) (PEG-g-PDMA, PgP), and hyaluronic acid (HA) anchored reduced graphene oxide (rGO) hybrid nanoparticles. The obtained rGO nanoparticles (PgP/HA-rGO) showed pH-dependent fluorescence emission and excellent near-infrared (NIR) irradiation of cancer cells targeted in vitro to provide cytotoxicity. Using intravenously administered PTT agents, the time-dependent in vivo tumor target accumulation was exactly defined, presenting eminent photothermal conversion at 4 and 8 h post-injection, which was demonstrated from the ex vivo biodistribution of tumors. These tumor environment responsive hybrid nanoparticles generated photothermal heat, which caused dominant suppression of tumor growth. The histopathological studies obtained by H&E staining demonstrated complete healing from malignant tumor. In an area of limited successes in cancer therapy, our translation will pave the road to design stimulus environment responsive targeted PTT agents for the safe eradication of devastating cancer.

Novel Secondary Somatic Mutations in Ewing's Sarcoma and Desmoplastic Small Round Cell Tumors

PubMed Central

Janku, Filip; Ludwig, Joseph A.; Naing, Aung; Benjamin, Robert S.; Brown, Robert E.; Anderson, Pete; Kurzrock, Razelle

2014-01-01

Background Ewing's sarcoma (ES) and desmoplastic small round cell tumors (DSRCT) are small round blue cell tumors driven by an N-terminal containing EWS translocation. Very few somatic mutations have been reported in ES, and none have been identified in DSRCT. The aim of this study is to explore potential actionable mutations in ES and DSRCT. Methodology Twenty eight patients with ES or DSRCT had tumor tissue available that could be analyzed by one of the following methods: 1) Next-generation exome sequencing platform; 2) Multiplex PCR/Mass Spectroscopy; 3) Polymerase chain reaction (PCR)-based single- gene mutation screening; 4) Sanger sequencing; 5) Morphoproteomics. Principal Findings Novel somatic mutations were identified in four out of 18 patients with advanced ES and two of 10 patients with advanced DSRCT (six out of 28 (21.4%));KRAS (n = 1), PTPRD (n = 1), GRB10 (n = 2), MET (n = 2) and PIK3CA (n = 1). One patient with both PTPRD and GRB10 mutations and one with a GRB10 mutation achieved a complete remission (CR) on an Insulin like growth factor 1 receptor (IGF1R) inhibitor based treatment. One patient, who achieved a partial remission (PR) with IGF1R inhibitor treatment, but later developed resistance, demonstrated a KRAS mutation in the post-treatment resistant tumor, but not in the pre-treatment tumor suggesting that the RAF/RAS/MEK pathway was activated with progression. Conclusions We have reported several different mutations in advanced ES and DSRCT that have direct implications for molecularly-directed targeted therapy. Our technology agnostic approach provides an initial mutational roadmap used in the path towards individualized combination therapy. PMID:25119929

TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis.

PubMed

Matsuo, Yo; Park, Jae-Hyun; Miyamoto, Takashi; Yamamoto, Shinji; Hisada, Shoji; Alachkar, Houda; Nakamura, Yusuke

2014-10-22

TOPK (T-lymphokine-activated killer cell-originated protein kinase) is highly and frequently transactivated in various cancer tissues, including lung and triple-negative breast cancers, and plays an indispensable role in the mitosis of cancer cells. We report the development of a potent TOPK inhibitor, OTS964 {(R)-9-(4-(1-(dimethylamino)propan-2-yl)phenyl)-8-hydroxy-6-methylthieno[2,3-c]quinolin-4(5H)-one}, which inhibits TOPK kinase activity with high affinity and selectivity. Similar to the knockdown effect of TOPK small interfering RNAs (siRNAs), this inhibitor causes a cytokinesis defect and the subsequent apoptosis of cancer cells in vitro as well as in xenograft models of human lung cancer. Although administration of the free compound induced hematopoietic adverse reactions (leukocytopenia associated with thrombocytosis), the drug delivered in a liposomal formulation effectively caused complete regression of transplanted tumors without showing any adverse reactions in mice. Our results suggest that the inhibition of TOPK activity may be a viable therapeutic option for the treatment of various human cancers. Copyright © 2014, American Association for the Advancement of Science.

Prospective evaluation of a 5 × 4 Gy prescription for palliation of canine nasal tumors.

PubMed

Tan-Coleman, Birgitte; Lyons, Jarred; Lewis, Craig; Rosenberg, Mona; Ruiz, Azucena

2013-01-01

We evaluated the efficacy of palliative radiation therapy using 5 × 4 Gy given daily in 18 dogs with nasal tumors. Dogs with malignant nasal tumors were evaluated for response rate, response duration, and survival. Seventy-eight percent of the dogs achieved complete resolution of clinical signs, and 16.5% had partial resolution of their signs. Overall median response duration for all dogs was 178 days after one course of radiation therapy. Six dogs received a second course of therapy when their disease progressed using the same daily 5 × 4 Gy scheme, and all six responded for a median time of 129.5 days for an overall median survival time in these six dogs of 309 days. Based on these results, a radiation prescription of 5 × 4 Gy appears to be useful palliatively in dogs with a malignant nasal tumor. © 2012 Veterinary Radiology & Ultrasound.

The immunization site of cytokine-secreting tumor cell vaccines influences the trafficking of tumor-specific T lymphocytes and antitumor efficacy against regional tumors.

PubMed

Chang, Chun-Jung; Tai, Kuo-Feng; Roffler, Steve; Hwang, Lih-Hwa

2004-11-15

Tumor cells engineered to secrete cytokines, referred to as tumor cell vaccines, can often generate systemic antitumor immunity and, in many cases, cause tumor regression. We compared the efficacy of s.c. immunization or intrahepatic immunization of GM-CSF-expressing tumor cell vaccines on the growth of s.c. or orthotopic liver tumors. A chemically transformed hepatic epithelial cell line, GP7TB, derived from Fischer 344 rats, was used to generate tumor models and tumor cell vaccines. Our results demonstrated that two s.c. injections of an irradiated tumor cell vaccine significantly controlled the growth of s.c. tumors, but was completely ineffective against orthotopic liver tumors. Effector cell infiltration in liver tumors was markedly reduced compared with s.c. tumors. Enhanced apoptosis of some effector cells was observed in the liver tumors compared with the s.c. tumors. Furthermore, the T cells induced by s.c. immunization preferentially migrated to s.c. tumor sites, as demonstrated by adoptive transfer experiments. In contrast, intrahepatic immunization, using parental tumor cells admixed with adenoviruses carrying the GM-CSF gene, yielded significantly better therapeutic effects on the liver tumors than on the s.c. tumors. Adoptive transfer experiments further confirmed that the T cells induced by liver immunization preferentially migrated to the liver tumor sites. Our results demonstrate that distinct T cell populations are induced by different immunization routes. Thus, the homing behavior of T cells depends on the route of immunization and is an important factor determining the efficacy of immunotherapy for regional tumors.

Microvascular Perfusion Changes following Transarterial Hepatic Tumor Embolization

PubMed Central

Johnson, Carmen Gacchina; Sharma, Karun V.; Levy, Elliot B.; Woods, David L.; Morris, Aaron H.; Bacher, John D.; Lewis, Andrew L.; Wood, Bradford J.; Dreher, Matthew R.

2015-01-01

Purpose To quantify changes in tumor microvascular (< 1 mm) perfusion relative to commonly used angiographic endpoints. Materials and Methods Rabbit Vx2 liver tumors were embolized with 100–300-µm LC Bead particles to endpoints of substasis or complete stasis (controls were not embolized). Microvascular perfusion was evaluated by delivering two different fluorophore-conjugated perfusion markers (ie, lectins) through the catheter before embolization and 5 min after reaching the desired angiographic endpoint. Tumor microvasculature was labeled with an anti-CD31 antibody and analyzed with fluorescence microscopy for perfusion marker overlap/mismatch. Data were analyzed by analysis of variance and post hoc test (n = 3–5 per group; 18 total). Results Mean microvascular density was 70 vessels/mm2 ± 17 (standard error of the mean), and 81% ± 1 of microvasculature (ie, CD31+ structures) was functionally perfused within viable Vx2 tumor regions. Embolization to the extent of substasis eliminated perfusion in 37% ± 9 of perfused microvessels (P > .05 vs baseline), whereas embolization to the extent of angiographic stasis eliminated perfusion in 56% ± 8 of perfused microvessels. Persistent microvascular perfusion following embolization was predominantly found in the tumor periphery, adjacent to normal tissue. Newly perfused microvasculature was evident following embolization to substasis but not when embolization was performed to complete angiographic stasis. Conclusions Nearly half of tumor microvasculature remained patent despite embolization to complete angiographic stasis. The observed preservation of tumor microvasculature perfusion with angiographic endpoints of substasis and stasis may have implications for tumor response to embolotherapy. PMID:26321051

Malignant tumors of the liver in children.

PubMed

Aronson, Daniel C; Meyers, Rebecka L

2016-10-01

This article aims to give an overview of pediatric liver tumors; in particular of the two most frequently occurring groups of hepatoblastomas and hepatocellular carcinomas. Focus lays on achievements gained through worldwide collaboration. We present recent advances in insight, treatment results, and future questions to be asked. Increasing international collaboration between the four major Pediatric Liver Tumor Study Groups (SIOPEL/GPOH, COG, and JPLT) may serve as a paradigm to approach rare tumors. This international effort has been catalyzed by the Children's Hepatic tumor International Collaboration (CHIC) formation of a large collaborative database. Interrogation of this database has led to a new universal risk stratification system for hepatoblastoma using PRETEXT/POSTTEXT staging as a backbone. Pathologists in this international collaboration have established a new histopathological consensus classification for pediatric liver tumors. Concomitantly there have been advances in chemotherapy options, an increased role of liver transplantation for unresectable tumors, and a web portal system developed at www.siopel.org for international education, consultation, and collaboration. These achievements will be further tested and validated in the upcoming Paediatric Hepatic International Tumour Trial (PHITT). Copyright © 2016 Elsevier Inc. All rights reserved.

Reprogramming of Melanoma Tumor-Infiltrating Lymphocytes to Induced Pluripotent Stem Cells

PubMed Central

Saito, Hidehito; Okita, Keisuke; Fusaki, Noemi; Sabel, Michael S.; Chang, Alfred E.; Ito, Fumito

2016-01-01

Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients hold great promise for autologous cell therapies. One of the possible applications of iPSCs is to use them as a cell source for producing autologous lymphocytes for cell-based therapy against cancer. Tumor-infiltrating lymphocytes (TILs) that express programmed cell death protein-1 (PD-1) are tumor-reactive T cells, and adoptive cell therapy with autologous TILs has been found to achieve durable complete response in selected patients with metastatic melanoma. Here, we describe the derivation of human iPSCs from melanoma TILs expressing high level of PD-1 by Sendai virus-mediated transduction of the four transcription factors, OCT3/4, SOX2, KLF4, and c-MYC. TIL-derived iPSCs display embryonic stem cell-like morphology, have normal karyotype, express stem cell-specific surface antigens and pluripotency-associated transcription factors, and have the capacity to differentiate in vitro and in vivo. A wide variety of T cell receptor gene rearrangement patterns in TIL-derived iPSCs confirmed the heterogeneity of T cells infiltrating melanomas. The ability to reprogram TILs containing patient-specific tumor-reactive repertoire might allow the generation of patient- and tumor-specific polyclonal T cells for cancer immunotherapy. PMID:27057178

Treatment-related toxicities in tumor-bearing cats treated with temozolomide alone or in combination with doxorubicin: a pilot assessment.

PubMed

Gagnon, Jerome; Dervisis, Nikolaos G; Kitchell, Barbara E

2012-08-01

A retrospective study assessing treatment-related toxicities in tumor-bearing cats treated with temozolomide (TMZ) alone or in combination with doxorubicin was conducted. TMZ was administered orally once a day for 5 days every 3 weeks at a dose of 20 mg/cat. Tumor response was evaluated with standard World Health Organization criteria and toxicity was monitored using veterinary co-operative oncology group-common terminology criteria for adverse events (VCOG--CTCAE) criteria. Ten tumor-bearing cats with various types of malignancies were treated with TMZ-based chemotherapy. Eight cats were evaluable for response. Two cats achieved a complete response, one achieved stable disease and five achieved a partial response. Four grade III and one grade IV hematological toxicities, and one grade IV gastrointestinal toxicity were observed. Four cats were euthanased as a result of apparent toxicity. One cat was euthanased as a result of severe and prolonged myelosuppression with fever. Three were euthanased for grade III pleural and pericardial effusions. Effusion was seen in cats treated with higher cumulative dose of TMZ (P = 0.0046). Planned additional case accrual was discontinued because of unacceptable levels of toxicity despite evidence of efficacy in some of the cats. Additional investigation is needed to elucidate this unexpected apparent cumulative toxicity.

Pattern of Retained Contrast on Immediate Postprocedure Computed tomography (CT) After Particle Embolization of Liver Tumors Predicts Subsequent Treatment Response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Xiaodong, E-mail: wangxde@gmail.com; Erinjeri, Joseph P., E-mail: erinjerj@mskcc.org; Jia Xiaoyu, E-mail: jiax@mskcc.org

2013-08-01

PurposeTo determine if the pattern of retained contrast on immediate postprocedure computed tomography (CT) after particle embolization of hepatic tumors predicts modified Response Evaluation Criteria in Solid Tumors (mRECIST) response.Materials and MethodsThis study was approved by the Institutional Review Board with a waiver of authorization. One hundred four liver tumors were embolized with spherical embolic agents (Embospheres, Bead Block, LC Bead) and polyvinyl alcohol. Noncontrast CT was performed immediately after embolization to assess contrast retention in the targeted tumors, and treatment response was assessed by mRECIST criteria on follow-up CT (average time 9.0 {+-} 7.7 weeks after embolization). Tumor contrastmore » retention (TCR) was determined based on change in Hounsfield units (HUs) of the index tumors between the preprocedure and immediate postprocedure scans; vascular contrast retention (VCR) was rated; and defects in contrast retention (DCR) were also documented. The morphology of residual enhancing tumor on follow-up CT was described as partial, circumferential, or total. Association between TCR variables and tumor response were assessed using multivariate logistic regression.ResultsOf 104 hepatic tumors, 51 (49 %) tumors had complete response (CR) by mRECIST criteria; 23 (22.1 %) had partial response (PR); 21 (20.2 %) had stable disease (SD); and 9 (8.7 %) had progressive disease (PD). By multivariate analysis, TCR, VCR, and tumor size are independent predictors of CR (p = 0.02, 0.05, and 0.005 respectively). In 75 tumors, DCR was found to be an independent predictor of failure to achieve complete response (p < 0.0001) by imaging criteria.ConclusionTCR, VCR, and DCR on immediate posttreatment CT are independent predictors of CR by mRECIST criteria.« less

Temperature uniformity in hyperthermal tumor therapy

NASA Technical Reports Server (NTRS)

Harrison, G. H.; Robinson, J. E.; Samaras, G. M.

1978-01-01

Mouse mammary tumors heated by water bath or by microwave-induced hyperthermia exhibit a response that varies sharply with treatment temperature; therefore, uniform heating of the tumor is essential to quantitate the biological response as a function of temperature. C3H tumors implanted on the mouse flank were easily heated to uniformities within 0.1 C by using water baths. Cold spots up to 1 C below the desired treatment temperature were observed in the same tumors implanted on the hind leg. These cold spots were attributed to cooling by major blood vessels near the tumor. In this case temperature uniformity was achieved by the deposition of 2450 MHz microwave energy into the tumor volume by using parallel-opposed applicators.

Helicobacter pylori-Negative Primary Rectal MALT Lymphoma: Complete Remission after Radiotherapy

PubMed Central

Okamura, Takuma; Suga, Tomoaki; Iwaya, Yugo; Ito, Tetsuya; Yokosawa, Shuichi; Arakura, Norikazu; Ota, Hiroyoshi; Tanaka, Eiji

2012-01-01

Rectal mucosa-associated lymphoid tissue (MALT) lymphoma is a rare condition. Although the majority of patients undergo surgical resection, a definitive treatment for rectal MALT lymphoma has not yet been established. In the present study, we report the outcome of radiotherapy in 3 patients with rectal MALT lymphoma. Our cohort ranged from 56 to 65 years of age. The male/female ratio was 1:2, and all patients were in stage I (Lugano classification) of the disease. Endoscopic findings revealed elevated lesions resembling submucosal tumors in 2 patients, and a sessile elevated lesion with a nodular surface in 1 patient. One of the 3 patients underwent magnifying endoscopy with crystal violet staining that demonstrated a type I pit pattern (Kudo's classification) lesion with a broad intervening area caused by the upthrust of the tumor from the submucosa. All patients tolerated radiotherapy at doses of 30 Gy without major complications and achieved complete remission. Follow-up ranged from 13 to 75 months (mean 51.0 months), revealing no recurrence of MALT lymphoma. As such, we propose radiotherapy to be a safe and effective means for treating rectal MALT lymphoma. PMID:22754493

Development of Advanced Technologies for Complete Genomic and Proteomic Characterization of Quantized Human Tumor Cells

DTIC Science & Technology

2013-07-01

extending the period of performance soon. The Ivy Center for Advanced Brain Tumor Treatment at the Swedish Neuroscience Institute (SNI) has...markers: (A) GFAP/astrocytes, (B), TUJ-1/neurons and (C) O4/oligodendrocytes. Cells were grown in NSA media without growth factors (EGF and FGF-2...Treatment at the Swedish Neuroscience Institute (SNI) has collected potentially eligible tumor tissue from over forty GBM patients. • Primary GBM cell

Double-Targeting Explosible Nanofirework for Tumor Ignition to Guide Tumor-Depth Photothermal Therapy.

PubMed

Zhang, Ming-Kang; Wang, Xiao-Gang; Zhu, Jing-Yi; Liu, Miao-Deng; Li, Chu-Xin; Feng, Jun; Zhang, Xian-Zheng

2018-04-17

This study reports a double-targeting "nanofirework" for tumor-ignited imaging to guide effective tumor-depth photothermal therapy (PTT). Typically, ≈30 nm upconversion nanoparticles (UCNP) are enveloped with a hybrid corona composed of ≈4 nm CuS tethered hyaluronic acid (CuS-HA). The HA corona provides active tumor-targeted functionality together with excellent stability and improved biocompatibility. The dimension of UCNP@CuS-HA is specifically set within the optimal size window for passive tumor-targeting effect, demonstrating significant contributions to both the in vivo prolonged circulation duration and the enhanced size-dependent tumor accumulation compared with ultrasmall CuS nanoparticles. The tumors featuring hyaluronidase (HAase) overexpression could induce the escape of CuS away from UCNP@CuS-HA due to HAase-catalyzed HA degradation, in turn activating the recovery of initially CuS-quenched luminescence of UCNP and also driving the tumor-depth infiltration of ultrasmall CuS for effective PTT. This in vivo transition has proven to be highly dependent on tumor occurrence like a tumor-ignited explosible firework. Together with the double-targeting functionality, the pathology-selective tumor ignition permits precise tumor detection and imaging-guided spatiotemporal control over PTT operation, leading to complete tumor ablation under near infrared (NIR) irradiation. This study offers a new paradigm of utilizing pathological characteristics to design nanotheranostics for precise detection and personalized therapy of tumors. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mental-health and educational achievement: the link between poor mental-health and upper secondary school completion and grades.

PubMed

Brännlund, Annica; Strandh, Mattias; Nilsson, Karina

2017-08-01

Education profoundly affects adult socioeconomic status, so it is important to ensure that all children have the capability and opportunity to achieve educational goals. The study aimed to examine the relationship between mental-health during adolescence and upper secondary school completion and grades, which has received comparatively little research attention to date. Longitudinal administrative and registered data were used to analyse the relationship between school achievement and prescriptions of psycholeptic and psycho-analeptic drugs. The sample consisted of all children born in Sweden in 1990 (n = 109 223), who were followed from birth to age 20. Logistic and OLS regressions were performed separately for boys and girls, controlling for birth health and family characteristics. A negative relationship between mental-health problems and educational outcomes was found; this result was almost independent of the controls. Only minor differences between the sexes were detected. Poor mental-health during childhood correlated negatively with educational attainment. Given the strong link between educational success and adult life, more resources are needed to support children with mental-health problems.

Endoscopic Complete Remission of Crohn Disease After Anti-Tumor Necrosis Factor-α Therapy: CT Enterographic Findings and Their Clinical Implications.

PubMed

Kim, Cherry; Park, Seong Ho; Yang, Suk-Kyun; Ye, Byong Duk; Park, Sang Hyoung; Lee, Jong Seok; Kim, Hyun Jin; Kim, Ah Young; Ha, Hyun Kwon

2016-06-01

The purpose of this study was to describe the CT enterographic (CTE) findings after endoscopic complete remission (CR) of Crohn disease in patients treated with anti-tumor necrosis factor-α (anti-TNF-α) and the clinical implications of these findings. The records of 27 patients with Crohn disease (14 men, 13 women; mean age, 28.4 ± 8.6 [SD] years) who achieved endoscopic (ileocolonoscopic) CR after anti-TNF-α therapy and underwent CTE both before therapy and at endoscopic CR were identified. Two readers independently assessed the frequencies and severities of mural and perienteric CTE abnormalities, generally regarded as active inflammatory findings, in the terminal ileum and colorectum in the endoscopic CR state and compared them with the corresponding findings before anti-TNF-α therapy. The association between the presence of CTE abnormalities in the face of endoscopic CR and patient outcome during subsequent follow-up was investigated. CTE abnormalities were present in the face of endoscopic CR in 11-18 (26-42%) of 43 bowel sections (18 terminal ileum, 25 colorectum), the most frequent being mural hyperenhancement (21-40%) followed by mural thickening (12-16%). Both findings were mild and unaccompanied by other findings. The frequency and severity of mural and perienteric CTE abnormalities were statistically significantly reduced at endoscopic CR compared with the pre-treatment state. Patients with (n = 10) and without (n = 17) CTE abnormalities at endoscopic CR did not significantly differ with respect to Crohn disease aggravation during subsequent follow-up periods averaging 27.4 and 28.5 months (0/10 versus 2/17, p = 0.516). More than one-fourth of bowel sections in endoscopic CR after anti-TNF-α therapy had residual CTE abnormalities, predominantly mild mural thickening or hyperenhancement. These findings may not have any clinical significance.

Nestin expression in neuroepithelial tumors.

PubMed

Schiffer, Davide; Manazza, Andrea; Tamagno, Ilaria

2006-05-29

Nestin is a marker of early stages of neurocytogenesis. It has been studied in 50 neuroepithelial tumors, mostly gliomas of different malignancy grades, by immunohistochemistry, immunofluorescence, immunoblotting, and confocal microscopy and compared with GFAP and Vimentin. As an early marker of differentiation, Nestin is almost not expressed in diffuse astrocytomas, variably expressed in anaplastic astrocytomas and strongly and irregularly expressed in glioblastomas. Negative in oligodendrogliomas, it stains ependymomas and shows a gradient of expression in pilocytic astrocytomas. In glioblastomas, Nestin distribution does not completely correspond to that of GFAP and Vimentin with which its expression varies in tumor cells in a complementary way, as confirmed by confocal microscopy. Tumor cells can thus either derive from or differentiate toward the neurocytogenetic stages. Hypothetically, they could be put in relation with radial glia where during embriogenesis the three antigens are successively expressed. Completely negative cells of invasive or recurrent glioblastomas may represent malignant selected clones after accumulation of mutations or early stem cells not expressing antigens.

Neoadjuvant chemotherapy for brain tumors in infants and young children.

PubMed

Iwama, Junya; Ogiwara, Hideki; Kiyotani, Chikako; Terashima, Keita; Matsuoka, Kentaro; Iwafuchi, Hideto; Morota, Nobuhito

2015-05-01

Because of their large size and high vascularity, complete removal of brain tumors in infants and young children is often difficult. In most cases the degree of resection is associated with prognosis. Neoadjuvant chemotherapy may facilitate resection by reducing the vascularity of the tumor. The authors evaluated the effectiveness of neoadjuvant chemotherapy in the management of these tumors. The authors performed a retrospective review of infants and young children who underwent tumor removal after neoadjuvant chemotherapy. Nine consecutive patients underwent resection after neoadjuvant chemotherapy during the period February 2004 to December 2012. The mean age at diagnosis was 18 months (range 2-50 months). The average largest tumor diameter was 71 mm (range 30-130 mm) at initial surgery. Five patients underwent partial resection, and 4 underwent biopsy as the initial surgery. The histopathological diagnoses were ependymoma in 2 patients, anaplastic ependymoma in 1, primitive neuroectodermal tumor (PNET) in 2, choroid plexus carcinoma in 1, atypical teratoid/rhabdoid tumor (AT/RT) in 1, glioblastoma in 1, and embryonal tumor with abundant neuropil and true rosettes in 1. After 2-4 courses of multiagent chemotherapy (mainly with vincristine, cyclophosphamide, etoposide, and cisplatin), the second-look surgery was performed. In 1 patient with a PNET, intratumoral hemorrhage was observed after 2 courses of chemotherapy. The mean interval between the initial and the second-look surgery was 3 months. The tumor volume was reduced to varying degrees in 5 patients (56%) after chemotherapy. Intraoperatively, the vascularity of the tumor was considerably reduced, and the tumor was more circumscribed in all cases. Gross-total resection was achieved in 8 patients (89%) and neartotal resection in 1 (11%). Histopathological examination demonstrated fibrotic tissue circumscribing the tumor in 6 of 9 cases (67%). The average blood loss was 20% of the estimated blood volume, and

Capturing tumor heterogeneity and clonal evolution in solid cancers using circulating tumor DNA analysis.

PubMed

Perdigones, Nieves; Murtaza, Muhammed

2017-06-01

Circulating tumor DNA analysis has emerged as a potential noninvasive alternative to tissue biopsies for tumor genotyping in patients with metastatic cancer. This is particularly attractive in cases where tissue biopsies are contraindicated or repeat genotyping after progression on treatment is required. However, tissue and plasma analysis results are not always concordant and clinical interpretation of discordant results is not completely understood. Discordant results could arise due to analytical limits of assays used for tumor and plasma DNA analysis or due to low overall contribution of tumor-specific DNA in plasma. Once these factors are ruled out, tissue-plasma concordance and quantitative levels of somatic mutations in plasma can capture tumor heterogeneity. During longitudinal follow-up of patients, this feature can be leveraged to track subclonal evolution and to guide combination or sequential adaptive treatment. Here, we summarize recent results evaluating the opportunities and limitations of circulating tumor DNA analysis in the context of tumor heterogeneity and subclonal evolution in patients with advanced cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacokinetics and Histopathological Findings of Chemoembolization Using Cisplatin Powder Mixed with Degradable Starch Microspheres in a Rabbit Liver Tumor Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sato, Takeshi; Tanaka, Toshihiro, E-mail: toshihir@bf6.so-net.ne.jp; Nishiofuku, Hideyuki

PurposeThe purpose of this study is to evaluate the pharmacokinetics and histopathological findings of transarterial chemoembolization (TACE) using cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE) compared with cisplatin arterial infusion (Cis-AI).Materials and MethodsEighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of cisplatin powder and DSM was injected until stasis of hepatic arterial flow was achieved. In the Cis-AI group, cisplatin solution was infused.ResultsThe platinum concentrations in VX2 tumors in the Cis/DSM-TACE group at 24 and 72 h were significantly elevated compared with those inmore » the Cis-AI group (P = .016 and .019, respectively). There were no significant differences in the platinum concentrations in plasma. Histopathological examination revealed the presence of several microspheres inside the tumors at 1 h, which completely disappeared at 24 h. Tumor cell apoptosis at 1 h in the Cis/DSM-TACE group was more frequently observed compared with that in the Cis-AI group (P = .006).ConclusionsTACE using cisplatin powder mixed with DSM provides a higher drug concentration in tumors, thereby achieving stronger antitumor effects compared with arterial infusion of cisplatin solution.« less

Tumor Biology and Immunology | Center for Cancer Research

Cancer.gov

Tumor Biology and Immunology The Comparative Brain Tumor Consortium is collaborating with National Center for Advanced Translational Sciences to complete whole exome sequencing on canine meningioma samples. Results will be published and made publicly available.

Modified Gompertz equation for electrotherapy murine tumor growth kinetics: predictions and new hypotheses

PubMed Central

2010-01-01

Background Electrotherapy effectiveness at different doses has been demonstrated in preclinical and clinical studies; however, several aspects that occur in the tumor growth kinetics before and after treatment have not yet been revealed. Mathematical modeling is a useful instrument that can reveal some of these aspects. The aim of this paper is to describe the complete growth kinetics of unperturbed and perturbed tumors through use of the modified Gompertz equation in order to generate useful insight into the mechanisms that underpin this devastating disease. Methods The complete tumor growth kinetics for control and treated groups are obtained by interpolation and extrapolation methods with different time steps, using experimental data of fibrosarcoma Sa-37. In the modified Gompertz equation, a delay time is introduced to describe the tumor's natural history before treatment. Different graphical strategies are used in order to reveal new information in the complete kinetics of this tumor type. Results The first stage of complete tumor growth kinetics is highly non linear. The model, at this stage, shows different aspects that agree with those reported theoretically and experimentally. Tumor reversibility and the proportionality between regions before and after electrotherapy are demonstrated. In tumors that reach partial remission, two antagonistic post-treatment processes are induced, whereas in complete remission, two unknown antitumor mechanisms are induced. Conclusion The modified Gompertz equation is likely to lead to insights within cancer research. Such insights hold promise for increasing our understanding of tumors as self-organizing systems and, the possible existence of phase transitions in tumor growth kinetics, which, in turn, may have significant impacts both on cancer research and on clinical practice. PMID:21029411

Modified Gompertz equation for electrotherapy murine tumor growth kinetics: predictions and new hypotheses.

PubMed

Cabrales, Luis E Bergues; Nava, Juan J Godina; Aguilera, Andrés Ramírez; Joa, Javier A González; Ciria, Héctor M Camué; González, Maraelys Morales; Salas, Miriam Fariñas; Jarque, Manuel Verdecia; González, Tamara Rubio; Mateus, Miguel A O'Farril; Brooks, Soraida C Acosta; Palencia, Fabiola Suárez; Zamora, Lisset Ortiz; Quevedo, María C Céspedes; Seringe, Sarah Edward; Cuitié, Vladimir Crombet; Cabrales, Idelisa Bergues; González, Gustavo Sierra

2010-10-28

Electrotherapy effectiveness at different doses has been demonstrated in preclinical and clinical studies; however, several aspects that occur in the tumor growth kinetics before and after treatment have not yet been revealed. Mathematical modeling is a useful instrument that can reveal some of these aspects. The aim of this paper is to describe the complete growth kinetics of unperturbed and perturbed tumors through use of the modified Gompertz equation in order to generate useful insight into the mechanisms that underpin this devastating disease. The complete tumor growth kinetics for control and treated groups are obtained by interpolation and extrapolation methods with different time steps, using experimental data of fibrosarcoma Sa-37. In the modified Gompertz equation, a delay time is introduced to describe the tumor's natural history before treatment. Different graphical strategies are used in order to reveal new information in the complete kinetics of this tumor type. The first stage of complete tumor growth kinetics is highly non linear. The model, at this stage, shows different aspects that agree with those reported theoretically and experimentally. Tumor reversibility and the proportionality between regions before and after electrotherapy are demonstrated. In tumors that reach partial remission, two antagonistic post-treatment processes are induced, whereas in complete remission, two unknown antitumor mechanisms are induced. The modified Gompertz equation is likely to lead to insights within cancer research. Such insights hold promise for increasing our understanding of tumors as self-organizing systems and, the possible existence of phase transitions in tumor growth kinetics, which, in turn, may have significant impacts both on cancer research and on clinical practice.

Simple instruments facilitating achievement of transanal total mesorectal excision in male patients.

PubMed

Xu, Chang; Song, Hua-Yu; Han, Shao-Liang; Ni, Shi-Chang; Zhang, Hu-Xiang; Xing, Chun-Gen

2017-08-21

To assess the efficacy of a modified approach with transanal total mesorectal excision (taTME) using simple customized instruments in male patients with low rectal cancer. A total of 115 male patients with low rectal cancer from December 2006 to August 2015 were retrospectively studied. All patients had a bulky tumor (tumor diameter ≥ 40 mm). Forty-one patients (group A) underwent a classical approach of transabdominal total mesorectal excision (TME) and transanal intersphincteric resection (ISR), and the other 74 patients (group B) underwent a modified approach with transabdominal TME, transanal ISR, and taTME. Some simple instruments including modified retractors and an anal dilator with a papilionaceous fixture were used to perform taTME. The operative time, quality of mesorectal excision, circumferential resection margin, local recurrence, and postoperative survival were evaluated. All 115 patients had successful sphincter preservation. The operative time in group B (240 min, range: 160-330 min) was significantly shorter than that in group A (280 min, range: 200-360 min; P = 0.000). Compared with group A, more complete distal mesorectum and total mesorectum were achieved in group B (100% vs 75.6%, P = 0.000; 90.5% vs 70.7%, P = 0.008, respectively). After 46.1 ± 25.6 mo follow-up, group B had a lower local recurrence rate and higher disease-free survival rate compared with group A, but these differences were not statistically significant (5.4% vs 14.6%, P = 0.093; 79.5% vs 65.1%, P = 0.130). Retrograde taTME with simple customized instruments can achieve high-quality TME, and it might be an effective and economical alternative for male patients with bulky tumors.

Submucosal tunneling endoscopic resection using methylene-blue guidance for cardial subepithelial tumors originating from the muscularis propria layer.

PubMed

Mao, X-L; Ye, L-P; Zheng, H-H; Zhou, X-B; Zhu, L-H; Zhang, Y

2017-04-01

Submucosal tunneling endoscopic resection (STER) of subepithelial tumors (SETs) originating from the muscularis propria (MP) layer in the cardia is rarely performed due to the difficulty of creating a submucosal tunnel for resection. The aim of this study is to evaluate the feasibility of STER using methylene-blue guidance for SETs originating from the MP layer in the cardia. From January 2012 to December 2014, 56 patients with SETs originating from the MP layer in the cardia were treated with STER using methylene-blue guidance. The complete resection rate and adverse event rate were the main outcome measurements. Successful complete resection by STER was achieved in all 56 cases (100%). The median size of the tumor was 1.8 cm. Nine patients (15.3%) had adverse events including subcutaneous emphysema, pneumoperitoneum, pneumothorax, and pleural effusion. These nine patients recovered successfully after conservative treatment without endoscopic or surgical intervention. No residual or recurrent tumors were detected in any patient during the follow-up period (median, 25 months). The adverse event rate was significantly higher for tumors originating in the deeper MP layers (46.7%) than in the superficial MP layers (4.9%) (P < 0.05), differed significantly according to tumor size (5.4% for tumors < 2.0 cm vs. 36.8% for tumors ≥ 2.0 cm; P < 0.05), and also differed significantly in relation to the tumor growth pattern (4.1% for the intraluminal growth vs. 100% for the extraluminal growth; P < 0.001). STER using methylene-blue guidance appears to be a feasible method for removing SETs originating from the MP layer in the cardia. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

[The standardized practice of laparoscopic-assisted radical right hemicolectomy in order to achieve complete mesocolic excision].

PubMed

Li, Bing-gen; Nie, Xiang-yang; He, Yong-zhong; Xie, Hui-hua; Yu, Guo-zhong; Du, Han-peng; Kong, Fan-dong; Gong, Du-hui; Lin, Wei-bin; Wu, Ming-jian

2012-03-01

To explore the feasibility of laparoscopic-assisted radical right hemicolectomy with the outcome being a complete mesocolic excision (CME). Between February 2010 and June 2011, we performed the standardized surgery of laparoscopic-assisted radical right hemicolectomy with an aim of CME on 14 patients. There were 10 males and 4 females, with an average age of 57 years (range 36 to 74 years). All the pathologic results in 14 cases were primary colonic adenocarcinoma. The TNM stages were distributed as follows: 2 in II A, 3 in II B, 3 in III A, 5 in III B and 1 in III C. Surgery was successfully performed for all patients without open conversion. The average operation time was (178 ± 37) minutes (range 127 to 221 minutes), average intraoperative blood loss was (67 ± 23) ml (range 30 to 110 ml), while the average number of lymph node harvest was 21 ± 7 (range 14 to 31), and the postoperative hospital stay was (10.0 ± 2.2) days (range 7 to 15 days). Minor complications occured in 2 patients. Major complications and post-operative mortality were not observed. All the patients were followed up for 3 to 19 months, no tumor recurrence or metastasis was identified. The standardized surgery of laparoscopic-assisted radical right hemicolectomy with the final outcome of CME is safe and feasible.

Perivascular epithelioid cell tumor (PEComa) of the cheek.

PubMed

Ghazali, Naseem; Cascarini, Luke; Norris, Paul; Barrett, A W; Lavery, Kenneth M

2010-07-01

We present the unusual case of a perivascular epithelioid cell tumor (PEComa) occurring within the cheek of a 32-year-old woman. PEComa is a rare, recently described, family of tumors with diverse clinicopathologic expression and which express melanocytic and muscle markers. It mainly affects the abdominopelvic region and rarely occurs in somatic soft tissue or skin. To our knowledge, this is the first reported case of PEComa occurring in the facial cutaneous tissues. Other possible diagnoses considered included benign mesenchymal tumors of smooth muscle or neural origin. However, the cytomorphologic and immunohistochemical profile were most suggestive of PEComa. The tumor was completely excised, but in view of uncertainty as to how this entity would behave in an unusual location, lifelong follow up is recommended. After complete excision, there was no recurrence in 4 years. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Targeting Therapy Resistant Tumor Vessels

DTIC Science & Technology

2007-05-01

Porkka K, Laakko- nen P, Ruoslahti E. Nucleolin expressed at the cell surface is a marker of endothelial cells in angiogenic blood vessels. J Cell...anti-angiogenic therapy. Markers of such vessels will be useful in developing strategies for complete destruction of breast cancer vasculature, and in...express specific markers , and that these lymphatic markers are tumor type specific and distinct from blood vessel markers in the same tumors. The

NKT Cells as an Ideal Anti-Tumor Immunotherapeutic

PubMed Central

Fujii, Shin-ichiro; Shimizu, Kanako; Okamoto, Yoshitaka; Kunii, Naoki; Nakayama, Toshinori; Motohashi, Shinichiro; Taniguchi, Masaru

2013-01-01

Human natural killer T (NKT) cells are characterized by their expression of an invariant T cell antigen receptor α chain variable region encoded by a Vα24Jα18 rearrangement. These NKT cells recognize α-galactosylceramide (α-GalCer) in conjunction with the MHC class I-like CD1d molecule and bridge the innate and acquired immune systems to mediate efficient and augmented immune responses. A prime example of one such function is adjuvant activity: NKT cells augment anti-tumor responses because they can rapidly produce large amounts of IFN-γ, which acts on NK cells to eliminate MHC negative tumors and also on CD8 cytotoxic T cells to kill MHC positive tumors. Thus, upon administration of α-GalCer-pulsed DCs, both MHC negative and positive tumor cells can be effectively eliminated, resulting in complete tumor eradication without tumor recurrence. Clinical trials have been completed in a cohort of 17 patients with advanced non-small cell lung cancers and 10 cases of head and neck tumors. Sixty percent of advanced lung cancer patients with high IFN-γ production had significantly prolonged median survival times of 29.3 months with only the primary treatment. In the case of head and neck tumors, 10 patients who completed the trial all had stable disease or partial responses 5 weeks after the combination therapy of α-GalCer-DCs and activated NKT cells. We now focus on two potential powerful treatment options for the future. One is to establish artificial adjuvant vector cells containing tumor mRNA and α-GalCer/CD1d. This stimulates host NKT cells followed by DC maturation and NK cell activation but also induces tumor-specific long-term memory CD8 killer T cell responses, suppressing tumor metastasis even 1 year after the initial single injection. The other approach is to establish induced pluripotent stem (iPS) cells that can generate unlimited numbers of NKT cells with adjuvant activity. Such iPS-derived NKT cells produce IFN-γ in vitro and in vivo upon

Radiofrequency ablation, an effective modality of treatment in tumor-induced osteomalacia: a case series of three patients.

PubMed

Jadhav, Swati; Kasaliwal, Rajeev; Shetty, Nitin S; Kulkarni, Suyash; Rathod, Krantikumar; Popat, Bhavesh; Kakade, Harshal; Bukan, Amol; Khare, Shruti; Budyal, Sweta; Jagtap, Varsha S; Lila, Anurag R; Bandgar, Tushar; Shah, Nalini S

2014-09-01

Tumor-induced osteomalacia is curable if the tumors can be totally excised. However, when the tumors are present in locations that make surgery disproportionately risky, the need for less invasive strategies like radiofrequency ablation (RFA) is realized. We describe three patients with suspected tumor-induced osteomalacia who were treated in our department between 2006 and 2013 with tumors in surgically difficult locations and were subjected to single or multiple sessions of RFA. The response was documented in terms of symptomatic improvement, phosphorus normalization, and follow-up (99m)Technitium-labelled hydrazinonicotinyl-Tyr3-octreotide ((99m)Tc HYNIC TOC) scan. Two of the three individuals, patient A (with a 1.5 × 1.2-cm lesion in the head of the right femur) and patient B (with a 1.3 × 1.2-cm lesion on the endosteal surface of the shaft of the left femur), achieved complete remission with single sessions of RFA. Three months after the procedure, (99m)Tc HYNIC TOC scans revealed the absence of uptake at the previous sites, corroborating with the clinical improvement and phosphorus normalization. Patient C had a large 5.6 × 6.5-cm complex lesion in the lower end of the left femur with irregular margins, loculations, and bone grafts placed in previous surgery. He failed to achieve remission after multiple sessions of RFA due to the complex nature of the lesion, although the tumor burden was reduced significantly as documented on serial (99m)Tc HYNIC TOC scans. Although surgery remains the treatment of choice, RFA could be an effective, less invasive, and safe modality of treatment in judiciously selected patients.

Complete remission of liver metastasis in a lung cancer patient with epidermal growth factor mutation achieved with Icotinib

PubMed Central

Zhu, Zhouyu

2016-01-01

A 65‐year‐old Chinese male was referred to our hospital for epidermal growth factor receptor (EGFR)‐mutated advanced non‐small cell lung cancer (NSCLC). Aggressive combined therapy with surgical resection of the right upper lung lesion and chemotherapy was performed. One month later, continued Icotinib treatment was used as magnetic resonance imaging revealed liver metastasis (LM). Interestingly, complete remission of the patient's LM lesions was achieved in six months. To our knowledge, this is the first report documenting a successful case of an NSCLC patient with LM treated with Icotinib after receiving a radical resection for pulmonary carcinoma. Our experience could provide a treatment strategy for patients with similar disease. PMID:27807951

[Long term results of exclusive chemotherapy for glottic squamous cell carcinoma complete clinical responders after induction chemotherapy].

PubMed

Vachin, F; Hans, S; Atlan, D; Brasnu, D; Menard, M; Laccourreye, O

2004-06-01

To evaluate the long-term results of exclusive chemotherapy for T1-T3N0M0 glottic squamous cell carcinoma complete clinical responders after induction chemotherapy. Between 1985 and 2000, 69 patients with glottic squamous cell carcinoma complete clinical responders after induction chemotherapy were managed with exclusive chemotherapy at our department. Chemotherapy associated platinum and fluorouracil. This retrospective analysis evaluated actuarial survival, treatment morbidity, oncologic events and laryngeal preservation. Various independent factors were tested for potential correlation with survival and local recurrence. The 5-year Kaplan-Meier actuarial survival, local control, lymph node control estimate were 83,6%, 64,8%, 98,6% respectively. Chemotherapy never resulted in death. The 10-year actuarial metachronous second primary tumors estimate was 32%. The overall laryngeal preservation rate was 98,6%. Altogether our data and the review of the literature suggest that in patients achieving a complete clinical response after and induction based chemotherapy regimen, the completion of an exclusive chemotherapy regimen appears to be a valid alternative to the conventional use of radiotherapy or chemo-radiation protocols.

Curative potential of GM-CSF-secreting tumor cell vaccines on established orthotopic liver tumors: mechanisms for the superior antitumor activity of live tumor cell vaccines.

PubMed

Tai, Kuo-Feng; Chen, Ding-Shinn; Hwang, Lih-Hwa

2004-01-01

In preclinical studies, tumor cells genetically engineered to secrete cytokines, hereafter referred to as tumor cell vaccines, can often generate systemic antitumor immunity. This study investigated the therapeutic effects of live or irradiated tumor cell vaccines that secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) on established orthotopic liver tumors. Experimental results indicated that two doses (3 x 10(7) cells per dose) of irradiated tumor cell vaccines were therapeutically ineffective, whereas one dose (3 x 10(6) cells) of live tumor cell vaccines caused complete tumor regression. In vivo depletion of CD8+ T cells, but not natural killer cells, restored tumor formation in the live vaccine-treated animals. Additionally, the treatment of cells with live vaccine induced markedly higher levels of cytotoxic T lymphocyte activity than the irradiated vaccines in the draining lymph nodes. The higher levels of cytokine and antigen loads could partly explain the superior antitumor activity of live tumor cell vaccines, but other unidentified mechanisms could also play a role in the early T cell activation in the lymph nodes. A protocol using multiple and higher dosages of irradiated tumor cell vaccines also caused significant regression of liver tumors. These results suggest that the GM-CSF-secreting tumor cell vaccines are highly promising for orthotopic liver tumors if higher levels of immune responses are elicited during early tumor development. Copyright 2004 National Science Council, ROC and S. Karger AG, Basel

A Platform to Monitor Tumor Cellular and Vascular Response to Radiation Therapy by Optical Coherence Tomography and Fluorescence Microscopy in vivo

NASA Astrophysics Data System (ADS)

Leung, Michael Ka Kit

Radiotherapy plays a significant role in cancer treatment, and is thought to be curative by mainly killing tumor cells through damage to their genetic material. However, recent findings indicate that the tumor's vascular blood supply is also a major determinant of radiation response. The goals of this thesis are to: (1) develop an experimental platform for small animals to deliver ionizing radiation and perform high-resolution optical imaging to treatment targets, and (2) use this toolkit to longitudinally monitor the response of tumors and the associated vasculature. The thesis has achieved: (1) customization of a novel micro-irradiator for mice, (2) technical development of an improved optical coherence tomography imaging system, (3) comprehensive experimental protocol and imaging optimization for optical microscopy in a specialized animal model, and (4) completion of a feasibility study to demonstrate the capabilities of the experimental platform in monitoring the response of tumor and vasculature to radiotherapy.

Antitumor effectiveness of different amounts of electrical charge in Ehrlich and fibrosarcoma Sa-37 tumors

PubMed Central

Ciria, HC; Quevedo, MS; Cabrales, LB; Bruzón, RP; Salas, MF; Pena, OG; González, TR; López, DS; Flores, JM

2004-01-01

Background In vivo studies were conducted to quantify the effectiveness of low-level direct electric current for different amounts of electrical charge and the survival rate in fibrosarcoma Sa-37 and Ehrlich tumors, also the effect of direct electric in Ehrlich tumor was evaluate through the measurements of tumor volume and the peritumoral and tumoral findings. Methods BALB/c male mice, 7–8 week old and 20–22 g weight were used. Ehrlich and fibrosarcoma Sa-37 cell lines, growing in BALB/c mice. Solid and subcutaneous Ehrlich and fibrosarcoma Sa-37 tumors, located dorsolaterally in animals, were initiated by the inoculation of 5 × 106 and 1 × 105 viable tumor cells, respectively. For each type of tumor four groups (one control group and three treated groups) consisting of 10 mice randomly divided were formed. When the tumors reached approximately 0.5 cm3, four platinum electrodes were inserted into their bases. The electric charge delivered to the tumors was varied in the range of 5.5 to 110 C/cm3 for a constant time of 45 minutes. An additional experiment was performed in BALB/c male mice bearing Ehrlich tumor to examine from a histolological point of view the effects of direct electric current. A control group and a treated group with 77 C/cm3 (27.0 C in 0.35 cm3) and 10 mA for 45 min were formed. In this experiment when the tumor volumes reached 0.35 cm3, two anodes and two cathodes were inserted into the base perpendicular to the tumor long axis. Results Significant tumor growth delay and survival rate were achieved after electrotherapy and both were dependent on direct electric current intensity, being more marked in fibrosarcoma Sa-37 tumor. Complete regressions for fibrosarcoma Sa-37 and Ehrlich tumors were observed for electrical charges of 80 and 92 C/cm3, respectively. Histopathological and peritumoral findings in Ehrlich tumor revealed in the treated group marked tumor necrosis, vascular congestion, peritumoral neutrophil infiltration, an acute

Tumor Burden Analysis on Computed Tomography by Automated Liver and Tumor Segmentation

PubMed Central

Linguraru, Marius George; Richbourg, William J.; Liu, Jianfei; Watt, Jeremy M.; Pamulapati, Vivek; Wang, Shijun; Summers, Ronald M.

2013-01-01

The paper presents the automated computation of hepatic tumor burden from abdominal CT images of diseased populations with images with inconsistent enhancement. The automated segmentation of livers is addressed first. A novel three-dimensional (3D) affine invariant shape parameterization is employed to compare local shape across organs. By generating a regular sampling of the organ's surface, this parameterization can be effectively used to compare features of a set of closed 3D surfaces point-to-point, while avoiding common problems with the parameterization of concave surfaces. From an initial segmentation of the livers, the areas of atypical local shape are determined using training sets. A geodesic active contour corrects locally the segmentations of the livers in abnormal images. Graph cuts segment the hepatic tumors using shape and enhancement constraints. Liver segmentation errors are reduced significantly and all tumors are detected. Finally, support vector machines and feature selection are employed to reduce the number of false tumor detections. The tumor detection true position fraction of 100% is achieved at 2.3 false positives/case and the tumor burden is estimated with 0.9% error. Results from the test data demonstrate the method's robustness to analyze livers from difficult clinical cases to allow the temporal monitoring of patients with hepatic cancer. PMID:22893379

High-frequency cortical subdural stimulation enhanced plasticity in surgery of a tumor in Broca's area.

PubMed

Barcia, Juan A; Sanz, Ana; Balugo, Paloma; Alonso-Lera, Pedro; Brin, Juan Raúl; Yus, Miguel; Gonzalez-Hidalgo, Mercedes; Acedo, Victoria M; Oliviero, Antonio

2012-03-28

Functional areas located near or within brain gliomas prevent the complete resection of these tumors. It has recently been described that slow tumor invasion promotes neural reorganization, and even topographic plasticity, allowing a staged resection of those tumors. Thus, our aim was to promote plasticity by mimicking the tumor's capability to displace brain function. This proceeded through the production of a 'virtual lesion' in eloquent areas within a tumor using continuous high-frequency cortical electrical stimulation (cHFCS). An anaplastic astrocytoma located in Broca's area progressed in a patient whose lateralization of language to the side of the lesion was demonstrated with functional MRI. After partial tumor resection using awake cortical monitoring, we implanted a subdural grid over the eloquent cortex located within residual tumor. We then applied cHFCS for 25 days, using a frequency of 130 Hz and a pulse width of 1 ms. Stimulus intensity was set to the threshold wherein mild speech disturbance was evident without any other neurological effects. This treatment successfully achieved the displacement of speech functions, and a more radical resection of the tumor was possible in a second surgery. Critically, a reorganization of motor language areas was demonstrated both with functional MRI and cortical stimulation. Furthermore, motor language areas were also identified in the right hemisphere, where previously they were absent. The patient's speech fluency improved both after stimulation and resection. We therefore demonstrate the first evidence of induced topographic plasticity using cHFCS in eloquent areas within a tumor, which allowed for increased tumor removal. Our results open the possibility to induce plasticity before the resection of brain tumors near eloquent areas, in order to increase the extent of resection.

Esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer: frequency and prediction.

PubMed

Atsumi, Kazushige; Shioyama, Yoshiyuki; Arimura, Hidetaka; Terashima, Kotaro; Matsuki, Takaomi; Ohga, Saiji; Yoshitake, Tadamasa; Nonoshita, Takeshi; Tsurumaru, Daisuke; Ohnishi, Kayoko; Asai, Kaori; Matsumoto, Keiji; Nakamura, Katsumasa; Honda, Hiroshi

2012-04-01

To determine clinical factors for predicting the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. The study group consisted of 109 patients with esophageal cancer of T1-4 and Stage I-III who were treated with definitive radiotherapy and achieved a complete response of their primary lesion at Kyushu University Hospital between January 1998 and December 2007. Esophageal stenosis was evaluated using esophagographic images within 3 months after completion of radiotherapy. We investigated the correlation between esophageal stenosis after radiotherapy and each of the clinical factors with regard to tumors and therapy. For validation of the correlative factors for esophageal stenosis, an artificial neural network was used to predict the esophageal stenotic ratio. Esophageal stenosis tended to be more severe and more frequent in T3-4 cases than in T1-2 cases. Esophageal stenosis in cases with full circumference involvement tended to be more severe and more frequent than that in cases without full circumference involvement. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. In the multivariate analysis, T stage, extent of involved circumference, and wall thickness of the tumor region were significantly correlated to esophageal stenosis (p = 0.031, p < 0.0001, and p = 0.0011, respectively). The esophageal stenotic ratio predicted by the artificial neural network, which learned these three factors, was significantly correlated to the actual observed stenotic ratio, with a correlation coefficient of 0.864 (p < 0.001). Our study suggested that T stage, extent of involved circumference, and esophageal wall thickness of the tumor region were useful to predict the frequency and severity of esophageal stenosis associated with tumor regression in radiotherapy for esophageal cancer. Copyright © 2012 Elsevier Inc. All rights reserved.

Fluid shear stress and tumor metastasis

PubMed Central

Huang, Qiong; Hu, Xingbin; He, Wanming; Zhao, Yang; Hao, Shihui; Wu, Qijing; Li, Shaowei; Zhang, Shuyi; Shi, Min

2018-01-01

The tumor microenvironment (TME) is a key factor regulating tumor cell invasion and metastasis. The effects of biochemical factors such as stromal cells, immune cells, and cytokines have been previously investigated. Owing to restrictions by the natural barrier between physical and biochemical disciplines, the role of physical factors in tumorigenesis is unclear. However, with the emergence of interdisciplinary mechanobiology and continuous advancements therein in the past 30 years, studies on the effect of physical properties such as hardness or shear stress on tumorigenesis and tumor progression are constantly renewing our understanding of mechanotransduction mechanisms. Shear stress, induced by liquid flow, is known to actively participate in proliferation, apoptosis, invasion, and metastasis of tumor cells. The present review discusses the progress and achievements in studies on tumor fluid microenvironment in recent years, especially fluid shear stress, on tumor metastasis, and presents directions for future study.

Transcatheter arterial embolization of acute gastrointestinal tumor hemorrhage with Onyx.

PubMed

Sun, C J; Wang, C E; Wang, Y H; Xie, L L; Liu, T H; Ren, W C

2015-02-01

Endovascular embolization has been used to control gastrointestinal tumor bleeding. Lots of embolic agents have been applied in embolization, but liquid embolic materials such as Onyx have been rarely used because of concerns about severe ischemic complications. To evaluate the clinical efficacy and safety of transcatheter arterial embolization (TAE) with Onyx for acute gastrointestinal tumor hemorrhage. Between September 2011 and July 2013, nine patients were diagnosed as acute gastrointestinal tumor hemorrhage by clinical feature and imaging examination. The angiographic findings were extravasation of contrast media in the five patients. The site of hemorrhage included upper gastrointestinal bleeding in seven cases and lower gastrointestinal bleeding in two cases. TAE was performed using Onyx in all the patients, and the blood pressure and heart rate were monitored, the angiographic and clinical success rate, recurrent bleeding rate, procedure related complications and clinical outcomes were evaluated after therapy. The clinical parameters and embolization data were studied retrospectively. All the patients (100%) who underwent TAE with Onyx achieved complete hemostasis without rebleeding and the patients were discharged after clinical improvement without a second surgery. No one of the patients expired during the hospital course. All the patients were discharged after clinical improvement without a second surgery. Postembolization bowel ischemia or necrosis was not observed in any of the patients who received TAE with Onyx. TAE with Onyx is a highly effective and safe treatment modality for acute gastrointestinal tumor hemorrhage, even with pre-existing coagulopathy.

Loss of pace capture on the ablation line: a new marker for complete radiofrequency lesions to achieve pulmonary vein isolation.

PubMed

Steven, Daniel; Reddy, Vivek Y; Inada, Keiichi; Roberts-Thomson, Kurt C; Seiler, Jens; Stevenson, William G; Michaud, Gregory F

2010-03-01

Catheter ablation procedures for atrial fibrillation (AF) often involve circumferential antral isolation of pulmonary veins (PV). Inability to reliably identify conduction gaps on the ablation line necessitates placing additional lesions within the intended lesion set. This pilot study investigated the relationship between loss of pace capture directly along the ablation line and electrogram criteria for PV isolation (PVI). Using a 3-dimensional anatomic mapping system and irrigated-tip radiofrequency (RF) ablation catheter, lesions were placed in the PV antra to encircle ipsilateral vein pairs until pace capture at 10 mA/2 ms no longer occurred along the line. During ablation, a circular mapping catheter was placed in an ipsilateral PV, but the electrograms were not revealed until loss-of-pace capture. The procedural end point was PVI (entrance and exit block). Thirty patients (57 +/- 12 years; 15 male [50%]) undergoing PVI in 2 centers (3 primary operators) were included (left atrial diameter 40 +/- 4 mm, left ventricular ejection fraction 60 +/- 7%). All patients reached the end points of complete PVI and loss of pace capture. When PV electrograms were revealed after loss of pace capture along the line, PVI was present in 57 of 60 (95%) vein pairs. In the remaining 3 of 60 (5%) PV pairs, further RF applications achieved PVI. The procedure duration was 237 +/- 46 minutes, with a fluoroscopy time of 23 +/- 9 minutes. Analysis of the blinded PV electrograms revealed that even after PVI was achieved, additional sites of pace capture were present on the ablation line in 30 of 60 (50%) of the PV pairs; 10 +/- 4 additional RF lesions were necessary to fully achieve loss of pace capture. After ablation, the electrogram amplitude was lower at unexcitable sites (0.25 +/- 0.15 mV vs. 0.42 +/- 0.32 mV, P < .001), but there was substantial overlap with pace capture sites, suggesting that electrogram amplitude lacks specificity for identifying pace capture sites. Complete

Malignant Mixed Tumor of the Finger: A Case Report.

PubMed

Nakanishi, Akito; Honoki, Kanya; Omokawa, Shohei; Tanaka, Yasuhito

2018-06-01

We present a very rare case of malignant chondroid syringoma of the fingertip in a 44-year-old man that was reconstruced by neurovascular island flap after the complete tumor resection of the fingertip. Although it is a rare tumor at an unusual area, it should be included in the differential diagnosis of the finger tumors.

Predictors of outcome in patients with advanced nonseminomatous germ cell testicular tumors.

PubMed

Yetisyigit, Tarkan; Babacan, Nalan; Urun, Yuksel; Seber, Erdogan Selcuk; Cihan, Sener; Arpaci, Erkan; Yildirim, Nuriye; Aksoy, Sercan; Budakoglu, Burcin; Zengin, Nurullah; Oksuzoglu, Berna; Yalcin, Banu Cicek; Alkis, Necati

2014-01-01

Predictor factors determining complete response to treatment are still not clearly defined. We aimed to evaluate clinicopathological features, risk factors, treatment responses, and survival analysis of patient with advanced nonseminomatous GCTs (NSGCTs). Between November 1999 and September 2011, 140 patients with stage II and III NSGCTs were referred to our institutions and 125 patients with complete clinical data were included in this retrospective study. Four cycles of BEP regimen were applied as a first-line treatment. Salvage chemotherapy and/or high-dose chemotherapy (HDCT) with autologous stem cell transplantation were given in patients who progressed after BEP chemotherapy. Post-chemotherapy surgery was performed in selected patients with incomplete radiographic response and normal tumor markers. The median age was 28 years. For the good, intermediate and poor risk groups, compete response rates (CRR) were, 84.6%, 67.9% and 59.4%, respectively. Extragonadal tumors, stage 3 disease, intermediate and poor risk factors, rete testis invasion were associated with worse outcomes. There were 32 patients (25.6%) with non-CR who were treated with salvage treatment. Thirty-one patients died from GCTs and 94% of them had stage III disease. Even though response rates are high, some patients with GCTs still need salvage treatment and cure cannot be achieved. Non-complete response to platinium-based first-line treatment is a negative prognostic factor. Our study confirmed the need for a prognostic and predictive model and more effective salvage approaches.

Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine Tumors

PubMed Central

Metz, David C.

2008-01-01

Pancreatic endocrine tumors (PETs) have long fascinated clinicians and investigators despite their relative rarity. Their clinical presentation varies depending upon whether the tumor is functional or not and also according to the specific hormonal syndrome produced. Tumors may be sporadic or inherited but little is known about their molecular pathology, especially the sporadic forms. Chromogranin A appears to be the most useful serum marker for diagnosis, staging and monitoring. Initially, therapy should be directed at the hormonal syndrome as this has the major initial impact on the patient's health. Most PETs are relatively indolent but ultimately malignant, except for insulinomas which are predominantly benign. Surgery is the only modality that offers the possibility of cure although it is generally noncurative in patients with Zollinger-Ellison syndrome or nonfunctional PETs with MEN1. Preoperative staging of disease extent is necessary to determine the likelihood of complete resection though debulking surgery is often felt to be useful in unresectable patients. Once metastatic, biotherapy is usually the first modality employed because it is generally well tolerated. Systemic or regional therapies are generally reserved until symptoms occur or tumor growth is rapid. Recently a number of newer agents, as well as receptor-directed radiotherapy, are being evalulated for patients with advanced disease. This review addresses a number of recent advances regarding the molecular pathology, diagnosis, localization and management of PETs including discussion of peptide receptor radionuclide therapy and other novel antitumor approaches. We conclude with a discussion of future directions and unsettled problems in the field. PMID:18703061

Administration of 6-gingerol greatly enhances the number of tumor-infiltrating lymphocytes in murine tumors.

PubMed

Ju, Seong-A; Park, Sang-Min; Lee, Yea-Sol; Bae, Jun-Hyeong; Yu, Rina; An, Won G; Suh, Jae-Hee; Kim, Byung-Sam

2012-06-01

Tumor-infiltrating lymphocytes (TILs) play critical roles in host antitumor immune responses. It is known that cancer patients with tumor-reactive lymphocyte infiltration in their tumors have better prognoses, while patients with tumors infiltrated by immunosuppressive cells have worse prognoses. We found that administration of 6-gingerol, which is a component of ginger, inhibited tumor growth in several types of murine tumors, such as B16F1 melanomas, Renca renal cell carcinomas and CT26 colon carcinomas, which were established by inoculating tumor cells on the flanks of mice. However, administration of 6-gingerol did not lead to complete eradication of the tumors. 6-Gingerol treatment of tumor-bearing mice caused massive infiltration of CD4 and CD8 T-cells and B220(+) B-cells, but reduced the number of CD4(+) Foxp3(+) regulatory T-cells. The CD8 tumor-infiltrating T lymphocytes in 6-gingerol-treated mice strongly expressed IFN-γ, a marker of activation of cytotoxic T lymphocytes (CTL) CD107a and chemokine receptors that are expressed on T(H) 1 cells, such as CXCR3 and CCR5. To test whether 6-gingerol could promote infiltration of tumor antigen-specific CD8 T-cells into tumors, we adoptively transferred CFSE-labeled OT-1 CD8 T-cells into EG7 tumor-bearing mice. We found that CD8 T cells isolated from 6-gingerol pretreated OT-1 mice, but not from control OT-1 mice, massively infiltrated tumors and tumor draining lymph nodes and divided several times. Our results strongly suggest that 6-gingerol can be used in tumor immunotherapy to increase the number of TILs. Copyright © 2011 UICC.

Parameterizing the Logistic Model of Tumor Growth by DW-MRI and DCE-MRI Data to Predict Treatment Response and Changes in Breast Cancer Cellularity during Neoadjuvant Chemotherapy1

PubMed Central

Atuegwu, Nkiruka C; Arlinghaus, Lori R; Li, Xia; Chakravarthy, A Bapsi; Abramson, Vandana G; Sanders, Melinda E; Yankeelov, Thomas E

2013-01-01

Diffusion-weighted and dynamic contrast-enhanced magnetic resonance imaging (MRI) data of 28 patients were obtained pretreatment, after one cycle, and after completion of all cycles of neoadjuvant chemotherapy (NAC). For each patient at each time point, the tumor cell number was estimated using the apparent diffusion coefficient and the extravascular extracellular (ve) and plasma volume (vp) fractions. The proliferation/death rate was obtained using the number of tumor cells from the first two time points in conjunction with the logistic model of tumor growth, which was then used to predict tumor cellularity at the conclusion of NAC. The Pearson correlation coefficient between the predicted and the experimental number of tumor cells measured at the end of NAC was 0.81 (P = .0043). The proliferation rate estimated after the first cycle of therapy was able to separate patients who went on to achieve pathologic complete response from those who did not (P = .021) with a sensitivity and specificity of 82.4% and 72.7%, respectively. These data provide preliminary results indicating that incorporating readily available quantitative MRI data into a simple model of tumor growth can lead to potentially clinically relevant information for predicting an individual patient's response to NAC. PMID:23730404

Highly personalized detection of minimal Ewing sarcoma disease burden from plasma tumor DNA.

PubMed

Hayashi, Masanori; Chu, David; Meyer, Christian F; Llosa, Nicolas J; McCarty, Gregory; Morris, Carol D; Levin, Adam S; Wolinsky, Jean-Paul; Albert, Catherine M; Steppan, Diana A; Park, Ben Ho; Loeb, David M

2016-10-01

Even though virtually all patients with Ewing sarcoma achieve a radiographic complete response, up to 30% of patients who present with localized disease and up to 90% of those who present with metastases experience a metastatic disease recurrence, highlighting the inability to identify patients with residual disease at the end of therapy. Up to 95% of Ewing sarcomas carry a driving EWS-ETS translocation that has an intronic breakpoint that is specific to each tumor, and the authors developed a system to quantitatively detect the specific breakpoint DNA fragment in patient plasma. The authors used a long-range multiplex polymerase chain reaction (PCR) technique to identify tumor-specific EWS-ETS breakpoints in Ewing sarcoma cell lines, patient-derived xenografts, and patient tumors, and this sequence was used to design tumor-specific primer sets to detect plasma tumor DNA (ptDNA) by droplet digital PCR in xenograft-bearing mice and patients. Tumor-specific breakpoint DNA fragments were detected in the plasma of xenograft-bearing mice, and the signal correlated with tumor burden during primary tumor growth, after surgical resection, and at the time of metastatic disease recurrence. Furthermore, the authors were able to detect the specific breakpoint in plasma DNA obtained from 3 patients with Ewing sarcoma and in 2 patients the authors were able to detect ptDNA when there was radiographically undetectable disease present. The use of droplet digital PCR to detect tumor-specific EWS-ETS fusion gene breakpoint ptDNA fragments can be developed into a highly personalized biomarker of disease recurrence that can be optimized in animal studies for ultimate use in patients. Cancer 2016;122:3015-3023. © 2016 American Cancer Society. © 2016 American Cancer Society.

Surgical treatment of tumor-induced osteomalacia: a retrospective review of 40 cases with extremity tumors.

PubMed

Sun, Zhi-jian; Jin, Jin; Qiu, Gui-xing; Gao, Peng; Liu, Yong

2015-02-26

Tumor-induced osteomalacia (TIO) is a rare syndrome typically caused by mesenchymal tumors. It has been shown that complete tumor resection may be curative. However, to our knowledge, there has been no report of a large cohort to exam different surgical approaches. This study was aimed to assess outcomes of different surgical options of patients with tumor-induced osteomalacia at a single institution. Patients with extremity tumors treated in our hospital from January, 2004 to July, 2012 were identified. The minimum follow-up period was 12 months. Patient's demography, tumor location, preoperative preparation, type of surgeries were summarized, and clinical outcomes were recorded. Successful treatment was defined as significant symptom improvement, normal serum phosphorus and significant improvement or normalization of bone mineral density at the last follow-up. Differences between patients with soft tissue tumors and bone tumors were compared. There were 40 (24 male and 16 female) patients identified, with an average age of 44 years. The tumors were isolated in either soft tissue (25 patients) or bone (12 patients) and combined soft tissue and bone invasion was observed in 3 patients. For the primary surgery, tumor resection and tumor curettage were performed. After initial surgical treatment, six patients then received a second surgery. Four patients were found to have malignant tumors base on histopathology. With a minimum follow-up period of 12 months, 80% of patients (32/40) were treated successfully, including 50% of patients (2/4) with malignant tumors. Compared to patients with bone tumor, surgical results were better in patient with soft tissue tumor. Surgical treatment was an effective way for TIO. Other than tumor curettage surgery, tumor resection is the preferred options for these tumors.

Brick by brick: metabolism and tumor cell growth

PubMed Central

DeBerardinis, Ralph J.; Sayed, Nabil; Ditsworth, Dara; Thompson, Craig B.

2008-01-01

Summary Tumor cells display increased metabolic autonomy in comparison to non-transformed cells, taking up nutrients and metabolizing them in pathways that support growth and proliferation. Classical work in tumor cell metabolism focused on bioenergetics, particularly enhanced glycolysis and suppressed oxidative phosphorylation (the ‘Warburg effect’). But the biosynthetic activities required to create daughter cells are equally important for tumor growth, and recent studies are now bringing these pathways into focus. In this review, we discuss how tumor cells achieve high rates of nucleotide and fatty acid synthesis, how oncogenes and tumor suppressors influence these activities, and how glutamine metabolism enables macromolecular synthesis in proliferating cells. PMID:18387799

Augmented reality in a tumor resection model.

PubMed

Chauvet, Pauline; Collins, Toby; Debize, Clement; Novais-Gameiro, Lorraine; Pereira, Bruno; Bartoli, Adrien; Canis, Michel; Bourdel, Nicolas

2018-03-01

Augmented Reality (AR) guidance is a technology that allows a surgeon to see sub-surface structures, by overlaying pre-operative imaging data on a live laparoscopic video. Our objectives were to evaluate a state-of-the-art AR guidance system in a tumor surgical resection model, comparing the accuracy of the resection with and without the system. Our system has three phases. Phase 1: using the MRI images, the kidney's and pseudotumor's surfaces are segmented to construct a 3D model. Phase 2: the intra-operative 3D model of the kidney is computed. Phase 3: the pre-operative and intra-operative models are registered, and the laparoscopic view is augmented with the pre-operative data. We performed a prospective experimental study on ex vivo porcine kidneys. Alginate was injected into the parenchyma to create pseudotumors measuring 4-10 mm. The kidneys were then analyzed by MRI. Next, the kidneys were placed into pelvictrainers, and the pseudotumors were laparoscopically resected. The AR guidance system allows the surgeon to see tumors and margins using classical laparoscopic instruments, and a classical screen. The resection margins were measured microscopically to evaluate the accuracy of resection. Ninety tumors were segmented: 28 were used to optimize the AR software, and 62 were used to randomly compare surgical resection: 29 tumors were resected using AR and 33 without AR. The analysis of our pathological results showed 4 failures (tumor with positive margins) (13.8%) in the AR group, and 10 (30.3%) in the Non-AR group. There was no complete miss in the AR group, while there were 4 complete misses in the non-AR group. In total, 14 (42.4%) tumors were completely missed or had a positive margin in the non-AR group. Our AR system enhances the accuracy of surgical resection, particularly for small tumors. Crucial information such as resection margins and vascularization could also be displayed.

Simple instruments facilitating achievement of transanal total mesorectal excision in male patients

PubMed Central

Xu, Chang; Song, Hua-Yu; Han, Shao-Liang; Ni, Shi-Chang; Zhang, Hu-Xiang; Xing, Chun-Gen

2017-01-01

AIM To assess the efficacy of a modified approach with transanal total mesorectal excision (taTME) using simple customized instruments in male patients with low rectal cancer. METHODS A total of 115 male patients with low rectal cancer from December 2006 to August 2015 were retrospectively studied. All patients had a bulky tumor (tumor diameter ≥ 40 mm). Forty-one patients (group A) underwent a classical approach of transabdominal total mesorectal excision (TME) and transanal intersphincteric resection (ISR), and the other 74 patients (group B) underwent a modified approach with transabdominal TME, transanal ISR, and taTME. Some simple instruments including modified retractors and an anal dilator with a papilionaceous fixture were used to perform taTME. The operative time, quality of mesorectal excision, circumferential resection margin, local recurrence, and postoperative survival were evaluated. RESULTS All 115 patients had successful sphincter preservation. The operative time in group B (240 min, range: 160-330 min) was significantly shorter than that in group A (280 min, range: 200-360 min; P = 0.000). Compared with group A, more complete distal mesorectum and total mesorectum were achieved in group B (100% vs 75.6%, P = 0.000; 90.5% vs 70.7%, P = 0.008, respectively). After 46.1 ± 25.6 mo follow-up, group B had a lower local recurrence rate and higher disease-free survival rate compared with group A, but these differences were not statistically significant (5.4% vs 14.6%, P = 0.093; 79.5% vs 65.1%, P = 0.130). CONCLUSION Retrograde taTME with simple customized instruments can achieve high-quality TME, and it might be an effective and economical alternative for male patients with bulky tumors. PMID:28883706

Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer.

PubMed

Strunk, H M; Henseler, J; Rauch, M; Mücke, M; Kukuk, G; Cuhls, H; Radbruch, L; Zhang, L; Schild, H H; Marinova, M

2016-07-01

Evaluation of ultrasound-guided high-intensity focused ultrasound (HIFU) used for the first time in Germany in patients with inoperable pancreatic cancer for reduction of tumor volume and relief of tumor-associated pain. 15 patients with locally advanced inoperable pancreatic cancer and tumor-related pain symptoms were treated by HIFU (n = 6 UICC stage III, n = 9 UICC stage IV). 13 patients underwent simultaneous standard chemotherapy. Ablation was performed using the JC HIFU system (Chongqing, China HAIFU Company) with an ultrasonic device for real-time imaging. Imaging follow-up (US, CT, MRI) and clinical assessment using validated questionnaires (NRS, BPI) was performed before and up to 15 months after HIFU. Despite biliary or duodenal stents (4/15) and encasement of visceral vessels (15/15), HIFU treatment was performed successfully in all patients. Treatment time and sonication time were 111 min and 1103 s, respectively. The applied total energy was 386 768 J. After HIFU ablation, contrast-enhanced imaging showed devascularization of treated tumor regions with a significant average volume reduction of 63.8 % after 3 months. Considerable pain relief was achieved in 12 patients after HIFU (complete or partial pain reduction in 6 patients). US-guided HIFU with a suitable acoustic pathway can be used for local tumor control and relief of tumor-associated pain in patients with locally advanced pancreatic cancer. • US-guided HIFU allows an additive treatment of unresectable pancreatic cancer.• HIFU can be used for tumor volume reduction.• Using HIFU, a significant reduction of cancer-related pain was achieved.• HIFU provides clinical benefit in patients with pancreatic cancer. Citation Format: • Strunk HM, Henseler J, Rauch M et al. Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer. Fortschr Röntgenstr 2016; 188: 662 - 670. © Georg Thieme Verlag KG

Insights into the regulation of tumor dormancy by angiogenesis in experimental tumors.

PubMed

Indraccolo, Stefano

2013-01-01

While it is well established that an angiogenic switch marks escape from tumor dormancy in xenograft models, the molecular pathways involved in the control of tumor cell proliferation or survival by angiogenesis remain substantially uncharted. We recently demonstrated that signals stemming from angiogenic endothelial cells (EC) regulate the behavior of dormant cancer cells. Specifically, we observed that the Notch ligand Dll4, induced by angiogenic factors in EC, triggers Notch3 activation in neighboring tumor cells and promotes a tumorigenic phenotype. Evidence that Notch signaling is involved in tumor dormancy was further strengthened by the observation that MKP-1 levels-a broadly expressed phosphatase-are controlled by Notch3 by regulation of protein ubiquitination and stability. Notch3 and MKP-1 levels are consistently low in dormant tumors, and this is accompanied by relatively high levels of phosphorylated p38, a canonical MKP-1 target previously associated with maintenance of tumor dormancy. These results elucidate a novel angiogenesis-driven mechanism involving the Notch and MAPK pathways that controls tumor dormancy. More in general, angiogenic EC could form part of the vascular niche, a specialized microenvironment which appears to regulate metastatic outgrowth and future studies are needed to clarify the contribution of EC in the regulation of cancer stem cell behavior in the niche.The notion that EC could communicate signals to tumor cells raises questions about the possibility of achieving tumor dormancy by counteracting angiogenesis. In experimental tumors, anti-VEGF drugs typically prune the newly formed vasculature, thus reducing microvessel density, blood flow, and perfusion. These drugs eventually increase hypoxia and cause tumor necrosis but dormancy is rarely observed. Our group recently reported that anti-VEGF therapy causes a dramatic depletion of glucose and an exhaustion of ATP levels in tumors. Moreover, we found that the central metabolic

Gastrointestinal stromal tumors: A multidisciplinary challenge

PubMed Central

Sanchez-Hidalgo, Juan Manuel; Duran-Martinez, Manuel; Molero-Payan, Rafael; Rufian-Peña, Sebastian; Arjona-Sanchez, Alvaro; Casado-Adam, Angela; Cosano-Alvarez, Antonio; Briceño-Delgado, Javier

2018-01-01

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors located in the alimentary tract. Its usual manifestation is gastrointestinal bleeding. However, small asymptomatic lesions are frequently detected as incidental finding. Characteristically, most GISTs (> 95%) are positive for the KIT protein (CD117) by IHC staining and approximately 80%-90% of GISTs carry a mutation in the c-KIT or PDGFRA genes. Mutational analysis should be performed when planning adjuvant and neoadjuvant therapy, due to its possible resistance to conventional treatment. The arise of tyrosine kinase inhibitor has supposed a revolution in GISTs treatment being useful as adjuvant, neoadjuvant or recurrence disease treatment. That is why a multidisciplinary approach to this disease is required. The correct characterization of the tumor at diagnosis (the diagnosis of recurrences and the evaluation of the response to treatment with tyrosine kinase inhibitors) is fundamental for facing these tumors and requires specialized Endoscopist, Radiologists and Nuclear Medicine Physician. Surgery is the only potentially curative treatment for suspected resectable GIST. In the case of high risk GISTs, surgery plus adjuvant Imatinib-Mesylate for 3 years is the standard treatment. Neoadjuvant imatinib-mesylate should be considered to shrink the tumor in case of locally advanced primary or recurrence disease, unresectable or potentially resectable metastasic tumors, and potentially resectable disease in complex anatomic locations to decrease the related morbidity. In the case of Metastatic GIST under Neoadjuvant treatment, when there are complete response, stable disease or limited disease progression, complete cytoreductive surgery could be a therapeutic option if feasible. PMID:29760538

[Surgical management of minor salivary gland tumors].

PubMed

Zhou, Liang; Chen, Xiaoling; Huang, Weiting; Li, Kelan; Zhang, Xiaotong; Wang, Wei

2007-11-01

To study the clinical features of minor salivary gland tumors and to discuss the treatment modalities for these tumors. Retrospective analysis of 54 cases with minor salivary gland tumor operated in our hospital from 1997 to 2004. Among 54 cases with minor salivary gland tumors in this series, 16 patients lost of follow up. Among the remaining 38 patients, 2 patients with nasal cavity adenoid cystic carcinoma died of tumor recurrence 2 and 3 years after the surgery respectively, one patient with laryngeal myoepithelial carcinoma died of tumor recurrence 3 years after the surgery and one patient with paranasal sinus mucoepidermoid carcinoma died of recurrence 17 months after the surgery. Two patients with paranasal sinus adenoid cystic carcinoma recurred after the primary surgery and were survived without tumor after salvage surgery. The other patients survived with no tumor recurrence. While different histopathology of minor salivary gland tumors were found in this group, malignant tumors were predominant, accounting for 81.4%. The choice of treatment for minor salivary gland tumors depends upon the location and the histopathology of the tumors. The treatment policy for benign tumors is simple tumor excision, while that for malignant tumors is surgery combined with pre- or post-operative radiation therapy. Complete surgical resection of tumor masses and tumor free margin is essential for successful treatment of malignant minor salivary gland tumors.

Improved in-plane visibility of tumors using breast tomosynthesis

NASA Astrophysics Data System (ADS)

Ruschin, Mark; Timberg, Pontus; Svahn, Tony; Andersson, Ingvar; Hemdal, Bengt; Mattsson, Sören; Båth, Magnus; Tingberg, Anders

2007-03-01

The purpose of this work was to evaluate and compare the visibility of tumors in digital mammography (DM) and breast tomosynthesis (BT) images. Images of the same women were acquired on both a DM system (Mammomat Novation, Siemens) and a BT prototype system adapted from the same type of DM system. Simulated 3D tumors (average dimension: 8.4 mm x 6.6 mm x 5 mm) were projected and added to each DM image as well as each BT projection image prior to 3D reconstruction. The same beam quality and approximately the same total absorbed dose were used for each breast image acquisition on both systems. Two simulated tumors were added to each of thirty breast scans, yielding sixty cases. A series of 4-alternative forced choice (4-AFC) human observer performance experiments were conducted in order to determine what projected tumor signal intensity in the DM images would be needed to achieve the same detectability as in the reconstructed BT images. Nine observers participated. For the BT experiment, when the tumor signal intensity on the central projection was 0.010 the mean percent of correct responses (PC) was measured to be 81.5%, which converted to a detectability index value (d') of 1.96. For the DM experiments, the same detectability was achieved at a signal intensity determined to be 0.038. Equivalent tumor detection in BT images were thus achieved at around four times less projected signal intensity than in DM images, indicating that the use of BT may lead to earlier detection of breast cancer.

Extravascular use of drug-eluting beads: A promising approach in compartment-based tumor therapy

PubMed Central

Binder, Simon; Lewis, Andrew L; Löhr, J-Matthias; Keese, Michael

2013-01-01

Intraperitoneal carcinomatosis (PC) may occur with several tumor entities. The prognosis of patients suffering from PC is usually poor. Present treatment depends on the cancer entity and includes systemic chemotherapy, radiation therapy, hormonal therapy and surgical resection. Only few patients may also benefit from hyperthermic intraperitoneal chemotherapy with a complete tumor remission. These therapies are often accompanied by severe systemic side-effects. One approach to reduce side effects is to target chemotherapeutic agents to the tumor with carrier devices. Promising experimental results have been achieved using drug-eluting beads (DEBs). A series of in vitro and in vitro experiments has been conducted to determine the suitability of their extravascular use. These encapsulation devices were able to harbor CYP2B1 producing cells and to shield them from the hosts immune system when injected intratumorally. In this way ifosfamide - which is transformed into its active metabolites by CYP2B1 - could be successfully targeted into pancreatic tumor growths. Furthermore DEBs can be used to target chemotherapeutics into the abdominal cavity for treatment of PC. If CYP2B1 producing cells are proven to be save for usage in man and if local toxic effects of chemotherapeutics can be controlled, DEBs will become promising tools in compartment-based anticancer treatment. PMID:24282349

The effect of surgery and grade on outcome of gastrointestinal stromal tumors.

PubMed

Pierie, J P; Choudry, U; Muzikansky, A; Yeap, B Y; Souba, W W; Ott, M J

2001-04-01

Gastrointestinal stromal tumors (GIST) are aggressive, rare, and difficult-to-cure gastrointestinal tumors. We believe that the clinical behavior of these tumors can be predicted by reproducible prognostic factors. A retrospective review of all patients (N = 70) with GIST treated at a tertiary care center from 1973 to 1998. Adequate data for evaluation were available for 69 patients. Male-female distribution was 40:29. Median age was 60 years. Median follow-up duration was 38 months. Tumor grade, stage, and histologic subtype at presentation; effect of grade, surgery and adjuvant therapy on recurrence, salvage, and survival. Tumor distribution included 61% in the upper, 23% in the middle, and 16% in the lower digestive tract, with a median tumor size of 7.9 cm (range, 1.8-25 cm). Tumors with more than 1 mitosis per 10 high-power fields constituted 57% of neoplasia in the series. Distant disease at initial visit occurred in 49% of patients. Complete gross resection occurred in 59% of patients. After complete resection, the 5-year survival rate was 42%, compared with 9% after incomplete resection (hazard ratio = 0.27, P<.001). Neither radiation nor chemotherapy demonstrated any significant benefit. Among 39 patients who were disease free after complete resection, 2% developed lymph node recurrence, 25% developed local recurrence, and 33% developed distant recurrences (54% liver, 20% peritoneum). By multivariate analysis the risk of local and/or distant metastases was significantly increased for tumors with more than 1 mitosis and size larger than 5 cm (P<.05). Multivariate analysis in all 69 patients revealed that incomplete resection, age greater than 50 years, non-smooth muscle histological feature, tumor with more than 1 mitosis, and tumor size larger than 5 cm significantly decreased survival. Complete gross surgical resection is presently the only means of cure for GIST. Tumors with more than 1 mitosis and a size larger than 5 cm have an especially poor

Anti-tumor effects of nitrosylcobalamin against spontaneous tumors in dogs.

PubMed

Bauer, Joseph A; Frye, Gerald; Bahr, Anne; Gieg, Jennifer; Brofman, Peter

2010-10-01

Given the limited options available to treat canine cancers, the use of companion animals for evaluating new drugs may identify better therapies for veterinary and human oncology. The anti-tumor effects of nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin B12-based carrier of nitric oxide (NO), was evaluated in four dogs with spontaneous cancer. (1) A 13 year-old female spayed Giant Schnauzer with inoperable thyroid carcinoma and hypercalcemia. (2) A 6 year-old male neutered Golden Retriever with a malignant peripheral nerve sheath tumor (MPNST). (3) A ten yr-old neutered male Bichon Frise with apocrine gland anal sac adenocarcinoma (AGACA). (4) A 7 year-old female spayed Labrador mix with spinal meningioma following partial surgical resection. Tumor regression was measured by physical exam and verified using ultrasound (case 1) and MRI (case 2-4). Serum chemistries and hematologic parameters were monitored throughout the studies. (1) The Giant Schnauzer demonstrated a 77% reduction in tumor volume after ten weeks of daily NO-Cbl treatment. (2) The Golden Retriever demonstrated a 53% reduction in tumor volume after 15 months of daily NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43% regression of the primary tumor and a 90% regression of an iliac lymph node measured by MRI after 15 months of treatment. After 61 months, the dog currently has stable disease, normal liver enzymes, CBC analysis, and no evidence of toxicity. (4) The Labrador demonstrated complete regression of the residual tumor after 6 months of treatment. We have shown previously that NO-Cbl is endocytosed by malignant cells, resulting in intra-tumoral NO release. In this study, we have shown that daily long-term use of NO-Cbl induced responses in all dogs without any signs of toxicity. The use of NO-Cbl capitalizes on the tumor-specific properties of the vitamin B12 receptor and represents a promising anti-cancer therapy.

Highly Specific and Sensitive Fluorescent Nanoprobes for Image-Guided Resection of Sub-Millimeter Peritoneal Tumors.

PubMed

Colby, Aaron H; Berry, Samantha M; Moran, Ann M; Pasion, Kristine Amber; Liu, Rong; Colson, Yolonda L; Ruiz-Opazo, Nelson; Grinstaff, Mark W; Herrera, Victoria L M

2017-02-28

A current challenge in the treatment of peritoneal carcinomatosis is the inability to detect, visualize, and resect small or microscopic tumors of pancreatic, ovarian, or mesothelial origin. In these diseases, the completeness of primary tumor resection is directly correlated with patient survival, and hence, identifying small sub-millimeter tumors (i.e., disseminated disease) is critical. Thus, new imaging techniques and probes are needed to improve cytoreductive surgery and patient outcomes. Highly fluorescent rhodamine-labeled expansile nanoparticles (HFR-eNPs) are described for use as a visual aid during cytoreductive surgery of pancreatic carcinomatosis. The covalent incorporation of rhodamine into ∼30 nm eNPs increases the fluorescent signal compared to free rhodamine, thereby affording a brighter and more effective probe than would be achieved by a single rhodamine molecule. Using the intraperitoneal route of administration, HFR-eNPs localize to regions of large (∼1 cm), sub-centimeter, and sub-millimeter intraperitoneal tumor in three different animal models, including pancreatic, mesothelioma, and ovarian carcinoma. Tumoral localization of the HFR-eNPs depends on both the material property (i.e., eNP polymer) as well as the surface chemistry (anionic surfactant vs PEGylated noncharged surfactant). In a rat model of pancreatic carcinomatosis, HFR-eNP identification of tumor is validated against gold-standard histopathological analysis to reveal that HFR-eNPs possess high specificity (99%) and sensitivity (92%) for tumors, in particular, sub-centimeter and microscopic sub-millimeter tumors, with an overall accuracy of 95%. Finally, as a proof-of-concept, HFR-eNPs are used to guide the resection of pancreatic tumors in a rat model of peritoneal carcinomatosis.

Oncogene cooperation in tumor maintenance and tumor recurrence in mouse mammary tumors induced by Myc and mutant Kras.

PubMed

Podsypanina, Katrina; Politi, Katerina; Beverly, Levi J; Varmus, Harold E

2008-04-01

Most, if not all, cancers are composed of cells in which more than one gene has a cancer-promoting mutation. Although recent evidence has shown the benefits of therapies targeting a single mutant protein, little attention has been given to situations in which experimental tumors are induced by multiple cooperating oncogenes. Using combinations of doxycycline-inducible and constitutive Myc and mutant Kras transgenes expressed in mouse mammary glands, we show that tumors induced by the cooperative actions of two oncogenes remain dependent on the activity of a single oncogene. Deinduction of either oncogene individually, or both oncogenes simultaneously, led to partial or complete tumor regression. Prolonged remission followed deinduction of Kras(G12D) in the context of continued Myc expression, deinduction of a MYC transgene with continued expression of mutant Kras produced modest effects on life extension, whereas simultaneous deinduction of both MYC and Kras(G12D) transgenes further improved survival. Disease relapse after deinduction of both oncogenes was associated with reactivation of both oncogenic transgenes in all recurrent tumors, often in conjunction with secondary somatic mutations in the tetracycline transactivator transgene, MMTV-rtTA, rendering gene expression doxycycline-independent. These results demonstrate that tumor viability is maintained by each gene in a combination of oncogenes and that targeted approaches will also benefit from combination therapies.

High School Completion Longitudinal Study

ERIC Educational Resources Information Center

Alberta Education, 2009

2009-01-01

While Alberta enjoys proven high, world-class results in student achievement, raising high school completion rates is one of the top priorities in improving the provincial education system. The 2011-12 targeted high school completion rate is 82% five years after entering Grade 10--a 2.5% increase from the current average rate of 79.5%. The purpose…

Complete remission of liver metastasis in a lung cancer patient with epidermal growth factor mutation achieved with Icotinib.

PubMed

Zhu, Zhouyu; Chai, Ying

2016-11-01

A 65-year-old Chinese male was referred to our hospital for epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC). Aggressive combined therapy with surgical resection of the right upper lung lesion and chemotherapy was performed. One month later, continued Icotinib treatment was used as magnetic resonance imaging revealed liver metastasis (LM). Interestingly, complete remission of the patient's LM lesions was achieved in six months. To our knowledge, this is the first report documenting a successful case of an NSCLC patient with LM treated with Icotinib after receiving a radical resection for pulmonary carcinoma. Our experience could provide a treatment strategy for patients with similar disease. © 2016 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Social Perceptions of Achieving Students and Achievement Goals of Students in Malaysia and the Philippines

ERIC Educational Resources Information Center

Bernardo, Allan B. I.; Ismail, Rosnah

2010-01-01

The study investigates the hypothesis that country differences in achievement goals of students are associated with differences in how students with different achievement goals are perceived by students in different cultures. University students from Malaysia and the Philippine were asked to complete questionnaires on their achievement goals and…

Desmoid tumors of the abdominal wall: A case report

PubMed Central

Overhaus, Marcus; Decker, Pan; Fischer, Hans Peter; Textor, Hans Jochen; Hirner, Andreas

2003-01-01

Background Desmoid tumors are slow growing deep fibromatoses with aggressive infiltration of adjacent tissue but without any metastatic potential. Case Presentation We report on two female patients with desmoid tumor of the abdominal wall who underwent primary resection. Both patients had a history of an earlier abdominal surgery. Preoperative evaluation included abdominal ultrasound, magnetic resonance imaging and computed tomography. The histology in both cases revealed a desmoid tumor. Conclusion Complete surgical resection is the first line management of this tumor entity. PMID:12890284

Effect of increasing radiation dose on pathologic complete response in rectal cancer patients treated with neoadjuvant chemoradiation therapy.

PubMed

Hall, Matthew D; Schultheiss, Timothy E; Smith, David D; Fakih, Marwan G; Wong, Jeffrey Y C; Chen, Yi-Jen

2016-12-01

Neoadjuvant chemoradiation therapy (CRT) increases pathological complete response (pCR) rates compared to radiotherapy alone in patients with stage II-III rectal cancer. Limited evidence addresses whether radiotherapy dose escalation further improves pCR rates. Our purpose is to measure the effects of radiotherapy dose and other factors on post-therapy pathologic tumor (ypT) and nodal stage in rectal cancer patients treated with neoadjuvant CRT followed by mesorectal excision. A non-randomized comparative effectiveness analysis was performed of rectal cancer patients treated in 2000-2013 from the National Oncology Data Alliance™ (NODA), a pooled database of cancer registries from >150 US hospitals. The NODA contains the same data submitted to state cancer registries and SEER combined with validated radiotherapy and chemotherapy records. Eligible patients were treated with neoadjuvant CRT followed by proctectomy and had complete data on treatment start dates, radiotherapy dose, clinical tumor (cT) and ypT stage, and number of positive nodes at surgery (n = 3298 patients). Multivariable logistic regression was used to assess the predictive value of independent variables on achieving a pCR. On multivariable regression, radiotherapy dose, cT stage, and time interval between CRT and surgery were significant predictors of achieving a pCR. After adjusting for the effect of other variates, patients treated with higher radiotherapy doses were also more likely to have negative nodes at surgery and be downstaged from cT3-T4 and/or node positive disease to ypT0-T2N0 after neoadjuvant CRT. Our study suggests that increasing dose significantly improved pCR rates and downstaging in rectal cancer patients treated with neoadjuvant CRT followed by surgery.

[A Case of Duodenal Invasive Advanced Gastric Cancer in Which the Primary Tumor Achieved pCR, but Viable Cancer Cells Remained in Lymph Node No.13 after Neoadjuvant Chemotherapy].

PubMed

Kubota, Tetsushi; Choda, Yasuhiro; Morito, Toshiaki; Miyake, Soichiro; Ishida, Michihiro; Sato, Daisuke; Sumitani, Daisuke; Nakano, Kanyu; Harano, Masao; Matsukawa, Hiroyoshi; Ojima, Yasutomo; Idani, Hitoshi; Shiozaki, Shigehiro; Okajima, Masazumi

2017-11-01

A woman approximately 70-years-old with duodenal invasive advanced gastric cancer was referred to our hospital. Meta- stasis to lymph node(LN)No.13 was suspected based on FDG/PET-CT. For better curability, we selected neoadjuvant chemotherapy( NAC)with S-1 plus oxaliplatin(SOX therapy). After 3 courses of SOX, distal gastrectomy with D2(+No.13) lymphadenectomy was performed. Upon pathological evaluation, no viable cancer cells were found in the primary tumor, but viable cancer cells were identified in LN No.6 and 13. LN No.13 was defined as M1 according to the current Japanese classification of gastric carcinoma. On the other hand, the 2014 Japanese gastric cancer treatment guidelines(ver. 4)mentioned that D2(+No.13)lymphadenectomy may be an option in potentially curative gastrectomy for tumors invading the duodenum. This case suggests that No.13 lymphadenectomy is necessary as a curative operation for duodenal invasive advanced gastric cancer, even if the primary tumor has achieved pCR after NAC.

Enhancement of Cancer Vaccine Therapy by Systemic Delivery of a Tumor Targeting Salmonella-based STAT3 shRNA Suppresses the Growth of Established Melanoma Tumors

PubMed Central

Manuel, Edwin R.; Blache, Céline A.; Paquette, Rebecca; Kaltcheva, Teodora I.; Ishizaki, Hidenobu; Ellenhorn, Joshua D.I.; Hensel, Michael; Metelitsa, Leonid; Diamond, Don J.

2011-01-01

Cancer vaccine therapies have only achieved limited success when focusing on effector immunity with the goal of eliciting robust tumor-specific T cell responses. More recently, there is an emerging understanding that effective immunity can only be achieved by coordinate disruption of tumor-derived immune suppression. Towards that goal, we have developed a potent Salmonella-based vaccine expressing codon-optimized survivin (CO-SVN) referred to as 3342Max. When used alone as a therapeutic vaccine, 3342Max can attenuate growth of aggressive murine melanomas overexpressing SVN. However, under more immunosuppressive conditions, such as those associated with larger tumor volumes, we found that the vaccine was ineffective. Vaccine efficacy could be rescued if tumor-bearing mice were treated initially with Salmonella encoding a shRNA targeting the tolerogenic molecule STAT3 (YS1646-shSTAT3). In vaccinated mice, silencing STAT3 increased the proliferation and granzyme B levels of intratumoral CD4+ and CD8+ T cells. The combined strategy also increased apoptosis in tumors of treated mice, enhancing tumor-specific killing of tumor targets. Interestingly, mice treated with YS1646-shSTAT3 or 3342Max alone were similarly unsuccessful in rejecting established tumors, while the combined regimen was highly potent. Our findings establish that a combined strategy of silencing immunosuppressive molecules followed by vaccination can act synergistically to attenuate tumor growth, and they offer a novel translational direction to improve tumor immunotherapy. PMID:21527558

Targeting tumor hypoxia with 2-nitroimidazole-indocyanine green dye conjugates

PubMed Central

Xu, Yan; Zanganeh, Saeid; Mohammad, Innus; Aguirre, Andres; Wang, Tianheng; Yang, Yi; Kuhn, Liisa; Smith, Michael B.

2013-01-01

Abstract. Tumor hypoxia is a major indicator of treatment resistance to chemotherapeutic drugs, and fluorescence optical tomography has tremendous potential to provide clinically useful, functional information by identifying tumor hypoxia. The synthesis of a 2-nitroimidazole-indocyanine green conjugate using a piperazine linker (piperazine-2-nitroimidazole-ICG) capable of robust fluorescent imaging of tumor hypoxia is described. In vivo mouse tumor imaging studies were completed and demonstrate an improved imaging capability of the new dye relative to an earlier version of the dye that was synthesized with an ethanolamine linker (ethanolamine-2-nitroimidazole-ICG). Mouse tumors located at imaging depths of 1.5 and 2.0 cm in a turbid medium were imaged at various time points after intravenous injection of the dyes. On average, the reconstructed maximum fluorescence concentration of the tumors injected with piperazine-2-nitroimidazole-ICG was twofold higher than that injected with ethanolamine-2-nitroimidazole-ICG within 3 h postinjection period and 1.6 to 1.7 times higher beyond 3 h postinjection. The untargeted bis-carboxylic acid ICG completely washed out after 3 h postinjection. Thus, the optimal window to assess tumor hypoxia is beyond 3 h postinjection. These findings were supported with fluorescence images of histological sections of tumor samples and an immunohistochemistry technique for identifying tumor hypoxia. PMID:23764695

Submucosal tunneling endoscopic resection using methylene-blue guidance for cardial subepithelial tumors originating from the muscularis propria layer.

PubMed

Mao, Xin-Li; Ye, Li-Ping; Zheng, Hai-Hong; Zhou, Xian-Bin; Zhu, Lin-Hong; Zhang, Yu

2017-02-01

Submucosal tunneling endoscopic resection (STER) of subepithelial tumors (SETs) originating from the muscularis propria (MP) layer in the cardia is rarely performed due to the difficulty of creating a submucosal tunnel for resection. The aim of this study was to evaluate the feasibility of STER using methylene-blue guidance for SETs originating from the MP layer in the cardia. From January 2012 to December 2014, 56 patients with SETs originating from the MP layer in the cardia were treated with STER using methylene-blue guidance. The complete resection rate and adverse event rate were the main outcome measurements. Successful complete resection by STER was achieved in all 56 cases (100%). The median size of the tumor was 1.8 cm. Nine patients (15.3%) had adverse events including subcutaneous emphysema, pneumoperitoneum, pneumothorax, and pleural effusion. These nine patients recovered successfully after conservative treatment without endoscopic or surgical intervention. No residual or recurrent tumors were detected in any patient during the follow-up period (median, 25 months). The adverse event rate was significantly higher for tumors originating in the deeper MP layers (46.7%) than in the superficial MP layers (4.9%) (P < 0.05), differed significantly according to tumor size (5.4% for tumors < 2.0 cm vs. 36.8% for tumors ≥ 2.0 cm; P < 0.05), and also differed significantly in relation to the tumor growth pattern (4.1% for the intraluminal growth vs. 100% for the extraluminal growth; P < 0.001). STER using methylene-blue guidance appears to be a feasible method for removing SETs originating from the MP layer in the cardia. © 2017 International Society for Diseases of the Esophagus.

College Enrollment and Completion among Nationally Recognized High-Achieving Hispanic Students

ERIC Educational Resources Information Center

Gurantz, Oded; Hurwitz, Michael; Smith, Jonathan

2017-01-01

Hispanic high school graduates have lower college completion rates than academically similar white students. As Hispanic students have been theorized to be more constrained in the college search and selection process, one potential policy lever is to increase the set of colleges to which these students apply and attend. In this paper, we…

Spontaneous complete necrosis of advanced hepatocellular carcinoma.

PubMed

Yokoyama, Tadashi; Yoshida, Hiroshi; Hirakata, Atsushi; Makino, Hiroshi; Maruyama, Hiroshi; Suzuki, Seiji; Matsutani, Takeshi; Hayakawa, Tomohiro; Hosone, Masaru; Uchida, Eiji

2012-01-01

We present a rare case of hepatocellular carcinoma (HCC) in which spontaneous complete necrosis was confirmed with surgical resection. An 80-year-old man with HCC was referred to Nippon Medical School Tama Nagayama Hospital. The medical history included hypertension, managed with medication, and partial lobectomy of the lung owing to a lung schwannoma. A previously untreated abdominal aortic aneurysm, 51 mm in maximum diameter, was detected. The serum concentration of proteins induced by vitamin k antagonism or absence (PIVKA-2) was 14,300 mAU/mL, and that of alpha-fetoprotein was 184.2 ng/mL. Antibodies against hepatitis B surface antigens and hepatitis C virus were not detected in the serum. Computed tomography (CT) demonstrated a hypervascular tumor, 68 mm in diameter, in the left paramedian sector of the liver with washout of contrast medium in the delayed phase. An HCC in the left paramedian sector was diagnosed. Laparotomy was performed 40 days after CT scanning. Intraoperative ultrasonography showed that the HCC had shrunk to 30 mm in diameter. A left paramedian sectionectomy was performed. On macroscopic examination the surgical specimen was a firm mass, 30 mm in diameter, with a fibrous capsule. Histologic examination showed that the tumor in the cirrhotic liver had been completely replaced by central coagulative necrosis, circumferential fibrosis, and dense infiltrates of inflammatory cells. No viable HCC cells were observed in the coagulative necrosis. Organized thrombi in the hepatic artery were detected in the tumor. The tumor also contained multiple foci of old hemorrhage, ductular proliferation, and granulation tissue. The patient was discharged 10 days after the operation. After 1 month, the serum concentrations of PIVKA-2 (25 mAU/mL) and alpha-fetoprotein (5.9 ng/mL) had decreased to within their normal ranges.

Recurrence of chronic active Epstein-Barr virus infection from donor cells after achieving complete response through allogeneic bone marrow transplantation.

PubMed

Arai, Ayako; Imadome, Ken-ichi; Wang, Ludan; Wu, Nan; Kurosu, Tetsuya; Wake, Atsushi; Yamamoto, Hisashi; Ota, Yasunori; Harigai, Masayoshi; Fujiwara, Shigeyoshi; Miura, Osamu

2012-01-01

We report the case of a 35-year-old woman with chronic active Epstein-Barr virus (EBV) infection (CAEBV). She underwent allogeneic bone marrow transplantation (BMT) from an unrelated male donor and achieved a complete response. However, her CAEBV relapsed one year after BMT. EBV-infected cells proliferated clonally and revealed a 46XY karyotype. In addition, the infecting EBV strain differed from that detected before BMT. These findings indicated that her disease had developed from donor cells. This is the first report of donor cell-derived CAEBV that recurred after transplantation, suggesting that host factors may be responsible for the development of this disease.

Innovative Delivery of siRNA to Solid Tumors by Super Carbonate Apatite

PubMed Central

Wu, Xin; Yamamoto, Hirofumi; Nakanishi, Hiroyuki; Yamamoto, Yuki; Inoue, Akira; Tei, Mitsuyoshi; Hirose, Hajime; Uemura, Mamoru; Nishimura, Junichi; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Hossain, Sharif; Akaike, Toshihiro; Matsuura, Nariaki; Doki, Yuichiro; Mori, Masaki

2015-01-01

RNA interference (RNAi) technology is currently being tested in clinical trials for a limited number of diseases. However, systemic delivery of small interfering RNA (siRNA) to solid tumors has not yet been achieved in clinics. Here, we introduce an in vivo pH-sensitive delivery system for siRNA using super carbonate apatite (sCA) nanoparticles, which is the smallest class of nanocarrier. These carriers consist simply of inorganic ions and accumulate specifically in tumors, yet they cause no serious adverse events in mice and monkeys. Intravenously administered sCA-siRNA abundantly accumulated in the cytoplasm of tumor cells at 4 h, indicating quick achievement of endosomal escape. sCA-survivin-siRNA induced apoptosis in HT29 tumors and significantly inhibited in vivo tumor growth of HCT116, to a greater extent than two other in vivo delivery reagents. With innovative in vivo delivery efficiency, sCA could be a useful nanoparticle for the therapy of solid tumors. PMID:25738937

Innovative delivery of siRNA to solid tumors by super carbonate apatite.

PubMed

Wu, Xin; Yamamoto, Hirofumi; Nakanishi, Hiroyuki; Yamamoto, Yuki; Inoue, Akira; Tei, Mitsuyoshi; Hirose, Hajime; Uemura, Mamoru; Nishimura, Junichi; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Hossain, Sharif; Akaike, Toshihiro; Matsuura, Nariaki; Doki, Yuichiro; Mori, Masaki

2015-01-01

RNA interference (RNAi) technology is currently being tested in clinical trials for a limited number of diseases. However, systemic delivery of small interfering RNA (siRNA) to solid tumors has not yet been achieved in clinics. Here, we introduce an in vivo pH-sensitive delivery system for siRNA using super carbonate apatite (sCA) nanoparticles, which is the smallest class of nanocarrier. These carriers consist simply of inorganic ions and accumulate specifically in tumors, yet they cause no serious adverse events in mice and monkeys. Intravenously administered sCA-siRNA abundantly accumulated in the cytoplasm of tumor cells at 4 h, indicating quick achievement of endosomal escape. sCA-survivin-siRNA induced apoptosis in HT29 tumors and significantly inhibited in vivo tumor growth of HCT116, to a greater extent than two other in vivo delivery reagents. With innovative in vivo delivery efficiency, sCA could be a useful nanoparticle for the therapy of solid tumors.

Adenocarcinoma arising in warthin tumor of the parotid gland.

PubMed

Sayar, Hamide; Öztarakçi, Hüseyin; Sayar, Çağdaş; Ağirbaş, Şule

2012-01-01

Warthin tumor is a well-defined benign salivary gland neoplasm consisting of both epithelial and lymphoid components. The tumor is the second most common benign tumor next to pleomorphic adenoma. We present a case of adenocarcinoma, not otherwise classified, arising in unilateral Warthin tumor of the parotid gland in a 63-year-old male patient. Carcinomas arising in or from the epithelial component of a preexisting parotid Warthin tumor are rare and differential diagnosis of metastasis from an adenocarcinoma in Warthin tumor is important. The patient underwent a complete and thorough work-up, and no other primary malignant lesion was found. No other primary malignant lesion had manifested at the last one year follow-up period.

Prognostic value of tumor-stroma ratio combined with the immune status of tumors in invasive breast carcinoma.

PubMed

Vangangelt, K M H; van Pelt, G W; Engels, C C; Putter, H; Liefers, G J; Smit, V T H B M; Tollenaar, R A E M; Kuppen, P J K; Mesker, W E

2018-04-01

Complex interactions occur between cancer cells and cells in the tumor microenvironment. In this study, the prognostic value of the interplay between tumor-stroma ratio (TSR) and the immune status of tumors in breast cancer patients was evaluated. A cohort of 574 breast cancer patients was analyzed. The percentage of tumor stroma was visually estimated on Hematoxylin and Eosin (H&E) stained histological tumor tissue sections. Immunohistochemical staining was performed for classical human leukocyte antigen (HLA) class I, HLA-E, HLA-G, markers for regulatory T (Treg) cells, natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs). TSR (P < .001) and immune status of tumors (P < .001) were both statistically significant for recurrence free period (RFP) and both independent prognosticators (P < .001) in which tumors with a high stromal content behave more aggressively as well as tumors with a low immune status. Ten years RFP for patients with a stroma-low tumor and high immune status profile was 87% compared to 17% of patients with a stroma-high tumor combined with low immune status profile (P < .001). Classical HLA class I is the most prominent immune marker in the immune status profiles. Determination of TSR is a simple, fast and cheap method. The effect on RFP of TSR when combined with immune status of tumors or expression of classical HLA class I is even stronger. Both are promising for further prediction and achievement of tailored treatment for breast cancer patients.

Phase I study of single-agent ribociclib in Japanese patients with advanced solid tumors.

PubMed

Doi, Toshihiko; Hewes, Becker; Kakizume, Tomoyuki; Tajima, Takeshi; Ishikawa, Norifumi; Yamada, Yasuhide

2018-01-01

The cyclin D-CDK4/6-INK4-Rb pathway is frequently dysregulated in cancers. Ribociclib, an orally available, selective CDK4/6 inhibitor, showed preliminary clinical activity in a phase I study in the USA and Europe for patients with solid tumors and lymphomas. The present study aimed to determine the single-agent maximum tolerated dose (MTD) and recommended dose for expansion (RDE) in Japanese patients with advanced solid tumors. Ribociclib safety, tolerability, pharmacokinetic profile, and preliminary antitumor activity were also assessed. Japanese patients with solid tumors that had progressed on prior therapies received escalating doses of single-agent ribociclib on a 3-weeks-on/1-week-off schedule. Treatment continued until the development of toxicity or disease progression. A dose escalation was planned for patients with esophageal cancer. In the dose-escalation phase, 4 patients received 400 mg ribociclib and 13 patients received 600 mg ribociclib. Four patients experienced dose-limiting toxicities, 3 of whom were in the 600 mg group. The RDE was declared to be 600 mg, and the MTD was not determined. The most frequent adverse events were hematologic and gastrointestinal. Four patients achieved stable disease at the 600 mg dose; no patients achieved complete or partial response. All patients discontinued the study, the majority due to disease progression. No patients discontinued due to adverse events. Dose escalation was not pursued due to lack of observed efficacy in esophageal cancer. At the RDE of 600 mg/d on a 3-weeks-on/1-week-off schedule, ribociclib showed acceptable safety and tolerability profiles in Japanese patients with advanced solid tumors. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Angiogenic inhibitors delivered by the type III secretion system of tumor-targeting Salmonella typhimurium safely shrink tumors in mice.

PubMed

Shi, Lei; Yu, Bin; Cai, Chun-Hui; Huang, Jian-Dong

2016-12-01

Despite of a growing number of bacterial species that apparently exhibit intrinsic tumor-targeting properties, no bacterium is able to inhibit tumor growth completely in the immunocompetent hosts, due to its poor dissemination inside the tumors. Oxygen and inflammatory reaction form two barriers and restrain the spread of the bacteria inside the tumors. Here, we engineered a Salmonella typhimurium strain named ST8 which is safe and has limited ability to spread beyond the anaerobic regions of tumors. When injected systemically to tumor-bearing immunocompetent mice, ST8 accumulated in tumors at levels at least 100-fold greater than parental obligate anaerobic strain ST4. ST8/pSEndo harboring therapeutic plasmids encoding Endostatin fused with a secreted protein SopA could target vasculature at the tumor periphery, can stably maintain and safely deliver a therapeutic vector, release angiogenic inhibitors through a type III secretion system (T3SS) to interfere with the pro-angiogenic action of growth factors in tumors. Mice with murine CT26 colon cancer that had been injected with ST8/pSEndo showed efficient tumor suppression by inducing more severe necrosis and inhibiting blooding vessel density within tumors. Our findings provide a therapeutic platform for indirectly acting therapeutic strategies such as anti-angiogenesis and immune therapy.

Impact of Race, Ethnicity and BMI on Achievement of Pathologic Complete Response Following Neoadjuvant Chemotherapy for Breast Cancer: A Pooled Analysis of Four Prospective Alliance Clinical Trials (A151426)

PubMed Central

Warner, Erica T.; Ballman, Karla V.; Strand, Carrie; Boughey, Judy; Buzdar, Aman U.; Carey, Lisa A.; Sikov, William M.; Partridge, H.

2016-01-01

Purpose Previous studies demonstrated poor response to neoadjuvant systemic therapy (NST) for breast cancer among black women and women who are overweight or obese but this may be due to chemotherapy under dosing. We assessed associations of race, ethnicity and body mass index (BMI) with pathologic complete response (pCR) in clinical trial populations. Methods 1797 women enrolled in four NST trials (CALGB 40601, 40603; ACOSOG Z1041, Z1071) were included. Tumor subtypes were defined by estrogen receptor (ER) and HER2 status. Logistic regression generated odds ratios (OR) and 95% confidence intervals (CI) for the associations of race, ethnicity, and BMI with pCR adjusting for subtype, study arm, lymph node status, tumor size, and tumor grade. Results 253 (14.1%) were black, 199 (11.1%) Hispanic, 520 (28.9%) overweight, and 743 (41.4%) obese. Compared to whites, Blacks and Hispanics were more likely to be obese and Blacks were more likely to have triple-negative cancer. pCR rates differed significantly by tumor subtype. In multivariate analyses, neither race (black vs. white: OR: 1.18, 95% CI: 0.85–1.62) nor ethnicity (Hispanic vs. non-Hispanic: OR: 1.30, 95% CI: 0.67–2.53) were significant predictors of pCR overall or by subtype. Overweight and obese women had lower pCR rates in ER+/HER2+, but higher pCR rates in ER−/HER2+ cancers. Conclusions There was no difference in breast pCR according to race or ethnicity. Overall, there was no major difference in pCR rates by BMI. These findings suggest that pCR with optimally dosed NST is a function of tumor, rather than patient, biology. PMID:27449492

Impact of race, ethnicity, and BMI on achievement of pathologic complete response following neoadjuvant chemotherapy for breast cancer: a pooled analysis of four prospective Alliance clinical trials (A151426).

PubMed

Warner, Erica T; Ballman, Karla V; Strand, Carrie; Boughey, Judy C; Buzdar, Aman U; Carey, Lisa A; Sikov, William M; Partridge, Ann H

2016-08-01

Previous studies demonstrated poor response to neoadjuvant systemic therapy (NST) for breast cancer among black women and women who are overweight or obese, but this may be due to chemotherapy underdosing. We assessed associations of race, ethnicity, and body mass index (BMI) with pathologic complete response (pCR) in clinical trial populations. 1797 women enrolled in four NST trials (CALGB 40601, 40603; ACOSOG Z1041, Z1071) were included. Tumor subtypes were defined by estrogen receptor (ER) and HER2 status. Logistic regression generated odds ratios (OR) and 95 % confidence intervals (CI) for the associations of race, ethnicity, and BMI with in-breast pCR adjusting for subtype, study arm, lymph node status, tumor size, and tumor grade. 253 (14.1 %) were black, 199 (11.1 %) Hispanic, 520 (28.9 %) overweight, and 743 (41.4 %) obese. Compared to whites, Blacks and Hispanics were more likely to be obese and Blacks were more likely to have triple-negative cancer. pCR rates differed significantly by tumor subtype. In multivariate analyses, neither race (black vs white: OR 1.18, 95 % CI 0.85-1.62) nor ethnicity (Hispanic vs non-Hispanic; OR 1.30, 95 % CI 0.67-2.53) were significant predictors of pCR overall or by subtype. Overweight and obese women had lower pCR rates in ER+/HER2+, but higher pCR rates in ER-/HER2+ cancers. There was no difference in pCR according to race or ethnicity. Overall, there was no major difference in pCR rates by BMI. These findings suggest that pCR with optimally dosed NST is a function of tumor, rather than patient, biology.

Gold Nanoparticles for Brain Tumor Imaging: A Systematic Review.

PubMed

Meola, Antonio; Rao, Jianghong; Chaudhary, Navjot; Sharma, Mayur; Chang, Steven D

2018-01-01

Demarcation of malignant brain tumor boundaries is critical to achieve complete resection and to improve patient survival. Contrast-enhanced brain magnetic resonance imaging (MRI) is the gold standard for diagnosis and pre-surgical planning, despite limitations of gadolinium (Gd)-based contrast agents to depict tumor margins. Recently, solid metal-based nanoparticles (NPs) have shown potential as diagnostic probes for brain tumors. Gold nanoparticles (GNPs) emerged among those, because of their unique physical and chemical properties and biocompatibility. The aim of the present study is to review the application of GNPs for in vitro and in vivo brain tumor diagnosis. We performed a PubMed search of reports exploring the application of GNPs in the diagnosis of brain tumors in biological models including cells, animals, primates, and humans. The search words were "gold" AND "NP" AND "brain tumor." Two reviewers performed eligibility assessment independently in an unblinded standardized manner. The following data were extracted from each paper: first author, year of publication, animal/cellular model, GNP geometry, GNP size, GNP coating [i.e., polyethylene glycol (PEG) and Gd], blood-brain barrier (BBB) crossing aids, imaging modalities, and therapeutic agents conjugated to the GNPs. The PubMed search provided 100 items. A total of 16 studies, published between the 2011 and 2017, were included in our review. No studies on humans were found. Thirteen studies were conducted in vivo on rodent models. The most common shape was a nanosphere (12 studies). The size of GNPs ranged between 20 and 120 nm. In eight studies, the GNPs were covered in PEG. The BBB penetration was increased by surface molecules (nine studies) or by means of external energy sources (in two studies). The most commonly used imaging modalities were MRI (four studies), surface-enhanced Raman scattering (three studies), and fluorescent microscopy (three studies). In two studies, the GNPs were conjugated

Validation of Heat Shock Protein 70 as a Tumor-Specific Biomarker for Monitoring the Outcome of Radiation Therapy in Tumor Mouse Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bayer, Christine; Liebhardt, Michael E.; Schmid, Thomas E.

2014-03-01

Purpose: Tumor cells, in contrast to normal cells, frequently overexpress heat shock protein 70 (Hsp70) in the cytosol, present it on their cell surface, and actively release it. Therefore, soluble Hsp70 (sHsp70) was investigated as a potential tumor biomarker for monitoring the outcome of radiation therapy. Methods and Materials: Plasma from mice bearing membrane Hsp70 (mHsp70)-positive FaDu human squamous cell carcinoma of the head and neck and spontaneous pancreatic ductal adenocarcinoma (PDAC) was investigated. A cohort of mice with FaDu tumors (0.32 cm{sup 3}) was irradiated with 30 Gy, and plasma was collected 24 hours after irradiation, after the tumors had shrunk tomore » 50% of their starting volume and after complete remission. sHsp70 levels in the plasma were quantified by enzyme-linked immunosorbent assay. Results: sHsp70 levels were significantly higher in the blood of tumor-bearing mice than that of control animals. A correlation between increasing sHsp70 plasma levels and tumor volume in the range of 0.01 cm{sup 3} to 0.66 cm{sup 3} was observed. Radiation-induced regression of the tumors was associated with significantly decreased sHsp70 levels, which returned to the level of control animals after complete remission. Conclusion: We propose sHsp70 as an innovative biomarker for detecting tumors and for monitoring the clinical outcome of radiation therapy in cancer patients.« less

Maintaining tumor targeting accuracy in real-time motion compensation systems for respiration-induced tumor motion.

PubMed

Malinowski, Kathleen; McAvoy, Thomas J; George, Rohini; Dieterich, Sonja; D'Souza, Warren D

2013-07-01

To determine how best to time respiratory surrogate-based tumor motion model updates by comparing a novel technique based on external measurements alone to three direct measurement methods. Concurrently measured tumor and respiratory surrogate positions from 166 treatment fractions for lung or pancreas lesions were analyzed. Partial-least-squares regression models of tumor position from marker motion were created from the first six measurements in each dataset. Successive tumor localizations were obtained at a rate of once per minute on average. Model updates were timed according to four methods: never, respiratory surrogate-based (when metrics based on respiratory surrogate measurements exceeded confidence limits), error-based (when localization error ≥ 3 mm), and always (approximately once per minute). Radial tumor displacement prediction errors (mean ± standard deviation) for the four schema described above were 2.4 ± 1.2, 1.9 ± 0.9, 1.9 ± 0.8, and 1.7 ± 0.8 mm, respectively. The never-update error was significantly larger than errors of the other methods. Mean update counts over 20 min were 0, 4, 9, and 24, respectively. The same improvement in tumor localization accuracy could be achieved through any of the three update methods, but significantly fewer updates were required when the respiratory surrogate method was utilized. This study establishes the feasibility of timing image acquisitions for updating respiratory surrogate models without direct tumor localization.

Preoperative Onyx embolization of hypervascular head, neck, and spinal tumors: experience with 100 consecutive cases from a single tertiary center.

PubMed

Rangel-Castilla, Leonardo; Shah, Ankit H; Klucznik, Richard Paul; Diaz, Orlando M

2014-01-01

Preoperative embolization of head, neck, and spinal tumors is frequently used to control tumor bleeding, reduce operative time, and achieve better resection. Numerous embolic materials have been used. The use of the liquid embolic agent Onyx is rapidly increasing but current experience is limited to small case series. Our purpose was to evaluate the indications, techniques, angiographic devascularization, blood loss, outcome, and general efficacy of preoperative tumor embolization with Onyx in a large series. Retrospective analysis of 100 consecutive cases of head, neck, and spinal tumors embolized with Onyx and prospective follow-up. 100 patients (63 women, 37 men) were included. Tumors included 39 meningiomas, 23 metastases, 16 parangliomas, five juvenile nasal angiofibromas, five giant cell bone tumors, three Ewing's sarcomas, three hemangiomas, three hemangioblastomas, two multiple myelomas, and one osteoblastoma. In all patients, angiographic analysis of the feeding arteries and branches was performed and all embolizations were completed in a single session. Additional materials were used in 28 patients. No mortality or major complications were observed. Minor complications were seen in 11 patients. 85 patients underwent surgery; 79 within the next 48 h and six of them 4-188 days after embolization. Embolization of intracranial, head, neck, and spinal tumors with Onyx is effective and safe by a transarterial route or by direct puncture. Onyx penetrates well into the tumor capillary with less arterial catheterization. Studies are necessary to establish long term utility in adjunct or palliative tumor embolization.

Heritability of Creative Achievement

ERIC Educational Resources Information Center

Piffer, Davide; Hur, Yoon-Mi

2014-01-01

Although creative achievement is a subject of much attention to lay people, the origin of individual differences in creative accomplishments remain poorly understood. This study examined genetic and environmental influences on creative achievement in an adult sample of 338 twins (mean age = 26.3 years; SD = 6.6 years). Twins completed the Creative…

Surgical management of spinal intramedullary tumors: radical and safe strategy for benign tumors.

PubMed

Takami, Toshihiro; Naito, Kentaro; Yamagata, Toru; Ohata, Kenji

2015-01-01

Surgery for spinal intramedullary tumors remains one of the major challenges for neurosurgeons, due to their relative infrequency, unknown natural history, and surgical difficulty. We are sure that safe and precise resection of spinal intramedullary tumors, particularly encapsulated benign tumors, can result in acceptable or satisfactory postoperative outcomes. General surgical concepts and strategies, technical consideration, and functional outcomes after surgery are discussed with illustrative cases of spinal intramedullary benign tumors such as ependymoma, cavernous malformation, and hemangioblastoma. Selection of a posterior median sulcus, posterolateral sulcus, or direct transpial approach was determined based on the preoperative imaging diagnosis and careful inspection of the spinal cord surface. Tumor-cord interface was meticulously delineated in cases of benign encapsulated tumors. Our retrospective functional analysis of 24 consecutive cases of spinal intramedullary ependymoma followed for at least 6 months postoperatively demonstrated a mean grade on the modified McCormick functional schema of 1.8 before surgery, deteriorating significantly to 2.6 early after surgery (< 1 month after surgery), and finally returning to 1.7 in the late postoperative period (> 6 months after surgery). The risk of functional deterioration after surgery should be taken into serious consideration. Functional deterioration after surgery, including neuropathic pain even long after surgery, significantly affects patient quality of life. Better balance between tumor control and functional preservation can be achieved not only by the surgical technique or expertise, but also by intraoperative neurophysiological monitoring, vascular image guidance, and postoperative supportive care. Quality of life after surgery should inarguably be given top priority.

Residual tumor size and IGCCCG risk classification predict additional vascular procedures in patients with germ cell tumors and residual tumor resection: a multicenter analysis of the German Testicular Cancer Study Group.

PubMed

Winter, Christian; Pfister, David; Busch, Jonas; Bingöl, Cigdem; Ranft, Ulrich; Schrader, Mark; Dieckmann, Klaus-Peter; Heidenreich, Axel; Albers, Peter

2012-02-01

Residual tumor resection (RTR) after chemotherapy in patients with advanced germ cell tumors (GCT) is an important part of the multimodal treatment. To provide a complete resection of residual tumor, additional surgical procedures are sometimes necessary. In particular, additional vascular interventions are high-risk procedures that require multidisciplinary planning and adequate resources to optimize outcome. The aim was to identify parameters that predict additional vascular procedures during RTR in GCT patients. A retrospective analysis was performed in 402 GCT patients who underwent 414 RTRs in 9 German Testicular Cancer Study Group (GTCSG) centers. Overall, 339 of 414 RTRs were evaluable with complete perioperative data sets. The RTR database was queried for additional vascular procedures (inferior vena cava [IVC] interventions, aortic prosthesis) and correlated to International Germ Cell Cancer Collaborative Group (IGCCCG) classification and residual tumor volume. In 40 RTRs, major vascular procedures (23 IVC resections with or without prosthesis, 11 partial IVC resections, and 6 aortic prostheses) were performed. In univariate analysis, the necessity of IVC intervention was significantly correlated with IGCCCG (14.1% intermediate/poor vs 4.8% good; p=0.0047) and residual tumor size (3.7% size < 5 cm vs 17.9% size ≥ 5 cm; p < 0.0001). In multivariate analysis, IVC intervention was significantly associated with residual tumor size ≥ 5 cm (odds ratio [OR]: 4.61; p=0.0007). In a predictive model combining residual tumor size and IGCCCG classification, every fifth patient (20.4%) with a residual tumor size ≥ 5 cm and intermediate or poor prognosis needed an IVC intervention during RTR. The need for an aortic prosthesis showed no correlation to either IGCCCG (p=0.1811) or tumor size (p=0.0651). The necessity for IVC intervention during RTR is correlated to residual tumor size and initial IGCCCG classification. Patients with high-volume residual tumors and

Evaluation of nuclear unrest and p53 immunostaining in Wilms' tumor.

PubMed

Salama, Asmaa; Kamel, Ahmad

2011-03-01

Nuclear unrest is a term applied to Wilms' tumors (WT) that show nuclear abnormalities close to anaplasia but without abnormal mitoses. p53 is claimed to be associated with anaplasia and poor prognosis. This study was undertaken to evaluate the clinical significance of nuclear unrest and p53 immunostaining in Wilms' tumor. This is a retrospective study of 63 patients who presented at NCI with Wilms' tumors, and underwent preoperative chemotherapy followed by nephrectomy. Histopathologic assessment and p53 immunohistochemistry were done. WT with nuclear unrest grade III closely resembled anaplastic tumors and both of them (group 1) constituted 19% of cases. Group 1 constituted 29% of cases showing blastema dominant morphology compared to 9.4% of cases without blastema dominant morphology with significant statistical difference (p=0.047). Almost 83% of cases that achieved 1st complete remission were stages I, II and III, while 17% were stages IV and V with significant statistical difference (p<0.001). Stage affected the 3-year relapse-free-survival (RFS) significantly (p=0.014) as it was more in stages I, II and III than in stages IV and V (75.4% versus 50%). Blastema dominant morphology and high risk state significantly lowered the 3-year overall survival (OS) into 54.8% in comparison to 80.9% for cases with non-blastema dominant morphology (p=0.042). Regarding p53 immunohistochemistry, group 1 tumors showed positive p53 more than group 2 with significant statistical difference (p=0.014). p53 Positive immunostaining was significantly associated with high risk nephroblastoma (p=0.004). Tumor stage and blastema dominant morphology are potent prognostic factors. p53 is linked to blastema dominant morphology. WT with nuclear unrest grade III closely resembles anaplastic WT. It may be appropriate to group tumors with nuclear unrest grade III with anaplastic histology regarding treatment stratification. Copyright © 2011. Published by Elsevier B.V.

Expanding the limits of endoscopic intraorbital tumor resection using 3-dimensional reconstruction.

PubMed

Gregorio, Luciano Lobato; Busaba, Nicolas Y; Miyake, Marcel M; Freitag, Suzanne K; Bleier, Benjamin S

2017-12-26

Endoscopic orbital surgery is a nascent field and new tools are required to assist with surgical planning and to ascertain the limits of the tumor resectability. We purpose to utilize three-dimensional radiographic reconstruction to define the theoretical lateral limit of endoscopic resectability of primary orbital tumors and to apply these boundary conditions to surgical cases. A three-dimensional orbital model was rendered in 4 representative patients presenting with primary orbital tumors using OsiriX open source imaging software. A 2-Dimensional plane was propagated between the contralateral nare and a line tangential to the long axis of the optic nerve reflecting the trajectory of a trans-septal approach. Any tumor volume falling medial to the optic nerve and/or within the space inferior to this plane of resectability was considered theoretically resectable regardless of how far it extended lateral to the optic nerve as nerve retraction would be unnecessary. Actual tumor volumes were then superimposed over this plan and correlated with surgical outcomes. Among the 4 lesions analyzed, two were fully medial to the optic nerve, one extended lateral to the optic nerve but remained inferior to the plane of resectability, and one extended both lateral to the optic nerve and superior to the plane of resectability. As predicted by the three-dimensional modeling, a complete resection was achieved in all lesions except one that transgressed the plane of resectability. No new diplopia or vision loss was observed in any patient. Three-dimensional reconstruction enhances preoperative planning for endoscopic orbital surgery. Tumors that extend lateral to the optic nerve may still be candidates for a purely endoscopic resection as long as they do not extend above the plane of resectability described herein. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Adenomatous tumors of the middle ear and temporal bone: clinical, morphological and tumor biological characteristics of challenging neoplastic lesions.

PubMed

Duderstadt, M; Förster, Christine; Welkoborsky, H-J; Ostertag, H

2012-03-01

Adenomatous tumors of the middle ear and temporal bone are rare tumors. In this retrospective study, we examined nine patients who underwent surgery for an adenomatous tumor of the middle ear, mastoid cavity or eustachian tube. In seven patients, a middle ear adenoma (MEA) and in two patients an aggressive papillary tumor (APT) was diagnosed. We report the clinical, radiologic, morphologic, immunohistochemical and DNA image cytometrical characteristics that can help to correctly classify these tumors. Therapy consisted of surgical excision of the tumors in eight cases. In one elderly patient, only a large biopsy was taken, because this patient suffered from cardial and kidney disorders and was not suitable for an extended surgical approach. This patient received stereotactic radiotherapy. Seven patients underwent planned second look operation. Recurrences occurred in three patients (one with APT, two with MEA), whereas in two of these cases rather a residual tumor due to initial incomplete tumor resection occurred. By image analysis, DNA cytometry MEA were considered benign, whereas the appearance of aneuploid tumor cells in APT confirmed these tumors as low grade malignant lesions. The proliferation rates were equally low in both entities. APT and MEA are tumor entities which can only be correctly classified by a synopsis of histopathology, immunohistochemistry and DNA image cytometry. The recommended therapy is the complete tumor excision. In cases of APT, von Hippel-Lindau syndrome has to be excluded.

NF-κB functions as a molecular link between tumor cells and Th1/Tc1 T cells in the tumor microenvironment to exert radiation-mediated tumor suppression

PubMed Central

Simon, Priscilla S.; Bardhan, Kankana; Chen, May R.; Paschall, Amy V.; Lu, Chunwan; Bollag, Roni J.; Kong, Feng-Chong; Jin, JianYue; Kong, Feng-Ming; Waller, Jennifer L.; Pollock, Raphael E.; Liu, Kebin

2016-01-01

Radiation modulates both tumor cells and immune cells in the tumor microenvironment to exert its anti-tumor activity; however, the molecular connection between tumor cells and immune cells that mediates radiation-exerted tumor suppression activity in the tumor microenvironment is largely unknown. We report here that radiation induces rapid activation of the p65/p50 and p50/p50 NF-κB complexes in human soft tissue sarcoma (STS) cells. Radiation-activated p65/p50 and p50/p50 bind to the TNFα promoter to activate its transcription in STS cells. Radiation-induced TNFα induces tumor cell death in an autocrine manner. A sublethal dose of Smac mimetic BV6 induces cIAP1 and cIAP2 degradation to increase tumor cell sensitivity to radiation-induced cell death in vitro and to enhance radiation-mediated suppression of STS xenografts in vivo. Inhibition of caspases, RIP1, or RIP3 blocks radiation/TNFα-induced cell death, whereas inhibition of RIP1 blocks TNFα-induced caspase activation, suggesting that caspases and RIP1 act sequentially to mediate the non-compensatory cell death pathways. Furthermore, we determined in a syngeneic sarcoma mouse model that radiation up-regulates IRF3, IFNβ, and the T cell chemokines CCL2 and CCL5 in the tumor microenvironment, which are associated with activation and increased infiltration of Th1/Tc1 T cells in the tumor microenvironment. Moreover, tumor-infiltrating T cells are in their active form since both the perforin and FasL pathways are activated in irradiated tumor tissues. Consequently, combined BV6 and radiation completely suppressed tumor growth in vivo. Therefore, radiation-induced NF-κB functions as a molecular link between tumor cells and immune cells in the tumor microenvironment for radiation-mediated tumor suppression. PMID:27014915

Neoadjuvant chemotherapy for atypical teratoid rhabdoid tumors: case report.

PubMed

Thatikunta, Meena; Mutchnick, Ian; Elster, Jennifer; Thompson, Matthew P; Huang, Michael A; Spalding, Aaron C; Moriarty, Thomas

2017-05-01

Atypical teratoid rhabdoid tumors (ATRTs) are a rare pediatric brain tumor with high mortality rate. Several large series have reported achieving gross-total resection (GTR) in less than 50% of patients due to the lesions' large size, vascularity, and limited blood volume in young patients. While neoadjuvant chemotherapy for choroid plexus carcinomas in pediatric patients has become widely accepted, it has not been used as widely for other pediatric brain tumors. To the best of the authors' knowledge, there are only 3 published cases of neoadjuvant chemotherapy for ATRTs. In the present report, the authors present a fourth case of neoadjuvant chemotherapy for ATRT and review the available literature on this strategy. A 17-month-old child presented with a left ventricular ATRT for which imaging raised concern for a highly vascularized tumor. The authors undertook neoadjuvant chemotherapy with 2 cycles of Head Start II therapy, which reduced the size of the ventricular tumor by 35% and decreased the vascularity of the lesion on imaging. The estimated blood loss during resection was 425 ml and GTR was achieved. The patient continued with postoperative chemotherapy but suffered an on-therapy recurrence. While higher-quality data are necessary, available evidence suggests that neoadjuvant chemotherapy can reduce the size and vascularity of ATRTs and facilitate a surgical avenue for large or "inoperable" tumors.

Parental Involvement and Academic Achievement

ERIC Educational Resources Information Center

Goodwin, Sarah Christine

2015-01-01

This research study examined the correlation between student achievement and parent's perceptions of their involvement in their child's schooling. Parent participants completed the Parent Involvement Project Parent Questionnaire. Results slightly indicated parents of students with higher level of achievement perceived less demand or invitations…

Targeted drug delivery and penetration into solid tumors.

PubMed

Corti, Angelo; Pastorino, Fabio; Curnis, Flavio; Arap, Wadih; Ponzoni, Mirco; Pasqualini, Renata

2012-09-01

Delivery and penetration of chemotherapeutic drugs into tumors are limited by a number of factors related to abnormal vasculature and altered stroma composition in neoplastic tissues. Coupling of chemotherapeutic drugs with tumor vasculature-homing peptides or administration of drugs in combination with biological agents that affect the integrity of the endothelial lining of tumor vasculature is an appealing strategy to improve drug delivery to tumor cells. Promising approaches to achieve this goal are based on the use of Asn-Gly-Arg (NGR)-containing peptides as ligands for drug delivery and of NGR-TNF, a peptide-tumor necrosis factor-α fusion protein that selectively alters drug penetration barriers and that is currently tested in a randomized Phase III trial in patients with malignant pleural mesothelioma. © 2011 Wiley Periodicals, Inc.

Computational modeling of brain tumors: discrete, continuum or hybrid?

NASA Astrophysics Data System (ADS)

Wang, Zhihui; Deisboeck, Thomas S.

2008-04-01

In spite of all efforts, patients diagnosed with highly malignant brain tumors (gliomas), continue to face a grim prognosis. Achieving significant therapeutic advances will also require a more detailed quantitative understanding of the dynamic interactions among tumor cells, and between these cells and their biological microenvironment. Data-driven computational brain tumor models have the potential to provide experimental tumor biologists with such quantitative and cost-efficient tools to generate and test hypotheses on tumor progression, and to infer fundamental operating principles governing bidirectional signal propagation in multicellular cancer systems. This review highlights the modeling objectives of and challenges with developing such in silicobrain tumor models by outlining two distinct computational approaches: discrete and continuum, each with representative examples. Future directions of this integrative computational neuro-oncology field, such as hybrid multiscale multiresolution modeling are discussed.

Primary Tumors of the Osseous Chest Wall and Their Management.

PubMed

Thomas, Mathew; Shen, K Robert

2017-05-01

Primary osseous tumors of the chest wall are uncommon neoplasms. They occur in a wide variety of pathologic forms, most of which can be distinguished by unique radiologic appearance. Management of these tumors depends on the diagnosis and stage. Adequate surgical resection is critical in achieving the best outcomes for most of these tumors. Chemotherapy and radiation may have an adjuvant role. Surgeons considering resection of any chest wall tumor should have a sound knowledge of the principles of resection and reconstruction. Copyright © 2017 Elsevier Inc. All rights reserved.

Completable scheduling: An integrated approach to planning and scheduling

NASA Technical Reports Server (NTRS)

Gervasio, Melinda T.; Dejong, Gerald F.

1992-01-01

The planning problem has traditionally been treated separately from the scheduling problem. However, as more realistic domains are tackled, it becomes evident that the problem of deciding on an ordered set of tasks to achieve a set of goals cannot be treated independently of the problem of actually allocating resources to the tasks. Doing so would result in losing the robustness and flexibility needed to deal with imperfectly modeled domains. Completable scheduling is an approach which integrates the two problems by allowing an a priori planning module to defer particular planning decisions, and consequently the associated scheduling decisions, until execution time. This allows a completable scheduling system to maximize plan flexibility by allowing runtime information to be taken into consideration when making planning and scheduling decision. Furthermore, through the criteria of achievability placed on deferred decision, a completable scheduling system is able to retain much of the goal-directedness and guarantees of achievement afforded by a priori planning. The completable scheduling approach is further enhanced by the use of contingent explanation-based learning, which enables a completable scheduling system to learn general completable plans from example and improve its performance through experience. Initial experimental results show that completable scheduling outperforms classical scheduling as well as pure reactive scheduling in a simple scheduling domain.

Targeting of drugs and nanoparticles to tumors

PubMed Central

Bhatia, Sangeeta N.; Sailor, Michael J.

2010-01-01

The various types of cells that comprise the tumor mass all carry molecular markers that are not expressed or are expressed at much lower levels in normal cells. These differentially expressed molecules can be used as docking sites to concentrate drug conjugates and nanoparticles at tumors. Specific markers in tumor vessels are particularly well suited for targeting because molecules at the surface of blood vessels are readily accessible to circulating compounds. The increased concentration of a drug in the site of disease made possible by targeted delivery can be used to increase efficacy, reduce side effects, or achieve some of both. We review the recent advances in this delivery approach with a focus on the use of molecular markers of tumor vasculature as the primary target and nanoparticles as the delivery vehicle. PMID:20231381

Mild elevation of body temperature reduces tumor interstitial fluid pressure and hypoxia and enhances efficacy of radiotherapy in murine tumor models.

PubMed

Sen, Arindam; Capitano, Maegan L; Spernyak, Joseph A; Schueckler, John T; Thomas, Seneca; Singh, Anurag K; Evans, Sharon S; Hylander, Bonnie L; Repasky, Elizabeth A

2011-06-01

Human and rodent solid tumors often exhibit elevated interstitial fluid pressure (IFP). This condition is recognized as a prognostic indicator for reduced responses to therapy and decreased disease-free survival rate. In the present study, we tested whether induction of a thermoregulatory-mediated increase in tissue blood flow, induced by exposure of mice to mild environmental heat stress, could influence IFP and other vascular parameters within tumors. Using several murine tumor models, we found that heating results in a sustained reduction in tumor IFP correlating with increased tumor vascular perfusion (measured by fluorescent imaging of perfused vessels, laser Doppler flowmetry, and MRI) as well as a sustained reduction in tumor hypoxia. Furthermore, when radiation therapy was administered 24 hours postheating, we observed a significant improvement in efficacy that may be a result of the sustained reduction in tumor hypoxia. These data suggest, for the first time, that environmental manipulation of normal vasomotor function is capable of achieving therapeutically beneficial changes in IFP and microvascular function in the tumor microenvironment.

[Characteristics of polyamine biosynthesis regulation and tumor growth rate in hormone-dependant grafted breast tumors of mice and rats].

PubMed

Orlovskiĭ, A A

2007-01-01

Effect of the inhibitors of polyamines biosynthesis on completely or partially hormone-dependant breast tumors (mouse Ca755 carcinoma and Walker W-256 carcinosarcoma) is essentially special: in contrary to hormone-dependant tumors, this effect may be not only breaking but stimulating as well. Change-over from one to another mode of reaction is conditioned, most probable, by hormonal status, which is determined by one or another estral cycle phase. Biochemical mechanisms of this change-over are closely connected with polyamines metabolism, namely the degree of polyamines (especially spermine) interconvertion and physiological reactivity level of the system controlling expression of ornithin-decarboxilase. At that, the first of these pathways is predominant for completely hormone-dependant Ca755 and the second one -for partially hormone-dependant W-256.

Prodrugs for Improving Tumor Targetability and Efficiency

PubMed Central

Mahato, Rubi; Tai, Wanyi; Cheng, Kun

2011-01-01

As the mainstay in the treatment of various cancers for several decades, chemotherapy is successful but still faces challenges including non-selectivity and high toxicity. Improving the selectivity is therefore a critical step to improve the therapeutic efficacy of chemotherapy. Prodrug is one of the most promising approaches to increase the selectivity and efficacy of a chemotherapy drug. The classical prodrug approach is to improve the pharmaceutical properties (solubility, stability, permeability, irritation, distribution, etc.) via a simple chemical modification. This review will focus on various targeted prodrug designs that have been developed to increase the selectivity of chemotherapy drugs. Various tumor-targeting ligands, transporter-associated ligands, and polymers can be incorporated in a prodrug to enhance the tumor uptake. Prodrugs can also be activated by enzymes that are specifically expressed at a higher level in tumors, leading to a selective anti-tumor effect. This can be achieved by conjugating the enzyme to a tumor-specific antibody, or delivering a vector expressing the enzyme into tumor cells. PMID:21333700

Quantifying the Benefit of a Pathologic Complete Response After Neoadjuvant Chemoradiotherapy in the Treatment of Esophageal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scheer, Richard V.; Fakiris, Achilles J.; Johnstone, Peter A.S., E-mail: pajohnst@iupui.edu

Purpose: To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. Methods and Materials: In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally,more » stratified median survival times were also analyzed. Results: Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). Conclusion: In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not.« less

Quantifying the benefit of a pathologic complete response after neoadjuvant chemoradiotherapy in the treatment of esophageal cancer.

PubMed

Scheer, Richard V; Fakiris, Achilles J; Johnstone, Peter A S

2011-07-15

To better define the benefit of a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy in the treatment of esophageal and gastroesophageal cancer, we undertook a comprehensive review of the literature to derive a pooled analysis of crude survival data and quantify the survival benefit of pCR vs. residual disease at esophagectomy. In all, 22 articles were reviewed. Crude overall survival data, stratified by patients with pCR vs. those with residual disease at esophagectomy, were collected and analyzed using a chi-square analysis. The relative and absolute survival benefit of achieving a pCR were calculated and analyzed. Finally, stratified median survival times were also analyzed. Overall survival for patients with pCR was 93.1%, 75.0%, and 50.0% at 2, 3, and 5 years, respectively, whereas it was 36.8%, 29.0%, and 22.6% for patients with residual tumor (p < 0.025). The mean relative survival benefit of pCR at 2, 3, and 5 years was 2.05, 2.35, and 2.84, respectively. The mean absolute survival benefit of pCR was 35.66%, 33.79%, and 33.20%, respectively. Median survival times for patients with pCR were significantly longer than for those with residual tumor (p = 0.011). In esophageal and gastroesophageal cancers, pCR seems to significantly increase overall survival in patients undergoing neoadjuvant chemoradiotherapy. Specifically, the data suggest that patients with pCR are two to three times more likely to survive than are those with residual tumor at esophagectomy. Moreover, these data suggest that 33-36% more patients survive when pCR is achieved than when it is not. Copyright © 2011 Elsevier Inc. All rights reserved.

Enumeration of Circulating Tumor Cells and Disseminated Tumor Cells in Blood and Bone Marrow by Immunomagnetic Enrichment and Flow Cytometry (IE/FC).

PubMed

Magbanua, Mark Jesus M; Solanki, Tulasi I; Ordonez, Andrea D; Hsiao, Feng; Park, John W

2017-01-01

Enumerating circulating tumor cells (CTCs) in blood and disseminated tumor cells (DTCs) in bone marrow has shown to be clinically useful, as elevated numbers of these cells predict poor clinical outcomes. Accurate detection and quantification is, however, difficult and technically challenging because CTCs and DTCs are extremely rare. We have developed a novel quantitative detection method for enumeration of CTCs and DTCs. Our approach consists of two steps: (1) EPCAM-based immunomagnetic enrichment followed by (2) flow cytometry (IE/FC). The assay takes approximately 2 h to complete. In addition to tumor cell enumeration, IE/FC offers opportunities for direct isolation of highly pure tumor cells for downstream molecular characterization.

Maintaining tumor targeting accuracy in real-time motion compensation systems for respiration-induced tumor motion

PubMed Central

Malinowski, Kathleen; McAvoy, Thomas J.; George, Rohini; Dieterich, Sonja; D’Souza, Warren D.

2013-01-01

Purpose: To determine how best to time respiratory surrogate-based tumor motion model updates by comparing a novel technique based on external measurements alone to three direct measurement methods. Methods: Concurrently measured tumor and respiratory surrogate positions from 166 treatment fractions for lung or pancreas lesions were analyzed. Partial-least-squares regression models of tumor position from marker motion were created from the first six measurements in each dataset. Successive tumor localizations were obtained at a rate of once per minute on average. Model updates were timed according to four methods: never, respiratory surrogate-based (when metrics based on respiratory surrogate measurements exceeded confidence limits), error-based (when localization error ≥3 mm), and always (approximately once per minute). Results: Radial tumor displacement prediction errors (mean ± standard deviation) for the four schema described above were 2.4 ± 1.2, 1.9 ± 0.9, 1.9 ± 0.8, and 1.7 ± 0.8 mm, respectively. The never-update error was significantly larger than errors of the other methods. Mean update counts over 20 min were 0, 4, 9, and 24, respectively. Conclusions: The same improvement in tumor localization accuracy could be achieved through any of the three update methods, but significantly fewer updates were required when the respiratory surrogate method was utilized. This study establishes the feasibility of timing image acquisitions for updating respiratory surrogate models without direct tumor localization. PMID:23822413

Achieving consensus for clinical trials

PubMed Central

Blakeley, Jaishri O.; Dombi, Eva; Fisher, Michael J.; Hanemann, C. Oliver; Walsh, Karin S.; Wolters, Pamela L.; Widemann, Brigitte C.

2013-01-01

The neurofibromatoses (NF)—including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2), and schwannomatosis—are related tumor-suppressor syndromes characterized by a predisposition to multiple tumor types and other disease manifestations, which often result in functional disability, reduced quality of life, pain, and, in some cases, malignancy. With increasing knowledge of the biology and pathogenesis of NF, clinical trials with targeted agents directed at NF tumors have become available. Most clinical trials for patients with NF have used designs and endpoints similar to oncology trials. However, differences in the disease manifestations and natural history of NF (compared to cancers) require the development of new designs and endpoints to perform meaningful NF clinical trials. The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration was established in 2011 at the Children's Tumor Foundation meeting to achieve consensus within the NF community about the design of future clinical trials, with a specific emphasis on endpoints. The REiNS Collaboration includes 7 working groups that focus on imaging of tumor response; functional, visual, patient-reported, and neurocognitive outcomes; whole-body MRI; and disease biomarkers. This supplement includes the first series of recommendations by the REiNS Collaboration. The hope is that these recommendations will be used by members of the group and by researchers outside of the REiNS International Collaboration to standardize the measurement of outcomes and thus improve clinical trials for patients with NF. Ultimately, we plan to engage industry partners and national regulatory agencies in this process to facilitate the approval of drugs for patients with NF. PMID:24249801

Infrared-Transparent Gold Nanoparticles Converted by Tumors to Infrared Absorbers Cure Tumors in Mice by Photothermal Therapy

PubMed Central

Hainfeld, James F.; O'Connor, Michael J.; Lin, Ping; Qian, Luping; Slatkin, Daniel N.; Smilowitz, Henry M.

2014-01-01

Gold nanoparticles (AuNPs) absorb light and can be used to heat and ablate tumors. The “tissue window” at ∼800 nm (near infrared, NIR) is optimal for best tissue penetration of light. Previously, large, 50–150 nm, gold nanoshells and nanorods that absorb well in the NIR have been used. Small AuNPs that may penetrate tumors better unfortunately barely absorb at 800 nm. We show that small AuNPs conjugated to anti-tumor antibodies are taken up by tumor cells that catalytically aggregate them (by enzyme degradation of antibodies and pH effects), shifting their absorption into the NIR region, thus amplifying their photonic absorption. The AuNPs are NIR transparent until they accumulate in tumor cells, thus reducing background heating in blood and non-targeted cells, increasing specificity, in contrast to constructs that are always NIR-absorptive. Treatment of human squamous cell carcinoma A431 which overexpresses epidermal growth factor receptor (EGFr) in subcutaneous murine xenografts with anti-EGFr antibodies conjugated to 15 nm AuNPs and NIR resulted in complete tumor ablation in most cases with virtually no normal tissue damage. The use of targeted small AuNPs therefore provides a potent new method of selective NIR tumor therapy. PMID:24520385

Anti-tumor response induced by immunologically modified carbon nanotubes and laser irradiation using rat mammary tumor model

NASA Astrophysics Data System (ADS)

Acquaviva, Joseph T.; Hasanjee, Aamr M.; Bahavar, Cody F.; Zhou, Fefian; Liu, Hong; Howard, Eric W.; Bullen, Liz C.; Silvy, Ricardo P.; Chen, Wei R.

2015-03-01

Laser immunotherapy (LIT) is being developed as a treatment modality for metastatic cancer which can destroy primary tumors and induce effective systemic anti-tumor responses by using a targeted treatment approach in conjunction with the use of a novel immunoadjuvant, glycated chitosan (GC). In this study, Non-invasive Laser Immunotherapy (NLIT) was used as the primary treatment mode. We incorporated single-walled carbon nanotubes (SWNTs) into the treatment regimen to boost the tumor-killing effect of LIT. SWNTs and GC were conjugated to create a completely novel, immunologically modified carbon nanotube (SWNT-GC). To determine the efficacy of different laser irradiation durations, 5 minutes or 10 minutes, a series of experiments were performed. Rats were inoculated with DMBA-4 cancer cells, a highly aggressive metastatic cancer cell line. Half of the treatment group of rats receiving laser irradiation for 10 minutes survived without primary or metastatic tumors. The treatment group of rats receiving laser irradiation for 5 minutes had no survivors. Thus, Laser+SWNT-GC treatment with 10 minutes of laser irradiation proved to be effective at reducing tumor size and inducing long-term anti-tumor immunity.

Predictive factors of esophageal stenosis associated with tumor regression in radiation therapy for locally advanced esophageal cancer.

PubMed

Atsumi, Kazushige; Shioyama, Yoshiyuki; Nakamura, Katsumasa; Nomoto, Satoshi; Ohga, Saiji; Yoshitake, Tadamasa; Nonoshita, Takeshi; Ueda, Masanobu; Hirata, Hideki; Honda, Hiroshi

2010-01-01

The purpose of this retrospective study was to clarify the predictive factors correlated with esophageal stenosis within three months after radiation therapy for locally advanced esophageal cancer. We enrolled 47 patients with advanced esophageal cancer with T2-4 and stage II-III who were treated with definitive radiation therapy and achieving complete response of primary lesion at Kyushu University Hospital between January 1998 and December 2005. Esophagography was performed for all patients before treatment and within three months after completion of the radiation therapy, the esophageal stenotic ratio was evaluated. The stenotic ratio was used to define four levels of stenosis: stenosis level 1, stenotic ratio of 0-25%; 2, 25-50%; 3,50-75%; 4,75-100%. We then estimated the correlation between the esophageal stenosis level after radiation therapy and each of numerous factors. The numbers and total percentages of patients at each stenosis level were as follows: level 1: n = 14 (30%); level 2: 8 (17%); level 3: 14 (30%); and level 4: 11 (23%). Esophageal stenosis in the case of full circumference involvement tended to be more severe and more frequent. Increases in wall thickness tended to be associated with increases in esophageal stenosis severity and frequency. The extent of involved circumference and wall thickness of tumor region were significantly correlated with esophageal stenosis associated with tumor regression in radiation therapy (p = 0.0006, p = 0.005). For predicting the possibility of esophageal stenosis with tumor regression within three months in radiation therapy, the extent of involved circumference and esophageal wall thickness of the tumor region may be useful.

Discovery of NKT cells and development of NKT cell-targeted anti-tumor immunotherapy

PubMed Central

TANIGUCHI, Masaru; HARADA, Michishige; DASHTSOODOL, Nyambayar; KOJO, Satoshi

2015-01-01

Natural Killer T (NKT) cells are unique lymphocytes characterized by their expression of a single invariant antigen receptor encoded by Vα14Jα18 in mice and Vα24Jα18 in humans, which recognizes glycolipid antigens in association with the monomorphic CD1d molecule. NKT cells mediate adjuvant activity to activate both CD8T cells to kill MHC-positive tumor cells and NK cells to eliminate MHC-negative tumor at the same time in patients, resulting in the complete eradication of tumors without relapse. Therefore, the NKT cell-targeted therapy can be applied to any type of tumor and also to anyone individual, regardless of HLA type. Phase IIa clinical trials on advanced lung cancers and head and neck tumors have been completed and showed significantly prolonged median survival times with only the primary treatment. Another potential treatment option for the future is to use induced pluripotent stem cell (iPS)-derived NKT cells, which induced adjuvant effects on anti-tumor responses, inhibiting in vivo tumor growth in a mouse model. PMID:26194854

Management of non metastatic phyllodes tumors of the breast: review of the literature.

PubMed

Khosravi-Shahi, Parham

2011-12-01

Phyllodes tumors of the breast are rare tumors, accounting for less than 0.5% of all breast tumors. These tumors are comprised of both stromal and epithelial elements; and traditionally they are graded by the use of a set of histologic features into benign, borderline, and malignant subtypes. Unfortunately, the histologic classification of phyllodes tumors does not reliably predict clinical behavior. The mainstay of treatment of non metastatic phyllodes tumors of the breast is complete surgical resection with wide resection margins. Lumpectomy or partial mastectomy is the preferred surgical therapy. However, despite the complete surgical resection, local failure rate may be high; and 22% of malignant tumors may give rise to haematogenous metastases. The most frequent site of distant metastases is the lungs. Several predictive factors of recurrence and metastases have been described in the literature, such as positive surgical margins, increased stromal cellularity, stromal overgrowth, stromal atypia and increased mitotic activity. Nevertheless, the role of adjuvant therapies (radiotherapy and chemotherapy) is presently undefined and should be tested in multicenter, prospective, randomized trials. Copyright © 2011 Elsevier Ltd. All rights reserved.

Regulatory T cells as suppressors of anti-tumor immunity: Role of metabolism.

PubMed

De Rosa, Veronica; Di Rella, Francesca; Di Giacomo, Antonio; Matarese, Giuseppe

2017-06-01

Novel concepts in immunometabolism support the hypothesis that glucose consumption is also used to modulate anti-tumor immune responses, favoring growth and expansion of specific cellular subsets defined in the past as suppressor T cells and currently reborn as regulatory T (Treg) cells. During the 1920s, Otto Warburg and colleagues observed that tumors consumed high amounts of glucose compared to normal tissues, even in the presence of oxygen and completely functioning mitochondria. However, the role of the Warburg Effect is still not completely understood, particularly in the context of an ongoing anti-tumor immune response. Current experimental evidence suggests that tumor-derived metabolic restrictions can drive T cell hyporesponsiveness and immune tolerance. For example, several glycolytic enzymes, deregulated in cancer, contribute to tumor progression independently from their canonical metabolic activity. Indeed, they can control apoptosis, gene expression and activation of specific intracellular pathways, thus suggesting a direct link between metabolic switches and pro-tumorigenic transcriptional programs. Focus of this review is to define the specific metabolic pathways controlling Treg cell immunobiology in the context of anti-tumor immunity and tumor progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Long-Term Survival and Tumor Recurrence in Patients with Superficial Esophageal Cancer after Complete Non-Curative Endoscopic Resection: A Single-Center Case Series.

PubMed

Lee, Ji Wan; Cho, Charles J; Kim, Do Hoon; Ahn, Ji Yong; Lee, Jeong Hoon; Choi, Kee Don; Song, Ho June; Park, Sook Ryun; Lee, Hyun Joo; Kim, Yong Hee; Lee, Gin Hyug; Jung, Hwoon-Yong; Kim, Sung-Bae; Kim, Jong Hoon; Park, Seung-Il

2018-06-01

To report the long-term survival and tumor recurrence outcomes in patients with superficial esophageal cancer (SEC) after complete non-curative endoscopic resection (ER). We retrieved ER data for 24 patients with non-curatively resected SEC. Non-curative resection was defined as the presence of submucosal and/or lymphovascular invasion on ER pathology. Relevant clinical and tumor-specific parameters were reviewed. The mean age of the 24 study patients was 66.3±8.3 years. Ten patients were closely followed up without treatment, while 14 received additional treatment. During a mean follow-up of 59.0±33.2 months, the 3- and 5-year survival rates of all cases were 90.7% and 77.6%, respectively. The 5-year overall survival rates were 72.9% in the close observation group and 82.1% in the additional treatment group (p=0.958). The 5-year cumulative incidences of all cases of recurrence (25.0% vs. 43.3%, p=0.388), primary EC recurrence (10.0% vs. 16.4%, p=0.558), and metachronous EC recurrence (16.7% vs. 26.7%, p=0.667) were similar between the two groups. Patients with non-curatively resected SEC showed good long-term survival outcomes. Given the similar oncologic outcomes, close observation may be an option with appropriate caution taken for patients who are medically unfit to receive additional therapy.

Local tumor control probability modeling of primary and secondary lung tumors in stereotactic body radiotherapy.

PubMed

Guckenberger, Matthias; Klement, Rainer J; Allgäuer, Michael; Andratschke, Nicolaus; Blanck, Oliver; Boda-Heggemann, Judit; Dieckmann, Karin; Duma, Marciana; Ernst, Iris; Ganswindt, Ute; Hass, Peter; Henkenberens, Christoph; Holy, Richard; Imhoff, Detlef; Kahl, Henning K; Krempien, Robert; Lohaus, Fabian; Nestle, Ursula; Nevinny-Stickel, Meinhard; Petersen, Cordula; Semrau, Sabine; Streblow, Jan; Wendt, Thomas G; Wittig, Andrea; Flentje, Michael; Sterzing, Florian

2016-03-01

To evaluate whether local tumor control probability (TCP) in stereotactic body radiotherapy (SBRT) varies between lung metastases of different primary cancer sites and between primary non-small cell lung cancer (NSCLC) and secondary lung tumors. A retrospective multi-institutional (n=22) database of 399 patients with stage I NSCLC and 397 patients with 525 lung metastases was analyzed. Irradiation doses were converted to biologically effective doses (BED). Logistic regression was used for local tumor control probability (TCP) modeling and the second-order bias corrected Akaike Information Criterion was used for model comparison. After median follow-up of 19 months and 16 months (n.s.), local tumor control was observed in 87.7% and 86.7% of the primary and secondary lung tumors (n.s.), respectively. A strong dose-response relationship was observed in the primary NSCLC and metastatic cohort but dose-response relationships were not significantly different: the TCD90 (dose to achieve 90% TCP; BED of maximum planning target volume dose) estimates were 176 Gy (151-223) and 160 Gy (123-237) (n.s.), respectively. The dose-response relationship was not influenced by the primary cancer site within the metastatic cohort. Dose-response relationships for local tumor control in SBRT were not different between lung metastases of various primary cancer sites and between primary NSCLC and lung metastases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Successful correction of tibial bone deformity through multiple surgical procedures, liquid nitrogen-pretreated bone tumor autograft, three-dimensional external fixation, and internal fixation in a patient with primary osteosarcoma: a case report.

PubMed

Takeuchi, Akihiko; Yamamoto, Norio; Shirai, Toshiharu; Nishida, Hideji; Hayashi, Katsuhiro; Watanabe, Koji; Miwa, Shinji; Tsuchiya, Hiroyuki

2015-12-07

In a previous report, we described a method of reconstruction using tumor-bearing autograft treated by liquid nitrogen for malignant bone tumor. Here we present the first case of bone deformity correction following a tumor-bearing frozen autograft via three-dimensional computerized reconstruction after multiple surgeries. A 16-year-old female student presented with pain in the left lower leg and was diagnosed with a low-grade central tibial osteosarcoma. Surgical bone reconstruction was performed using a tumor-bearing frozen autograft. Bone union was achieved at 7 months after the first surgical procedure. However, local tumor recurrence and lung metastases occurred 2 years later, at which time a second surgical procedure was performed. Five years later, the patient developed a 19° varus deformity and underwent a third surgical procedure, during which an osteotomy was performed using the Taylor Spatial Frame three-dimensional external fixation technique. A fourth corrective surgical procedure was performed in which internal fixation was achieved with a locking plate. Two years later, and 10 years after the initial diagnosis of tibial osteosarcoma, the bone deformity was completely corrected, and the patient's limb function was good. We present the first report in which a bone deformity due to a primary osteosarcoma was corrected using a tumor-bearing frozen autograft, followed by multiple corrective surgical procedures that included osteotomy, three-dimensional external fixation, and internal fixation.

Computational modeling of brain tumors: discrete, continuum or hybrid?

NASA Astrophysics Data System (ADS)

Wang, Zhihui; Deisboeck, Thomas S.

In spite of all efforts, patients diagnosed with highly malignant brain tumors (gliomas), continue to face a grim prognosis. Achieving significant therapeutic advances will also require a more detailed quantitative understanding of the dynamic interactions among tumor cells, and between these cells and their biological microenvironment. Data-driven computational brain tumor models have the potential to provide experimental tumor biologists with such quantitative and cost-efficient tools to generate and test hypotheses on tumor progression, and to infer fundamental operating principles governing bidirectional signal propagation in multicellular cancer systems. This review highlights the modeling objectives of and challenges with developing such in silico brain tumor models by outlining two distinct computational approaches: discrete and continuum, each with representative examples. Future directions of this integrative computational neuro-oncology field, such as hybrid multiscale multiresolution modeling are discussed.

[Lung metastases: tumor reduction as an oncologic concept].

PubMed

Dienemann, H; Hoffmann, H; Trainer, C; Muley, T

1998-01-01

The principle of surgery for lung metastases is the removal of all lesions in the lung that are either visible or detectable by palpation. This may be combined with complete dissection of all ipsilateral lymph nodes. Therefore, "tumor reduction" rather than "complete" or "radical resection" may be an adequate description of this surgical approach. Since the dissemination of--macroscopically not detectable--tumor cells represents the major mannerism of every metastatic disease, any local therapy appears to be a discrepancy. However, in most cases the rationale of surgery for lung metastases is the lack of effective systemic therapy and the low morbidity of surgery, along with up to 60% 5-year survival rates.

Tumor-specific novel taxoid-monoclonal antibody conjugates.

PubMed

Ojima, Iwao; Geng, Xudong; Wu, Xinyuan; Qu, Chuanxing; Borella, Christopher P; Xie, Hongsheng; Wilhelm, Sharon D; Leece, Barbara A; Bartle, Laura M; Goldmacher, Victor S; Chari, Ravi V J

2002-12-19

Taxoids bearing methyldisulfanyl(alkanoyl) groups for taxoid-antibody immunoconjugates were designed, synthesized and their activities evaluated. A highly cytotoxic C-10 methyldisulfanylpropanoyl taxoid was conjugated to monoclonal antibodies recognizing the epidermal growth factor receptor (EGFR) expressed in human squamous cancers. These conjugates were shown to possess remarkable target-specific antitumor activity in vivo against EGFR-expressing A431 tumor xenografts in severe combined immune deficiency mice, resulting in complete inhibition of tumor growth in all the treated mice.

Serotonergic system antagonists target breast tumor initiating cells and synergize with chemotherapy to shrink human breast tumor xenografts

PubMed Central

Gwynne, William D; Hallett, Robin M; Girgis-Gabardo, Adele; Bojovic, Bojana; Dvorkin-Gheva, Anna; Aarts, Craig; Dias, Kay; Bane, Anita; Hassell, John A

2017-01-01

Breast tumors comprise an infrequent tumor cell population, termed breast tumor initiating cells (BTIC), which sustain tumor growth, seed metastases and resist cytotoxic therapies. Hence therapies are needed to target BTIC to provide more durable breast cancer remissions than are currently achieved. We previously reported that serotonergic system antagonists abrogated the activity of mouse BTIC resident in the mammary tumors of a HER2-overexpressing model of breast cancer. Here we report that antagonists of serotonin (5-hydroxytryptamine; 5-HT) biosynthesis and activity, including US Federal Food and Drug Administration (FDA)-approved antidepressants, targeted BTIC resident in numerous breast tumor cell lines regardless of their clinical or molecular subtype. Notably, inhibitors of tryptophan hydroxylase 1 (TPH1), required for 5-HT biosynthesis in select non-neuronal cells, the serotonin reuptake transporter (SERT) and several 5-HT receptors compromised BTIC activity as assessed by functional sphere-forming assays. Consistent with these findings, human breast tumor cells express TPH1, 5-HT and SERT independent of their molecular or clinical subtype. Exposure of breast tumor cells ex vivo to sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI), reduced BTIC frequency as determined by transplanting drug-treated tumor cells into immune-compromised mice. Moreover, another SSRI (vilazodone; Viibryd) synergized with chemotherapy to shrink breast tumor xenografts in immune-compromised mice by inhibiting tumor cell proliferation and inducing their apoptosis. Collectively our data suggest that antidepressants in combination with cytotoxic anticancer therapies may be an appropriate treatment regimen for testing in clinical trials. PMID:28404880

Serotonergic system antagonists target breast tumor initiating cells and synergize with chemotherapy to shrink human breast tumor xenografts.

PubMed

Gwynne, William D; Hallett, Robin M; Girgis-Gabardo, Adele; Bojovic, Bojana; Dvorkin-Gheva, Anna; Aarts, Craig; Dias, Kay; Bane, Anita; Hassell, John A

2017-05-09

Breast tumors comprise an infrequent tumor cell population, termed breast tumor initiating cells (BTIC), which sustain tumor growth, seed metastases and resist cytotoxic therapies. Hence therapies are needed to target BTIC to provide more durable breast cancer remissions than are currently achieved. We previously reported that serotonergic system antagonists abrogated the activity of mouse BTIC resident in the mammary tumors of a HER2-overexpressing model of breast cancer. Here we report that antagonists of serotonin (5-hydroxytryptamine; 5-HT) biosynthesis and activity, including US Federal Food and Drug Administration (FDA)-approved antidepressants, targeted BTIC resident in numerous breast tumor cell lines regardless of their clinical or molecular subtype. Notably, inhibitors of tryptophan hydroxylase 1 (TPH1), required for 5-HT biosynthesis in select non-neuronal cells, the serotonin reuptake transporter (SERT) and several 5-HT receptors compromised BTIC activity as assessed by functional sphere-forming assays. Consistent with these findings, human breast tumor cells express TPH1, 5-HT and SERT independent of their molecular or clinical subtype. Exposure of breast tumor cells ex vivo to sertraline (Zoloft), a selective serotonin reuptake inhibitor (SSRI), reduced BTIC frequency as determined by transplanting drug-treated tumor cells into immune-compromised mice. Moreover, another SSRI (vilazodone; Viibryd) synergized with chemotherapy to shrink breast tumor xenografts in immune-compromised mice by inhibiting tumor cell proliferation and inducing their apoptosis. Collectively our data suggest that antidepressants in combination with cytotoxic anticancer therapies may be an appropriate treatment regimen for testing in clinical trials.

Gastrointestinal Stromal Tumors - Diagnosis and Surgical Treatment.

PubMed

Alecu, L; Tulin, A; Enciu, O; Bărbulescu, M; Ursuţ, B; Obrocea, F

2015-01-01

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract, previously classified as leiomyomas, leiomyosarcomas, leiomyoblastomas or schwannomas. They are now recognized as a distinct entity with origin in the mesodermal interstitial cell of Cajal, cells that express the c-KIT protein (tirozine kinase receptor). The definitive diagnosis is established by immunohistochemistry, more than 95% of GISTs being positive for CD117. Despite the major progress of chemotherapy, the treatment of choice is surgery, and it implies the complete resection of the tumor. The evolution of these tumors is unpredictable and the prognosis depends on localization, tumor size and mitotic index. Benign tumors have an excellent prognosis after surgery, with a 5 year survival of 90%, while malignant tumors resistant to radiotherapy and chemotherapy have a dismal prognosis even after surgical resection, with a median survival of 1 year. We studied a group of 15 patients diagnosed with TSGI in the Surgery Clinic of the œProf. Dr. Agrippa Ionescu Clinical Emergency Hospital, between 2003 and 2013, following the particularities of presentation, diagnosis and treatment, with focus on the prognostic factors according to available literature data. Celsius.

Tumor Immunotargeting Using Innovative Radionuclides

PubMed Central

Kraeber-Bodéré, Françoise; Rousseau, Caroline; Bodet-Milin, Caroline; Mathieu, Cédric; Guérard, François; Frampas, Eric; Carlier, Thomas; Chouin, Nicolas; Haddad, Ferid; Chatal, Jean-François; Faivre-Chauvet, Alain; Chérel, Michel; Barbet, Jacques

2015-01-01

This paper reviews some aspects and recent developments in the use of antibodies to target radionuclides for tumor imaging and therapy. While radiolabeled antibodies have been considered for many years in this context, only a few have reached the level of routine clinical use. However, alternative radionuclides, with more appropriate physical properties, such as lutetium-177 or copper-67, as well as alpha-emitting radionuclides, including astatine-211, bismuth-213, actinium-225, and others are currently reviving hopes in cancer treatments, both in hematological diseases and solid tumors. At the same time, PET imaging, with short-lived radionuclides, such as gallium-68, fluorine-18 or copper-64, or long half-life ones, particularly iodine-124 and zirconium-89 now offers new perspectives in immuno-specific phenotype tumor imaging. New antibody analogues and pretargeting strategies have also considerably improved the performances of tumor immunotargeting and completely renewed the interest in these approaches for imaging and therapy by providing theranostics, companion diagnostics and news tools to make personalized medicine a reality. PMID:25679452

BRCA mutations and their influence on pathological complete response and prognosis in a clinical cohort of neoadjuvantly treated breast cancer patients.

PubMed

Wunderle, Marius; Gass, Paul; Häberle, Lothar; Flesch, Vivien M; Rauh, Claudia; Bani, Mayada R; Hack, Carolin C; Schrauder, Michael G; Jud, Sebastian M; Emons, Julius; Erber, Ramona; Ekici, Arif B; Hoyer, Juliane; Vasileiou, Georgia; Kraus, Cornelia; Reis, Andre; Hartmann, Arndt; Lux, Michael P; Beckmann, Matthias W; Fasching, Peter A; Hein, Alexander

2018-05-03

BRCA1/2 mutations influence the molecular characteristics and the effects of systemic treatment of breast cancer. This study investigates the impact of germline BRCA1/2 mutations on pathological complete response and prognosis in patients receiving neoadjuvant systemic chemotherapy. Breast cancer patients were tested for a BRCA1/2 mutation in clinical routine work and were treated with anthracycline-based or platinum-based neoadjuvant chemotherapy between 1997 and 2015. These patients were identified in the tumor registry of the Breast Center of the University of Erlangen (Germany). Logistic regression and Cox regression analyses were performed to investigate the associations between BRCA1/2 mutation status, pathological complete response, disease-free survival, and overall survival. Among 355 patients, 59 had a mutation in BRCA1 or in BRCA2 (16.6%), 43 in BRCA1 (12.1%), and 16 in BRCA2 (4.5%). Pathological complete response defined as "ypT0; ypN0" was observed in 54.3% of BRCA1/2 mutation carriers, but only in 22.6% of non-carriers. The adjusted odds ratio was 2.48 (95% CI 1.26-4.91) for BRCA1/2 carriers versus non-carriers. Patients who achieved a pathological complete response had better disease-free survival and overall survival rates compared with those who did not achieve a pathological complete response, regardless of BRCA1/2 mutation status. BRCA1/2 mutation status leads to better responses to neoadjuvant chemotherapy in breast cancer. Pathological complete response is the main predictor of disease-free survival and overall survival, independently of BRCA1/2 mutation status.

Minimally Invasive Electrochemotherapy Procedure for Treating Nasal Duct Tumors in Dogs using a Single Needle Electrode

PubMed Central

Maglietti, Felipe; Tellado, Matías; Olaiz, Nahuel; Michinski, Sebastian; Marshall, Guillermo

2017-01-01

Abstract Background Nasal cavity tumors are usually diagnosed late, when they already have infiltrated adjacent tissues thus requiring very aggressive treatments with serious side effects. Here we use electrochemotherapy (ECT), a well demonstrated treatment modality for superficial tumors. Materials and methods In the case of deep-seated tumors, the main limitation of ECT is reaching the tumor with an appropriate electric field. To overcome this limitation we introduce the single needle electrode (SiNE), a minimally invasive device that can deliver an appropriate electric field with a simple procedure. Twenty-one canine patients with spontaneous tumors were selected, eleven were treated using the SiNE with ECT, and ten with surgery plus adjuvant chemotherapy as a control group. Results In the SiNE group, 27% achieved a complete response, 64% had a partial response, and 9% had a stable disease. This means that 91% of objective responses were obtained. The mean overall survival was 16.86 months (4–32 months, median 16.5 months), with a survival rate significantly higher (p = 0.0008) when compared with control group. The only side effect observed was the inflammation of the treated nasal passage, which was controlled with corticosteroid therapy for one week. One year after the treatment, 60% of the canine of the SiNE group vs. 10% of the control group remained alive, and after the 32 months follow-up, the survival rate were 30% and 0%, respectively. Conclusions ECT with the SiNE can be safely used in canine to treat nasal tumors with encouraging results. PMID:29333121

Salvage Reirradiaton With Stereotactic Body Radiotherapy for Locally Recurrent Head-and-Neck Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cengiz, Mustafa, E-mail: mcengiz@hacettepe.edu.tr; Ozyigit, Goekhan; Yazici, Goezde

2011-09-01

Purpose: In this study, we present our results of reirradiation of locally recurrent head-and-neck cancer with image-guided, fractionated, frameless stereotactic body radiotherapy technique. Methods and Materials: From July 2007 to February 2009, 46 patients were treated using the CyberKnife (Accuray, Sunnyvale, CA) at the Department of Radiation Oncology, Hacettepe University, Ankara, Turkey. All patients had recurrent, unresectable, and previously irradiated head-and-neck cancer. The most prominent site was the nasopharynx (32.6%), and the most common histopathology was epidermoid carcinoma. The planning target volume was defined as the gross tumor volume identified on magnetic resonance imaging and computed tomography. There were 22more » female and 24 male patients. Median age was 53 years (range, 19-87 years). The median tumor dose with stereotactic body radiotherapy was 30 Gy (range, 18-35 Gy) in a median of five (range, one to five) fractions. Results: Of 37 patients whose response to therapy was evaluated, 10 patients (27%) had complete tumor regression, 11 (29.8%) had partial response, and 10 (27%) had stable disease. Ultimate local disease control was achieved in 31 patients (83.8%). The overall survival was 11.93 months in median (ranged, 11.4 - 17.4 months), and the median progression free survival was 10.5 months. One-year progression-free survival and overall survival were 41% and 46%, respectively. Grade II or greater long-term complications were observed in 6 (13.3%) patients. On follow-up, 8 (17.3%) patients had carotid blow-out syndrome, and 7 (15.2%) patients died of bleeding from carotid arteries. We discovered that this fatal syndrome occurred only in patients with tumor surrounding carotid arteries and carotid arteries receiving all prescribed dose. Conclusions: Stereotactic body radiotherapy is an appealing treatment option for patients with recurrent head-and-neck cancer previously treated with radiation to high doses. Good local control

OVOL2 antagonizes TGF-β signaling to regulate epithelial to mesenchymal transition during mammary tumor metastasis

PubMed Central

Wu, Di; Liu, Na; Liu, Qing-Feng; Wu, Qiu-Wan; Xie, Yuan-Yuan; Liu, Yun-Jia; Zheng, Zhong-Zheng; Chan, Err-Cheng; Zhang, Zhi-Ming; Li, Bo-An

2017-01-01

Great progress has been achieved in the study of the role of TGF-β signaling in triggering epithelial-mesenchymal transition (EMT) in a variety of cancers; however, the regulation of TGF-β signaling during EMT in mammary tumor metastasis has not been completely defined. In the present study, we demonstrated that OVOL2, a zinc finger transcription factor, inhibits TGF-β signaling-induced EMT in mouse and human mammary tumor cells, as well as in mouse tumor models. Data from the Oncomine databases indicated a strong negative relationship between OVOL2 expression and breast cancer progression. Moreover, our experiments revealed that OVOL2 inhibits TGF-β signaling at multiple levels, including inhibiting Smad4 mRNA expression and inducing Smad7 mRNA expression, blocking the binding between Smad4 and target DNA, and interfering with complex formation between Smad4 and Smad2/3. These findings reveal a novel mechanism that controls the TGF-β signaling output level in vitro and in vivo. The modulation of these molecular processes may represent a strategy for inhibiting breast cancer invasion by restoring OVOL2 expression. PMID:28455959

Computational Model for Tumor Oxygenation Applied to Clinical Data on Breast Tumor Hemoglobin Concentrations Suggests Vascular Dilatation and Compression

PubMed Central

Welter, Michael; Fredrich, Thierry; Rinneberg, Herbert; Rieger, Heiko

2016-01-01

We present a computational model for trans-vascular oxygen transport in synthetic tumor and host tissue blood vessel networks, aiming at qualitatively explaining published data of optical mammography, which were obtained from 87 breast cancer patients. The data generally show average hemoglobin concentration to be higher in tumors versus host tissue whereas average oxy-to total hemoglobin concentration (vascular segment RBC-volume-weighted blood oxygenation) can be above or below normal. Starting from a synthetic arterio-venous initial network the tumor vasculature was generated by processes involving cooption, angiogenesis, and vessel regression. Calculations of spatially resolved blood flow, hematocrit, oxy- and total hemoglobin concentrations, blood and tissue oxygenation were carried out for ninety tumor and associated normal vessel networks starting from various assumed geometries of feeding arteries and draining veins. Spatial heterogeneity in the extra-vascular partial oxygen pressure distribution can be related to various tumor compartments characterized by varying capillary densities and blood flow characteristics. The reported higher average hemoglobin concentration of tumors is explained by growth and dilatation of tumor blood vessels. Even assuming sixfold metabolic rate of oxygen consumption in tumorous versus host tissue, the predicted oxygen hemoglobin concentrations are above normal. Such tumors are likely associated with high tumor blood flow caused by high-caliber blood vessels crossing the tumor volume and hence oxygen supply exceeding oxygen demand. Tumor oxy- to total hemoglobin concentration below normal could only be achieved by reducing tumor vessel radii during growth by a randomly selected factor, simulating compression caused by intra-tumoral solid stress due to proliferation of cells and extracellular matrix. Since compression of blood vessels will impede chemotherapy we conclude that tumors with oxy- to total hemoglobin concentration

Computational Model for Tumor Oxygenation Applied to Clinical Data on Breast Tumor Hemoglobin Concentrations Suggests Vascular Dilatation and Compression.

PubMed

Welter, Michael; Fredrich, Thierry; Rinneberg, Herbert; Rieger, Heiko

2016-01-01

We present a computational model for trans-vascular oxygen transport in synthetic tumor and host tissue blood vessel networks, aiming at qualitatively explaining published data of optical mammography, which were obtained from 87 breast cancer patients. The data generally show average hemoglobin concentration to be higher in tumors versus host tissue whereas average oxy-to total hemoglobin concentration (vascular segment RBC-volume-weighted blood oxygenation) can be above or below normal. Starting from a synthetic arterio-venous initial network the tumor vasculature was generated by processes involving cooption, angiogenesis, and vessel regression. Calculations of spatially resolved blood flow, hematocrit, oxy- and total hemoglobin concentrations, blood and tissue oxygenation were carried out for ninety tumor and associated normal vessel networks starting from various assumed geometries of feeding arteries and draining veins. Spatial heterogeneity in the extra-vascular partial oxygen pressure distribution can be related to various tumor compartments characterized by varying capillary densities and blood flow characteristics. The reported higher average hemoglobin concentration of tumors is explained by growth and dilatation of tumor blood vessels. Even assuming sixfold metabolic rate of oxygen consumption in tumorous versus host tissue, the predicted oxygen hemoglobin concentrations are above normal. Such tumors are likely associated with high tumor blood flow caused by high-caliber blood vessels crossing the tumor volume and hence oxygen supply exceeding oxygen demand. Tumor oxy- to total hemoglobin concentration below normal could only be achieved by reducing tumor vessel radii during growth by a randomly selected factor, simulating compression caused by intra-tumoral solid stress due to proliferation of cells and extracellular matrix. Since compression of blood vessels will impede chemotherapy we conclude that tumors with oxy- to total hemoglobin concentration

Improved Tumor-Specific Drug Accumulation by Polymer Therapeutics with pH-Sensitive Drug Release Overcomes Chemotherapy Resistance.

PubMed

Heinrich, Anne-Kathrin; Lucas, Henrike; Schindler, Lucie; Chytil, Petr; Etrych, Tomáš; Mäder, Karsten; Mueller, Thomas

2016-05-01

The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA-doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA-doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging-based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998-1007. ©2016 AACR. ©2016 American Association for Cancer Research.

Computer modeling of the combined effects of perfusion, electrical conductivity, and thermal conductivity on tissue heating patterns in radiofrequency tumor ablation.

PubMed

Ahmed, Muneeb; Liu, Zhengjun; Humphries, Stanley; Goldberg, S Nahum

2008-11-01

To use an established computer simulation model of radiofrequency (RF) ablation to characterize the combined effects of varying perfusion, and electrical and thermal conductivity on RF heating. Two-compartment computer simulation of RF heating using 2-D and 3-D finite element analysis (ETherm) was performed in three phases (n = 88 matrices, 144 data points each). In each phase, RF application was systematically modeled on a clinically relevant template of application parameters (i.e., varying tumor and surrounding tissue perfusion: 0-5 kg/m(3)-s) for internally cooled 3 cm single and 2.5 cm cluster electrodes for tumor diameters ranging from 2-5 cm, and RF application times (6-20 min). In the first phase, outer thermal conductivity was changed to reflect three common clinical scenarios: soft tissue, fat, and ascites (0.5, 0.23, and 0.7 W/m- degrees C, respectively). In the second phase, electrical conductivity was changed to reflect different tumor electrical conductivities (0.5 and 4.0 S/m, representing soft tissue and adjuvant saline injection, respectively) and background electrical conductivity representing soft tissue, lung, and kidney (0.5, 0.1, and 3.3 S/m, respectively). In the third phase, the best and worst combinations of electrical and thermal conductivity characteristics were modeled in combination. Tissue heating patterns and the time required to heat the entire tumor +/-a 5 mm margin to >50 degrees C were assessed. Increasing background tissue thermal conductivity increases the time required to achieve a 50 degrees C isotherm for all tumor sizes and electrode types, but enabled ablation of a given tumor size at higher tissue perfusions. An inner thermal conductivity equivalent to soft tissue (0.5 W/m- degrees C) surrounded by fat (0.23 W/m- degrees C) permitted the greatest degree of tumor heating in the shortest time, while soft tissue surrounded by ascites (0.7 W/m- degrees C) took longer to achieve the 50 degrees C isotherm, and complete ablation

Genetic analysis of circulating tumor cells in pancreatic cancer patients: A pilot study.

PubMed

Görner, Karin; Bachmann, Jeannine; Holzhauer, Claudia; Kirchner, Roland; Raba, Katharina; Fischer, Johannes C; Martignoni, Marc E; Schiemann, Matthias; Alunni-Fabbroni, Marianna

2015-07-01

Pancreatic cancer is one of the most aggressive malignant tumors, mainly due to an aggressive metastasis spreading. In recent years, circulating tumor cells became associated to tumor metastasis. Little is known about their expression profiles. The aim of this study was to develop a complete workflow making it possible to isolate circulating tumor cells from patients with pancreatic cancer and their genetic characterization. We show that the proposed workflow offers a technical sensitivity and specificity high enough to detect and isolate single tumor cells. Moreover our approach makes feasible to genetically characterize single CTCs. Our work discloses a complete workflow to detect, count and genetically analyze individual CTCs isolated from blood samples. This method has a central impact on the early detection of metastasis development. The combination of cell quantification and genetic analysis provides the clinicians with a powerful tool not available so far. Copyright © 2015. Published by Elsevier Inc.

Biodegradable brain-penetrating DNA nanocomplexes and their use to treat malignant brain tumors

PubMed Central

Mastorakos, Panagiotis; Zhang, Clark; Song, Eric; Kim, Young Eun; Park, Hee Won; Berry, Sneha; Choi, Won Kyu; Hanes, Justin; Suk, Jung Soo

2018-01-01

The discovery of powerful genetic targets has spurred clinical development of gene therapy approaches to treat patients with malignant brain tumors. However, lack of success in the clinic has been attributed to the inability of conventional gene vectors to achieve gene transfer throughout highly disseminated primary brain tumors. Here, we demonstrate ex vivo that small nanocomplexes composed of DNA condensed by a blend of biodegradable polymer, poly(β-amino ester) (PBAE), with PBAE conjugated with 5 kDa polyethylene glycol (PEG) molecules (PBAE-PEG) rapidly penetrate healthy brain parenchyma and orthotopic brain tumor tissues in rats. Rapid diffusion of these DNA-loaded nanocomplexes observed in fresh tissues ex vivo demonstrated that they avoided adhesive trapping in the brain owing to their dense PEG coating, which was critical to achieving widespread transgene expression throughout orthotopic rat brain tumors in vivo following administration by convection enhanced delivery. Transgene expression with the PBAE/PBAE-PEG blended nanocomplexes (DNA-loaded brain-penetrating nanocomplexes, or DNA-BPN) was uniform throughout the tumor core compared to nanocomplexes composed of DNA with PBAE only (DNA-loaded conventional nanocomplexes, or DNA-CN), and transgene expression reached beyond the tumor edge, where infiltrative cancer cells are found, only for the DNA-BPN formulation. Finally, DNA-BPN loaded with anti-cancer plasmid DNA provided significantly enhanced survival compared to the same plasmid DNA loaded in DNA-CN in two aggressive orthotopic brain tumor models in rats. These findings underscore the importance of achieving widespread delivery of therapeutic nucleic acids within brain tumors and provide a promising new delivery platform for localized gene therapy in the brain. PMID:28694032

[Solid cystic papillary tumor of the pancreas].

PubMed

Bahri, I; Njim, L; Khabir, A; Mahmoudi, H; Ghorbel, A; Zakhama, A; Jlidi, R

2001-11-01

Solid cystic papillary tumors of the pancreas are rare; they occur most commonly in young women. Despite their characteristic microscopic appearance, their immunophenotype is not specific. Their prognosis is excellent after complete surgical resection. The study aim was to report two cases in female patients who were 15 and 20 years old; the first tumor was discovered fortuitously and the second girl presented with abdominal pain and vomiting. Both tumors were encapsulated and located in the tail of the pancreas. The histological study showed the papillary architecture mixed with solid areas. Immunohistochemical staining was positive only for vimentin in one case and positive for cytokeratin, chromogranin, synaptophysin, neuron specific enolase, vimentin and protein S100 in the second case.

A noninvasive multimodal technique to monitor brain tumor vascularization

NASA Astrophysics Data System (ADS)

Saxena, Vishal; Gonzalez-Gomez, Ignacio; Laug, Walter E.

2007-09-01

Determination of tumor oxygenation at the microvascular level will provide important insight into tumor growth, angiogenesis, necrosis and therapeutic response and will facilitate to develop protocols for studying tumor behavior. The non-ionizing near infrared spectroscopy (NIRS) technique has the potential to differentiate lesion and hemoglobin dynamics; however, it has a limited spatial resolution. On the other hand, magnetic resonance imaging (MRI) has achieved high spatial resolution with excellent tissue discrimination but is more susceptible to limited ability to monitor the hemoglobin dynamics. In the present work, the vascular status and the pathophysiological changes that occur during tumor vascularization are studied in an orthotopic brain tumor model. A noninvasive multimodal approach based on the NIRS technique, namely steady state diffuse optical spectroscopy (SSDOS) along with MRI, is applied for monitoring the concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor region. The concentrations of oxyhemoglobin, deoxyhemoglobin and water within tumor vasculature are extracted at 15 discrete wavelengths in a spectral window of 675-780 nm. We found a direct correlation between tumor size, intratumoral microvessel density and tumor oxygenation. The relative decrease in tumor oxygenation with growth indicates that though blood vessels infiltrate and proliferate the tumor region, a hypoxic trend is clearly present.

[Vitamin-resistant rickets cured by removal of a bone tumor. Review of the literature].

PubMed

François, S; Lefort, G; Poli-Merol, M L; Gaillard, D; Roussel, B; Sulmont, V; Daoud, S

1997-01-01

Rickets secondary to bone or soft tissue tumors are rare in children. Majority of the reported cases occurred in adults older than thirty. This entity can be cured after tumor removal. The authors present a case in a ten year boy and literature review. A ten year boy complained of diffuse bone and muscle weakness for two years. A diagnosis of arthritis was made but the patient continued to complain. Serum calcium level was normal (2.33 mmol/l), phosphorus was very low (0.43 mmol/l), serum alkaline phosphatase was high, parathyroid hormone and vitamin D level were normal. Urinalysis showed abnormal phosphate excretion. The absence of malabsorption, no family history of rickets or hypophosphatermy presence of a marked excess of urinary phosphate, very low serum phosphate and normal serum calcium, vitamin D and parathyroid hormone levels led us to consider a diagnosis of tumor induced osteomalacia. Radiographs showed a large round radiolucent lesion in the left superior pubic ramus and generalized demineralisation. We performed a complete tumor resection and the space was filled with bone graft. On histopathologic examination it was a benign mesenchymal tumor. Rapid reversal of biochemical anomalies, radiographs anomalies and clinical manifestation were observed after complete tumor resection. The authors have described the tumor, the osteomalacia and the pathogenesis of tumor rickets. Histologically the most common causative tumors were vascular tumors, mesenchymal tumors and non ossifying tumors. The tumor were of bone or soft tissue origin. Clinical symptoms were muscular weakness, bone and muscle pain. Biochemically there is a very low phosphate level, a normal serum calcium level as well as a normal vitamin D and PTH level. There is a significant high level of urinal phosphate. The mechanism proposed to explain oncogenic osteomalacia includes tumor secretion of phosphaturic substance other than PTH and calcitonin. Another hypothesis is a substance interfering

Imitation-tumor targeting based on continuous-wave near-infrared tomography.

PubMed

Liu, Dan; Liu, Xin; Zhang, Yan; Wang, Qisong; Lu, Jingyang; Sun, Jinwei

2017-12-01

Continuous-wave Near-Infrared (NIR) optical spectroscopy has shown great diagnostic capability in the early tumor detection with advantages of low-cost, portable, non-invasive, and non-radiative. In this paper, Modified Lambert-Beer Theory is deployed to address the low-resolution issues of the NIR technique and to design the tumor detecting and imaging system. Considering that tumor tissues have features such as high blood flow and hypoxia, the proposed technique can detect the location, size, and other information of the tumor tissues by comparing the absorbance between pathological and normal tissues. Finally, the tumor tissues can be imaged through tomographic method. The simulation experiments prove that the proposed technique and designed system can efficiently detect the tumor tissues, achieving imaging precision within 1 mm. The work of the paper has shown great potential in the diagnosis of tumor close to body surface.

Development of Advanced Technologies for Complete Genomic and Proteomic Characterization of Quantized Human Tumor Cells

DTIC Science & Technology

2015-09-01

glioblastoma . We have successfully established several patient-derived cell lines from glioblastoma tumors and further established a number of...and single-cell technologies. Although the focus of this research is glioblastoma , the proposed tools are generally applicable to all cancer-based...studies. 15. SUBJECT TERMS Human cohorts, Glioblastoma , Genomic, Proteomic, Single-cell technologies, Hypothesis-driven, integrative systems approach

Recent advances in molecular biology and treatment strategies for intracranial germ cell tumors.

PubMed

Huang, Xiang; Zhang, Rong; Mao, Ying; Zhou, Liang-Fu; Zhang, Chao

2016-08-01

Intracranial germ cell tumors (IGCTs) are a group of rare pediatric brain tumors which include various subtypes. The current understanding of the etiology of the tumors and their optimal management strategies remain controversial. The data on IGCTs were collected from articles published in the past 20 years, and the origin and etiology of IGCTs at molecular level as well as the relative roles of varied treatment strategies in different prognosis groups according to Matsutani's classification were reviewed. Recent cellular and molecular evidence suggests that IGCTs may arise from the transformation of endogenous brain cells; and findings in the molecular characterization of IGCTs suggest roles of CCND2, RB1, and PRDM14 in the pathogenesis of IGCTs and identify the KIT/RAS and AKT1/mTOR pathways as potential therapeutic targets in future. According to Matsutani's classification of IGCTs, the good prognosis group includes both germinomas and mature teratomas. For germinomas, both radiation alone and reduced-dose radiotherapy in combination with adjuvant chemotherapy are effective, while complete surgical excision is recommended for mature teratomas. In the intermediate prognosis group, immature teratoma has been successfully treated with gamma knife surgery. However, for intermediate prognosis IGCTs other than immature teratomas, gross total resection with adjuvant chemotherapy and radiotherapy or gamma knife surgery may be necessary to achieve cure. In the poor prognosis group, survival outcomes are unsatisfactory, and complete surgical resection combined with more intensive chemotherapy and radiotherapy remains the best available treatment option at this time. IGCTs should be strictly classified according to their pathological categories before administering pathology-specific treatments. Although open microsurgical excision is the traditional surgical strategy for IGCTs, recent publications also support the role of endoscopic surgical options for pineal region

Patient-Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

PubMed

Riva, Francesca; Bidard, Francois-Clement; Houy, Alexandre; Saliou, Adrien; Madic, Jordan; Rampanou, Aurore; Hego, Caroline; Milder, Maud; Cottu, Paul; Sablin, Marie-Paule; Vincent-Salomon, Anne; Lantz, Olivier; Stern, Marc-Henri; Proudhon, Charlotte; Pierga, Jean-Yves

2017-03-01

In nonmetastatic triple-negative breast cancer (TNBC) patients, we investigated whether circulating tumor DNA (ctDNA) detection can reflect the tumor response to neoadjuvant chemotherapy (NCT) and detect minimal residual disease after surgery. Ten milliliters of plasma were collected at 4 time points: before NCT; after 1 cycle; before surgery; after surgery. Customized droplet digital PCR (ddPCR) assays were used to track tumor protein p53 ( TP53 ) mutations previously characterized in tumor tissue by massively parallel sequencing (MPS). Forty-six patients with nonmetastatic TNBC were enrolled. TP53 mutations were identified in 40 of them. Customized ddPCR probes were validated for 38 patients, with excellent correlation with MPS ( r = 0.99), specificity (≥2 droplets/assay), and sensitivity (at least 0.1%). At baseline, ctDNA was detected in 27/36 patients (75%). Its detection was associated with mitotic index ( P = 0.003), tumor grade ( P = 0.003), and stage ( P = 0.03). During treatment, we observed a drop of ctDNA levels in all patients but 1. No patient had detectable ctDNA after surgery. The patient with rising ctDNA levels experienced tumor progression during NCT. Pathological complete response (16/38 patients) was not correlated with ctDNA detection at any time point. ctDNA positivity after 1 cycle of NCT was correlated with shorter disease-free ( P < 0.001) and overall ( P = 0.006) survival. Customized ctDNA detection by ddPCR achieved a 75% detection rate at baseline. During NCT, ctDNA levels decreased quickly and minimal residual disease was not detected after surgery. However, a slow decrease of ctDNA level during NCT was strongly associated with shorter survival. © 2016 American Association for Clinical Chemistry.

High Achievers: 23rd Annual Survey. Attitudes and Opinions from the Nation's High Achieving Teens.

ERIC Educational Resources Information Center

Who's Who among American High School Students, Northbrook, IL.

This report presents data from an annual survey of high school student leaders and high achievers. It is noted that of the nearly 700,000 high achievers featured in this edition, 5,000 students were sent the survey and 2,092 questionnaires were completed. Subjects were high school juniors and seniors selected for recognition by their principals or…

Central nervous system tumors and agricultural exposures in the prospective cohort AGRICAN.

PubMed

Piel, Clément; Pouchieu, Camille; Tual, Séverine; Migault, Lucile; Lemarchand, Clémentine; Carles, Camille; Boulanger, Mathilde; Gruber, Anne; Rondeau, Virginie; Marcotullio, Elisabeth; Lebailly, Pierre; Baldi, Isabelle

2017-11-01

Studies in farmers suggest a possible role of pesticides in the occurrence of Central Nervous System (CNS) tumors but scientific evidence is still insufficient. Using data from the French prospective agricultural cohort AGRICAN (Agriculture & Cancer), we investigated the associations between exposure of farmers and pesticide users to various kinds of crops and animal farming and the incidence of CNS tumors, overall and by subtypes. Over the 2005-2007, 181,842 participants completed the enrollment questionnaire that collected a complete job calendar with lifetime history of farming types. Associations were estimated using proportional hazards models with age as underlying timescale. During a 5.2 years average follow-up, 273 incident cases of CNS tumors occurred, including 126 gliomas and 87 meningiomas. Analyses showed several increased risks of CNS tumors in farmers, especially in pesticide users (hazard ratio = 1.96; 95% confidence interval: 1.11-3.47). Associations varied with tumor subtypes and kinds of crop and animal farming. The main increases in risk were observed for meningiomas in pig farmers and in farmers growing sunflowers, beets and potatoes and for gliomas in farmers growing grasslands. In most cases, more pronounced risk excesses were observed among pesticide applicators. Even if we cannot completely rule out the contribution of other factors, pesticide exposures could be of primary concern to explain these findings. © 2017 UICC.

High-Resolution Microscopy-Coil MR Imaging of Skin Tumors: Techniques and Novel Clinical Applications.

PubMed

Budak, Matthew J; Weir-McCall, Jonathan R; Yeap, Phey M; White, Richard D; Waugh, Shelley A; Sudarshan, Thiru A P; Zealley, Ian A

2015-01-01

High-resolution magnetic resonance (MR) imaging performed with a microscopy coil is a robust radiologic tool for the evaluation of skin lesions. Microscopy-coil MR imaging uses a small surface coil and a 1.5-T or higher MR imaging system. Simple T1- and T2-weighted imaging protocols can be implemented to yield high-quality, high-spatial-resolution images that provide an excellent depiction of dermal anatomy. The primary application of microscopy-coil MR imaging is to delineate the deep margins of skin tumors, thereby providing a preoperative road map for dermatologic surgeons. This information is particularly useful for surgeons who perform Mohs micrographic surgery and in cases of nasofacial neoplasms, where the underlying anatomy is complex. Basal cell carcinoma is the most common nonmelanocytic skin tumor and has a predilection to manifest on the face, where it can be challenging to achieve complete surgical excision while preserving the cosmetic dignity of the patient. Microscopy-coil MR imaging provides dermatologic surgeons with valuable preoperative anatomic information that is not available at conventional clinical examination. ©RSNA, 2015.

Activated dendritic cells delivered in tissue compatible biomatrices induce in-situ anti-tumor CTL responses leading to tumor regression

PubMed Central

Verma, Vivek; Kim, Young; Lee, Min-Cheol; Lee, Jae-Tae; Cho, Sunghoon; Park, In-Kyu; Min, Jung Joon; Lee, Je Jung; Lee, Shee Eun; Rhee, Joon Haeng

2016-01-01

Dendritic cell (DC) based anti-cancer immunotherapy is well tolerated in patients with advanced cancers. However, the clinical responses seen after adoptive DC therapy have been suboptimal. Several factors including scarce DC numbers in tumors and immunosuppressive tumor microenvironments contribute to the inefficacy of DCs as cellular vaccines. Hence DC based vaccines can benefit from novel methods of cell delivery that would prevent the direct exposure of immune cells to suppressive tumor microenvironments. Here we evaluated the ability of DCs harbored in biocompatible scaffolds (referred to as biomatrix entrapped DCs; beDCs) in activating specific anti-tumor immune responses against primary and post-surgery secondary tumors. Using a preclinical cervical cancer and a melanoma model in mice, we show that single treatment of primary and post-surgery secondary tumors using beDCs resulted in significant tumor growth retardation while multiple inoculations were required to achieve a significant anti-tumor effect when DCs were given in free form. Additionally, we found that, compared to the tumor specific E6/E7 peptide vaccine, total tumor lysate induced higher expression of CD80 and CD40 on DCs that induced increased levels of IFNγ production upon interaction with host lymphocytes. Remarkably, a strong immunocyte infiltration into the host-implanted DC-scaffold was observed. Importantly, the host-implanted beDCs induced the anti-tumor immune responses in the absence of any stromal cell support, and the biomatrix structure was eventually absorbed into the surrounding host tissue. Collectively, these data indicate that the scaffold-based DC delivery may provide an efficient and safe way of delivering cell-based vaccines for treatment of primary and post-surgery secondary tumors. PMID:27223090

Orbit-associated tumors: navigation and control of resection using intraoperative computed tomography.

PubMed

Terpolilli, Nicole A; Rachinger, Walter; Kunz, Mathias; Thon, Niklas; Flatz, Wilhelm H; Tonn, Jörg-Christian; Schichor, Christian

2016-05-01

OBJECT Treatment of skull base lesions is complex and usually requires a multidisciplinary approach. In meningioma, which is the most common tumor entity in this region, resection is considered to be the most important therapeutic step to avoid tumor recurrence. However, resection of skull base lesions with orbital or optic nerve involvement poses a challenge due to their anatomical structure and their proximity to eloquent areas. Therefore the main goal of surgery should be to achieve the maximum extent of resection while preserving neurological function. In the postoperative course, medical and radiotherapeutic strategies may then be successfully used to treat possible tumor residues. Methods to safely improve the extent of resection in skull base lesions therefore are desirable. The current study reports the authors' experience with the use of intraoperative CT (iCT) combined with neuronavigation with regard to feasibility and possible benefits of the method. METHODS Those patients with tumorous lesions in relationship to the orbit, sphenoid wing, or cavernous sinus who were surgically treated between October 2008 and December 2013 using iCT-based neuronavigation and in whom an intraoperative scan was obtained for control of resection were included. In all cases a second iCT scan was performed under sterile conditions after completion of navigation-guided microsurgical tumor resection. The surgical strategy was adapted accordingly; if necessary, resection was continued. RESULTS Twenty-three patients (19 with WHO Grade I meningioma and 4 with other lesions) were included. The most common clinical symptoms were loss of visual acuity and exophthalmus. Intraoperative control of resection by iCT was successfully obtained in all cases. Intraoperative imaging changed the surgical approach in more than half (52.2%) of these patients, either because iCT demonstrated unexpected residual tumor masses or because the second scan revealed additional tumor tissue that was not

Evaluation of Complete Blood Count Indices (NLR, PLR, MPV/PLT, and PLCRi) in Healthy Dogs, Dogs With Periodontitis, and Dogs With Oropharyngeal Tumors as Potential Biomarkers of Systemic Inflammatory Response.

PubMed

Rejec, Ana; Butinar, Janos; Gawor, Jerzy; Petelin, Milan

2017-12-01

The aim of the study was to retrospectively assess complete blood count (CBC) indices of dogs with periodontitis (PD; n = 73) and dogs with oropharyngeal tumors (OT; n = 92) in comparison to CBC indices of healthy dogs (HD; n = 71). Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, mean platelet volume to platelet ratio, and platelet large cell ratio index (PLCRi) were evaluated as biomarkers of systemic inflammatory response provoked by PD and OT. Results of multivariable polytomous logistic regression analysis indicated no significant associations between CBC indices and PD. Both NLR and PLCRi were significantly higher in dogs with OT when compared to HD and dogs with PD and could, therefore, indicate a tumor-associated systemic inflammatory response. Additional studies of CBC indices, along with other biomarkers of systemic inflammatory response, are recommended to validate them as reliable indicators of clinical disease activity.

16th Annual Survey of High Achievers: Attitudes and Opinions from the Nation's High Achieving Teens.

ERIC Educational Resources Information Center

Who's Who among American High School Students, Northbrook, IL.

The report presents data from 2,043 questionnaires completed by secondary student leaders and high achievers. Ss were selected for recognition in "Who's Who Among American High School Students" by their principals or guidance counselors, national youth organizations, or the publishing company because of high achievement in academics, activities,…

Limited Margin Radiation Therapy for Children and Young Adults With Ewing Sarcoma Achieves High Rates of Local Tumor Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Talleur, Aimee C.; Navid, Fariba; Spunt, Sheri L.

Purpose: To determine the rate of local failure using focal conformal, limited margin radiation therapy (RT) and dose escalation for tumors ≥8 cm (greatest dimension at diagnosis) in children and young adults with Ewing sarcoma (EWS). Methods and Materials: Eligible patients with EWS were treated on a phase 2 institutional trial of focal conformal, limited margin RT using conformal or intensity modulated techniques. The treatment volume incorporated a 1-cm constrained margin around the gross tumor. Unresected tumors, <8 cm at diagnosis, received a standard dose of 55.8 Gy and tumors ≥8 cm, an escalated dose to 64.8 Gy. Patients with microscopic residual disease after resectionmore » received adjuvant RT to 50.4 Gy. Adjuvant brachytherapy was permitted in selected patients. Results: Forty-five patients were enrolled: 26 with localized and 19 with metastatic disease. Median (range) age, tumor size, and follow-up were 13.0 years (2.9-24.7 years), 9.0 cm (2.4-17.0 cm), and 54.5 months (1.9-122.2 months), respectively. All patients received systemic chemotherapy. The median (range) RT dose for all patients was 56.1 Gy (45-65.5 Gy). Seventeen patients received adjuvant, 16 standard-dose, and 12 escalated-dose RT. Failures included 1 local, 10 distant, and 1 local/distant. The estimated 10-year cumulative incidence of local failure was 4.4% ± 3.1%, with no statistical difference seen between RT treatment groups and no local failures in the escalated-dose RT treatment group. Conclusions: Treatment with focal conformal, limited margin RT, including dose escalation for larger tumors, provides favorable local tumor control in EWS.« less

Tumor-specific CD4+ T cells develop cytotoxic activity and eliminate virus-induced tumor cells in the absence of regulatory T cells.

PubMed

Akhmetzyanova, Ilseyar; Zelinskyy, Gennadiy; Schimmer, Simone; Brandau, Sven; Altenhoff, Petra; Sparwasser, Tim; Dittmer, Ulf

2013-02-01

The important role of tumor-specific cytotoxic CD8(+) T cells is well defined in the immune control of the tumors, but the role of effector CD4(+) T cells is poorly understood. In the current research, we have used a murine retrovirus-induced tumor cell line of C57BL/6 mouse origin, namely FBL-3 cells, as a model to study basic mechanisms of immunological control and escape during tumor formation. This study shows that tumor-specific CD4(+) T cells are able to protect against virus-induced tumor cells. We show here that there is an expansion of tumor-specific CD4(+) T cells producing cytokines and cytotoxic molecule granzyme B (GzmB) in the early phase of tumor growth. Importantly, we demonstrate that in vivo depletion of regulatory T cells (Tregs) and CD8(+) T cells in FBL-3-bearing DEREG transgenic mice augments IL-2 and GzmB production by CD4(+) T cells and increases FV-specific CD4(+) T-cell effector and cytotoxic responses leading to the complete tumor regression. Therefore, the capacity to reject tumor acquired by tumor-reactive CD4(+) T cells largely depends on the direct suppressive activity of Tregs. We suggest that a cytotoxic CD4(+) T-cell immune response may be induced to enhance resistance against oncovirus-associated tumors.

Vaccination with Irradiated Tumor Cells Engineered to Secrete Murine Granulocyte-Macrophage Colony-Stimulating Factor Stimulates Potent, Specific, and Long-Lasting Anti-Tumor Immunity

NASA Astrophysics Data System (ADS)

Dranoff, Glenn; Jaffee, Elizabeth; Lazenby, Audrey; Golumbek, Paul; Levitsky, Hyam; Brose, Katja; Jackson, Valerie; Hamada, Hirofumi; Pardoll, Drew; Mulligan, Richard C.

1993-04-01

To compare the ability of different cytokines and other molecules to enhance the immunogenicity of tumor cells, we generated 10 retroviruses encoding potential immunomodulators and studied the vaccination properties of murine tumor cells transduced by the viruses. Using a B16 melanoma model, in which irradiated tumor cells alone do not stimulate significant anti-tumor immunity, we found that irradiated tumor cells expressing murine granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulated potent, long-lasting, and specific anti-tumor immunity, requiring both CD4^+ and CD8^+ cells. Irradiated cells expressing interleukins 4 and 6 also stimulated detectable, but weaker, activity. In contrast to the B16 system, we found that in a number of other tumor models, the levels of anti-tumor immunity reported previously in cytokine gene transfer studies involving live, transduced cells could be achieved through the use of irradiated cells alone. Nevertheless, manipulation of the vaccine or challenge doses made it possible to demonstrate the activity of murine GM-CSF in those systems as well. Overall, our results have important implications for the clinical use of genetically modified tumor cells as therapeutic cancer vaccines.

Tumor-induced osteomalacia (TIO): atypical presentation.

PubMed

Khaliq, Waseem; Cheripalli, Praveen; Tangella, Krishnarao

2011-05-01

Tumor-induced osteomalacia is a rare acquired condition characterized by phosphaturia, hypophosphatemia and osteomalacia. We report an unusual presentation in a 15-year-old healthy male with a two-week history of cough and chest pain. The chest radiograph showed right middle lobe opacity and chest CT revealed a mass in the extra pleural space. A biopsy showed chondro-myxoidstroma with osteoid formation. Diagnosis was confirmed with the above findings and hypophosphatemia. The patient's symptoms resolved after complete surgical excision of the mass. Tumor-induced osteomalacia, although a rare disorder, can be a diagnostic challenge, especially in patients presenting with atypical symptoms.

Massive hematemesis after radiofrequency ablation of metastatic liver tumor with successful hemostasis achieved through transarterial embolization.

PubMed

Liu, Chien-An; Chiu, Nai-Chi; Chiou, Yi-You

2018-03-03

Hemorrhagic complications are the most common major complications that occur after radiofrequency ablation, but hematemesis as a complication after radiofrequency ablation for hepatic tumor has not been mentioned before. A hepatogastric fistula as a delayed complication is also rare. We present the case of a 77-year-old man with severe hematemesis that occurred 2 months after radiofrequency ablation of a liver metastasis of gastric cancer. A ruptured hepatic artery pseudoaneurysm and a hepatogastric fistula were confirmed through serial imaging examinations. The current case is reported in combination with 2 rare major complications after radiofrequency ablation of a liver tumor. Copyright © 2018. Published by Elsevier Inc.

ALA-induced PpIX spectroscopy for brain tumor image-guided surgery

NASA Astrophysics Data System (ADS)

Valdes, Pablo A.; Leblond, Frederic; Kim, Anthony; Harris, Brent T.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.

2011-03-01

Maximizing the extent of brain tumor resection correlates with improved survival and quality of life outcomes in patients. Optimal surgical resection requires accurate discrimination between normal and abnormal, cancerous tissue. We present our recent experience using quantitative optical spectroscopy in 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence-guided resection. Exogenous administration of ALA leads to preferential accumulation in tumor tissue of the fluorescent compound, PpIX, which can be used for in vivo surgical guidance. Using the state of the art approach with a fluorescence surgical microscope, we have been able to visualize a subset of brain tumors, but the sensitivity and accuracy of fluorescence detection for tumor tissue with this system are low. To take full advantage of the biological selectivity of PpIX accumulation in brain tumors, we used a quantitative optical spectroscopy system for in vivo measurements of PpIX tissue concentrations. We have shown that, using our quantitative approach for determination of biomarker concentrations, ALA-induced PpIX fluorescence-guidance can achieve accuracies of greater than 90% for most tumor histologies. Here we show multivariate analysis of fluorescence and diffuse reflectance signals in brain tumors with comparable diagnostic performance to our previously reported quantitative approach. These results are promising, since they show that technological improvements in current fluorescence-guided surgical technologies and more biologically relevant approaches are required to take full advantage of fluorescent biomarkers, achieve better tumor identification, increase extent of resection, and subsequently, lead to improve survival and quality of life in patients.

Predictive analysis of optical ablation in several dermatological tumoral tissues

NASA Astrophysics Data System (ADS)

Fanjul-Vélez, F.; Blanco-Gutiérrez, A.; Salas-García, I.; Ortega-Quijano, N.; Arce-Diego, J. L.

2013-06-01

Optical techniques for treatment and characterization of biological tissues are revolutionizing several branches of medical praxis, for example in ophthalmology or dermatology. The non-invasive, non-contact and non-ionizing character of optical radiation makes it specially suitable for these applications. Optical radiation can be employed in medical ablation applications, either for tissue resection or surgery. Optical ablation may provide a controlled and clean cut on a biological tissue. This is particularly relevant in tumoral tissue resection, where a small amount of cancerous cells could make the tumor appear again. A very important aspect of tissue optical ablation is then the estimation of the affected volume. In this work we propose a complete predictive model of tissue ablation that provides an estimation of the resected volume. The model is based on a Monte Carlo approach for the optical propagation of radiation inside the tissue, and a blow-off model for tissue ablation. This model is applied to several types of dermatological tumoral tissues, specifically squamous cells, basocellular and infiltrative carcinomas. The parameters of the optical source are varied and the estimated resected volume is calculated. The results for the different tumor types are presented and compared. This model can be used for surgical planning, in order to assure the complete resection of the tumoral tissue.

Rare angioproliferative tumors mimicking aggressive spinal hemangioma with epidural expansion.

PubMed

Kulcsár, Zsolt; Veres, Róbert; Hanzély, Zoltán; Berentei, Zsolt; Marosfoi, Miklós; Nyáry, István; Szikora, István

2012-01-30

We present two cases of angio-proliferative tumors that were misdiagnosed and treated as typical hemangiomas with epidural expansion. Two middle-aged women presented with symptoms and radiological signs characteristic for aggressive hemangioma with epidural expansion. In the first case preoperative embolization and decompressive surgery with open transpedicular vertebroplasty was performed. Within less than a year, epidural recurrence of the tumor prompted for radical excision and corpectomy. The diagnosis after the histological studies and the further clinical evolution was metastasizing leiomyomatosis. No further recurrence occured during the next 6 years. In the second case percutaneous vertebroplasty was performed and complicated by epidural polymethyl-methacrylcate (PMMA) leakage, requiring urgent decompressive surgery. Histological study of the lesion raised the possibility of myopericytoma. This was confirmed 16 months later when complete vertebrectomy was performed due to severe epidural propagation of the recurring tumor. No further recurrence occurred in next the two years. Rare angio-proliferative tumors, like benign metastasizing leiomyoma and myopericytoma radiologically may resemble aggressive vertebral hemangiomas of the spine. Unlike hemangiomas, such tumors require radical removal due to their likely recurrence. As imaging studies may not be able to completely exclude such pathologies, bone biopsy and thorough histopathological studies are warranted prior to the therapeutic decision.

Cervical lymph node metastases from remote primary tumor sites

PubMed Central

López, Fernando; Rodrigo, Juan P.; Silver, Carl E.; Haigentz, Missak; Bishop, Justin A.; Strojan, Primož; Hartl, Dana M.; Bradley, Patrick J.; Mendenhall, William M.; Suárez, Carlos; Takes, Robert P.; Hamoir, Marc; Robbins, K. Thomas; Shaha, Ashok R.; Werner, Jochen A.; Rinaldo, Alessandra; Ferlito, Alfio

2016-01-01

Although most malignant lymphadenopathy in the neck represent lymphomas or metastases from head and neck primary tumors, occasionally, metastatic disease from remote, usually infraclavicular, sites presents as cervical lymphadenopathy with or without an obvious primary tumor. In general, these tumors metastasize to supraclavicular lymph nodes, but occasionally may present at an isolated higher neck level. A search for the primary tumor includes information gained by histology, immunohistochemistry, and evaluation of molecular markers that may be unique to the primary tumor site. In addition, 18F-fluoro-2-deoxyglocose positron emission tomography combined with CT (FDG-PET/CT) has greatly improved the ability to detect the location of an unknown primary tumor, particularly when in a remote location. Although cervical metastatic disease from a remote primary site is often incurable, there are situations in which meaningful survival can be achieved with appropriate local treatment. Management is quite complex and requires a truly multidisciplinary approach. PMID:26713674

Complete necrosis of hepatocellular carcinoma after preoperative portal vein embolization: a case report.

PubMed

El Bacha, H; Salihoun, M; Kabbaj, N; Benkabbou, A

2017-01-04

Hepatocellular carcinoma has a poor prognosis; few patients can undergo surgical curative treatment according to Barcelona Clinic Liver Cancer guidelines. Progress in surgical techniques has led to operations for more patients outside these guidelines. Our case shows a patient with intermediate stage hepatocellular carcinoma presenting a good outcome after curative treatment. We report the case of an 80-year-old Moroccan man, who was positive for hepatitis c virus, presenting an intermediate stage hepatocellular carcinoma (three lesions between 20 and 60 mm). He presented a complete tumor necrosis after portal vein embolization and achieved 24-month disease-free survival after surgery. Perioperative care in liver surgery and multidisciplinary discussion can help to extend indications for liver resection for hepatocellular carcinoma outside European Association for the Study of the Liver/American Association for the Study of Liver Diseases recommendations and offer a curative approach to selected patients with intermediate and advanced stage hepatocellular carcinoma.

[Research advances of anti-tumor immune response induced by pulse electric field ablation].

PubMed

Cui, Guang-ying; Diao, Hong-yan

2015-11-01

As a novel tumor therapy, pulse electric field has shown a clinical perspective. This paper reviews the characteristics of tumor ablation by microsecond pulse and nanosecond pulse electric field, and the research advances of anti-tumor immune response induced by pulse electric field ablation. Recent researches indicate that the pulse electric field not only leads to a complete ablation of local tumor, but also stimulates a protective immune response, thereby inhibiting tumor recurrence and metastasis. These unique advantages will show an extensive clinical application in the future. However, the mechanism of anti-tumor immune response and the development of related tumor vaccine need further studies.

Laparoscopic resection of gastric and small bowel gastrointestinal stromal tumors: 10-year experience at a single center.

PubMed

Tabrizian, Parissa; Sweeney, Robert E; Uhr, Joshua H; Nguyen, Scott Q; Divino, Celia M

2014-03-01

Complete curative resection remains the treatment of choice for nonmetastatic gastrointestinal stromal tumors (GISTs). The safety and feasibility of laparoscopy in the treatment of this disease has been shown, however, the long-term oncologic outcomes of this technique remain unclear. An ongoing prospectively maintained database including all laparoscopically resected gastric and small bowel GISTs (n = 116) at Mount Sinai Medical Center from July 1999 to December 2011 was retrospectively analyzed. Recurrence and survival outcomes were calculated using the Kaplan-Meier method and compared with log-rank test. Tumors were of gastric (77.6%) and small bowel (22.4%) origins. Overall mean tumor size was 4.0 cm (±2.7 cm) and R0 resection was achieved in 113 (97.4%) cases. Overall perioperative complication rate was 14.7%, with a reoperative rate of 4.3% at 90 days. When comparing gastric with small bowel GISTs, a more acute presentation requiring emergent resections was noted in patients with small bowel GISTs (p = 008). However tumor size, operative data, and perioperative outcomes were comparable in both groups (p = NS). At a median follow-up of 56.4 months (range 0.1 to 162.4 months), recurrence rate was 7.8% and comparable in both gastric and small bowel GISTs (p = NS). Risk factors for recurrence on univariate analysis were presence of ulceration/necrosis (p < 0.001) and tumor size >5 cm (p = 0.05). Overall 10-year survival rate was 90.8%. Gastric and small bowel overall survival rates were similar (90.7% vs 91.3%, respectively). Overall 10-year disease-free survival was 80.0% (84.3% gastric vs 71.6% small bowel; p = NS). Our series demonstrates the safety and feasibility of laparoscopy in patients undergoing resection of small bowel and gastric GISTs. Comparable long-term oncologic outcomes with a 10-year survival of 90.8% were achieved. Copyright © 2014. Published by Elsevier Inc.

Development of Mouse Models of Ovarian Cancer for Studying Tumor Biology and Testing Novel Molecularly Targeted Therapeutic Strategies

DTIC Science & Technology

2011-09-01

Treatment of tumor-bearing mice with cisplatin accompanied by MRI and BLI (completed years 2 and 3, Rehemtulla and Cho laboratories) Task 10: Treatment...of tumor-bearing mice with perifosine accompanied by MRI and BLI (completed, years 2 and 3, Rehemtulla and Cho laboratories). Task 11: Treatment of...tumor-bearing mice with SC-560 accompanied by MRI and BLI (not performed) Task 12: Histological and immunohistochemical analysis of β-catenin

Comparison of cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium nanoparticles in tumor-bearing mice.

PubMed

Oyewumi, Moses O; Yokel, Robert A; Jay, Michael; Coakley, Tricia; Mumper, Russell J

2004-03-24

The purpose of these studies was to compare the cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium (Gd) nanoparticles. Gd is a potential agent for neutron capture therapy (NCT) of tumors. Gd nanoparticles were engineered from oil-in-water microemulsion templates. To obtain folate-coated nanoparticles, a folate ligand [folic acid chemically linked to distearoylphosphatidylethanolamine (DSPE) via a PEG spacer MW 3350] was included in nanoparticle preparations. Similarly, control nanoparticles were coated with DSPE-PEG-MW 3350 (PEG-coated). Nanoparticles were characterized based on size, size distribution, morphology, biocompatibility and tumor cell uptake. In vivo studies were carried out in KB (human nasopharyngeal carcinoma) tumor-bearing athymic mice. Biodistribution and tumor retention studies were carried out at pre-determined time intervals after injection of nanoparticles (10 mg/kg). Gd nanoparticles did not aggregate platelets or activate neutrophils. The retention of nanoparticles in the blood 8, 16 and 24 h post-injection was 60%, 13% and 11% of the injected dose (ID), respectively. A maximum Gd tumor localization of 33+/-7 microg Gd/g was achieved. Both folate-coated and PEG-coated nanoparticles had comparable tumor accumulation. However, the cell uptake and tumor retention of folate-coated nanoparticles was significantly enhanced over PEG-coated nanoparticles. Thus, the benefits of folate ligand coating were to facilitate tumor cell internalization and retention of Gd-nanoparticles in the tumor tissue. The engineered nanoparticles may have potential in tumor-targeted delivery of Gd thereby enhancing the therapeutic success of NCT.

Successful Resection of a Large Carotid Body Tumor Masquerading Complete Encasement of the Internal Carotid Artery on Preoperative Imaging.

PubMed

Kakkos, Stavros K; Zampakis, Peter; Lampropoulos, George C; Paridis, Leonidas; Kaplanis, Charalampos; Bantouna, Dimitra; Nikolakopoulos, Konstantinos M; Papageorgopoulou, Chrysanthi P; Kalogeropoulou, Christina; Tsolakis, Ioannis A

2018-05-01

A 41-year-old woman presented with a large painful and tender mass of the left side of her neck located just below the angle of the mandible. She was also complaining of frequent attacks of symptoms ranging from dizziness upon resuming the erect position to frank syncope. Color-coded duplex showed a large well-vascularized vascular mass at the level of the carotid bifurcation, suggesting the diagnosis of a carotid body tumor (CBT). A computerized tomographic angiography confirmed the diagnosis of a CBT, which measured 5.7 cm in its craniocaudal axis. The tumor appeared to encase the internal carotid artery (ICA) at the level of its origin, indicating the presence of a Shamblin group 3 tumor. During surgery, the CBT seemingly encased the ICA; however, it was successfully taken off the ICA, by establishing an adventitial dissection place, obviating the need for arterial resection and replacement. A brief intraoperative episode of cardiac arrest was successfully managed. Postoperative course was uneventful, and all symptoms were cured. Pathology confirmed the clinical diagnosis and did not show malignancy. In conclusion, meticulous surgical techniques can spare the ICA from removal or inadvertent injury during CBT surgery and reduce the morbidity often associated with the resection of large or advanced tumors but also cure atypical patient symptoms.

Parenting Style and Parental Involvement: Relations with Adolescent Achievement.

ERIC Educational Resources Information Center

Paulson, Sharon E.

1994-01-01

Eighty ninth-grade students completed questionnaires regarding their parents' demandingness, responsiveness, school involvement, and commitment to achievement. Boys' reports of both maternal and paternal parenting significantly predicted their achievement, with parental values toward achievement significantly predicting achievement in boys above…

Chondroitin sulfate-functionalized polyamidoamine as a tumor-targeted carrier for miR-34a delivery.

PubMed

Chen, Wenqi; Liu, Yong; Liang, Xiao; Huang, Yu; Li, Quanshun

2017-07-15

Chondroitin sulfate (CS) was modified on a polyamidoamine dendrimer (PAMAM) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The derivative CS-PAMAM was demonstrated to achieve an efficient cellular uptake of miR-34a in a CD44-dependent endocytosis way and further facilitate the endosomal escape of miR-34a after 4h. Through the miR-34a delivery, obvious inhibition of cell proliferation could be detected which was attributed to the enhancement of cell apoptosis and cell cycle arrest, and meanwhile the cell migration and invasion has been observed to be inhibited. Finally, the intravenous injection of CS-PAMAM/miR-34a formulation into mice bearing human lung adenocarcinoma cell A549 xenografts could efficiently inhibit the tumor growth and induce the tumor apoptosis owing to the enhanced accumulation of miR-34a in tumor tissue. Overall, CS-PAMAM is potential to be used as a tumor-targeted oligonucleotide carrier for achieving tumor gene therapy. The cationic dendrimer PAMAM was modified by chondroitin sulfate (CS) through Michael addition to construct a tumor-targeted carrier CS-PAMAM for miR-34a delivery. The introduction of CS could achieve an efficient cellular uptake and intracellular transfection of miR-34a in a CD44-dependent endocytosis manner. The miR-34a delivery could execute the anti-proliferation activity by simultaneously inducing cell apoptosis and cell cycle arrest, and also the anti-migration activity. The CS-PAMAM-mediated systemic delivery of miR-34a showed significant inhibition of tumor growth and induction of tumor apoptosis using a mice model of subcutaneously implanted tumors. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Pancreatic cystic tumors.

PubMed

Salvia, R; Festa, L; Butturini, G; Tonsi, A; Sartori, N; Biasutti, C; Capelli, P; Pederzoli, P

2004-04-01

literature. Except for inoperable cases due to the critical condition of the patient or non-resectable lesions, surgical treatment differs with the diagnosis. Cystic tumors of the pancreas, therefore, are a heterogeneous group of tumors, with a real problem regarding differential diagnosis between neoplastic and inflammatory lesions. Even with a proper work up, some perplexity may remain about the nature of the lesion and in these cases the surgical procedure has a therapeutic value as well as playing a diagnostic role. The role of surgery is central in the treatment of these tumors because it could be curative when complete resection is possible. In this way, the lack of good therapeutic results with chemotherapy and radiotherapy force the surgeon to go ahead with the procedure. Intraductal papillary mucinous neoplasms represent a new and, from the epidemiological point of view, important chapter in the world of cystic tumors. The margin of resection is important and the surgeon has to be aware that in order to have a curative resection, total pancreatectomy is sometimes required. In the last few years the therapeutic approach has changed thanks to new knowledge of the biological behavior of these tumors. In fact, from a surgical approach in all cases, we are now discussing the possibility of a follow-up not only for asymptomatic serous cystadenomas but also for the little branch side intraductal papillary mucinous neoplasms (IPMNs) in critical patients. A follow-up could be planned even for solid pseudopapillary tumors but it seems risky to leave untreated big tumors in young patients without a certain diagnosis and with so few studies reported in the literature.

Loss of 11q and 16q in Wilms tumors is associated with anaplasia, tumor recurrence, and poor prognosis.

PubMed

Wittmann, Stefanie; Zirn, Birgit; Alkassar, Muhannad; Ambros, Peter; Graf, Norbert; Gessler, Manfred

2007-02-01

Allele loss of chromosome arms 11q and 16q in Wilms tumors has been associated with different clinical parameters in prior studies. To substantiate these findings in a large collection of tumors treated according to the GPOH/SIOP protocol and to narrow down critical regions, we performed loss of heterozygosity (LOH) analyses of chromosome arms 11q and 16q on 225 Wilms tumors. On chromosome arm 11q an overall rate of allele loss of 19.6% (44 of 225 tumors) was found using eleven markers that were almost evenly distributed along the long arm. Chromosome arm 16q was analyzed with six markers selected from gene-rich regions that identified an LOH rate of 18.4% (41/223). Evaluation of LOH with respect to clinical data revealed significant associations of LOH 11q with histology: LOH 11q was 3-4 times more frequent in mixed type and diffuse anaplastic tumors. In contrast, epithelial as well as stromal type tumors never exhibited allele loss on 11q. Furthermore, a significant correlation with tumor recurrence and death was detected, but only for tumors that lost the entire long arm of chromosome 11. Similarly, LOH 16q was correlated with higher risks of later relapse, especially in tumors with complete loss of the long arm. Hence, analyses of LOH on 11q and 16q appear to be helpful to identify tumors with a higher risk of relapse and adverse outcome, which need adjusted therapeutic approaches. Copyright 2006 Wiley-Liss, Inc.

Foxp3 and IL17 expression in tumor infiltrating lymphocytes (TIL) and tumor cells - correlated or independent factors?

PubMed

Vasilescu, Florina; Arsene, D; Cionca, Florina; Comănescu, Maria; Enache, V; Iosif, Cristina; Alexandru, D O; Georgescu, D; Dobrea, Camelia; Bălan, Adina; Ardeleanu, Carmen

2013-01-01

Tumor infiltrating lymphocytes (TIL), as a microenvironment component were studied in various epithelial tumors, with contradictory results. Recent data about regulatory T-cells (Treg) revealed new explanations for pro- and anti-tumor implications of TIL. Tregs immunoprofile was recently completed with Foxp3 expression. A T-cell fraction (Th) is producing cytokine IL17 and is now considered acting in tumor progression. Our study aimed to analyze immunohistochemically (IHC) Foxp3+ and IL17 expression in resected lung adenocarcinomas, since they could become possible targets in the antitumor immunotherapy. The studied material was represented by paraffin-embedded tumor fragments from 59 patients with TIL identified on HE staining. The antibodies used were Foxp3 and IL17. The statistical analysis used logistical regression on SPSS19 software (Chicago, IL, USA). TIL was usually mild or scarce. A positive statistic correlation resulted between the amounts of TIL in peritumoral and intratumoral location but without correlation to histopathological grading. Foxp3 and IL17 were present in TIL lymphocytes, tumor cells and fibroblasts; IL17 was expressed also in periendothelial cells (PEC). Foxp3 positivity was significantly correlated for lymphocytes÷tumor cells, lymphocytes÷fibroblasts and tumor cells÷fibroblasts, suggesting their concerted action. Tumor cells and lymphocytes Foxp3 expression was inversely correlated with the amount of TIL. Between lymphocytic Foxp3 and PEC IL17, we found a weak negative correlation. The TIL had a quite positive correlation with PEC IL17. In these conditions, Foxp3 could be a mediator of the tumor cells inhibitory aggression upon the immune system and could be used as a molecular target for biological antitumor therapy.

Suppression of Rabbit VX‐2 Subcutaneous Tumor Growth by Gadolinium Neutron Capture Therapy

PubMed Central

Tokita, Nobuhiko; Tokuuye, Koichi; Satoh, Michinao; Churei, Hisahiko; Pechoux, Cécile Le; Kobayashi, Tooru; Kanda, Keiji

1993-01-01

VX‐2 tumors growing in hind legs of New Zealand White rabbits (n=4) were exposed to thermal neutrons for 40 min (2.1 × 1012 neutrons cm−2) while one of two hind leg tumors of each rabbit was infused continuously with meglumine gadopentetate through a branch of the left femoral artery. The contralateral (uninfused) tumors served as controls. Although no differential distribution of gadolinium was achieved between the tumor and its adjacent normal tissue, the gadolinium concentration in the infused tumor was approximately 5–6 fold higher than that in the contralateral tumor. Growth of gadolinium‐infused tumors was significantly inhibited compared to that of control tumors (P<0.05) between the 16th and 23rd days after treatment. PMID:8407547

Gastrointestinal Stromal Tumors with Unusual Localization: Report of Three Cases with a Brief Literature Review

PubMed Central

Yucel, Ahmet Fikret; Sunar, Haldun; Hut, Adnan; Kocakusak, Ahmet; Pergel, Ahmet; Barut, Gul; Dikici, Suleyman

2010-01-01

The most common tumors derived from the mesenchyme of the gastrointestinal system are stromal tumors. These tumors are typically seen in the stomach and small intestine and less frequently in the colon, rectum and esophagus and are very rarely located outside the gastrointestinal system. Cure is provided with complete surgical resection with resection borders free of tumor. Tumor size, mitotic index, localization, CD117 and CD34 negativity in immunohistochemical studies, mucosal ulceration and presence of necrosis help to predict recurrence of the illness and patient survival. In high-risk gastrointestinal stromal tumors (GISTs) there is an increased rate of recurrence and shortened survival despite complete surgical resection. Thus patients with a high-risk GIST should be given adjuvant therapy with imatinib mesylate. Sunitinib maleate is another FDA-approved agent only for cases who cannot tolerate imatinib or who are resistant to it. Herein we present three cases with GISTs in different locations of the gastrointestinal system with a review of the relevant literature. PMID:20805952

Gastrointestinal Stromal Tumors with Unusual Localization: Report of Three Cases with a Brief Literature Review.

PubMed

Yucel, Ahmet Fikret; Sunar, Haldun; Hut, Adnan; Kocakusak, Ahmet; Pergel, Ahmet; Barut, Gul; Dikici, Suleyman

2010-07-26

The most common tumors derived from the mesenchyme of the gastrointestinal system are stromal tumors. These tumors are typically seen in the stomach and small intestine and less frequently in the colon, rectum and esophagus and are very rarely located outside the gastrointestinal system. Cure is provided with complete surgical resection with resection borders free of tumor. Tumor size, mitotic index, localization, CD117 and CD34 negativity in immunohistochemical studies, mucosal ulceration and presence of necrosis help to predict recurrence of the illness and patient survival. In high-risk gastrointestinal stromal tumors (GISTs) there is an increased rate of recurrence and shortened survival despite complete surgical resection. Thus patients with a high-risk GIST should be given adjuvant therapy with imatinib mesylate. Sunitinib maleate is another FDA-approved agent only for cases who cannot tolerate imatinib or who are resistant to it. Herein we present three cases with GISTs in different locations of the gastrointestinal system with a review of the relevant literature.

Blockade of the ERK pathway enhances the therapeutic efficacy of the histone deacetylase inhibitor MS-275 in human tumor xenograft models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sakamoto, Toshiaki; Ozaki, Kei-ichi; Fujio, Kohsuke

2013-04-19

Highlights: •Blockade of the ERK pathway enhances the anticancer efficacy of HDAC inhibitors. •MEK inhibitors sensitize human tumor xenografts to HDAC inhibitor cytotoxicity. •Such the enhanced efficacy is achieved by a transient blockade of the ERK pathway. •This drug combination provides a promising therapeutic strategy for cancer patients. -- Abstract: The ERK pathway is up-regulated in various human cancers and represents a prime target for mechanism-based approaches to cancer treatment. Specific blockade of the ERK pathway alone induces mostly cytostatic rather than pro-apoptotic effects, however, resulting in a limited therapeutic efficacy of the ERK kinase (MEK) inhibitors. We previously showedmore » that MEK inhibitors markedly enhance the ability of histone deacetylase (HDAC) inhibitors to induce apoptosis in tumor cells with constitutive ERK pathway activation in vitro. To evaluate the therapeutic efficacy of such drug combinations, we administered the MEK inhibitor PD184352 or AZD6244 together with the HDAC inhibitor MS-275 in nude mice harboring HT-29 or H1650 xenografts. Co-administration of the MEK inhibitor markedly sensitized the human xenografts to MS-275 cytotoxicity. A dose of MS-275 that alone showed only moderate cytotoxicity thus suppressed the growth of tumor xenografts almost completely as well as induced a marked reduction in tumor cellularity when administered with PD184352 or AZD6244. The combination of the two types of inhibitor also induced marked oxidative stress, which appeared to result in DNA damage and massive cell death, specifically in the tumor xenografts. The enhanced therapeutic efficacy of the drug combination was achieved by a relatively transient blockade of the ERK pathway. Administration of both MEK and HDAC inhibitors represents a promising chemotherapeutic strategy with improved safety for cancer patients.« less

Tumor-Intrinsic and Tumor-Extrinsic Factors Impacting Hsp90-Targeted Therapy

PubMed Central

Alarcon, S. V.; Mollapour, M.; Lee, M.-J.; Tsutsumi, S.; Lee, S.; Kim, Y. S.; Prince, T.; Apolo, A.; Giaccone, G.; Xu, W.; Neckers, L. M.; Trepel, J. B.

2012-01-01

In 1994 the first heat shock protein 90 (Hsp90) inhibitor was identified and Hsp90 was reported to be a target for anticancer therapeutics. In the past 18 years there have been 17 distinct Hsp90 inhibitors entered into clinical trial, and the small molecule Hsp90 inhibitors have been highly valuable as probes of the role of Hsp90 and its client proteins in cancer. Although no Hsp90 inhibitor has achieved regulatory approval, recently there has been significant progress in Hsp90 inhibitor clinical development, and in the past year RECIST responses have been documented in HER2-positive breast cancer and EML4-ALK-positive non-small cell lung cancer. All of the clinical Hsp90 inhibitors studied to date are specific in their target, i.e. they bind exclusively to Hsp90 and two related heat shock proteins. However, Hsp90 inhibitors are markedly pleiotropic, causing degradation of over 200 client proteins and impacting critical multiprotein complexes. Furthermore, it has only recently been appreciated that Hsp90 inhibitors can, paradoxically, cause transient activation of the protein kinase clients they are chaperoning, resulting in initiation of signal transduction and significant physiological events in both tumor and tumor microenvironment. An additional area of recent progress in Hsp90 research is in studies of the posttranslational modifications of Hsp90 itself and Hsp90 co-chaperone proteins. Together, a picture is emerging in which the impact of Hsp90 inhibitors is shaped by the tumor intracellular and extracellular milieu, and in which Hsp90 inhibitors impact tumor and host on a microenvironmental and systems level. Here we review the tumor intrinsic and extrinsic factors that impact the efficacy of small molecules engaging the Hsp90 chaperone machine. PMID:22804236

[Diagnosis and surgical management in gastrointestinal neuroendocrine tumors].

PubMed

Tomulescu, V; Stănciulea, O; Dima, S; Herlea, V; Stoica Mustafa, E; Dumitraşcu, T; Pechianu, C; Popescu, I

2011-01-01

Neuroendocrine tumors, known as carcinoid tumors constitute a heterogeneous group of neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause specific clinical syndromes. Assessment of specific or general tumors markers offers high sensitivity in establishing the diagnosis and they also have prognostic significance. Management strategies include curative surgery, whenever possible-that can be rarely achieved, palliative surgery, chemotherapy, radiologic therapy, such as radiofrequency ablation and chemoembolisations and somatostatin analogues therapy in order to control the symptoms. The aim of this paper is to review recent publications in this field and to give recommendations that take into account current advances in order to facilitate improvement in management and outcome.

Cancer Management in Kabuki Syndrome: The First Case of Wilms Tumor and a Literature Review.

PubMed

Teranishi, Hideto; Koga, Yuhki; Nakashima, Kentaro; Morihana, Eiji; Ishii, Kanako; Sakai, Yasunari; Taguchi, Tomoaki; Oda, Yoshinao; Miyake, Noriko; Matsumoto, Naomichi; Ohga, Shouichi

2018-02-27

A 3-year-old Japanese girl treated for hypoplastic left heart syndrome and Dandy-Walker syndrome was diagnosed with Kabuki syndrome (KS) with a mutation of KMT2D; c.13285C>T:p.Q4429*. Concurrently, macrohematuria portended the diagnosis of Wilms tumor. Postoperative chemotherapy has achieved complete remission despite a prolonged and reduced regimen due to liver dysfunction and convulsions. Cancer predisposition has been suggested for KS due to oncogenic mutations in KMT2D or KDM6A. The first case of nephroblastoma exemplified the treatability of malignancies in KS patients, as shown in the 9 cases reviewed. Active screening and intervention are recommended for the cure of malignancy in KS children.

A quantitative microscopic approach to predict local recurrence based on in vivo intraoperative imaging of sarcoma tumor margins

PubMed Central

Mueller, Jenna L.; Fu, Henry L.; Mito, Jeffrey K.; Whitley, Melodi J.; Chitalia, Rhea; Erkanli, Alaattin; Dodd, Leslie; Cardona, Diana M.; Geradts, Joseph; Willett, Rebecca M.; Kirsch, David G.; Ramanujam, Nimmi

2015-01-01

The goal of resection of soft tissue sarcomas located in the extremity is to preserve limb function while completely excising the tumor with a margin of normal tissue. With surgery alone, one-third of patients with soft tissue sarcoma of the extremity will have local recurrence due to microscopic residual disease in the tumor bed. Currently, a limited number of intraoperative pathology-based techniques are used to assess margin status; however, few have been widely adopted due to sampling error and time constraints. To aid in intraoperative diagnosis, we developed a quantitative optical microscopy toolbox, which includes acriflavine staining, fluorescence microscopy, and analytic techniques called sparse component analysis and circle transform to yield quantitative diagnosis of tumor margins. A series of variables were quantified from images of resected primary sarcomas and used to optimize a multivariate model. The sensitivity and specificity for differentiating positive from negative ex vivo resected tumor margins was 82% and 75%. The utility of this approach was tested by imaging the in vivo tumor cavities from 34 mice after resection of a sarcoma with local recurrence as a bench mark. When applied prospectively to images from the tumor cavity, the sensitivity and specificity for differentiating local recurrence was 78% and 82%. For comparison, if pathology was used to predict local recurrence in this data set, it would achieve a sensitivity of 29% and a specificity of 71%. These results indicate a robust approach for detecting microscopic residual disease, which is an effective predictor of local recurrence. PMID:25994353

Octreotide LAR and Prednisone as Neoadjuvant Treatment in Patients with Primary or Locally Recurrent Unresectable Thymic Tumors: A Phase II Study

PubMed Central

Kirzinger, Lukas; Boy, Sandra; Marienhagen, Jörg; Schuierer, Gerhard; Neu, Reiner; Ried, Michael; Hofmann, Hans-Stefan; Wiebe, Karsten; Ströbel, Philipp; May, Christoph; Kleylein-Sohn, Julia; Baierlein, Claudia; Bogdahn, Ulrich; Marx, Alexander; Schalke, Berthold

2016-01-01

Therapeutic options to cure advanced, recurrent, and unresectable thymomas are limited. The most important factor for long-term survival of thymoma patients is complete resection (R0) of the tumor. We therefore evaluated the response to and the induction of resectability of primarily or locally recurrent unresectable thymomas and thymic carcinomas by octreotide Long-Acting Release (LAR) plus prednisone therapy in patients with positive octreotide scans. In this open label, single-arm phase II study, 17 patients with thymomas considered unresectable or locally recurrent thymoma (n = 15) and thymic carcinoma (n = 2) at Masaoka stage III were enrolled. Octreotide LAR (30 mg once every 2 weeks) was administered in combination with prednisone (0.6 mg/kg per day) for a maximum of 24 weeks (study design according to Fleming´s one sample multiple testing procedure for phase II clinical trials). Tumor size was evaluated by volumetric CT measurements, and a decrease in tumor volume of at least 20% at week 12 compared to baseline was considered as a response. We found that octreotide LAR plus prednisone elicited response in 15 of 17 patients (88%). Median reduction of tumor volume after 12 weeks of treatment was 51% (range 20%–86%). Subsequently, complete surgical resection was achieved in five (29%) and four patients (23%) after 12 and 24 weeks, respectively. Octreotide LAR plus prednisone treatment was discontinued in two patients before week 12 due to unsatisfactory therapeutic effects or adverse events. The most frequent adverse events were gastrointestinal (71%), infectious (65%), and hematological (41%) complications. In conclusion, octreotide LAR plus prednisone is efficacious in patients with primary or recurrent unresectable thymoma with respect to tumor regression. Octreotide LAR plus prednisone was well tolerated and adverse events were in line with the known safety profile of both agents. PMID:27992479

Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment

PubMed Central

Chen, Binlong; Dai, Wenbing; He, Bing; Zhang, Hua; Wang, Xueqing; Wang, Yiguang; Zhang, Qiang

2017-01-01

The development of traditional tumor-targeted drug delivery systems based on EPR effect and receptor-mediated endocytosis is very challenging probably because of the biological complexity of tumors as well as the limitations in the design of the functional nano-sized delivery systems. Recently, multistage drug delivery systems (Ms-DDS) triggered by various specific tumor microenvironment stimuli have emerged for tumor therapy and imaging. In response to the differences in the physiological blood circulation, tumor microenvironment, and intracellular environment, Ms-DDS can change their physicochemical properties (such as size, hydrophobicity, or zeta potential) to achieve deeper tumor penetration, enhanced cellular uptake, timely drug release, as well as effective endosomal escape. Based on these mechanisms, Ms-DDS could deliver maximum quantity of drugs to the therapeutic targets including tumor tissues, cells, and subcellular organelles and eventually exhibit the highest therapeutic efficacy. In this review, we expatiate on various responsive modes triggered by the tumor microenvironment stimuli, introduce recent advances in multistage nanoparticle systems, especially the multi-stimuli responsive delivery systems, and discuss their functions, effects, and prospects. PMID:28255348

Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment.

PubMed

Chen, Binlong; Dai, Wenbing; He, Bing; Zhang, Hua; Wang, Xueqing; Wang, Yiguang; Zhang, Qiang

2017-01-01

The development of traditional tumor-targeted drug delivery systems based on EPR effect and receptor-mediated endocytosis is very challenging probably because of the biological complexity of tumors as well as the limitations in the design of the functional nano-sized delivery systems. Recently, multistage drug delivery systems (Ms-DDS) triggered by various specific tumor microenvironment stimuli have emerged for tumor therapy and imaging. In response to the differences in the physiological blood circulation, tumor microenvironment, and intracellular environment, Ms-DDS can change their physicochemical properties (such as size, hydrophobicity, or zeta potential) to achieve deeper tumor penetration, enhanced cellular uptake, timely drug release, as well as effective endosomal escape. Based on these mechanisms, Ms-DDS could deliver maximum quantity of drugs to the therapeutic targets including tumor tissues, cells, and subcellular organelles and eventually exhibit the highest therapeutic efficacy. In this review, we expatiate on various responsive modes triggered by the tumor microenvironment stimuli, introduce recent advances in multistage nanoparticle systems, especially the multi-stimuli responsive delivery systems, and discuss their functions, effects, and prospects.

Photodynamic therapy platform for glioblastoma and intrabronchial tumors

NASA Astrophysics Data System (ADS)

Orsila, Lasse; Alanko, Jukka-Pekka; Kaivosoja, Visa; Uibu, Toomas

2018-02-01

Photodynamic therapy (PDT) is bringing new, effective, and less invasive, possibilities for cancer treatment. ML7710 (Modulight Inc.) medical laser system offers a platform for performing PDT for multiple indications and drugs. Latest avenue is glioblastoma treatment with 5-Aminolevulinic acid (ALA-5) and 635-nm light, where clinical trials are about to begin. Preliminary work suggests major advantages in treatment control, including active in-situ feedback. ML7710 platform has already proven itself for clinical work with intrabronchial obstructive tumors. Preliminary result with 10 patients show that intrabronchial tumors, that strongly affect both the survival and the performance of the patient, can be significantly reduced with ML7710 operated at 665 nm and sodium chlorine E6 photosensitizer. The aim in most of the patients has been a palliative recanalization of the bronchial lumen in order to alleviate the symptoms such as breathlessness and hemoptysis. The illumination dose for the target area was 50-75 J/cm2. All the patients have received multimodality cancer treatment using other intrabronchial interventions, radiotherapy and chemotherapy as needed. In most of the patients, satisfactory treatment results were achieved and it was possible to restart chemotherapy in several patients. In one patient with local cancer a complete remission was established. PDT has also the advantage that it is possible to give PDT after a maximum dose of radiation therapy has already been used and fewer side effects if used in locally advanced intraluminar lung cancer.

Development of Mouse Models of Ovarian Cancer for Studying Tumor Biology and Testing Novel Molecularly Targeted Therapeutic Strategies

DTIC Science & Technology

2011-09-01

years 2 and 3, Cho laboratory) Task 9: Treatment of tumor-bearing mice with cisplatin accompanied by MRI and BLI (completed years 2 and 3, Rehemtulla...and Cho laboratories) Task 10: Treatment of tumor-bearing mice with perifosine accompanied by MRI and BLI (completed, years 2 and 3, Rehemtulla and...Cho laboratories). Task 11: Treatment of tumor-bearing mice with SC-560 accompanied by MRI and BLI (not performed) Task 12: Histological and

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.

"How Do You Feel about Math?": Relationships between Competence and Value Appraisals, Achievement Emotions and Academic Achievement

ERIC Educational Resources Information Center

Peixoto, Francisco; Sanches, Cristina; Mata, Lourdes; Monteiro, Vera

2017-01-01

This study analyzes the relationships between cognitive appraisals, classroom and test emotions, and math achievement in a sample of 1,219 Portuguese students from the 6th and 8th grades. Participants completed measures of perceived value, perceived competence, and seven math achievement emotions (boredom, hopelessness, anger, anxiety, enjoyment,…

[Endoscopic assistance in surgery of cerebellopontine angle tumors].

PubMed

Poshataev, V K; Shimansky, V N; Tanyashin, S V; Karnaukhov, V V

2014-01-01

During the period of 2010-2012, 33 patients with cerebellopontine angle tumors were operated on at the Burdenko Neurosurgical Institute (Moscow, Russia) using different types of endoscopic assistance. All patients were operated on via the retrosigmoid suboccipital approach in semi-sitting and prone positions. 30° and 70° endoscopes were used during the surgery. Endoscopic assistance allowed us to increase the completeness of tumor removal and to reduce the risk of postoperative complications by retaining the anatomic integrity of cranial nerves and vascular structures in the base of the posterior cranial fossa. These benefits made it possible to maintain and improve quality of life in patients with CPA tumors in the postoperative period.

Adoptive Transfer of Tumor-Specific Th2 Cells Eradicates Tumors by Triggering an In Situ Inflammatory Immune Response.

PubMed

Lorvik, Kristina Berg; Hammarström, Clara; Fauskanger, Marte; Haabeth, Ole Audun Werner; Zangani, Michael; Haraldsen, Guttorm; Bogen, Bjarne; Corthay, Alexandre

2016-12-01

Adoptive cell therapy (ACT) trials to date have focused on transfer of autologous tumor-specific cytotoxic CD8 + T cells; however, the potential of CD4 + T helper (Th) cells for ACT is gaining interest. While encouraging results have been reported with IFNγ-producing Th1 cells, tumor-specific Th2 cells have been largely neglected for ACT due to their reported tumor-promoting properties. In this study, we tested the efficacy of idiotype-specific Th2 cells for the treatment of mice with MHC class II-negative myeloma. Th2 ACT efficiently eradicated subcutaneous myeloma in an antigen-specific fashion. Transferred Th2 cells persisted in vivo and conferred long-lasting immunity. Cancer eradication mediated by tumor-specific Th2 cells did not require B cells, natural killer T cells, CD8 + T cells, or IFNγ. Th2 ACT was also curative against B-cell lymphoma. Upon transfer, Th2 cells induced a type II inflammation at the tumor site with massive infiltration of M2-type macrophages producing arginase. In vivo blockade of arginase strongly inhibited Th2 ACT, consistent with a key role of arginase and M2 macrophages in myeloma elimination by Th2 cells. These results illustrate that cancer eradication may be achieved by induction of a tumor-specific Th2 inflammatory immune response at the tumor site. Thus, ACT with tumor-specific Th2 cells may represent a highly efficient immunotherapy protocol against cancer. Cancer Res; 76(23); 6864-76. ©2016 AACR. ©2016 American Association for Cancer Research.

Sub-lethal radiation enhances anti-tumor immunotherapy in a transgenic mouse model of pancreatic cancer

PubMed Central

Cao, Zhu Alexander; Daniel, Dylan; Hanahan, Douglas

2002-01-01

Background It is not uncommon to observe circulating tumor antigen-specific T lymphocytes in cancer patients despite a lack of significant infiltration and destruction of their tumors. Thus, an important goal for tumor immunotherapy is to identify ways to modulate in vivo anti-tumor immunity to achieve clinical efficacy. We investigate this proposition in a spontaneous mouse tumor model, Rip1-Tag2. Methods Experimental therapies were carried out in two distinctive trial designs, intended to either intervene in the explosive growth of small tumors, or regress bulky end-stage tumors. Rip1-Tag2 mice received a single transfer of splenocytes from Tag-specific, CD4+ T cell receptor transgenic mice, a single sub-lethal radiation, or a combination therapy in which the lymphocyte transfer was preceded by the sub-lethal radiation. Tumor burden, the extent of lymphocyte infiltration into solid tumors and host survival were used to assess the efficacy of these therapeutic approaches. Results In either intervention or regression, the transfer of Tag-specific T cells alone did not result in significant lymphocyte infiltration into solid tumors, not did it affect tumor growth or host survival. In contrast, the combination therapy resulted in significant reduction in tumor burden, increase in lymphocyte infiltration into solid tumors, and extension of survival. Conclusions The results indicate that certain types of solid tumors may be intrinsically resistant to infiltration and destruction by tumor-specific T lymphocytes. Our data suggest that such resistance can be disrupted by sub-lethal radiation. The combinatorial approach presented here merits consideration in the design of clinical trials aimed to achieve T cell-mediated anti-tumor immunity. PMID:12019035

Gastrointestinal stromal tumors as an incidental finding in patients with a presumptive diagnosis of ovarian cancer

PubMed Central

Muñoz, Mario; Ramirez, Pedro T.; Echeverri, Carolina; Álvarez, Luis Guillermo; Palomino, Maria Alejandra

2012-01-01

Objective To report the clinical presentation and oncologic outcomes of a series of patients who presented with an abdominal or pelvic mass and were diagnosed with a gastrointestinal stromal tumor (GIST). Methods Data were obtained on all patients who presented with an abdominal or pelvic mass between September 2007 and June 2010 and who were ultimately diagnosed with a GIST. The patients' medical records were reviewed. A literature review was also conducted. Results Six patients were identified who met the inclusion criteria. All six patients had a tumor in the intestinal tract arising from the small bowel. The mean tumor size was 12 cm (range, 6 to 22 cm). A complete resection was achieved in five of the six patients. There were no intraoperative complications; one patient had a postoperative complication. Two patients were treated with imatinib after surgery. The mean follow-up time was 32 months (range, 0.3 to 40 months). At the last follow-up, five of the six patients were without any evidence of disease. One patient died of an unrelated hepatic encephalopathy. The incidence in our institution is 3%. Conclusion GISTs are uncommon; however, they should be considered in the differential diagnosis of patients presenting with an abdominal or pelvic mass. PMID:22355467

Gastrointestinal stromal tumors as an incidental finding in patients with a presumptive diagnosis of ovarian cancer.

PubMed

Muñoz, Mario; Ramirez, Pedro T; Echeverri, Carolina; Alvarez, Luis Guillermo; Palomino, Maria Alejandra; Pareja, Luis René

2012-01-01

To report the clinical presentation and oncologic outcomes of a series of patients who presented with an abdominal or pelvic mass and were diagnosed with a gastrointestinal stromal tumor (GIST). Data were obtained on all patients who presented with an abdominal or pelvic mass between September 2007 and June 2010 and who were ultimately diagnosed with a GIST. The patients' medical records were reviewed. A literature review was also conducted. Six patients were identified who met the inclusion criteria. All six patients had a tumor in the intestinal tract arising from the small bowel. The mean tumor size was 12 cm (range, 6 to 22 cm). A complete resection was achieved in five of the six patients. There were no intraoperative complications; one patient had a postoperative complication. Two patients were treated with imatinib after surgery. The mean follow-up time was 32 months (range, 0.3 to 40 months). At the last follow-up, five of the six patients were without any evidence of disease. One patient died of an unrelated hepatic encephalopathy. The incidence in our institution is 3%. GISTs are uncommon; however, they should be considered in the differential diagnosis of patients presenting with an abdominal or pelvic mass.

Comparative Associations Between Achieved Bicultural Identity, Achieved Ego Identity, and Achieved Religious Identity and Adaptation Among Australian Adolescent Muslims.

PubMed

Abu-Rayya, Hisham M; Abu-Rayya, Maram H; White, Fiona A; Walker, Richard

2018-04-01

This study examined the comparative roles of biculturalism, ego identity, and religious identity in the adaptation of Australian adolescent Muslims. A total of 504 high school Muslim students studying at high schools in metropolitan Sydney and Melbourne, Australia, took part in this study which required them to complete a self-report questionnaire. Analyses indicated that adolescent Muslims' achieved religious identity seems to play a more important role in shaping their psychological and socio-cultural adaptation compared to adolescents' achieved bicultural identity. Adolescents' achieved ego identity tended also to play a greater role in their psychological and socio-cultural adaptation than achieved bicultural identity. The relationships between the three identities and negative indicators of psychological adaptation were consistently indifferent. Based on these findings, we propose that the three identity-based forces-bicultural identity development, religious identity attainment, and ego identity formation-be amalgamated into one framework in order for researchers to more accurately examine the adaptation of Australian adolescent Muslims.

[Treatment progress of gastrointestinal stromal tumor].

PubMed

Ji, Xin; Ji, Jia-fu

2013-03-01

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Its pathogenesis is defined by mutations within the KIT and PDGFRα gene. Surgical resection is the only radical treatment at present, but recurrence is common. In recent years, targeted therapy with imatinib mesylate, which inhibits KIT kinase activity, represents the other cornerstone for the treatment of GIST. For resectable GIST, operation combined with neoadjuvant and adjuvant therapy with imatinib mesylate or other tyrosine kinase inhibitors can improve the prognosis of high-risk patients before or after complete resection. For unresectable GIST, targeted therapy with imatinib mesylate can effectively inhibit and ameliorate the progression of GIST.

Outcomes of Adoptive Cell Transfer With Tumor-infiltrating Lymphocytes for Metastatic Melanoma Patients With and Without Brain Metastases.

PubMed

Mehta, Gautam U; Malekzadeh, Parisa; Shelton, Thomas; White, Donald E; Butman, John A; Yang, James C; Kammula, Udai S; Goff, Stephanie L; Rosenberg, Steven A; Sherry, Richard M

2018-06-01

Brain metastases cause significant morbidity and mortality in patients with metastatic melanoma. Although adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) can achieve complete and durable remission of advanced cutaneous melanoma, the efficacy of this therapy for brain metastases is unclear. Records of patients with M1c melanoma treated with ACT using TIL, including patients with treated and untreated brain metastases, were analyzed. Treatment consisted of preparative chemotherapy, autologous TIL infusion, and high-dose interleukin-2. Treatment outcomes, sites of initial tumor progression, and overall survival were analyzed. Among 144 total patients, 15 patients with treated and 18 patients with untreated brain metastases were identified. Intracranial objective responses (OR) occurred in 28% patients with untreated brain metastases. The systemic OR rates for patients with M1c disease without identified brain disease, treated brain disease, and untreated brain disease, and were 49%, 33% and 33%, respectively, of which 59%, 20% and 16% were durable at last follow-up. The site of untreated brain disease was the most likely site of initial tumor progression (61%) in patients with untreated brain metastases. Overall, we found that ACT with TIL can eliminate small melanoma brain metastases. However, following TIL therapy these patients frequently progress in the brain at a site of untreated brain disease. Patients with treated or untreated brain disease are less likely to achieve durable systemic ORs following TIL therapy compared with M1c disease and no history of brain disease. Melanoma brain metastases likely require local therapy despite the systemic effect of ACT.

Complete remission in a colon cancer patient with a large, irresectable liver metastasis after XELOX/cetuximab/bevacizumab treatment.

PubMed

Weihrauch, Martin R; Stippel, Dirk; Fries, Jochen W U; Arnold, Dirk; Bovenschulte, Henning; Coutelle, Oliver; Hacker, Ulrich

2008-09-01

Stage IV colorectal cancer is usually an incurable disease. However, patients with resectable metastases have 5-year disease-free survival rates of up to 30%. Even with primarily irresectable disease, cure can be achieved in patients who become operable after neoadjuvant treatment. To improve the prognosis of these patients, highly effective neoadjuvant regimens need to be developed. Here, we report the case of a 62-year-old male patient who had been diagnosed with International Union against Cancer (UICC) stage III colon cancer 7 years previously and now presented with a large, irresectable liver metastasis and enlarged perihepatic lymph nodes. After neoadjuvant treatment with cetuximab, bevacizumab and XELOX, the patient showed a complete remission and underwent surgery. Histopathologically, the resected tissue and lymph nodes were free of residual tumor. To our knowledge, this is the first report of a complete pathological response in a patient with irresectable colorectal cancer after intensive chemotherapy/anti-EGFR/ VEGF antibody therapy. This combination regimen may help to improve the survival rates for patients with irresectable disease. Copyright 2008 S. Karger AG, Basel.

In vivo cation exchange in quantum dots for tumor-specific imaging.

PubMed

Liu, Xiangyou; Braun, Gary B; Qin, Mingde; Ruoslahti, Erkki; Sugahara, Kazuki N

2017-08-24

In vivo tumor imaging with nanoprobes suffers from poor tumor specificity. Here, we introduce a nanosystem, which allows selective background quenching to gain exceptionally tumor-specific signals. The system uses near-infrared quantum dots and a membrane-impermeable etchant, which serves as a cation donor. The etchant rapidly quenches the quantum dots through cation exchange (ionic etching), and facilitates renal clearance of metal ions released from the quantum dots. The quantum dots are intravenously delivered into orthotopic breast and pancreas tumors in mice by using the tumor-penetrating iRGD peptide. Subsequent etching quenches excess quantum dots, leaving a highly tumor-specific signal provided by the intact quantum dots remaining in the extravascular tumor cells and fibroblasts. No toxicity is noted. The system also facilitates the detection of peritoneal tumors with high specificity upon intraperitoneal tumor targeting and selective etching of excess untargeted quantum dots. In vivo cation exchange may be a promising strategy to enhance specificity of tumor imaging.The imaging of tumors in vivo using nanoprobes has been challenging due to the lack of sufficient tumor specificity. Here, the authors develop a tumor-specific quantum dot system that permits in vivo cation exchange to achieve selective background quenching and high tumor-specific imaging.

Locally aggressive and multifocal phosphaturic mesenchymal tumors: two unusual cases of tumor-induced osteomalacia.

PubMed

Higley, Meghan; Beckett, Brooke; Schmahmann, Sandra; Dacey, Elizabeth; Foss, Erik

2015-12-01

Tumor-induced osteomalacia (TIO) has long been recognized as a clinical paraneoplastic syndrome. The identification of a unique histopathologic entity, the phosphaturic mesenchymal tumor (PMT), as a distinct etiology for TIO has been a more recent discovery. The majority of published cases describe a solitary, non-aggressive appearing soft tissue or osseous lesions in patients with osteomalacia; aggressive appearing or multifocal lesions appear to be exceedingly rare. These tumors characteristically secrete fibroblast growth factor 23 (FGF23). Elevated serum levels of FGF23 result in phosphate wasting and osteomalacia. In the majority of cases, laboratory abnormalities and clinical signs and symptoms of osteomalacia precede identification of the causative lesion by years. Following diagnosis, complete resection with wide margins to prevent local recurrence is most often curative. Imaging characteristics of PMT are diverse and remain incompletely defined, as the majority of previous publications are outside of the radiologic literature. We present multiple imaging modalities in two cases of patients with debilitating osteomalacia and unusual appearing PMTs: one with a locally aggressive lesion leading to pathologic fracture, the second presenting with exceedingly rare multifocal PMT.

Plasmacytoid dendritic cells induce NK cell-dependent, tumor antigen-specific T cell cross-priming and tumor regression in mice.

PubMed

Liu, Chengwen; Lou, Yanyan; Lizée, Gregory; Qin, Hong; Liu, Shujuan; Rabinovich, Brian; Kim, Grace J; Wang, Yi-Hong; Ye, Yang; Sikora, Andrew G; Overwijk, Willem W; Liu, Yong-Jun; Wang, Gang; Hwu, Patrick

2008-03-01

A prerequisite for strong adaptive antiviral immunity is the robust initial activation of the innate immune system, which is frequently mediated by TLR-activated plasmacytoid DCs (pDCs). Natural antitumor immunity is often comparatively weak, potentially due to the lack of TLR-mediated activation signals within the tumor microenvironment. To assess whether pDCs are capable of directly facilitating effective antitumor immune responses, mice bearing established subcutaneous B16 melanoma tumors were administered TLR9-activated pDCs directly into the tumor. We found that TLR9-activated pDCs induced robust, spontaneous CTL cross-priming against multiple B16 tumor antigens, leading to the regression of both treated tumors and untreated tumors at distant contralateral sites. This T cell cross-priming was mediated by conventional DCs (cDCs) and was completely dependent upon the early recruitment and activation of NK cells at the tumor site. NK cell recruitment was mediated by CCR5 via chemokines secreted by pDCs, and optimal IFN-gamma production by NK cells was mediated by OX40L expressed by pDCs. Our data thus demonstrated that activated pDCs are capable of initiating effective and systemic antitumor immunity through the orchestration of an immune cascade involving the sequential activation of NK cells, cDCs, and CD8(+) T cells.

Chemophototherapy: An Emerging Treatment Option for Solid Tumors

PubMed Central

Luo, Dandan; Carter, Kevin A.; Miranda, Dyego

2016-01-01

Near infrared (NIR) light penetrates human tissues with limited depth, thereby providing a method to safely deliver non‐ionizing radiation to well‐defined target tissue volumes. Light‐based therapies including photodynamic therapy (PDT) and laser‐induced thermal therapy have been validated clinically for curative and palliative treatment of solid tumors. However, these monotherapies can suffer from incomplete tumor killing and have not displaced existing ablative modalities. The combination of phototherapy and chemotherapy (chemophototherapy, CPT), when carefully planned, has been shown to be an effective tumor treatment option preclinically and clinically. Chemotherapy can enhance the efficacy of PDT by targeting surviving cancer cells or by inhibiting regrowth of damaged tumor blood vessels. Alternatively, PDT‐mediated vascular permeabilization has been shown to enhance the deposition of nanoparticulate drugs into tumors for enhanced accumulation and efficacy. Integrated nanoparticles have been reported that combine photosensitizers and drugs into a single agent. More recently, light‐activated nanoparticles have been developed that release their payload in response to light irradiation to achieve improved drug bioavailability with superior efficacy. CPT can potently eradicate tumors with precise spatial control, and further clinical testing is warranted. PMID:28105389

Developmental tumors and adjacent cortical dysplasia: single or dual pathology?

PubMed

Palmini, André; Paglioli, Eliseu; Silva, Vinicius Duval

2013-12-01

Developmental tumors often lead to refractory partial seizures and constitute a well-defined, surgically remediable epilepsy syndrome. Dysplastic features are often associated with these tumors, and their significance carries both practical and conceptual relevance. If associated focal cortical dysplasia (FCD) relates to the extent of the epileptogenic tissue, then presurgical evaluation and surgical strategies should target both the tumor and the surrounding dyslaminated cortex. Furthermore, the association has been included in the recently revised classification of FCD and the epileptogenicity of this associated dysplastic tissue is crucial to validate such revision. In addition to the possibility of representing dual pathology, the association of developmental tumors and adjacent dysplasia may instead represent a single developmental lesion with distinct parts distributed along a histopathologic continuum. Moreover, the possibility that this adjacent dyslamination is of minor epileptogenic relevance should also be entertained. Surgical data show that complete resection of the solid tumors and immediately adjacent tissue harboring satellites may disrupt epileptogenic networks and lead to high rates of seizure freedom, challenging the epileptogenic relevance of more extensive adjacent dyslaminated cortex. Whether the latter is a primary or secondary abnormality and whether dyslaminated cortex in the context of a second lesion may produce seizures after complete resection of the main lesion is still to be proven. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

CS2164, a novel multi-target inhibitor against tumor angiogenesis, mitosis and chronic inflammation with anti-tumor potency.

PubMed

Zhou, You; Shan, Song; Li, Zhi-Bin; Xin, Li-Jun; Pan, De-Si; Yang, Qian-Jiao; Liu, Ying-Ping; Yue, Xu-Peng; Liu, Xiao-Rong; Gao, Ji-Zhou; Zhang, Jin-Wen; Ning, Zhi-Qiang; Lu, Xian-Ping

2017-03-01

Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC 50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R + cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Durable Complete Response After Discontinuation of Pembrolizumab in Patients With Metastatic Melanoma.

PubMed

Robert, Caroline; Ribas, Antoni; Hamid, Omid; Daud, Adil; Wolchok, Jedd D; Joshua, Anthony M; Hwu, Wen-Jen; Weber, Jeffrey S; Gangadhar, Tara C; Joseph, Richard W; Dronca, Roxana; Patnaik, Amita; Zarour, Hassane; Kefford, Richard; Hersey, Peter; Zhang, Jin; Anderson, James; Diede, Scott J; Ebbinghaus, Scot; Hodi, F Stephen

2017-12-28

Purpose Pembrolizumab provides durable antitumor activity in metastatic melanoma, including complete response (CR) in about 15% of patients. Data are limited on potential predictors of CR and patient disposition after pembrolizumab discontinuation after CR. We describe baseline characteristics and long-term follow-up in patients who experienced CR with pembrolizumab in the KEYNOTE-001 study ( ClinicalTrials.gov identifier: NCT01295827). Patients and Methods Patients with ipilimumab-naive or -treated advanced/metastatic melanoma received one of three dose regimens of pembrolizumab. Eligible patients who received pembrolizumab for ≥ 6 months and at least two treatments beyond confirmed CR could discontinue therapy. Response was assessed every 12 weeks by central Response Evaluation Criteria in Solid Tumors version 1.1. For this analysis, CR was defined per investigator assessment, immune-related response criteria, and potential predictors of CR were evaluated using univariate and multivariate analyses. Results Of 655 treated patients, 105 (16.0%) achieved CR after median follow-up of 43 months. At data cutoff, 92 patients (87.6%) had CR, with median follow-up of 30 months from first CR. Fourteen (13.3%) patients continued to receive treatment for a median of ≥ 40 months. Pembrolizumab was discontinued by 91 patients (86.7%), including 67 (63.8%) who proceeded to observation without additional anticancer therapy. The 24-month disease-free survival rate from time of CR was 90.9% in all 105 patients with CR and 89.9% in the 67 patients who discontinued pembrolizumab after CR for observation. Tumor size and programmed death-ligand 1 status were among the baseline factors independently associated with CR by univariate analysis. Conclusion Patients with metastatic melanoma can have durable complete remission after discontinuation of pembrolizumab, and the low incidence of relapse after median follow-up of approximately 2 years from discontinuation provides hope for a

Structure of solid tumors and their vasculature: Implications for therapy with monoclonal antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dvorak, H.F.; Nagy, J.A.; Dvorak, A.M.

Delivery of monoclonal antibodies to solid tumors is a vexing problem that must be solved if these antibodies are to realize their promise in therapy. Such success as has been achieved with monoclonal antibodies is attributable to the local hyperpermeability of the tumor vasculature, a property that favors antibody extravasation at tumor sites and that is mediated by a tumor-secreted vascular permeability factor. However, leaky tumor blood vessels are generally some distance removed from target tumor cells, separated by stroma and by other tumor cells that together represent significant barriers to penetration by extravasated monoclonal antibodies. For this reason, alternativemore » approaches may be attractive. These include the use of antibody-linked cytotoxins, which are able to kill tumor cells without immediate contact, and direction of antibodies against nontumor cell targets, for example, antigens unique to the tumor vascular endothelium or to tumor stroma. 50 refs.« less

Complete suppression of in vivo growth of human leukemia cells by specific immunotoxins: nude mouse models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hara, H.; Seon, B.K.

1987-05-01

In this study, immunotoxins containing monoclonal anti-human T-cell leukemia antibodies are shown to be capable of completely suppressing the tumor growth of human T-cell leukemia cells in vivo without any overt undersirable toxicity. These immunotoxins were prepared by conjugating ricin A chain (RA) with our monoclonal antibodies, SN1 and SN2, directed specifically to the human T-cell leukemia cell surface antigens TALLA and GP37, respectively. The authors have shown that these monoclonal antibodies are highly specific for human T-cell leukemia cells and do not react with various normal cells including normal T and B cells, thymocytes, and bone marrow cells. Asciticmore » and solid human T-cell leukemia cell tumors were generated in nude mice. The ascitic tumor was generated by transplanting Ichikawa cells (a human T-cell leukemia cell) i.p. into nude mice, whereas the solid tumor was generated by transplanting s.c. MOLT-4 cells (a human T-cell leukemia cell line) and x-irradiated human fibrosarcoma cells into x-irradiated nude mice. To investigate the efficacy of specific immunotoxins in suppression the in vivo growth of the ascitic tumor, they divided 40 nude mice that were injected with Ichikawa cells into four groups. None of the mice in group 4 that were treated with SN1-RA and SN2-RA showed any signs of a tumor or undesirable toxic effects for the 20 weeks that they were followed after the transplantation. Treatment with SN1-RA plus SN2-RA completely suppressed solid tumor growth in 4 of 10 nude mice carrying solid tumors and partially suppressed the tumor growth in the remaining 6 nude mice. These results strongly suggest that SN1-RA and SN2-RA may be useful for clinical treatment.« less

SU-E-J-182: Reproducibility of Tumor Motion Probability Distribution Function in Stereotactic Body Radiation Therapy of Lung Using Real-Time Tumor-Tracking Radiotherapy System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shiinoki, T; Hanazawa, H; Park, S

2015-06-15

Purpose: We aim to achieve new four-dimensional radiotherapy (4DRT) using the next generation real-time tumor-tracking (RTRT) system and flattening-filter-free techniques. To achieve new 4DRT, it is necessary to understand the respiratory motion of tumor. The purposes of this study were: 1.To develop the respiratory motion analysis tool using log files. 2.To evaluate the reproducibility of tumor motion probability distribution function (PDF) during stereotactic body RT (SBRT) of lung tumor. Methods: Seven patients having fiducial markers closely implanted to the lung tumor were enrolled in this study. The positions of fiducial markers were measured using the RTRT system (Mitsubishi Electronics Co.,more » JP) and recorded as two types of log files during the course of SBRT. For each patients, tumor motion range and tumor motion PDFs in left-right (LR), anterior-posterior (AP) and superior-inferior (SI) directions were calculated using log files of all beams per fraction (PDFn). Fractional PDF reproducibility (Rn) was calculated as Kullback-Leibler (KL) divergence between PDF1 and PDFn of tumor motion. The mean of Rn (Rm) was calculated for each patient and correlated to the patient’s mean tumor motion range (Am). The change of Rm during the course of SBRT was also evluated. These analyses were performed using in-house developed software. Results: The Rm were 0.19 (0.07–0.30), 0.14 (0.07–0.32) and 0.16 (0.09–0.28) in LR, AP and SI directions, respectively. The Am were 5.11 mm (2.58–9.99 mm), 7.81 mm (2.87–15.57 mm) and 11.26 mm (3.80–21.27 mm) in LR, AP and SI directions, respectively. The PDF reproducibility decreased as the tumor motion range increased in AP and SI direction. That decreased slightly through the course of RT in SI direction. Conclusion: We developed the respiratory motion analysis tool for 4DRT using log files and quantified the range and reproducibility of respiratory motion for lung tumors.« less

Determinants of surgical resection for pancreatic neuroendocrine tumors.

PubMed

Doi, Ryuichiro

2015-08-01

Pancreatic neuroendocrine tumors (pNETs) include functioning and non-functional tumors. Functioning tumors consist of tumors that produce a variety of hormones and their clinical effects. Therefore, determinants of resection of pNETs should be discussed for each group of tumors. Less than 10% of insulinomas are malignant, therefore more than 90% of the cases can be cured by surgical resection. Lymphadenectomy is generally not necessary in insulinoma operation. If preoperative localization of the insulinoma is completed, enucleation from the pancreatic body or tail, and distal pancreatectomy can be performed safely by laparoscopy. When preoperative localization of a sporadic insulinoma is not confirmed, surgical exploration is needed. Intraoperative localization of a tumor, intraoperative insulin sampling and frozen section are required. The crucial purpose of surgical resection is to control inappropriate insulin secretion by removing all insulinomas. Gastrinomas are usually located in the duodenum or pancreas, which secrete gastrin and cause Zollinger-Ellison syndrome (ZES). Duodenal gastrinomas are usually small, therefore they are not seen on preoperative imaging studies or endoscopic ultrasound, and can be found only at surgery if a duodenotomy is performed. In addition, lymph node metastasis is found in 40-60% of cases. Therefore, the experienced surgeons should direct operation for gastrinomas. Surgical exploration with duodenotomy should be performed at a laparotomy. Other functioning pNETs can occur in the pancreas or in other locations. Curative resection is always recommended whenever possible after optimal symptomatic control of the clinical syndrome by medical treatment. Indications for surgery depend on clinical symptom control, tumor size, location, extent, malignancy and presence of metastasis. A lot of non-functioning pNETs are found incidentally according to the quality improvement of imaging techniques. Localized, small, malignant non

Scaling Completion College Services as a Model for Increasing Adult Degree Completion. Lumina Issue Papers

ERIC Educational Resources Information Center

Johnson, Nate; Bell, Alli

2014-01-01

An estimated 46 million adults have some college education but have not completed their degrees. For many, especially those who have accumulated several years' worth of credits, the inability to finish college remains a frustration. If the United States is to achieve its ambitious education attainment goals, many more adults with such experience…

Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity

PubMed Central

Adusumilli, Prasad S.; Cherkassky, Leonid; Villena-Vargas, Jonathan; Colovos, Christos; Servais, Elliot; Plotkin, Jason; Jones, David R.; Sadelain, Michel

2015-01-01

Translating the recent success of chimeric antigen receptor (CAR) T cell therapy for hematological malignancies to solid tumors will necessitate overcoming several obstacles, including inefficient T cell tumor infiltration and insufficient functional persistence. Taking advantage of an orthotopic model that faithfully mimics human pleural malignancy, we evaluated two routes of administration of mesothelin-targeted T cells using the M28z CAR. We found that intra-pleurally administered CAR T cells vastly out-performed systemically infused T cells, requiring 30-fold fewer M28z T cells to induce long-term complete remissions. Following intrapleural T cell administration, prompt in vivo antigen-induced T cell activation allowed robust CAR T cell expansion and effector differentiation, resulting in enhanced anti-tumor efficacy and functional T cell persistence for 200 days. Regional T cell administration also promoted efficient elimination of extrathoracic tumor sites. This therapeutic efficacy was dependent on early CD4+ T cell activation associated with a higher intra-tumoral CD4/CD8 cell ratios and CD28-dependent CD4+ T cell-mediated cytotoxicity. In contrast, intravenously delivered CAR T cells, even when accumulated at equivalent numbers in the pleural tumor, did not achieve comparable activation, tumor eradication or persistence. The remarkable ability of intrapleurally administered T cells to circulate and persist supports the concept of delivering optimal CAR T cell therapy through “regional distribution centers.” Based on these results, we are opening a phase I clinical trial to evaluate the safety of intrapleural administration of mesothelin-targeted CAR T cells in patients with primary or secondary pleural malignancies. PMID:25378643

[Imaging of breast tumors using MR elastography].

PubMed

Lorenzen, J; Sinkus, R; Schrader, D; Lorenzen, M; Leussler, C; Dargatz, M; Röschmann, P

2001-01-01

Imaging of breast tumors using MR-Elastography. Low-frequency mechanical waves are transmitted into breast-tissue by means of an oscillator. The local characteristics of the mechanical wave are determined by the elastic properties of the tissue. By means of a motion-sensitive spin-echo-sequence these waves can be displayed within the phase of the MR image. Subsequently, these images can be used to reconstruct the local distribution of elasticity. In-vivo measurements were performed in 3 female patients with malignant tumors of the breast. All patients tolerated the measurement set-up without any untoward sensation in the contact area of skin and oszillator. The waves completely penetrated the breast, encompassing the axilla and regions close to the chest wall. All tumors were localized by MRE as structures of markedly stiffer tissue when compared to the surrounding tissue. Furthermore, in one patient, a metastasis in an axillary lymph node was detected. In all patients, local regions of increased elasticity were found in the remaining parenchyma of the breast, which, however, did not reach the high levels of elasticity found in the tumors. MRE is an imaging modality enabling adjunct tissue differentiation of mammary tumors.

Digital tumor fluoroscopy (DTF)--a new direct imaging system in the therapy planning for brain tumors.

PubMed

Herbst, M; Fröder, M

1990-01-01

Digital Tumor Fluoroscopy is an expanded x-ray video chain optimized to iodine contrast with an extended Gy scale up to 64000 Gy values. Series of pictures are taken before and after injection of contrast medium. With the most recent unit, up to ten images can be taken and stored. The microprogrammable processor allows the subtraction of images recorded at any moment of the examination. Dynamic views of the distribution of contrast medium in the intravasal and extravasal spaces of brain and tumor tissue are gained by the subtraction of stored images. Tumors can be differentiated by studying the storage and drainage behavior of the contrast medium during the period of examination. Meningiomas store contrast medium very intensively during the whole time of investigation, whereas astrocytomas grade 2-3 pick it up less strongly at the beginning and release it within 2 min. Glioblastomas show a massive but delayed accumulation of contrast medium and a decreased flow-off-rate. In comparison with radiography and MR-imaging the most important advantage of Digital Tumor Fluoroscopy is that direct information on tumor localization is gained in relation to the skull-cap. This enables the radiotherapist to mark the treatment field directly on the skull. Therefore it is no longer necessary to calculate the tumor volume from several CT scans for localization. In radiotherapy Digital Tumor Fluoroscopy a unit combined with a simulator can replace CT planning. This would help overcome the disadvantages arising from the lack of a collimating system, and the inaccuracies which result from completely different geometric relationships between a CT unit and a therapy machine.

Children’s Oncology Group’s 2013 Blueprint for Research: Rare Tumors

PubMed Central

Rodriguez-Galindo, Carlos; Krailo, Mark; Frazier, Lindsay; Chintagumpala, Murali; Amatruda, James; Katzenstein, Howard; Malogolowkin, Marcio; Spector, Logan; Pashankar, Farzana; Meyers, Rebecka; Tomlinson, Gail

2015-01-01

In the US, approximately 2,000 children are diagnosed with rare cancers each year, with 5-year survival ranging from <20% for children with advanced carcinomas to >95% for children with intraocular retinoblastoma or localized germ cell tumors. During the last years, 12 clinical studies have been successfully completed in children with retinoblastoma, liver tumors, germ cell tumors, and infrequent malignancies, including therapeutic, epidemiologic, and biologic studies. Current efforts are centered in the development of large international collaborations to consolidate evidence-based definitions and risk stratifications that will support international Phase 3 clinical trials in germ cell tumors, hepatoblastoma, and other rare cancers. PMID:23255219

Is complete seizure control imperative?

PubMed

Andermann, Frederick

2002-01-01

Is complete control imperative? The answer depends on whether complete control is indeed possible, on the possibility of achieving modifications of lifestyle, and on the type of epilepsy, with particular reference to the presence of progressive dysfunction. This may be seen in patients with temporal lobe or other forms of focal epilepsy, in the epileptic encephalopathies such as West and Lennox Gastaut Syndromes and even in some patients with idiopathic generalized epilepsy. Progressive memory changes and global cognitive problems are examples. Progressive language deterioration, secondary epileptogenesis and phenomena analogous to kindling are also important issues. How long treatment should be continued depends on many factors, not least the preference of the patient and of the family. Weighing the benefits of complete control versus the side effects and risks of medication or surgery is crucial. There are obvious benefits to complete control; it is imperative if these benefits are greater than the cost.

Novel real-time tumor-contouring method using deep learning to prevent mistracking in X-ray fluoroscopy.

PubMed

Terunuma, Toshiyuki; Tokui, Aoi; Sakae, Takeji

2018-03-01

Robustness to obstacles is the most important factor necessary to achieve accurate tumor tracking without fiducial markers. Some high-density structures, such as bone, are enhanced on X-ray fluoroscopic images, which cause tumor mistracking. Tumor tracking should be performed by controlling "importance recognition": the understanding that soft-tissue is an important tracking feature and bone structure is unimportant. We propose a new real-time tumor-contouring method that uses deep learning with importance recognition control. The novelty of the proposed method is the combination of the devised random overlay method and supervised deep learning to induce the recognition of structures in tumor contouring as important or unimportant. This method can be used for tumor contouring because it uses deep learning to perform image segmentation. Our results from a simulated fluoroscopy model showed accurate tracking of a low-visibility tumor with an error of approximately 1 mm, even if enhanced bone structure acted as an obstacle. A high similarity of approximately 0.95 on the Jaccard index was observed between the segmented and ground truth tumor regions. A short processing time of 25 ms was achieved. The results of this simulated fluoroscopy model support the feasibility of robust real-time tumor contouring with fluoroscopy. Further studies using clinical fluoroscopy are highly anticipated.

Recent technological advances in pediatric brain tumor surgery.

PubMed

Zebian, Bassel; Vergani, Francesco; Lavrador, José Pedro; Mukherjee, Soumya; Kitchen, William John; Stagno, Vita; Chamilos, Christos; Pettorini, Benedetta; Mallucci, Conor

2017-01-01

X-rays and ventriculograms were the first imaging modalities used to localize intracranial lesions including brain tumors as far back as the 1880s. Subsequent advances in preoperative radiological localization included computed tomography (CT; 1971) and MRI (1977). Since then, other imaging modalities have been developed for clinical application although none as pivotal as CT and MRI. Intraoperative technological advances include the microscope, which has allowed precise surgery under magnification and improved lighting, and the endoscope, which has improved the treatment of hydrocephalus and allowed biopsy and complete resection of intraventricular, pituitary and pineal region tumors through a minimally invasive approach. Neuronavigation, intraoperative MRI, CT and ultrasound have increased the ability of the neurosurgeon to perform safe and maximal tumor resection. This may be facilitated by the use of fluorescing agents, which help define the tumor margin, and intraoperative neurophysiological monitoring, which helps identify and protect eloquent brain.

Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

But-Hadzic, Jasna, E-mail: jbut@onko-i.si; Anderluh, Franc; Brecelj, Erik

Background and Purpose: This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. Methods and Materials: Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825 mg/m{sup 2}/12 hours, including weekends. The primary endpoint was pathologic complete response (pCR). Results: Fifty patients completed preoperative treatment according to themore » protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2 G ≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. Conclusions: Preoperative IMRT-SIB without dose escalation is well tolerated, with a low acute toxicity profile, and can achieve a high rate of pCR and downstaging.« less

Acute Toxicity and Tumor Response in Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy With Shortening of the Overall Treatment Time Using Intensity-Modulated Radiation Therapy With Simultaneous Integrated Boost: A Phase 2 Trial.

PubMed

But-Hadzic, Jasna; Anderluh, Franc; Brecelj, Erik; Edhemovic, Ibrahim; Secerov-Ermenc, Ajra; Hudej, Rihard; Jeromen, Ana; Kozelj, Miran; Krebs, Bojan; Oblak, Irena; Omejc, Mirko; Vogrin, Andrej; Velenik, Vaneja

2016-12-01

This phase 2 study investigated the efficacy and safety of preoperative intensity modulated radiation therapy with a simultaneous integrated boost (IMRT-SIB) without dose escalation, concomitant with standard capecitabine chemotherapy in locally advanced rectal cancer. Between January 2014 and March 2015, 51 patients with operable stage II-III rectal adenocarcinoma received preoperative IMRT with pelvic dose of 41.8 Gy and simultaneously delivered 46.2 Gy to T2/3 and 48.4 Gy to T4 tumor in 22 fractions, concomitant with capecitabine, 825 mg/m 2 /12 hours, including weekends. The primary endpoint was pathologic complete response (pCR). Fifty patients completed preoperative treatment according to the protocol, and 47 underwent surgical resection. The sphincter preservation rate for the low rectal tumors was 62%, and the resection margins were free in all but 1 patient. Decrease in tumor and nodal stage was observed in 32 (68%) and 39 (83%) patients, respectively, with pCR achieved in 12 (25.5%) patients. There were only 2 G ≥ 3 acute toxicities, with infectious enterocolitis in 1 patient and dermatitis over the sacral area caused by the bolus effect of the treatment table in the second patient. Preoperative IMRT-SIB without dose escalation is well tolerated, with a low acute toxicity profile, and can achieve a high rate of pCR and downstaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Tailoring nanoparticle designs to target cancer based on tumor pathophysiology

PubMed Central

Sykes, Edward A.; Dai, Qin; Sarsons, Christopher D.; Chen, Juan; Rocheleau, Jonathan V.; Hwang, David M.; Zheng, Gang; Cramb, David T.; Rinker, Kristina D.; Chan, Warren C. W.

2016-01-01

Nanoparticles can provide significant improvements in the diagnosis and treatment of cancer. How nanoparticle size, shape, and surface chemistry can affect their accumulation, retention, and penetration in tumors remains heavily investigated, because such findings provide guiding principles for engineering optimal nanosystems for tumor targeting. Currently, the experimental focus has been on particle design and not the biological system. Here, we varied tumor volume to determine whether cancer pathophysiology can influence tumor accumulation and penetration of different sized nanoparticles. Monte Carlo simulations were also used to model the process of nanoparticle accumulation. We discovered that changes in pathophysiology associated with tumor volume can selectively change tumor uptake of nanoparticles of varying size. We further determine that nanoparticle retention within tumors depends on the frequency of interaction of particles with the perivascular extracellular matrix for smaller nanoparticles, whereas transport of larger nanomaterials is dominated by Brownian motion. These results reveal that nanoparticles can potentially be personalized according to a patient’s disease state to achieve optimal diagnostic and therapeutic outcomes. PMID:26884153

Lassa-Vesicular Stomatitis Chimeric Virus Safely Destroys Brain Tumors

PubMed Central

Wollmann, Guido; Drokhlyansky, Eugene; Davis, John N.; Cepko, Connie

2015-01-01

ABSTRACT High-grade tumors in the brain are among the deadliest of cancers. Here, we took a promising oncolytic virus, vesicular stomatitis virus (VSV), and tested the hypothesis that the neurotoxicity associated with the virus could be eliminated without blocking its oncolytic potential in the brain by replacing the neurotropic VSV glycoprotein with the glycoprotein from one of five different viruses, including Ebola virus, Marburg virus, lymphocytic choriomeningitis virus (LCMV), rabies virus, and Lassa virus. Based on in vitro infections of normal and tumor cells, we selected two viruses to test in vivo. Wild-type VSV was lethal when injected directly into the brain. In contrast, a novel chimeric virus (VSV-LASV-GPC) containing genes from both the Lassa virus glycoprotein precursor (GPC) and VSV showed no adverse actions within or outside the brain and targeted and completely destroyed brain cancer, including high-grade glioblastoma and melanoma, even in metastatic cancer models. When mice had two brain tumors, intratumoral VSV-LASV-GPC injection in one tumor (glioma or melanoma) led to complete tumor destruction; importantly, the virus moved contralaterally within the brain to selectively infect the second noninjected tumor. A chimeric virus combining VSV genes with the gene coding for the Ebola virus glycoprotein was safe in the brain and also selectively targeted brain tumors but was substantially less effective in destroying brain tumors and prolonging survival of tumor-bearing mice. A tropism for multiple cancer types combined with an exquisite tumor specificity opens a new door to widespread application of VSV-LASV-GPC as a safe and efficacious oncolytic chimeric virus within the brain. IMPORTANCE Many viruses have been tested for their ability to target and kill cancer cells. Vesicular stomatitis virus (VSV) has shown substantial promise, but a key problem is that if it enters the brain, it can generate adverse neurologic consequences, including death. We

Alcohol consumption and breast tumor mitochondrial DNA mutations.

PubMed

Platek, Mary E; Shields, Peter G; Tan, Duanjun; Marian, Catalin; Bonner, Matthew R; McCann, Susan E; Nie, Jing; Wilding, Gregory E; Ambrosone, Christine; Millen, Amy E; Trevisan, Maurizio; Russell, Marcia; Nochajski, Thomas H; Edge, Stephen B; Winston, Janet; Freudenheim, Jo L

2010-06-01

Mitochondrial DNA (mtDNA) mutations are frequent in breast tumors, but the etiology of these mutations is unknown. We hypothesized that these mutations are associated with exposures that affect oxidative stress such as alcohol metabolism. Using archived tumor blocks from incident breast cancer cases in a case control study, the Western New York Exposures and Breast Cancer (WEB) study, analysis of mtDNA mutations was conducted on 128 breast cancer cases selected based on extremes of alcohol intake. Temporal temperature gradient gel electrophoresis (TTGE) was used to screen the entire mtDNA genome and sequencing was completed for all TTGE positive samples. Case-case comparisons were completed using unconditional logistic regression to determine the relative prevalence of the mutations by exposures including alcohol consumption, manganese superoxide dismutase (MnSOD) genotype, nutrient intake related to oxidative stress and established breast cancer risk factors. Somatic mtDNA mutations were found in 60 of the 128 tumors examined. There were no differences in the prevalence of mtDNA mutations by alcohol consumption, MnSOD genotype or dietary intake. The likelihood of mtDNA mutations was reduced among those with a positive family history for breast cancer (OR = 0.33, CI = 0.12-0.92), among postmenopausal women who used hormone replacement therapy (OR = 0.46, CI = 0.19-1.08, P = 0.08) and was increased for ER negative tumors (OR = 2.05, CI = 0.95-4.43, P = 0.07). Consistent with previous studies, we found that mtDNA mutations are a frequent occurrence in breast tumors. An understanding of the etiology of mtDNA mutations may provide insight into breast carcinogenesis.

Treatment of natural mammary gland tumors in canines and felines using gold nanorods-assisted plasmonic photothermal therapy to induce tumor apoptosis

PubMed Central

Ali, Moustafa R K; Ibrahim, Ibrahim M; Ali, Hala R; Selim, Salah A; El-Sayed, Mostafa A

2016-01-01

Plasmonic photothermal therapy (PPTT) is a cancer therapy in which gold nanorods are injected at the site of a tumor before near-infrared light is transiently applied to the tumor causing localized cell death. Previously, PPTT studies have been carried out on xenograft mice models. Herein, we report a study showing the feasibility of PPTT as applied to natural tumors in the mammary glands of dogs and cats, which more realistically represent their human equivalents at the molecular level. We optimized a regime of three low PPTT doses at 2-week intervals that ablated tumors mainly via apoptosis in 13 natural mammary gland tumors from seven animals. Histopathology, X-ray, blood profiles, and comprehensive examinations were used for both the diagnosis and the evaluation of tumor statuses before and after treatment. Histopathology results showed an obvious reduction in the cancer grade shortly after the first treatment and a complete regression after the third treatment. Blood tests showed no obvious change in liver and kidney functions. Similarly, X-ray diffraction showed no metastasis after 1 year of treatment. In conclusion, our study suggests the feasibility of applying the gold nanorods-PPTT on natural tumors in dogs and cats without any relapse or toxicity effects after 1 year of treatment. PMID:27703351

Treatment of natural mammary gland tumors in canines and felines using gold nanorods-assisted plasmonic photothermal therapy to induce tumor apoptosis.

PubMed

Ali, Moustafa R K; Ibrahim, Ibrahim M; Ali, Hala R; Selim, Salah A; El-Sayed, Mostafa A

Plasmonic photothermal therapy (PPTT) is a cancer therapy in which gold nanorods are injected at the site of a tumor before near-infrared light is transiently applied to the tumor causing localized cell death. Previously, PPTT studies have been carried out on xenograft mice models. Herein, we report a study showing the feasibility of PPTT as applied to natural tumors in the mammary glands of dogs and cats, which more realistically represent their human equivalents at the molecular level. We optimized a regime of three low PPTT doses at 2-week intervals that ablated tumors mainly via apoptosis in 13 natural mammary gland tumors from seven animals. Histopathology, X-ray, blood profiles, and comprehensive examinations were used for both the diagnosis and the evaluation of tumor statuses before and after treatment. Histopathology results showed an obvious reduction in the cancer grade shortly after the first treatment and a complete regression after the third treatment. Blood tests showed no obvious change in liver and kidney functions. Similarly, X-ray diffraction showed no metastasis after 1 year of treatment. In conclusion, our study suggests the feasibility of applying the gold nanorods-PPTT on natural tumors in dogs and cats without any relapse or toxicity effects after 1 year of treatment.

Nonepithelial tumors of the nasal cavity, paranasal sinuses and nasopharynx. A clinicopathologic study. XII: Schwann cell tumors (neurilemoma, neurofibroma, malignant schwannoma).

PubMed

Perzin, K H; Panyu, H; Wechter, S

1982-11-15

Twelve Schwann cell tumors (two neurilemomas, six neurofibromas, and four malignant schwannomas), arising in the nasal cavity, paranasal sinuses or nasopharynx, are described. Schwann cell neoplasms only rarely develop in this area. Clinically, these tumors lead to nonspecific symptoms including nasal obstruction epistaxis, facial pain and swellling, and proptosis, similar to those produced by other neoplasms that involve this area. On radiologic examination, a mass lesion may be identified. Benign Schwann cell tumors may lead to bone erosion, which thus is not necessarily a sign of malignancy. The correct diagnosis of Schwann cell tumor is usually made only when histologic sections are studied. The histologic differentiation between Schwann cell neoplasms and myxomas, fibroblastic tumors, fibrous histiocytomas and fibro-osseous lesions is discussed. Treatment depends upon the type of tumor. Neurilemomas, which usually are encapsulated neoplasms, can be treated by local excision. Neurofibromas may infiltrate extensively, and thus may require an extensive surgical resection; however, functional and cosmetic considerations should be taken into account because neurofibromas, even if incompletely excised, may recur clinically only after many years. Malignant schwannomas tend to be aggressive neoplasms, but because of the anatomy of the area, radical resections leading to complete removal of the tumor cannot always be carried out.

An innovative pre-targeting strategy for tumor cell specific imaging and therapy

NASA Astrophysics Data System (ADS)

Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

2015-08-01

A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging

Multilobular tumor of bone in an African wild dog (Lycaon pictus).

PubMed

McAloose, Denise; Raske, Matthew; Moore, Robert; Rodriguez, Carlos E

2012-12-01

A 13-mo-old, captive-born, female African wild dog (Lycaon pictus) was presented with a progressively enlarging, firm mass on the dorsum of the head. Due to rapid tumor growth and the development of neurologic signs, elective euthanasia and a complete postmortem were performed 2 months after initial presentation. Histologic findings were similar in both antemortem biopsy and postmortem samples from the tumor and consisted of nodules of cartilage and/or bone separated by thin interconnected trabeculae that contained spindle-shaped cells, consistent with multilobular tumor of bone. Very few reports of tumors in the endangered African wild dog have been published to date. To the authors' knowledge, this is the first report of an osseous tumor in an African wild dog and the first report of a multilobular tumor of bone in a nondomestic canid.

Peri-tumoral leakage during intra-tumoral convection-enhanced delivery has implications for efficacy of peri-tumoral infusion before removal of tumor.

PubMed

Yang, Xiaoliang; Saito, Ryuta; Nakamura, Taigen; Zhang, Rong; Sonoda, Yukihiko; Kumabe, Toshihiro; Forsayeth, John; Bankiewicz, Krystof; Tominaga, Teiji

2016-01-01

In cases of malignant brain tumors, infiltrating tumor cells that exist at the tumor-surrounding brain tissue always escape from cytoreductive surgery and, protected by blood-brain barrier (BBB), survive the adjuvant chemoradiotherapy, eventually leading to tumor recurrence. Local interstitial delivery of chemotherapeutic agents is a promising strategy to target these cells. During our effort to develop effective drug delivery methods by intra-tumoral infusion of chemotherapeutic agents, we found consistent pattern of leakage from the tumor. Here we describe our findings and propose promising strategy to cover the brain tissue surrounding the tumor with therapeutic agents by means of convection-enhanced delivery. First, the intracranial tumor isograft model was used to define patterns of leakage from tumor mass after intra-tumoral infusion of the chemotherapeutic agents. Liposomal doxorubicin, although first distributed inside the tumor, distributed diffusely into the surrounding normal brain once the leakage happen. Trypan blue dye was used to evaluate the distribution pattern of peri-tumoral infusions. When infused intra- or peri-tumorally, infusates distributed robustly into the tumor border. Subsequently, volume of distributions with different infusion scheduling; including intra-tumoral infusion, peri-tumoral infusion after tumor resection, peri-tumoral infusion without tumor removal with or without systemic infusion of steroids, were compared with Evans-blue dye. Peri-tumoral infusion without tumor removal resulted in maximum volume of distribution. Prior use of steroids further increased the volume of distribution. Local interstitial drug delivery targeting tumor surrounding brain tissue before tumor removal should be more effective when targeting the invading cells.

eTumorType, An Algorithm of Discriminating Cancer Types for Circulating Tumor Cells or Cell-free DNAs in Blood.

PubMed

Zou, Jinfeng; Wang, Edwin

2017-04-01

With the technology development on detecting circulating tumor cells (CTCs) and cell-free DNAs (cfDNAs) in blood, serum, and plasma, non-invasive diagnosis of cancer becomes promising. A few studies reported good correlations between signals from tumor tissues and CTCs or cfDNAs, making it possible to detect cancers using CTCs and cfDNAs. However, the detection cannot tell which cancer types the person has. To meet these challenges, we developed an algorithm, eTumorType, to identify cancer types based on copy number variations (CNVs) of the cancer founding clone. eTumorType integrates cancer hallmark concepts and a few computational techniques such as stochastic gradient boosting, voting, centroid, and leading patterns. eTumorType has been trained and validated on a large dataset including 18 common cancer types and 5327 tumor samples. eTumorType produced high accuracies (0.86-0.96) and high recall rates (0.79-0.92) for predicting colon, brain, prostate, and kidney cancers. In addition, relatively high accuracies (0.78-0.92) and recall rates (0.58-0.95) have also been achieved for predicting ovarian, breast luminal, lung, endometrial, stomach, head and neck, leukemia, and skin cancers. These results suggest that eTumorType could be used for non-invasive diagnosis to determine cancer types based on CNVs of CTCs and cfDNAs. Copyright © 2017 Beijing Institute of Genomics, Chinese Academy of Sciences and Genetics Society of China. Production and hosting by Elsevier B.V. All rights reserved.

Automated Processing of Dynamic Contrast-Enhanced MRI: Correlation of Advanced Pharmacokinetic Metrics with Tumor Grade in Pediatric Brain Tumors.

PubMed

Vajapeyam, S; Stamoulis, C; Ricci, K; Kieran, M; Poussaint, T Young

2017-01-01

Pharmacokinetic parameters from dynamic contrast-enhanced MR imaging have proved useful for differentiating brain tumor grades in adults. In this study, we retrospectively reviewed dynamic contrast-enhanced perfusion data from children with newly diagnosed brain tumors and analyzed the pharmacokinetic parameters correlating with tumor grade. Dynamic contrast-enhanced MR imaging data from 38 patients were analyzed by using commercially available software. Subjects were categorized into 2 groups based on pathologic analyses consisting of low-grade (World Health Organization I and II) and high-grade (World Health Organization III and IV) tumors. Pharmacokinetic parameters were compared between the 2 groups by using linear regression models. For parameters that were statistically distinct between the 2 groups, sensitivity and specificity were also estimated. Eighteen tumors were classified as low-grade, and 20, as high-grade. Transfer constant from the blood plasma into the extracellular extravascular space (K trans ), rate constant from extracellular extravascular space back into blood plasma (K ep ), and extracellular extravascular volume fraction (V e ) were all significantly correlated with tumor grade; high-grade tumors showed higher K trans , higher K ep , and lower V e . Although all 3 parameters had high specificity (range, 82%-100%), K ep had the highest specificity for both grades. Optimal sensitivity was achieved for V e , with a combined sensitivity of 76% (compared with 71% for K trans and K ep ). Pharmacokinetic parameters derived from dynamic contrast-enhanced MR imaging can effectively discriminate low- and high-grade pediatric brain tumors. © 2017 by American Journal of Neuroradiology.

Multicenter validation study of pathologic response and tumor thickness at the tumor-normal liver interface as independent predictors of disease-free survival after preoperative chemotherapy and surgery for colorectal liver metastases.

PubMed

Brouquet, Antoine; Zimmitti, Giuseppe; Kopetz, Scott; Stift, Judith; Julié, Catherine; Lemaistre, Anne-Isabelle; Agarwal, Atin; Patel, Viren; Benoist, Stephane; Nordlinger, Bernard; Gandini, Alessandro; Rivoire, Michel; Stremitzer, Stefan; Gruenberger, Thomas; Vauthey, Jean-Nicolas; Maru, Dipen M

2013-08-01

To validate pathologic markers of response to preoperative chemotherapy as predictors of disease-free survival (DFS) after resection of colorectal liver metastases (CLM). One hundred seventy-one patients who underwent resection of CLM after preoperative chemotherapy at 4 centers were studied. Pathologic response-defined as the proportion of tumor cells remaining (complete, 0%; major, <50%; minor, ≥50%) and tumor thickness at the tumor-normal liver interface (TNI) (<0.5 mm, 0.5 to <5 mm, ≥5 mm)-was assessed by a central pathology reviewer and local pathologists. Pathologic response was complete in 8% of patients, major in 49% of patients, and minor in 43% of patients. Tumor thickness at the TNI was <0.5 mm in 21% of patients, 0.5 to <5 mm in 56% of patients, and ≥5 mm in 23% of patients. On multivariate analyses, using either pathologic response or tumor thickness at TNI, pathologic response (P = .002, .009), tumor thickness at TNI (P = 0.015, <.001), duration of preoperative chemotherapy (P = .028, .043), number of CLM (P = .038, . 037), and margin (P = .011, .016) were associated with DFS. In a multivariate analysis using both parameters, tumor thickness at TNI (P = .004, .015), duration of preoperative chemotherapy (P = .025), number of nodules (P = .027), and margin (P = .014) were associated with DFS. Tumor size by pathology examination was the predictor of pathologic response. Predictors of tumor thickness at the TNI were tumor size and chemotherapy regimen. There was near perfect agreement for pathologic response (κ = .82) and substantial agreement (κ = .76) for tumor thickness between the central reviewer and local pathologists. Pathologic response and tumor thickness at the TNI are valid predictors of DFS after preoperative chemotherapy and surgery for CLM. Copyright © 2013 American Cancer Society.

Laparoscopic radical nephrectomy for a right renal tumor with renal vein tumor thrombus in a patient with situs inversus totalis.

PubMed

Ito, Jun; Kaiho, Yasuhiro; Iwamura, Hiromichi; Anan, Go; Sato, Makoto

2018-05-23

Situs inversus totalis (SIT) is a rare congenital anomaly characterized by complete inversion of the thoracic and abdominal organs. Many intra-abdominal and vessel anomalies have been reported in association with SIT. However, there have been no reports on the use of laparoscopic radical nephrectomy with thrombectomy for renal vein thrombus, which is considered as a safe and feasible procedure, in patients with SIT. We herein present the case of an 80-year-old man with SIT who was preoperatively diagnosed with a right renal tumor and renal vein tumor thrombus. The patient underwent laparoscopic right nephrectomy and tumor thrombectomy with no intraoperative complications. To ensure a safe procedure, the anatomy and vessels were carefully evaluated preoperatively using 3-D multiplanar reconstructed CT imaging. Assessing anatomical structures leads to safer laparoscopic radical nephrectomy for renal cell carcinoma with venous tumor thrombus in patients with SIT. © 2018 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

The Returns to Completion or Partial Completion of a Qualification in the Trades. Research Report

ERIC Educational Resources Information Center

Lu, Tham

2015-01-01

Many students do not complete full qualifications in the vocational education and training (VET) system because their intention is to obtain only the particular skills they require. This can be achieved through the acquisition of skill sets; these enable flexibility in training to quickly respond to changes in the labour market. Skill sets may…

Anteriorly placed tumors to the conus: removal by interradicular window.

PubMed

Ciappetta, P; Taurone, S; Spoletini, M; Artico, M

2017-01-01

Tumors anteriorly situated to the medullary conus are rarely encountered and represent a true surgical challenge. We examined the literature on this topic, concluding that there are no previous reports on alternative surgical techniques different to the traditional one. We report two cases of intradural extramedullary tumor operated on by a technique performed through a window opened between the spinal roots, which allows an easy, effective and useful resection. We describe a new operative technique which ensures a complete removal of these tumors and discuss clinical implications in the light of the available literature on this topic.

Predictive factors for the regression of canine transmissible venereal tumor during vincristine therapy.

PubMed

Scarpelli, Karime C; Valladão, Maria L; Metze, Konradin

2010-03-01

Canine transmissible venereal tumor (CTVT) is a neoplasm transmitted by transplantation. Monochemotherapy with vincristine is considered to be effective, but treatment time until complete clinical remission may vary. The aim of this study was to determine which clinical data at diagnosis could predict the responsiveness of CTVT to vincristine chemotherapy. One hundred dogs with CTVT entered this prospective study. The animals were treated with vincristine sulfate (0.025 mg/kg) at weekly intervals until the tumor had macroscopically disappeared. The time to complete remission was recorded. A multivariate Cox regression model indicated that larger tumor mass, increased age and therapy during hot and rainy months were independent significant unfavorable predictive factors retarding remission, whereas sex, weight, status as owned dog or breed were of no predictive relevance. Further studies are necessary to investigate whether these results are due to changes in immunological response mechanisms in animals with a diminished immune surveillance, resulting in delays in tumor regression. 2008 Elsevier Ltd. All rights reserved.

Suppression of Metastasis by Primary Tumor and Acceleration of Metastasis Following Primary Tumor Resection: A Natural Law?

PubMed

Hanin, Leonid; Rose, Jason

2018-03-01

We study metastatic cancer progression through an extremely general individual-patient mathematical model that is rooted in the contemporary understanding of the underlying biomedical processes yet is essentially free of specific biological assumptions of mechanistic nature. The model accounts for primary tumor growth and resection, shedding of metastases off the primary tumor and their selection, dormancy and growth in a given secondary site. However, functional parameters descriptive of these processes are assumed to be essentially arbitrary. In spite of such generality, the model allows for computing the distribution of site-specific sizes of detectable metastases in closed form. Under the assumption of exponential growth of metastases before and after primary tumor resection, we showed that, regardless of other model parameters and for every set of site-specific volumes of detected metastases, the model-based likelihood-maximizing scenario is always the same: complete suppression of metastatic growth before primary tumor resection followed by an abrupt growth acceleration after surgery. This scenario is commonly observed in clinical practice and is supported by a wealth of experimental and clinical studies conducted over the last 110 years. Furthermore, several biological mechanisms have been identified that could bring about suppression of metastasis by the primary tumor and accelerated vascularization and growth of metastases after primary tumor resection. To the best of our knowledge, the methodology for uncovering general biomedical principles developed in this work is new.

Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning

PubMed Central

Pegram, Hollie J.; Lee, James C.; Hayman, Erik G.; Imperato, Gavin H.; Tedder, Thomas F.; Sadelain, Michel

2012-01-01

Adoptive cell therapy with tumor-targeted T cells is a promising approach to cancer therapy. Enhanced clinical outcome using this approach requires conditioning regimens with total body irradiation, lymphodepleting chemotherapy, and/or additional cytokine support. However, the need for prior conditioning precludes optimal application of this approach to a significant number of cancer patients intolerant to these regimens. Herein, we present preclinical studies demonstrating that treatment with CD19-specific, chimeric antigen receptor (CAR)–modified T cells that are further modified to constitutively secrete IL-12 are able to safely eradicate established disease in the absence of prior conditioning. We demonstrate in a novel syngeneic tumor model that tumor elimination requires both CD4+ and CD8+ T-cell subsets, autocrine IL-12 stimulation, and subsequent IFNγ secretion by the CAR+ T cells. Importantly, IL-12–secreting, tumor-targeted T cells acquire intrinsic resistance to T regulatory cell–mediated inhibition. Based on these preclinical data, we anticipate that adoptive therapy using CAR-targeted T cells modified to secrete IL-12 will obviate or reduce the need for potentially hazardous conditioning regimens to achieve optimal antitumor responses in cancer patients. PMID:22354001

Giant Solitary Fibrous Tumor of the Parotid Gland

PubMed Central

Chis, Octavian

2014-01-01

Solitary fibrous tumors (SFTs) are rare tumors that are mostly found arising from the pleura. SFT of the parotid gland is a rare tumor; only a few cases have been described in the literature. SFTs are benign in most cases. Clinically, SFTs usually manifest as well circumscribed, slow-growing, smooth, and painless masses. CT-Scan and MRI are the most sensitive imaging procedures used. The treatment of choice is complete surgical excision of the lesion. Since recurrence and metastasis can take place after several years, a lifelong clinical and imaging regular follow-up is compulsory. In this paper, we describe the diagnostic and therapeutic challenges of the up-to-now biggest parotid SFT. The clinical presentation, surgical management, and pathological and immunohistochemistry findings are described. PMID:25114687

Acellular organ scaffolds for tumor tissue engineering

NASA Astrophysics Data System (ADS)

Guller, Anna; Trusova, Inna; Petersen, Elena; Shekhter, Anatoly; Kurkov, Alexander; Qian, Yi; Zvyagin, Andrei

2015-12-01

Rationale: Tissue engineering (TE) is an emerging alternative approach to create models of human malignant tumors for experimental oncology, personalized medicine and drug discovery studies. Being the bottom-up strategy, TE provides an opportunity to control and explore the role of every component of the model system, including cellular populations, supportive scaffolds and signalling molecules. Objectives: As an initial step to create a new ex vivo TE model of cancer, we optimized protocols to obtain organ-specific acellular matrices and evaluated their potential as TE scaffolds for culture of normal and tumor cells. Methods and results: Effective decellularization of animals' kidneys, ureter, lungs, heart, and liver has been achieved by detergent-based processing. The obtained scaffolds demonstrated biocompatibility and growthsupporting potential in combination with normal (Vero, MDCK) and tumor cell lines (C26, B16). Acellular scaffolds and TE constructs have been characterized and compared with morphological methods. Conclusions: The proposed methodology allows creation of sustainable 3D tumor TE constructs to explore the role of organ-specific cell-matrix interaction in tumorigenesis.

Laparoscopic microwave thermosphere ablation of malignant liver tumors: An analysis of 53 cases.

PubMed

Zaidi, Nisar; Okoh, Alexis; Yigitbas, Hakan; Yazici, Pinar; Ali, Noaman; Berber, Eren

2016-02-01

Microwave thermosphere ablation (MTA) is a new technology that is designed to create spherical zones of ablation using a single antenna. The aim of this study is to assess the results of MTA in a large series of patients. This was a prospective study assessing the use of MTA in patients with malignant liver tumors. The procedures were done mostly laparoscopically and ablation zones created were assessed for completeness of tumor response, spherical geometry and recurrence on tri-phasic CT scans done on follow-up. There were a total of 53 patients with an average of 3 tumors measuring 1.5 cm. Ablations were performed laparoscopically in all but eight patients. Morbidity was 11.3% (n = 6), and mortality zero. On postoperative scans, there was 99.3% tumor destruction. Roundness indices A, B, and transverse were 1.1, 1.0, and 0.9, respectively. At a median follow-up of 4.5 months, incomplete ablation was seen in 1 of 149 lesions treated (0.7%) and local tumor recurrence in 1 lesion (0.7%). The results of this series confirm the safety and feasibility of MTA technology. The 99.3% rate of complete tumor ablation and low rate of local recurrence at short-term follow up are promising. © 2015 Wiley Periodicals, Inc.

[Missile-Type Tumor-Targeting Polymer Drug, P-THP, Seeks Tumors via Three Different Steps Based on the EPR Effect].

PubMed

Maeda, Hiroshi; Fang, Jun; Ulbrich, Karel; Etrych, Tomáš; Nakamura, Hideaki

2016-05-01

The enhanced permeability and retention (EPR) effect, a tumor-targeting principle of nanomedicine, serves as a standard for tumor-targeted anticancer drug design. There are 3 key issues in ideal EPR-based antitumor drug design: i) stability in blood circulation; ii) tumor-selective accumulation (EPR effect) and efficient release of the active anticancer moiety in tumor tissues; and iii) the active uptake of the active drug into tumor cells. Using these principles, we developed N-(2- hydroxypropyl)methacrylamide (HPMA) copolymer-conjugated pirarubicin (P-THP), which uses hydrazone bond linkage; it was shown to exhibit prolonged circulation time, thereby resulting in good tumor-selective accumulation. More importantly, the hydrazone bond ensured selective and rapid release of the active drug, pirarubicin (THP), in acidic tumor environments. Further, compared to other anthracycline anticancer drugs (eg, doxorubicin), THP demonstrated more rapid intracellular uptake. Consequently, P-THP showed remarkable antitumor effect with minimal side effects. In a clinical pilot study of a stage IV prostate cancer patient with multiple metastases in the lung and bone, P-THP (50-75 mg administered once every 2-3 weeks) was shown to clear the metastatic nodules in the lung almost completely after 3 treatments where 50-70 mg THP equivalent each was administerd per 70 kg body wt, and bone metastasis disappeared after 6 months. There was no recurrence after 2 years. The patient also retained an excellent quality of life during the treatment without any apparent side effects. Thus, we propose the clinical development of P-THP as an EPR-based tumor-targeted anticancer drug.

Elevated CRP levels predict poor outcome and tumor recurrence in patients with thymic epithelial tumors: A pro- and retrospective analysis

PubMed Central

Janik, Stefan; Bekos, Christine; Hacker, Philipp; Raunegger, Thomas; Ghanim, Bahil; Einwallner, Elisa; Beer, Lucian; Klepetko, Walter; Müllauer, Leonhard; Ankersmit, Hendrik J.; Moser, Bernhard

2017-01-01

Objective Scarce information exists on the pathogenesis of thymic epithelial tumors (TETs), comprising thymomas, thymic carcinomas (TCs) and neuroendocrine tumors. C-reactive protein (CRP) increases during certain malignancies. We aimed to investigate the clinical relevance of CRP in patients with TETs. Results Pretreatment CRP serum concentrations were significantly elevated in patients with TETs, particularly TCs and metastatic TETs. After complete tumor resection CRP serum concentrations were decreased (p = 0.135) but increased significantly in case of tumor recurrence (p = 0.001). High pretreatment CRP was associated with significantly worse 5- and 10-year freedom-from recurrence (FFR) (p = 0.010) and was a negative prognostic factor for FFR (HR 3.30; p = 0.015). IL-6 (not IL-1β) serum concentrations were significantly elevated in patients with TETs but we did not detect CRP tissue expression in TETs. Materials and Methods Pretreatment CRP serum concentrations were retrospectively analyzed from 128 surgical patients (1990–2015). In a subset of 68 patients longitudinal analysis of CRP was performed. Additionally, immunohistochemical tumor CRP expression and serum concentrations of interleukin (IL)-6 and IL-1β were measured. Conclusions Hence, diagnostic measurement of serum CRP might be useful to indicate highly aggressive TETs and to make doctors consider tumor recurrences during oncological follow-up. PMID:28514756

Selective anti-tumor activity of the novel fluoropyrimidine polymer F10 towards G48a orthotopic GBM tumors.

PubMed

Gmeiner, William H; Lema-Tome, Carla; Gibo, Denise; Jennings-Gee, Jamie; Milligan, Carol; Debinski, Waldemar

2014-02-01

F10 is a novel anti-tumor agent with minimal systemic toxicity in vivo and which displays strong cytotoxicity towards glioblastoma (GBM) cells in vitro. Here we investigate the cytotoxicity of F10 towards GBM cells and evaluate the anti-tumor activity of locally-administered F10 towards an orthotopic xenograft model of GBM. The effects of F10 on thymidylate synthase (TS) inhibition and Topoisomerase 1 (Top1) cleavage complex formation were evaluated using TS activity assays and in vivo complex of enzyme bioassays. Cytotoxicity of F10 towards normal brain was evaluated using cortices from embryonic (day 18) mice. F10 displays minimal penetrance of the blood-brain barrier and was delivered by intra-cerebral (i.c.) administration and prospective anti-tumor response towards luciferase-expressing G48a human GBM tumors in nude mice was evaluated using IVIS imaging. Histological examination of tumor and normal brain tissue was used to assess the selectivity of anti-tumor activity. F10 is cytotoxic towards G48a, SNB-19, and U-251 MG GBM cells through dual targeting of TS and Top1. F10 is not toxic to murine primary neuronal cultures. F10 is well-tolerated upon i.c. administration and induces significant regression of G48a tumors that is dose-dependent. Histological analysis from F10-treated mice revealed tumors were essentially completely eradicated in F10-treated mice while vehicle-treated mice displayed substantial infiltration into normal tissue. F10 displays strong efficacy for GBM treatment with minimal toxicity upon i.c. administration establishing F10 as a promising drug-candidate for treating GBM in human patients.

How much tumor surgery do early-career orthopaedic oncologists perform?

PubMed

Miller, Benjamin J; Rajani, Rajiv; Leddy, Lee; Carmody Soni, Emily E; White, Jeremy R

2015-02-01

There are few data on the types of procedures orthopaedic oncologists perform in their first years of practice. Because fellowships are graduating fellows each year and the number of tumor patients is limited, defining the practice patterns of early-career orthopaedic oncologists may help diminish early employment discontent and enhance workforce discussions. The aim of the study was to use the objective case log volumes of a cross-section of early career orthopaedic oncologists to describe (1) the number of operations performed annually; (2) the proportion of tumor, trauma, adult reconstruction, and other operations for individual participants, (3) individual practice characteristics that were associated with the number of tumor procedures; and (4) the sources of satisfaction and challenges in each individual's career and surgical practice. Fifteen fellowship-trained orthopaedic oncologists out of a potential pool of 33 (45%) in their first 4 years of practice responded to a survey by submitting complete operative case lists for a 2-year period. We recorded the type of procedure and determined associations between the annual number of tumor operations and total operative caseload, years in practice, and some details of individual practice patterns. Each participant completed a survey regarding practice-related sources of stress and satisfaction. A total of 5611 surgical cases were available for review. For the entire cohort, there were 3303 (59%) tumor procedures, 973 (17%) trauma, 890 (16%) adult reconstruction, and 445 (8%) other. The median annual number of total operations was 214 (range, 63-356) and median annual number of tumor operations was 135 (range, 47-216). The median proportion of tumor operations in an individual practice was 56% (range, 43%-94%). The annual number of tumor operations correlated with the total annual number of operations (r = 0.73, p < 0.001). Sources of stress and satisfaction were similar to the general membership of the

Tumor Response and Survival Predicted by Post-Therapy FDG-PET/CT in Anal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schwarz, Julie K.; Siegel, Barry A.; Dehdashti, Farrokh

2008-05-01

Purpose: To evaluate the response to therapy for anal carcinoma using post-therapy imaging with positron emission tomography (PET)/computed tomography and F-18 fluorodeoxyglucose (FDG) and to compare the metabolic response with patient outcome. Patients and Methods: This was a prospective cohort study of 53 consecutive patients with anal cancer. All patients underwent pre- and post-treatment whole-body FDG-PET/computed tomography. Patients had been treated with external beam radiotherapy and concurrent chemotherapy. Whole-body FDG-PET was performed 0.9-5.4 months (mean, 2.1) after therapy completion. Results: The post-therapy PET scan did not show any abnormal FDG uptake (complete metabolic response) in 44 patients. Persistent abnormal FDGmore » uptake (partial metabolic response) was found in the anal tumor in 9 patients. The 2-year cause-specific survival rate was 94% for patients with a complete vs. 39% for patients with a partial metabolic response in the anal tumor (p = 0.0008). The 2-year progression-free survival rate was 95% for patients with a complete vs. 22% for patients with a partial metabolic response in the anal tumor (p < 0.0001). A Cox proportional hazards model of survival outcome indicated that a complete metabolic response was the most significant predictor of progression-free survival in our patient population (p = 0.0003). Conclusions: A partial metabolic response in the anal tumor as determined by post-therapy FDG-PET is predictive of significantly decreased progression-free and cause-specific survival after chemoradiotherapy for anal cancer.« less

Parenting styles and adolescents' achievement strategies.

PubMed

Aunola, K; Stattin, H; Nurmi, J E

2000-04-01

The aim of the study was to investigate the extent to which adolescents' achievement strategies are associated with the parenting styles they experience in their families. Three hundred and fifty-four 14-year-old adolescents completed a Strategy and Attribution Questionnaire and a family parenting style inventory. Analogous questionnaires were also completed by the adolescents' parents. Based on adolescents' report of the parenting styles, four types of families were identified: those with Authoritative, Authoritarian, Permissive, and Neglectful parenting styles. The results further showed that adolescents from authoritative families applied most adaptive achievement strategies characterized by low levels of failure expectations, task-irrelevant behaviour and passivity, and the use of self-enhancing attributions. Adolescents from neglectful families, in turn, applied maladaptive strategies characterized by high levels of task-irrelevant behaviour, passivity and a lack of self-enhancing attributions. The results provide a basis for understanding some of the processes by which parenting styles may influence adolescents' academic achievement and performance.

Complete closure of artificial gastric ulcer after endoscopic submucosal dissection by combined use of a single over-the-scope clip and through-the-scope clips (with videos).

PubMed

Maekawa, Satoshi; Nomura, Ryosuke; Murase, Takayuki; Ann, Yasuyoshi; Harada, Masaru

2015-02-01

A 5-7 day hospital stay is usually needed after endoscopic submucosal dissection (ESD) of gastric tumor because of the possibility of delayed perforation or bleeding. The aim of this study was to evaluate the efficacy of combined use of a single over-the-scope clip (OTSC) and through-the-scope clips (TTSCs) to achieve complete closure of artificial gastric ulcer after ESD. We prospectively studied 12 patients with early gastric cancer or gastric adenoma. We performed complete closure of post-ESD artificial gastric ulcer using a combination of a single OTSC and TTSCs. Mean size of post-ESD artificial ulcer was 54.6 mm. The mean operating time for the closure procedure was 15.2 min., and the success rate was 91.7 % (11/12). Patients who underwent complete closure of post-ESD artificial gastric ulcer could be discharged the day after ESD and the closing procedure. Complete closure of post-ESD artificial gastric ulcer using a combination of a single OTSC and TTSCs is useful for shortening the period of hospitalization and reducing treatment cost.

Tumor cell-derived microparticles polarize M2 tumor-associated macrophages for tumor progression.

PubMed

Ma, Ruihua; Ji, Tiantian; Chen, Degao; Dong, Wenqian; Zhang, Huafeng; Yin, Xiaonan; Ma, Jingwei; Liang, Xiaoyu; Zhang, Yi; Shen, Guanxin; Qin, Xiaofeng; Huang, Bo

2016-04-01

Despite identification of macrophages in tumors (tumor-associated macrophages, TAM) as potential targets for cancer therapy, the origin and function of TAM in the context of malignancy remain poorly characterized. Here, we show that microparticles (MPs), as a by-product, released by tumor cells act as a general mechanism to mediate M2 polarization of TAM. Taking up tumor MPs by macrophages is a very efficient process, which in turn results in the polarization of macrophages into M2 type, not only leading to promoting tumor growth and metastasis but also facilitating cancer stem cell development. Moreover, we demonstrate that the underlying mechanism involves the activation of the cGAS/STING/TBK1/STAT6 pathway by tumor MPs. Finally, in addition to murine tumor MPs, we show that human counterparts also possess consistent effect on human M2 polarization. These findings provide new insights into a critical role of tumor MPs in remodeling of tumor microenvironment and better understanding of the communications between tumors and macrophages.

Risk factors for Wilms tumor. Report from the National Wilms Tumor Study.

PubMed

Olshan, A F; Breslow, N E; Falletta, J M; Grufferman, S; Pendergrass, T; Robison, L L; Waskerwitz, M; Woods, W G; Vietti, T J; Hammond, G D

1993-08-01

Previous epidemiologic studies have indicated that several factors may be associated with an increased risk of Wilms tumor including paternal occupational exposures, maternal exposure during pregnancy to cigarettes, coffee or tea, oral contraceptives, hormonal pregnancy tests, hair-coloring products, maternal hypertension, vaginal infection during pregnancy, and higher birth weight of the child. The current study examines the nonoccupational risk factors using questionnaire data from a large national collaborative clinical trial. Parents of 200 children registered with the National Wilms Tumor Study and 233 matched controls, identified using telephone random-digit dialing, completed a self-administered questionnaire about a variety of risk factors. As opposed to some previous studies, no association was found for mother's smoking during pregnancy (10+ cigarettes per day; odds ratio [OR] = 0.73; 95% confidence interval [CI] = 0.40-1.34), maternal consumption of coffee or tea during pregnancy (4+ cups per day; OR = 1.31; CI = 0.57-3.01), or hypertension during pregnancy (OR = 0.96; CI = 0.45-2.06). In addition, no association was found in this study for hormone exposure during pregnancy, hair dye use, vaginal infection during pregnancy, or high birth weight. A previously unreported association with a history of household insect extermination was found (OR = 2.16; CI = 1.24-3.75). In general, the study failed to confirm most of the previously reported maternal risk factors for Wilms tumor. Understanding the possible role of paternal exposures may be the best objective for further research on potential risk factors for Wilms tumor.

Irradiation combined with SU5416: Microvascular changes and growth delay in a human xenograft glioblastoma tumor line

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schuuring, Janneke; Department of Neurology, Groene Hart Hospital, Gouda; Bussink, Johan

Purpose: The combination of irradiation and the antiangiogenic compound SU5416 was tested and compared with irradiation alone in a human glioblastoma tumor line xenografted in nude mice. The aim of this study was to monitor microenvironmental changes and growth delay. Methods and materials: A human glioblastoma xenograft tumor line was implanted in nude mice. Irradiations consisted of 10 Gy or 20 Gy with and without SU5416. Several microenvironmental parameters (tumor cell hypoxia, tumor blood perfusion, vascular volume, and microvascular density) were analyzed after imunohistochemical staining. Tumor growth delay was monitored for up to 200 days after treatment. Results: SU5416, whenmore » combined with irradiation, has an additive effect over treatment with irradiation alone. Analysis of the tumor microenvironment showed a decreased vascular density during treatment with SU5416. In tumors regrowing after reaching only a partial remission, vascular characteristics normalized shortly after cessation of SU5416. However, in tumors regrowing after reaching a complete remission, permanent microenvironmental changes and an increase of tumor necrosis with a subsequent slower tumor regrowth was found. Conclusions: Permanent vascular changes were seen after combined treatment resulting in complete remission. Antiangiogenic treatment with SU5416 when combined with irradiation has an additive effect over treatment with irradiation or antiangiogenic treatment alone.« less

TU-CD-304-06: Using FFF Beams Improves Tumor Control in Radiotherapy of Lung Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vassiliev, O; Wang, H

Purpose: Electron disequilibrium at the lung-tumor interface results in an under-dosage of tumor regions close to its surface. This under-dosage is known to be significant and can compromise tumor control. Previous studies have shown that in FFF beams, disequilibrium effects are less pronounced, which is manifested in an increased skin dose. In this study we investigate the improvement in tumor dose coverage that can be achieved with FFF beams. The significance of this improvement is evaluated by comparing tumor control probabilities of FFF beams and conventional flattened beams. Methods: The dosimetric coverage was investigated in a virtual phantom representing themore » chest wall, lung tissue and the tumor. A range of tumor sizes was investigated, and two tumor locations – central and adjacent to the chest wall. Calculations were performed with BEAMnrc Monte Carlo code. Parallel-opposed and multiple coplanar 6-MV beams were simulated. The tumor control probabilities were calculated using the logistic model with parameters derived from clinical data for non-small lung cancer patients. Results: FFF beams were not entirely immune to disequilibrium effects. They nevertheless consistently delivered more uniform dose distribution throughout the volume of the tumor, and eliminated up to ∼15% of under-dosage in the most affected by disequilibrium 1-mm thick surface region of the tumor. A voxel-by-voxel comparison of tumor control probabilities between FFF and conventional flattened beams showed an advantage of FFF beams that, depending on the set up, was from a few to ∼9 percent. Conclusion: A modest improvement in tumor control probability on the order of a few percent can be achieved by replacing conventional flattened beams with FFF beams. However, given the large number of lung cancer patients undergoing radiotherapy, these few percent can potentially prevent local tumor recurrence for a significant number of patients.« less

Youth Perspectives of Achievement: Is Money Everything?

ERIC Educational Resources Information Center

Matope, Jasmine; Badroodien, Azeem

2015-01-01

This article draws from a qualitative research project completed at Victoria High School (pseudonym) in Cape Town in 2012 which explored 13 learners' perspectives of achievement and its influence on their lives and thinking. The piece problematises and analyses taken-for-granted connections between money, achievement, youth aspirations and views…

Optimization of spatiotemporally fractionated radiotherapy treatments with bounds on the achievable benefit

NASA Astrophysics Data System (ADS)

Gaddy, Melissa R.; Yıldız, Sercan; Unkelbach, Jan; Papp, Dávid

2018-01-01

Spatiotemporal fractionation schemes, that is, treatments delivering different dose distributions in different fractions, can potentially lower treatment side effects without compromising tumor control. This can be achieved by hypofractionating parts of the tumor while delivering approximately uniformly fractionated doses to the surrounding tissue. Plan optimization for such treatments is based on biologically effective dose (BED); however, this leads to computationally challenging nonconvex optimization problems. Optimization methods that are in current use yield only locally optimal solutions, and it has hitherto been unclear whether these plans are close to the global optimum. We present an optimization framework to compute rigorous bounds on the maximum achievable normal tissue BED reduction for spatiotemporal plans. The approach is demonstrated on liver tumors, where the primary goal is to reduce mean liver BED without compromising any other treatment objective. The BED-based treatment plan optimization problems are formulated as quadratically constrained quadratic programming (QCQP) problems. First, a conventional, uniformly fractionated reference plan is computed using convex optimization. Then, a second, nonconvex, QCQP model is solved to local optimality to compute a spatiotemporally fractionated plan that minimizes mean liver BED, subject to the constraints that the plan is no worse than the reference plan with respect to all other planning goals. Finally, we derive a convex relaxation of the second model in the form of a semidefinite programming problem, which provides a rigorous lower bound on the lowest achievable mean liver BED. The method is presented on five cases with distinct geometries. The computed spatiotemporal plans achieve 12-35% mean liver BED reduction over the optimal uniformly fractionated plans. This reduction corresponds to 79-97% of the gap between the mean liver BED of the uniform reference plans and our lower bounds on the lowest

A High-Performance Cellular Automaton Model of Tumor Growth with Dynamically Growing Domains

PubMed Central

Poleszczuk, Jan; Enderling, Heiko

2014-01-01

Tumor growth from a single transformed cancer cell up to a clinically apparent mass spans many spatial and temporal orders of magnitude. Implementation of cellular automata simulations of such tumor growth can be straightforward but computing performance often counterbalances simplicity. Computationally convenient simulation times can be achieved by choosing appropriate data structures, memory and cell handling as well as domain setup. We propose a cellular automaton model of tumor growth with a domain that expands dynamically as the tumor population increases. We discuss memory access, data structures and implementation techniques that yield high-performance multi-scale Monte Carlo simulations of tumor growth. We discuss tumor properties that favor the proposed high-performance design and present simulation results of the tumor growth model. We estimate to which parameters the model is the most sensitive, and show that tumor volume depends on a number of parameters in a non-monotonic manner. PMID:25346862

[Epithelioid leiomyosarcoma of the stomach. Clinical experiences with a rare stomach tumor].

PubMed

Hauser, H; Steindorfer, P; Mischinger, H J; Thalhammer, M; Kronberger, L; Rosanelli, G; Lax, S F

1995-01-01

Gastric epithelioid leiomyosarcoma (epLMS), which generally occurs in mid- or late adult life, is a rare smooth muscle tumor of the stomach. Out of 25 soft tissue tumors of the stomach operated at the Department of Surgery, University of Graz, two epLMS were diagnosed. This paper presents the case of a 67-year-old male with an epLMS in the corpus and of a 80-year-old female with an epLMS in the fundus of the stomach. The tumors were not diagnosed by gastroscopy; they were localized by sonography and CT-scan. In both cases the tumor was completely removed surgically, using a TA 90 4.8 mm respectively a TA 55 4.8 mm stapler. Diagnosis was reached by histological and immunohistochemical examination of the tumor tissue. Surgical excision with wide tumor-free resection margins is the therapy of choice in this tumor group.

Computer assisted diagnostic system in tumor radiography.

PubMed

Faisal, Ahmed; Parveen, Sharmin; Badsha, Shahriar; Sarwar, Hasan; Reza, Ahmed Wasif

2013-06-01

An improved and efficient method is presented in this paper to achieve a better trade-off between noise removal and edge preservation, thereby detecting the tumor region of MRI brain images automatically. Compass operator has been used in the fourth order Partial Differential Equation (PDE) based denoising technique to preserve the anatomically significant information at the edges. A new morphological technique is also introduced for stripping skull region from the brain images, which consequently leading to the process of detecting tumor accurately. Finally, automatic seeded region growing segmentation based on an improved single seed point selection algorithm is applied to detect the tumor. The method is tested on publicly available MRI brain images and it gives an average PSNR (Peak Signal to Noise Ratio) of 36.49. The obtained results also show detection accuracy of 99.46%, which is a significant improvement than that of the existing results.

Prognostic significance of tumor-associated macrophages in endometrial adenocarcinoma.

PubMed

Kübler, Kirsten; Ayub, Tiyasha H; Weber, Sarah K; Zivanovic, Oliver; Abramian, Alina; Keyver-Paik, Mignon-Denise; Mallmann, Michael R; Kaiser, Christina; Serçe, Nuran Bektas; Kuhn, Walther; Rudlowski, Christian

2014-11-01

Endometrial adenocarcinoma is one of the most common gynecologic malignancies worldwide and in stages confined to the uterus considered to have an excellent prognosis. However, in advanced or recurrent cases when surgery fails to achieve disease control other treatment options are less effective. Thus, new therapeutic avenues are needed. To provide the rationale for the use of novel agents that target immune checkpoints 163 type I endometrial cancer samples were immunohistochemically screened for the presence of CD163(+) tumor-associated macrophages and Foxp3(+) regulatory T cells. Further, a D2-40-based evaluation of lymph vessel density and lymphovascular space invasion was carried out. Correlation analysis with clinicopathological parameters was performed; Kaplan-Meier curves were generated; multivariate analysis was undertaken as appropriate. A substantial amount of tumor-associated macrophages and regulatory T cells was detected in all specimens characterizing endometrial cancer as an immunogenic tumor. However, only the increased infiltration of tumor-associated macrophages was proportionally associated with advanced FIGO stages, high tumor grade, increased lymph vessel density, lymphovascular space invasion and lymph node metastasis. Thus, the presence of tumor-associated macrophages indicates aggressive tumor behavior and appeared to be an independent prognostic factor for recurrence-free survival. Our results make future therapeutic approaches that target tumor-associated macrophages reasonable to improve the outcome of women with advanced or recurrent endometrial adenocarcinoma. Copyright © 2014 Elsevier Inc. All rights reserved.

Benefits and shortcomings of superselective transarterial embolization of renal tumors before zero ischemia laparoscopic partial nephrectomy.

PubMed

D'Urso, L; Simone, G; Rosso, R; Collura, D; Castelli, E; Giacobbe, A; Muto, G L; Comelli, S; Savio, D; Muto, G

2014-12-01

To report feasibility, safety and effectiveness of "zero-ischemia" laparoscopic partial nephrectomy (LPN) following preoperative superselective transarterial embolization (STE) for clinical T1 renal tumors. We retrospectively reviewed perioperative data of 23 consecutive patients, who underwent STE prior LPN between March 2010 and November 2012 for incidental clinical T1 renal mass. STE was performed by two experienced radiologists the day before surgery. Surgical procedures were performed in extended flank position, transperitoneally, by a single surgeon. Mean patients age was 68 years (range 56-74), mean tumor size was 3.5 cm (range 2.2-6.3 cm). STE was successfully completed in 16 patients 12-15 h before surgery. In 4 cases STE failed to provide a complete occlusion of all feeding arteries, while in 3 cases the ischemic area was larger than expected. LPN was successfully completed in all patients but one where open conversion was necessary; a "zero-ischemia" approach was performed in 19/23 patients (82.6%) while hilar clamp was necessary in 4 cases, with a mean warm-ischemia time of 14.8 min (range 5-22). Mean operative time was 123 min (range 115-130) and mean intraoperative blood loss was 250 mL (range 20-450). No patient experienced postoperative acute renal failure and no patient developed new onset IV stage chronic kidney disease at 1-yr follow-up. STE is a viable option to perform "zero-ischemia" LPN at beginning of learning curve; however, hilar clamp was necessary to achieve a relatively blood-less field in 17.4% of cases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Localization of liver tumors in freehand 3D laparoscopic ultrasound

NASA Astrophysics Data System (ADS)

Shahin, O.; Martens, V.; Besirevic, A.; Kleemann, M.; Schlaefer, A.

2012-02-01

The aim of minimally invasive laparoscopic liver interventions is to completely resect or ablate tumors while minimizing the trauma caused by the operation. However, restrictions such as limited field of view and reduced depth perception can hinder the surgeon's capabilities to precisely localize the tumor. Typically, preoperative data is acquired to find the tumor(s) and plan the surgery. Nevertheless, determining the precise position of the tumor is required, not only before but also during the operation. The standard use of ultrasound in hepatic surgery is to explore the liver and identify tumors. Meanwhile, the surgeon mentally builds a 3D context to localize tumors. This work aims to upgrade the use of ultrasound in laparoscopic liver surgery. We propose an approach to segment and localize tumors intra-operatively in 3D ultrasound. We reconstruct a 3D laparoscopic ultrasound volume containing a tumor. The 3D image is then preprocessed and semi-automatically segmented using a level set algorithm. During the surgery, for each subsequent reconstructed volume, a fast update of the tumor position is accomplished via registration using the previously segmented and localized tumor as a prior knowledge. The approach was tested on a liver phantom with artificial tumors. The tumors were localized in approximately two seconds with a mean error of less than 0.5 mm. The strengths of this technique are that it can be performed intra-operatively, it helps the surgeon to accurately determine the location, shape and volume of the tumor, and it is repeatable throughout the operation.

Achievement Motivation among Urban Adolescents: Work Hope, Autonomy Support, and Achievement-Related Beliefs

ERIC Educational Resources Information Center

Kenny, Maureen E.; Walsh-Blair, Lynn Y.; Blustein, David L.; Bempechat, Janine; Seltzer, Joanne

2010-01-01

Drawing upon expectancy value, hope, and self-determination theories, this study explores the contributions of work-based beliefs and autonomy support as predictors of adaptive achievement-related beliefs. Two hundred and one urban high school students who were enrolled in a work-based learning program completed measures of work hope, autonomy…

On-chip human microvasculature assay for visualization and quantitation of tumor cell extravasation dynamics

PubMed Central

Chen, Michelle B.; Whisler, Jordan A.; Fröse, Julia; Yu, Cathy; Shin, Yoojin

2017-01-01

Distant metastasis, which results in >90% of cancer related deaths, is enabled by hematogenous dissemination of tumor cells via the circulation. This requires the completion of a sequence of complex steps including transit, initial arrest, extravasation, survival and proliferation. Increased understanding of the cellular and molecular players enabling each of these steps is key in uncovering new opportunities for therapeutic intervention during early metastatic dissemination. Here, we describe an in vitro model of the human microcirculation with the potential to recapitulate discrete steps of early metastatic seeding, including arrest, transendothelial migration and early micrometastases formation. The microdevice features self-organized human microvascular networks formed over 4–5 days, after which tumor can be perfused and extravasation events easily tracked over 72 hours, via standard confocal microscopy. Contrary to most in vivo and in vitro extravasation assays, robust and rapid scoring of extravascular cells combined with high-resolution imaging can be easily achieved due to the confinement of the vascular network to one plane close to the surface of the device. This renders extravascular cells clearly distinct and allows tumor cells of interest to be identified quickly compared to those in thick tissues. The ability to generate large numbers of devices (~36) per experiment coupled with fast quantitation further allows for highly parametric studies, which is required when testing multiple genetic or pharmacological perturbations. This is coupled with the capability for live tracking of single cell extravasation events allowing both tumor and endothelial morphological dynamics to be observed in high detail with a moderate number of data points. This Protocol Extension describes an adaptation of an existing Protocol describing a microfluidic platform that offers additional applications. PMID:28358393

PDD applied in the dog transmissible venereal tumor

NASA Astrophysics Data System (ADS)

Hage, Raduan; Duarte, Janaina; Martin, Airton A.; Zangaro, Renato A.; Pacheco, Marcos T. T.

2003-07-01

The Transmissible Venereal Tumor (TVT) is a very common neoplasic disease in a free-roaming dogs which affects the extern genital and presenting resistance to conventional drugs that promote high toxicity. Photodynamic Therapy (PDT) is based in tumor cells irradiation after absorption of photosensitizer substance. At present, the protoporphirin IX (PP IX) has been explored in PDT due to be endogen, then it does not present toxicity effect. This substance can be obtained by exogenous way through aminolevulinic acid (5-ALA) administration in patient. The aim of this work was establish the optimal conditions for PDD (Phodynamic Diagnosis) to irradiate the tumor after ALA administration through fluorescence spectroscopy to improve the results with PDT. In this research was studied the 5-ALA 20% absorption in TVT of vaginal and penial mucous of a female and a male dog, respectivaly. This drug was administrated topically and after 30 minutes the fluorescence spectra were collected in intervals of 15 minutes during 120 minutes. The results showed that the maximum peak of PP IX in the tumor was between 60 and 105 minutes after the ALA application. In conclusion, the optimum effect will be achieved irradiating the tumor tissue into this period.

Presurgical evaluation of language using functional magnetic resonance imaging in brain tumor patients with previous surgery.

PubMed

Peck, Kyung K; Bradbury, Michelle; Petrovich, Nicole; Hou, Bob L; Ishill, Nicole; Brennan, Cameron; Tabar, Viviane; Holodny, Andrei I

2009-04-01

Functional magnetic resonance imaging (fMRI) is used to assess language laterality in preoperative brain tumor patients. In postsurgical patients, susceptibility artifacts can potentially alter ipsilateral fMRI activation volumes and the assessment of language laterality. The purpose of this study was to investigate the ability of fMRI to correctly measure language dominance in brain tumor patients with previous surgery because this patient cohort is vulnerable to type II statistical errors and subsequent misjudgment of laterality. Twenty-six right-handed patients with left-hemisphere gliomas (16 with and 10 without previous surgery) underwent preoperative language fMRI. Language laterality was measured using hemispheric and Broca's area regions of interest (ROIs). Hemisphere dominance, as established by laterality measurements, was compared with that determined by intraoperative electrocorticography and behavioral assessments. Localization of primary language cortices was achieved in 24 of 26 patients studied. The hemisphere dominance evaluated by fMRI was verified by intraoperative corticography in only 14 patients (10 with and 4 without previous surgery), and only 12 of them had complete neuropsychological testing. Complete concordance of the laterality with intraoperative electrocorticography and behavioral assessments was found in patients without previous surgery. In patients with previous surgery, concordance was 75% using Broca's area ROI and 88% using hemispheric ROI, notwithstanding susceptibility artifacts. Differences in laterality between pre- and postsurgical patients, based on either hemispheric (P = 0.81) or Broca's area (P = 0.19) ROI measurements were not statistically significant. However, hemispheric ROI analyses were found to be less affected by postsurgical artifacts and may be more suitable for establishing hemisphere dominance. fMRI mapping of eloquent language cortices in brain tumor patients after surgery is feasible and can serve as a

[Risk factors for malignant evolution of gastrointestinal stromal tumors].

PubMed

Andrei, S; Andrei, Adriana; Tonea, A; Andronesi, D; Becheanu, G; Dumbravă, Mona; Pechianu, C; Herlea, V; Popescu, I

2007-01-01

Gastrointestinal stromal tumors are the most frequent non-epithelial digestive tumors, being classified in the group of primitive mesenchymal tumors of the digestive tract. These tumors have a non predictable evolution and where stratified regarding the risk for malignant behavior in 4 categories: very low risk, low risk, intermediate risk and high risk. We performed a retrospective non randomised study including the patients with gastrointestinal stromal tumors treated in the Department of General Surgery and Liver Transplantation of Fundeni Clinical Institute in the period January 2002 - June 2007, to define the epidemiological, clinico-paraclinical, histological and especially evolutive features of the gastrointestinal stromal tumors from this group, with a special regard to the risk factors for their malignant behavior. The most important risk factors in gastrointestinal stromal tumors are the tumor size and the mitotic index, based on them being realised the classification of Fletcher in the 4 risk categories mentioned above. In our group all the local advanced or metastatic gastrointestinal stromal tumors, regardless of their location, were classified in the group of high risk for the malignant behavior. The gastric location and the epithelioid type were positive prognostic factors, and the complete resection of the tumor, an other important positive prognostic feature, was possible in about 80% of the cases, probably because the gastrointestinal stromal tumors in our study were diagnosed in less advanced evolutive situations, only about one third being metastatic and about 14% being locally advanced at the time of diagnose. The association with other neoplasias was in our cases insignificant, only 5% of the patients presenting concomitant malignant digestive tumors and 7.6% intraabdominal benign tumors. Gastrointestinal stromal tumors remain a challenge for the medical staff, regarding their diagnose and therapeutical management, the stratification of the

Adrenocortical carcinoma with inferior vena cava, left renal vein and right atrium tumor thrombus extension

PubMed Central

Annamaria, Pronio; Silvia, Piroli; Bernardo, Ciamberlano; Alessandro, De Luca; Antonino, Marullo; Antonio, Barretta; Giuseppe, Mazzesi; Massimo, Rossi; Montesani, Chiara

2015-01-01

Introduction Adrenocortical carcinoma (ACC) is a rare, but highly aggressive type of tumor with an annual incidence of 1–2 cases per million. The prognosis is poor with a five-year overall survival rate of ∼35%. The poor prognosis may be related to the advanced stage at which the majority of ACCs are detected. Complete surgical resection remains the most effective treatment. Presentation of the case A 51-year-old female patient with recent onset of dyspepsia, ascites and peripheral edema was referred to our institution. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) displayed a 8 cm Ø right adrenal mass. Moreover a tumor thrombus jutted out into the IVC, left renal vein and right atrium. An echocardiographic evaluation confirmed the presence of the tumor thrombus in the right atrium. The patient underwent adrenalectomy with removal of its intravascular extension with the assistance of cardiopulmonary bypass and hypothermia. Discussion ACC is a rare malignancy and ACC with tumor thrombus extension is a rare presentation. Patients can present with a variety of sign and symptoms, depending on the extent of the tumor. CT scan of chest and abdomen represents the gold standard in ACC staging while magnetic resonance imaging (MRI) is preferred for tumor thrombus characterization. Complete surgical resection with a negative margin, R0 resection, is the only curative option for localized disease. Kidney sparing surgery should be performed when possible. Conclusion We present a rare case of Adrenocortical carcinoma with tumor thrombus extending into the IVC and right atrium. Complete resection with negative margins represents the best therapeutic chance for these patients. PMID:26355237

Adrenocortical carcinoma with inferior vena cava, left renal vein and right atrium tumor thrombus extension.

PubMed