TLR9 agonists oppositely modulate DNA repair genes in tumor versus immune cells and enhance chemotherapy effects.

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Sommariva, Michele; De Cecco, Loris; De Cesare, Michelandrea; Sfondrini, Lucia; Ménard, Sylvie; Melani, Cecilia; Delia, Domenico; Zaffaroni, Nadia; Pratesi, Graziella; Uva, Valentina; Tagliabue, Elda; Balsari, Andrea

2011-10-15

Synthetic oligodeoxynucleotides expressing CpG motifs (CpG-ODN) are a Toll-like receptor 9 (TLR9) agonist that can enhance the antitumor activity of DNA-damaging chemotherapy and radiation therapy in preclinical mouse models. We hypothesized that the success of these combinations is related to the ability of CpG-ODN to modulate genes involved in DNA repair. We conducted an in silico analysis of genes implicated in DNA repair in data sets obtained from murine colon carcinoma cells in mice injected intratumorally with CpG-ODN and from splenocytes in mice treated intraperitoneally with CpG-ODN. CpG-ODN treatment caused downregulation of DNA repair genes in tumors. Microarray analyses of human IGROV-1 ovarian carcinoma xenografts in mice treated intraperitoneally with CpG-ODN confirmed in silico findings. When combined with the DNA-damaging drug cisplatin, CpG-ODN significantly increased the life span of mice compared with individual treatments. In contrast, CpG-ODN led to an upregulation of genes involved in DNA repair in immune cells. Cisplatin-treated patients with ovarian carcinoma as well as anthracycline-treated patients with breast cancer who are classified as "CpG-like" for the level of expression of CpG-ODN modulated DNA repair genes have a better outcome than patients classified as "CpG-untreated-like," indicating the relevance of these genes in the tumor cell response to DNA-damaging drugs. Taken together, the findings provide evidence that the tumor microenvironment can sensitize cancer cells to DNA-damaging chemotherapy, thereby expanding the benefits of CpG-ODN therapy beyond induction of a strong immune response.

Computed tomography of mast cell tumors in dogs: assessment before and after chemotherapy

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Lorigados, Carla A.B.; Matera, Julia Maria; Pinto, Ana Carolina B.C.F.; Macedo, Thais R.; Coppi, Antonio A.; Ladd, Fernando V.L.; Souza, Vanessa A.F. de

2013-01-01

Nineteen dogs with mast cell tumors treated with chemotherapy were evaluated by computed tomography (CT). Were evaluated aspects related to contours, attenuation, postcontrast enhancement and presence of cleavage with adjacent structures. The RECIST criteria and volumetric measurement of lesions were performed to assess the response to treatment. The mast cell tumors presented a homogeneous or heterogeneous attenuation, presented more frequently a well delineated and regular contours and moderate enhancement after intravenous administration of the iodinated contrast media. The methods RECIST and volumetric measurements showed an excellent agreement to the classification of therapeutic response, providing a good parameter of the response to treatment. The CT examination proved to be useful in the delimitation of the tumor and an important tool for planning of surgical margins. (author)

Chemotherapy synergizes with radioimmunotherapy targeting La autoantigen in tumors.

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Fares Al-Ejeh

Full Text Available To date, inefficient delivery of therapeutic doses of radionuclides to solid tumors limits the clinical utility of radioimmunotherapy. We aim to test the therapeutic utility of Yttrium-90 ((90Y-radio-conjugates of a monoclonal antibody, which we showed previously to bind specifically to the abundant intracellular La ribonucleoprotein revealed in dead tumor cells after DNA-damaging treatment.Immunoconjugates of the DAB4 clone of the La-specific monoclonal antibody, APOMAB, were prepared using the metal chelator, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA, and then radiolabeled with (90Y. Mice bearing established subcutaneous tumors were treated with (90Y-DOTA-DAB4 alone or after chemotherapy. Non-radiosensitizing cyclophosphamide/etoposide chemotherapy was used for the syngeneic EL4 lymphoma model. Radiosensitizing cisplatin/gemcitabine chemotherapy was used for the syngeneic Lewis Lung carcinoma (LL2 model, and for the xenograft models of LNCaP prostatic carcinoma and Panc-1 pancreatic carcinoma. We demonstrate the safety, specificity, and efficacy of (90Y-DOTA-DAB4-radioimmunotherapy alone or combined with chemotherapy. EL4 lymphoma-bearing mice either were cured at higher doses of radioimmunotherapy alone or lower doses of radioimmunotherapy in synergy with chemotherapy. Radioimmunotherapy alone was less effective in chemo- and radio-resistant carcinoma models. However, radioimmunotherapy synergized with radiosensitizing chemotherapy to retard significantly tumor regrowth and so prolong the survival of mice bearing LL2, LNCaP, or Panc-1 subcutaneous tumor implants.We report proof-of-concept data supporting a unique form of radioimmunotherapy, which delivers bystander killing to viable cancer cells after targeting the universal cancer antigen, La, created by DNA-damaging treatment in neighboring dead cancer cells. Subsequently we propose that DAB4-targeted ionizing radiation induces additional cycles of tumor cell death

CpG oligodeoxynucleotides are potent enhancers of radio- and chemoresponses of murine tumors

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Mason, Kathryn A.; Neal, Robert; Hunter, Nancy; Ariga, Hisanori; Ang, Kian; Milas, Luka

2006-01-01

Background and purpose: Synthetic oligodeoxynucleotides (ODNs) containing unmethylated cytosine-guanine (CpG) motifs bind to Toll-like receptor 9 (TLR9) and stimulate both innate and adaptive immune reactions and possess anti-tumor activity. We recently reported that CpG ODN 1826 strongly enhances radioresponse of both immunogenic [Milas L, Mason K, Ariga H, et al. CpG oligodeoxynucleotide enhances tumor response to radiation. Cancer Res 2004;64:5074-7] and non-immunogenic [Mason KA, Ariga H, Neal R, et al. Targeting toll-like receptor-9 with CpG oligodeoxynucleotides enhances tumor response to fractionated radiotherapy. Clin Cancer Res 2005;11:361-9] murine tumors. Using two immunogenic murine tumors, a fibrosarcoma (FSa) and a mammary carcinoma (MCa-K), the present study explored whether CpG ODN 1826 also improves the response of murine tumors to the chemotherapeutic agent docetaxel (DOC). Materials and methods: CpG ODN 1826 (100 μg) was given sc three times: when leg tumors were 6 mm, when they grew to 8 mm and again 1 week later. DOC (33 mg/kg iv) and local tumor radiation (10 Gy) were given when tumors were 8 mm. Effects of the treatments were assayed by tumor growth delay, defined as days for tumors to grow from 8 to 12 mm in diameter. Results: Treatment with CpG ODN 1826 resulted in strongly enhanced response of FSa tumors to radiation and MCa-K tumors to the chemotherapeutic agent DOC. Enhancement of tumor treatment response was demonstrated by a strong prolongation in the primary tumor treatment endpoint, tumor growth delay. Coincidentally, this treatment also resulted in a higher rate of tumor cure than that observed after tumor radiotherapy or chemotherapy alone. When all three agents were combined the effect was comparable to that of the combination of CpG ODN 1826 with radiation in the case of FSa or of the combination of CpG ODN 1826 with DOC in the case of MCa-K. Conclusion: Overall results show that CpG ODN 1826 can markedly improve tumor response

Computer-aided breast MR image feature analysis for prediction of tumor response to chemotherapy

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Aghaei, Faranak; Tan, Maxine; Liu, Hong; Zheng, Bin; Hollingsworth, Alan B.; Qian, Wei

2015-01-01

Purpose: To identify a new clinical marker based on quantitative kinetic image features analysis and assess its feasibility to predict tumor response to neoadjuvant chemotherapy. Methods: The authors assembled a dataset involving breast MR images acquired from 68 cancer patients before undergoing neoadjuvant chemotherapy. Among them, 25 patients had complete response (CR) and 43 had partial and nonresponse (NR) to chemotherapy based on the response evaluation criteria in solid tumors. The authors developed a computer-aided detection scheme to segment breast areas and tumors depicted on the breast MR images and computed a total of 39 kinetic image features from both tumor and background parenchymal enhancement regions. The authors then applied and tested two approaches to classify between CR and NR cases. The first one analyzed each individual feature and applied a simple feature fusion method that combines classification results from multiple features. The second approach tested an attribute selected classifier that integrates an artificial neural network (ANN) with a wrapper subset evaluator, which was optimized using a leave-one-case-out validation method. Results: In the pool of 39 features, 10 yielded relatively higher classification performance with the areas under receiver operating characteristic curves (AUCs) ranging from 0.61 to 0.78 to classify between CR and NR cases. Using a feature fusion method, the maximum AUC = 0.85 ± 0.05. Using the ANN-based classifier, AUC value significantly increased to 0.96 ± 0.03 (p < 0.01). Conclusions: This study demonstrated that quantitative analysis of kinetic image features computed from breast MR images acquired prechemotherapy has potential to generate a useful clinical marker in predicting tumor response to chemotherapy

Computer-aided breast MR image feature analysis for prediction of tumor response to chemotherapy

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Aghaei, Faranak; Tan, Maxine; Liu, Hong; Zheng, Bin, E-mail: Bin.Zheng-1@ou.edu [School of Electrical and Computer Engineering, University of Oklahoma, Norman, Oklahoma 73019 (United States); Hollingsworth, Alan B. [Mercy Women’s Center, Mercy Health Center, Oklahoma City, Oklahoma 73120 (United States); Qian, Wei [Department of Electrical and Computer Engineering, University of Texas, El Paso, Texas 79968 (United States)

2015-11-15

Purpose: To identify a new clinical marker based on quantitative kinetic image features analysis and assess its feasibility to predict tumor response to neoadjuvant chemotherapy. Methods: The authors assembled a dataset involving breast MR images acquired from 68 cancer patients before undergoing neoadjuvant chemotherapy. Among them, 25 patients had complete response (CR) and 43 had partial and nonresponse (NR) to chemotherapy based on the response evaluation criteria in solid tumors. The authors developed a computer-aided detection scheme to segment breast areas and tumors depicted on the breast MR images and computed a total of 39 kinetic image features from both tumor and background parenchymal enhancement regions. The authors then applied and tested two approaches to classify between CR and NR cases. The first one analyzed each individual feature and applied a simple feature fusion method that combines classification results from multiple features. The second approach tested an attribute selected classifier that integrates an artificial neural network (ANN) with a wrapper subset evaluator, which was optimized using a leave-one-case-out validation method. Results: In the pool of 39 features, 10 yielded relatively higher classification performance with the areas under receiver operating characteristic curves (AUCs) ranging from 0.61 to 0.78 to classify between CR and NR cases. Using a feature fusion method, the maximum AUC = 0.85 ± 0.05. Using the ANN-based classifier, AUC value significantly increased to 0.96 ± 0.03 (p < 0.01). Conclusions: This study demonstrated that quantitative analysis of kinetic image features computed from breast MR images acquired prechemotherapy has potential to generate a useful clinical marker in predicting tumor response to chemotherapy.

Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance in vitro.

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Khdair, Ayman; Handa, Hitesh; Mao, Guangzhao; Panyam, Jayanth

2009-02-01

Drug resistance limits the success of many anticancer drugs. Reduced accumulation of the drug at its intracellular site of action because of overexpression of efflux transporters such as P-glycoprotein (P-gp) is a major mechanism of drug resistance. In this study, we investigated whether photodynamic therapy (PDT) using methylene blue, also a P-gp inhibitor, can be used to enhance doxorubicin-induced cytotoxicity in drug-resistant tumor cells. Aerosol OT (AOT)-alginate nanoparticles were used as a carrier for the simultaneous cellular delivery of doxorubicin and methylene blue. Methylene blue was photoactivated using light of 665 nm wavelength. Induction of apoptosis and necrosis following treatment with combination chemotherapy and PDT was investigated in drug-resistant NCI/ADR-RES cells using flow cytometry and fluorescence microscopy. Effect of encapsulation in nanoparticles on the intracellular accumulation of doxorubicin and methylene blue was investigated qualitatively using fluorescence microscopy and was quantitated using HPLC. Encapsulation in AOT-alginate nanoparticles significantly enhanced the cytotoxicity of combination therapy in resistant tumor cells. Nanoparticle-mediated combination therapy resulted in a significant induction of both apoptosis and necrosis. Improvement in cytotoxicity could be correlated with enhanced intracellular and nuclear delivery of the two drugs. Further, nanoparticle-mediated combination therapy resulted in significantly elevated reactive oxygen species (ROS) production compared to single drug treatment. In conclusion, nanoparticle-mediated combination chemotherapy and PDT using doxorubicin and methylene blue was able to overcome resistance mechanisms and resulted in improved cytotoxicity in drug-resistant tumor cells.

Primitive neuroectodermal tumor arising 8 years after chemotherapy and radiotherapy for acute lymphoblastic leukemia. Case report

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Yoshida, Yuya; Toma, Yasuo; Arai, Masayuki; Higashi, Ryo; Kashihara, Kengo; Kaizaki, Yasuharu

2005-01-01

We report a case of primitive neuroectodermal tumor (PNET) arising 8 years after chemotherapy and radiotherapy for acute lymphoblastic leukemia. A 15-year-old boy with a history of acute lymphoblastic leukemia, at the age of 7, underwent chemotherapy and 14 Gy of radiotherapy to the whole brain. He was admitted to our department due to the development of aphasia, right hemiparesis and generalized convulsive seizure. MRI showed an irregularly enhanced mass in the left frontal lobe. A gross total removal of the tumor was performed and histological examination showed it to be PNET. Postoperatively, the patient underwent 20 Gy of radiotherapy to the whole brain and 42 Gy of local radiotherapy. Follow-up MRI showed no evidence of recurrent tumor 4 months after the radiotherapy. This tumor was thought to be a secondary brain tumor arising in this survivor of childhood acute lymphoblastic leukemia and it is a rare complication of successful leukemia treatment. (author)

The Impact of Induction Chemotherapy and the Associated Tumor Response on Subsequent Radiation-Related Changes in Lung Function and Tumor Response

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Mao Jingfang; Kocak, Zafer; Zhou Sumin; Garst, Jennifer; Evans, Elizabeth S.; Zhang Junan; Larrier, Nicole A.; Hollis, Donna R.; Folz, Rodney J.; Marks, Lawrence B.

2007-01-01

Purpose: To assess the impact of induction chemotherapy, and associated tumor shrinkage, on the subsequent radiation-related changes in pulmonary function and tumor response. Methods and Materials: As part of a prospective institutional review board-approved study, 91 evaluable patients treated definitively with thoracic radiation therapy (RT) for unresectable lung cancer were analyzed. The rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without pre-RT chemotherapy. In the patients receiving induction chemotherapy, the rates of RT-associated pulmonary toxicity and tumor response were compared in the patients with and without a response (modified Response Evaluation Criteria in Solid Tumor criteria) to the pre-RT chemotherapy. Comparisons of the rates of improvements in pulmonary function tests (PFTs) post-RT, dyspnea requiring steroids, and percent declines in PFTs post-RT were compared in patient subgroups using Fisher's exact test, analysis of variance, and linear or logistic regression. Results: The use of pre-RT chemotherapy appears to increase the rate of radiation-induced pneumonitis (p = 0.009-0.07), but has no consistent impact on changes in PFTs. The degree of induction chemotherapy-associated tumor shrinkage is not associated with the rate of subsequent RT-associated pulmonary toxicity. The degree of tumor response to chemotherapy is not related to the degree of tumor response to RT. Conclusions: Additional study is needed to better clarify the impact of chemotherapy on radiation-associated disfunction

Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy.

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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.

Canine transmissible venereal tumor and seminoma: a cytohistopathology and chemotherapy study of tumors in the growth phase and during regression after chemotherapy.

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Javanbakht, J; Pedram, B; Taheriyan, M R; Khadivar, F; Hosseini, S H; Abdi, F S; Hosseini, E; Moloudizargari, M; Aghajanshakeri, S H; Javaherypour, S; Shafiee, R; Emrani Bidi, R

2014-06-01

In this study, 12 dogs affected by canine transmissible venereal tumor (CTVT) and testicular seminoma tumor were studied retrospectively. The cytological sample was smeared onto a glass slide and either air-dried for May-Grünwald-stain, and masses were surgically removed. The tumors were grossly examined, and sections of 4-μm thick were obtained from each sample and stained with H&E. For chemotherapy, vincristine sulfate was administered weekly as an infusion over 3 min via the cephalic vein at a dose of 0.025 mg/kg after diluting with physiological saline to a total amount of 10 ml. If no remission was observed after 8 weeks, chemotherapy was continued with weekly doxorubicin infusion at a dose of 1 mg/kg. All the tumor samples were divided into four cytohistopathologic groups, namely: multilobular (six cases), papillary (two cases), pedunculated (two cases), and tubular (two cases of seminoma). The most frequently represented tumor type was multilobular (6/10, 60 %) followed by pedunculated (2/10, 20 %), papillary (2/10, 20 %), and tubular (two cases of seminoma, 100 %). Cytological smears from eight tumors in regression after chemotherapy were poorly cellular, and many cells were fragmented. In two progressive tumors, there was an average of 1,406 ± 972 CTVT 200 cells/μl or 96.71 % of total cells counted. Thus, tumor cells represented 96.71 % of total cells within the biopsy specimens and the leukocytes 4.29 % (leukocyte, tumor cell ratio=0.062 ± 0.031). In eight regressive tumors, there was an average of 1,245 ± 1,032 CTVT 200 cells/μl or 97.31 % of total cells counted. Thus, tumor cells represented 97.31 % of total cells and leukocytes 2.69 % (leukocyte, tumor cell ratio=0.071 ± 0.174). Our data suggested that combination treatment with vincristine and doxorubicin in the future could be an excellent therapeutic alternative for the treatment of TVT for probably reducing the resistance to vincristine, and also, treatment success could easily be followed

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

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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

Prognostic value of tumor suppressors in osteosarcoma before and after neoadjuvant chemotherapy

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Robl, Bernhard; Pauli, Chantal; Botter, Sander Martijn; Bode-Lesniewska, Beata; Fuchs, Bruno

2015-01-01

Primary bone cancers are among the deadliest cancer types in adolescents, with osteosarcomas being the most prevalent form. Osteosarcomas are commonly treated with multi-drug neoadjuvant chemotherapy and therapy success as well as patient survival is affected by the presence of tumor suppressors. In order to assess the prognostic value of tumor-suppressive biomarkers, primary osteosarcoma tissues were analyzed prior to and after neoadjuvant chemotherapy. We constructed a tissue microarray from high grade osteosarcoma samples, consisting of 48 chemotherapy naïve biopsies (BXs) and 47 tumor resections (RXs) after neoadjuvant chemotherapy. We performed immunohistochemical stainings of P53, P16, maspin, PTEN, BMI1 and Ki67, characterized the subcellular localization and related staining outcome with chemotherapy response and overall survival. Binary logistic regression analysis was used to analyze chemotherapy response and Kaplan-Meier-analysis as well as the Cox proportional hazards model was applied for analysis of patient survival. No significant associations between biomarker expression in BXs and patient survival or chemotherapy response were detected. In univariate analysis, positive immunohistochemistry of P53 (P = 0.008) and P16 (P16; P = 0.033) in RXs was significantly associated with poor survival prognosis. In addition, presence of P16 in RXs was associated with poor survival in multivariate regression analysis (P = 0.003; HR = 0.067) while absence of P16 was associated with good chemotherapy response (P = 0.004; OR = 74.076). Presence of PTEN on tumor RXs was significantly associated with an improved survival prognosis (P = 0.022). Positive immunohistochemistry (IHC) of P16 and P53 in RXs was indicative for poor overall patient survival whereas positive IHC of PTEN was prognostic for good overall patient survival. In addition, we found that P16 might be a marker of osteosarcoma chemotherapy resistance. Therefore, our study supports the use of tumor RXs to

Prognostic value of tumor suppressors in osteosarcoma before and after neoadjuvant chemotherapy.

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Robl, Bernhard; Pauli, Chantal; Botter, Sander Martijn; Bode-Lesniewska, Beata; Fuchs, Bruno

2015-05-09

Primary bone cancers are among the deadliest cancer types in adolescents, with osteosarcomas being the most prevalent form. Osteosarcomas are commonly treated with multi-drug neoadjuvant chemotherapy and therapy success as well as patient survival is affected by the presence of tumor suppressors. In order to assess the prognostic value of tumor-suppressive biomarkers, primary osteosarcoma tissues were analyzed prior to and after neoadjuvant chemotherapy. We constructed a tissue microarray from high grade osteosarcoma samples, consisting of 48 chemotherapy naïve biopsies (BXs) and 47 tumor resections (RXs) after neoadjuvant chemotherapy. We performed immunohistochemical stainings of P53, P16, maspin, PTEN, BMI1 and Ki67, characterized the subcellular localization and related staining outcome with chemotherapy response and overall survival. Binary logistic regression analysis was used to analyze chemotherapy response and Kaplan-Meier-analysis as well as the Cox proportional hazards model was applied for analysis of patient survival. No significant associations between biomarker expression in BXs and patient survival or chemotherapy response were detected. In univariate analysis, positive immunohistochemistry of P53 (P = 0.008) and P16 (P16; P = 0.033) in RXs was significantly associated with poor survival prognosis. In addition, presence of P16 in RXs was associated with poor survival in multivariate regression analysis (P = 0.003; HR = 0.067) while absence of P16 was associated with good chemotherapy response (P = 0.004; OR = 74.076). Presence of PTEN on tumor RXs was significantly associated with an improved survival prognosis (P = 0.022). Positive immunohistochemistry (IHC) of P16 and P53 in RXs was indicative for poor overall patient survival whereas positive IHC of PTEN was prognostic for good overall patient survival. In addition, we found that P16 might be a marker of osteosarcoma chemotherapy resistance. Therefore, our study supports the use of tumor RXs to

Assessment of serum tumor markers, tumor cell apoptosis and immune response in patients with advanced colon cancer after DC-CIK combined with intravenous chemotherapy

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Lei-Fan Li

2016-12-01

Full Text Available Objective: To study the effect of DC-CIK combined with intravenous chemotherapy on serum tumor markers, tumor cell apoptosis and immune response in patients with advanced colon cancer. Methods: A total of 79 patients with advanced colon cancer conservatively treated in our hospital between May 2012 and October 2015 were retrospectively studied and divided into DC-CIK group and intravenous chemotherapy group according to different therapeutic regimens, DC-CIK group received DC-CIK combined with intravenous chemotherapy and intravenous chemotherapy group received conventional intravenous chemotherapy. After three cycles of chemotherapy, the content of tumor markers in serum, expression levels of apoptotic molecules in tumor lesions as well as immune function indexes were determined. Results: After 3 cycles of chemotherapy, CEA, CA199, CA242, HIF-1α, IL-4, IL-5 and IL-10 content in serum of DC-CIK group were significantly lower than those of intravenous chemotherapy group; p53, FAM96B, PTEN, PHLPP, ASPP2 and RASSF10 mRNA content in tumor lesions of DC-CIK group were significantly higher than those of intravenous chemotherapy group; the fluorescence intensity of CD3, CD4 and CD56 on peripheral blood mononuclear cell surface of DC-CIK group were significantly higher than those of intravenous chemotherapy group while the fluorescence intensity of CD8 and CD25 were significantly lower than those of intravenous chemotherapy group; IL-2 and IFN-γ content in serum of DC-CIK group were significantly higher than those of intravenous chemotherapy group while IL-4, IL-5 and IL-10 content were significantly lower than those of intravenous chemotherapy group. Conclusions: DC-CIK combined with intravenous chemotherapy has better effect on killing colon cancer cells and inducing colon cancer cell apoptosis than conventional intravenous chemotherapy, and can also improve the body's anti-tumor immune response.

Biomaterial-based regional chemotherapy: Local anticancer drug delivery to enhance chemotherapy and minimize its side-effects.

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Krukiewicz, Katarzyna; Zak, Jerzy K

2016-05-01

Since the majority of anticancer pharmacological agents affect not only cancer tissue but also normal cells, chemotherapy is usually accompanied with severe side effects. Regional chemotherapy, as the alternative version of conventional treatment, leads to the enhancement of the therapeutic efficiency of anticancer drugs and, simultaneously, reduction of toxic effects to healthy tissues. This paper provides an insight into different approaches of local delivery of chemotherapeutics, such as the injection of anticancer agents directly into tumor tissue, the use of injectable in situ forming drug carriers or injectable platforms in a form of implants. The wide range of biomaterials used as reservoirs of anticancer drugs is described, i.e. poly(ethylene glycol) and its copolymers, polyurethanes, poly(lactic acid) and its copolymers, poly(ɛ-caprolactone), polyanhydrides, chitosan, cellulose, cyclodextrins, silk, conducting polymers, modified titanium surfaces, calcium phosphate based biomaterials, silicone and silica implants, as well as carbon nanotubes and graphene. To emphasize the applicability of regional chemotherapy in cancer treatment, the commercially available products approved by the relevant health agencies are presented. Copyright © 2016 Elsevier B.V. All rights reserved.

The Role of Chemotherapy in Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors.

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Strosberg, Jonathan; Goldman, Jamie; Costa, Frederico; Pavel, Marianne

2015-01-01

Even though the neuroendocrine tumor (NET) field has entered the era of 'targeted therapy', the role of cytotoxic chemotherapy continues to be debated. High response rates, ranging from 30 to 70% depending on the line of therapy, are consistently observed in the treatment of pancreatic NETs, with lesser evidence of activity in other foregut tumors. Activity in midgut carcinoid tumors appears to be negligible. Unfortunately, placebo-controlled randomized controlled trials using modern response criteria are lacking: the bulk of the literature consists of small phase II trials and retrospective series. There are also no completed trials comparing modern chemotherapy regimens, and therefore little data exist to favor the use of streptozocin- versus temozolomide- versus oxaliplatin-based therapies. Due to the absence of high-level evidence, it is difficult to generate data-based guidelines on the appropriate sequencing of cytotoxic drugs versus targeted agents. Although conventional wisdom holds that targeted agents such as everolimus or sunitinib are more tolerable than cytotoxic drugs, there is no evidence to support this perception. As a general principle, chemotherapy may be more appropriate as early-line therapy in patients with bulky and/or symptomatic and/or rapidly progressive tumors, particularly of pancreatic origin. In patients with low-volume disease or slow-growing tumors, noncytotoxic drugs may be preferable in early lines of therapy, reserving chemotherapy for the salvage setting. Validation of predictive factors is imperative in order to appropriately match patients with optimal treatment. Methyl-guanine-methyl-transferase (MGMT) deficiency is likely to be a positive predictive factor for alkylating agents, but needs to be evaluated prospectively. It is also unclear whether immunostaining for MGMT expression, which can be somewhat subjective, is superior to PCR-based techniques, which assess MGMT methylation status. Other basic predictive factors, such

Resectable hepatoblastoma with tumor thrombus extending into the right atrium after chemotherapy: A case report

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Kosuke Endo

2016-04-01

Full Text Available Hepatoblastoma with intraatrial tumor thrombus is relatively rare. We report a case of hepatoblastoma with tumor thrombus extending into the right atrium, which responded well to chemotherapy and was resected using extracorporeal circulation. A 4-year-old girl was referred to our hospital because of abdominal distention and tenderness. A computed tomography (CT scan showed a large tumor occupying the left 3 segments of the liver with tumor thrombus extending into the right atrium. There was also a small intrahepatic metastasis in the right lobe of the liver. She was diagnosed with hepatoblastoma on the basis of the results of open biopsy. Neoadjuvant chemotherapy with an intense CDDP-based regimen was performed. The tumor responded well to chemotherapy, and intrahepatic metastasis became undetectable on CT scan, although the tumor thrombus remained in the right atrium. After 7 courses of chemotherapy, we performed resection using extracorporeal circulation. The postoperative course was uneventful, and adjuvant chemotherapy was started 10 days after the operation. Her serum alpha-fetoprotein (AFP level decreased to the normal range, and she was free of disease for 1 year after the operation. Tumor resection using extracorporeal circulation can be performed safely and is justified in patients with intraatrial tumor thrombus.

Global stability and tumor clearance conditions for a cancer chemotherapy system

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Valle, Paul A.; Starkov, Konstantin E.; Coria, Luis N.

2016-11-01

In this paper we study the global dynamics of a cancer chemotherapy system presented by de Pillis et al. (2007). This mathematical model describes the interaction between tumor cells, effector-immune cells, circulating lymphocytes and chemotherapy treatment. By applying the localization method of compact invariant sets, we find lower and upper bounds for these three cells populations. Further, we define a bounded domain in R+,04 where all compact invariant sets of the system are located and provide conditions under which this domain is positively invariant. We apply LaSalle's invariance principle and one result concerning two-dimensional competitive systems in order to derive sufficient conditions for tumor clearance and global asymptotic stability of the tumor-free equilibrium point. These conditions are computed by using bounds of the localization domain and they are given in terms of the chemotherapy treatment. Finally, we perform numerical simulations in order to illustrate our results.

MRI evaluation of residual breast cancer after neoadjuvant chemotherapy: influence of patient, tumor and chemotherapy characteristics on the correlation with pathological response.

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Diguisto, Caroline; Ouldamer, Lobna; Arbion, Flavie; Vildé, Anne; Body, Gilles

2015-01-01

The aim of this study was to evaluate the correlation between the residual tumor measured on magnetic resonance imaging and pathological results and to assess whether this correlation varies according to patient, tumor or chemotherapy characteristics. The study population included women treated for breast cancer with indication of neoadjuvant chemotherapy in our tertiary breast cancer Unit between January 2008 and December 2011. Factors related to patients, tumor and chemotherapy were studied. Pearson's correlation coefficient between the size of the tumor on MRI and pathological response was calculated for the entire population. It was also calculated according to patient, tumor and chemotherapy characteristics. During the study period, 107 consecutive women were included. The size of residual tumor on the MRI significantly correlated with the size on pathological result with a Pearson correlation coefficient of 0.52 (pcorrelation was stronger for women aged 50 years and older (r=0.64, pcorrelation was stronger for those with triple-negative tumors (r=0.69, p=0.002) but weaker for those with tumors with a ductal carcinoma in situ component (r =0.18, p=0.42). The size of breast cancer obtained by MRI is significantly correlated to the pathological size of the tumor. This correlation was stronger among women aged 50 years and more, among post-menopausal women, and among women who had triple-negative tumors. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Mathematical Modelling and Analysis of the Tumor Treatment Regimens with Pulsed Immunotherapy and Chemotherapy.

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Pang, Liuyong; Shen, Lin; Zhao, Zhong

2016-01-01

To begin with, in this paper, single immunotherapy, single chemotherapy, and mixed treatment are discussed, and sufficient conditions under which tumor cells will be eliminated ultimately are obtained. We analyze the impacts of the least effective concentration and the half-life of the drug on therapeutic results and then find that increasing the least effective concentration or extending the half-life of the drug can achieve better therapeutic effects. In addition, since most types of tumors are resistant to common chemotherapy drugs, we consider the impact of drug resistance on therapeutic results and propose a new mathematical model to explain the cause of the chemotherapeutic failure using single drug. Based on this, in the end, we explore the therapeutic effects of two-drug combination chemotherapy, as well as mixed immunotherapy with combination chemotherapy. Numerical simulations indicate that combination chemotherapy is very effective in controlling tumor growth. In comparison, mixed immunotherapy with combination chemotherapy can achieve a better treatment effect.

Tumor vessel normalization after aerobic exercise enhances chemotherapeutic efficacy.

Science.gov (United States)

Schadler, Keri L; Thomas, Nicholas J; Galie, Peter A; Bhang, Dong Ha; Roby, Kerry C; Addai, Prince; Till, Jacob E; Sturgeon, Kathleen; Zaslavsky, Alexander; Chen, Christopher S; Ryeom, Sandra

2016-10-04

Targeted therapies aimed at tumor vasculature are utilized in combination with chemotherapy to improve drug delivery and efficacy after tumor vascular normalization. Tumor vessels are highly disorganized with disrupted blood flow impeding drug delivery to cancer cells. Although pharmacologic anti-angiogenic therapy can remodel and normalize tumor vessels, there is a limited window of efficacy and these drugs are associated with severe side effects necessitating alternatives for vascular normalization. Recently, moderate aerobic exercise has been shown to induce vascular normalization in mouse models. Here, we provide a mechanistic explanation for the tumor vascular normalization induced by exercise. Shear stress, the mechanical stimuli exerted on endothelial cells by blood flow, modulates vascular integrity. Increasing vascular shear stress through aerobic exercise can alter and remodel blood vessels in normal tissues. Our data in mouse models indicate that activation of calcineurin-NFAT-TSP1 signaling in endothelial cells plays a critical role in exercise-induced shear stress mediated tumor vessel remodeling. We show that moderate aerobic exercise with chemotherapy caused a significantly greater decrease in tumor growth than chemotherapy alone through improved chemotherapy delivery after tumor vascular normalization. Our work suggests that the vascular normalizing effects of aerobic exercise can be an effective chemotherapy adjuvant.

Radiation and concurrent chemotherapy for the treatment of Lewis lung tumor and B16 melanoma tumor in C57/BL mice

International Nuclear Information System (INIS)

Pedersen, J.E.; Barron, G.

1984-01-01

C57/BL mice bearing either Lewis lung tumor or B16 melanoma tumor were treated with radiation and concurrent chemotherapy. The treatment results were determined in vivo by tumor regrowth delay assay. When continuous infusion of either Cyclophosphamide (CYCLO) or 5-Fluorouracil (5-FU) or Adriamycin (ADRIA) or Mitomycin-C (MITO-C) was used in combination with continuous radiation at 1 cGy/min, no increase in tumor regrowth delay was observed over that of radiation alone. When multiple drug chemotherapy, FAM (5-FU, ADRIA, MITO-C) was administered in combination with radiation at 80 cGy/min, no increase in tumor regrowth delay was observed over that of radiation alone. In these two murine tumor models, when clinically relevant concentrations of commonly used chemotherapy agents were combined with radiation, no therapeutic advantage was observed

Activity of the hypoxia-activated pro-drug TH-302 in hypoxic and perivascular regions of solid tumors and its potential to enhance therapeutic effects of chemotherapy.

Science.gov (United States)

Saggar, Jasdeep K; Tannock, Ian F

2014-06-01

Many chemotherapy drugs have poor therapeutic activity in regions distant from tumor blood vessels because of poor tissue penetration and low cytotoxic activity against slowly-proliferating cells. The hypoxia-activated pro-drug TH-302 may have selective toxicity for hypoxic and neighboring cells in tumors. Here we characterize the spatial distribution and ability of TH-302 to selectively target hypoxic regions and complement the effect of doxorubicin and docetaxel by modifying biomarker distribution. Athymic nude mice bearing human breast MCF-7 or prostate PC-3 tumors were treated with doxorubicin or docetaxel respectively and TH-302 alone or in combination. Biomarkers of drug effect including γH2aX (a marker of DNA damage), cleaved caspase-3 or -6 (markers of apoptosis) and reduction in Ki-67 (a marker of cell proliferation) were quantified in tumor sections in relation to functional blood vessels (recognized by DiOC7) and hypoxia (recognized by EF5) using immunohistochemistry. γH2aX expression at 10 min and cleaved caspase-3 or -6 at 24 hr after doxorubicin or docetaxel decreased with increasing distance from tumor blood vessels, with minimal expression in hypoxic regions; maximum reduction in Ki67 levels was observed in regions closest to vasculature at 24 hr. TH-302 induced maximal cell damage in hypoxic and neighboring regions, but was also active in tumor regions closer to blood vessels. TH-302 given 4 hr before doxorubicin or docetaxel increased DNA damage and apoptosis throughout the tumor compared to chemotherapy alone. When given with doxorubicin or docetaxel, TH-302 complements and enhances anticancer effects in both perivascular and hypoxic regions but also increases toxicity. © 2013 UICC.

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

Science.gov (United States)

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.

Highly penetrative liposome nanomedicine generated by a biomimetic strategy for enhanced cancer chemotherapy.

Science.gov (United States)

Jia, Yali; Sheng, Zonghai; Hu, Dehong; Yan, Fei; Zhu, Mingting; Gao, Guanhui; Wang, Pan; Liu, Xin; Wang, Xiaobing; Zheng, Hairong

2018-04-25

Liposome nanomedicine has been successfully applied for cancer chemotherapy in patients. However, in general, the therapeutic efficacy is confined by its limited accumulation and penetration in solid tumors. Here, we established a biomimetic strategy for the preparation of highly penetrative liposome nanomedicine for enhanced chemotherapeutic efficacy. By applying this unique type of nanomedicine, membrane proteins on the cancer cells are used as highly penetrative targeting ligands. Biomimetic liposomes are highly stable, exhibiting a superior in vitro homologous targeting ability, and a 2.25-fold deeper penetration in 3D tumor spheroids when compared to conventional liposome nanomedicine. The fluorescence/photoacoustic dual-modal imaging approach demonstrated enhanced tumor accumulation and improved tumor penetration of the biomimetic liposome in C6 glioma tumor-bearing nude mice. Following the intravenous administration of biomimetic liposome nanomedicine, the tumor inhibition rate reached up to 93.3%, which was significantly higher when compared to that of conventional liposome nanomedicine (69.3%). Moreover, histopathological analyses demonstrated that biomimetic liposome nanomedicine has limited side effects. Therefore, these results suggested that a cancer cell membrane-based biomimetic strategy may provide a breakthrough approach for enhancing drug penetration and improving treatment efficacy, holding a great promise for further clinical studies.

Radio-chemotherapy in advanced tumors of the oral cavity, oro- and hypopharynx

International Nuclear Information System (INIS)

Schmitt, G.; Schnabel, T.

1992-01-01

Among combined radio-chemotherapy regimens of advanced head and neck tumors four modalities can be discriminated: 1. Induction chemotherapy, 2. simultaneous radio-chemotherapy, 3. adjuvant chemotherapy, 4. accelerated-hyperfractionated radiotherapy and chemotherapy. The results of the presently available randomized trials are as follows: 1. Induction chemotherapy has no influence on long-term recurrence-free survival. 2. With respect to simultaneous radio-chemotherapy, recurrence-free survival has been unproved with 5-FU and Mitomycin C. 3. There is evidence that adjuvant cis-platin therapy improves recurrence-free survival. 4. No results are available to date using hyperfractionated accelerated radiotherapy regimens in combination with chemotherapy. (orig.) [de

Tumor-stroma ratio predicts recurrence in patients with colon cancer treated with neoadjuvant chemotherapy

DEFF Research Database (Denmark)

Hansen, Torben Frøstrup; Kjær-Frifeldt, Sanne; Lindebjerg, Jan

2017-01-01

BACKGROUND: Neoadjuvant chemotherapy represents a new treatment approach to locally advanced colon cancer. The aim of this study was to analyze the ability of tumor-stroma ratio (TSR) to predict disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy....... MATERIAL AND METHODS: This study included 65 patients with colon cancer treated with neoadjuvant chemotherapy in a phase II trial. All patients were planned for three cycles of capecitabine and oxaliplatin before surgery. Hematoxylin and eosin stained tissue sections from surgically resected primary tumors...... was 55%, compared to 94% in the group of patients with a high TSR. CONCLUSIONS: TSR assessed in the surgically resected primary tumor from patients with locally advanced colon cancer treated with neoadjuvant chemotherapy provides prognostic value and may serve as a relevant parameter in selecting...

Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

Energy Technology Data Exchange (ETDEWEB)

Weir, Genevieve M. [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada); Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Liwski, Robert S. [Room 11-L1, Sir Charles Tupper Building, Department of Microbiology & Immunology, Dalhousie University, 5850 College St, Halifax, NS, B3H 1X5 (Canada); Room 206E, Dr. D. J. Mackenzie Building, Department of Pathology, Dalhousie University, 5788 University Avenue, Halifax, NS, B3H 2Y9 (Canada); Mansour, Marc [Suite 411, 1344 Summer St., Immunovaccine Inc., Halifax, NS, B3H 0A8 (Canada)

2011-08-05

Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments.

Immune Modulation by Chemotherapy or Immunotherapy to Enhance Cancer Vaccines

International Nuclear Information System (INIS)

Weir, Genevieve M.; Liwski, Robert S.; Mansour, Marc

2011-01-01

Chemotherapy has been a mainstay in cancer treatment for many years. Despite some success, the cure rate with chemotherapy remains unsatisfactory in some types of cancers, and severe side effects from these treatments are a concern. Recently, understanding of the dynamic interplay between the tumor and immune system has led to the development of novel immunotherapies, including cancer vaccines. Cancer vaccines have many advantageous features, but their use has been hampered by poor immunogenicity. Many developments have increased their potency in pre-clinical models, but cancer vaccines continue to have a poor clinical track record. In part, this could be due to an inability to effectively overcome tumor-induced immune suppression. It had been generally assumed that immune-stimulatory cancer vaccines could not be used in combination with immunosuppressive chemotherapies, but recent evidence has challenged this dogma. Chemotherapies could be used to condition the immune system and tumor to create an environment where cancer vaccines have a better chance of success. Other types of immunotherapies could also be used to modulate the immune system. This review will discuss how immune modulation by chemotherapy or immunotherapy could be used to bolster the effects of cancer vaccines and discuss the advantages and disadvantages of these treatments

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

Directory of Open Access Journals (Sweden)

Zhang Y

2016-01-01

Full Text Available Yu Zhang,1,* Linguo Xie,1,* Tao Chen,1,* Wanqin Xie,2 Zhouliang Wu,1 Hao Xu,1 Chen Xing,1 Nan Sha,1 Zhonghua Shen,1 Yunkai Qie,1 Xiaoteng Liu,1 Hailong Hu,1 Changli Wu1 1Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, 2Key Laboratory of Genetics and Birth Health of Hunan Province, The Family Planning Research Institute of Hunan Province, Changsha, People’s Republic of China *These authors contributed equally to this work Objective: The management of stage 1 and grade 3 (T1G3 bladder cancer continues to be controversial. Although the transurethral resection of bladder tumor (TURBT followed by intravesical chemotherapy is a conservative strategy for treatment of T1G3 bladder cancer, a relatively high risk of tumor recurrence and progression remains regarding the therapy. This study aimed to compare the efficacy of intravenous chemotherapy combined with intravesical chemotherapy versus intravesical chemotherapy alone for T1G3 bladder cancer after TURBT surgery. Methods: We retrospectively reviewed the cases of 457 patients who were newly diagnosed with T1G3 bladder urothelial carcinoma between January 2009 and March 2014. After TURBT, 281 patients received intravesical chemotherapy alone, whereas 176 patients underwent intravesical chemotherapy in combination with intravenous chemotherapy. Tumor recurrence and progression were monitored periodically by urine cytology and cystoscopy in follow-up. Recurrence-free survival and progression-free survival of the two chemotherapy strategies following TURBT were analyzed. Univariable and multivariable Cox hazards analyses were performed to predict the prognostic factors for tumor recurrence and progression. Results: The tumor recurrence rate was 36.7% for patients who received intravesical chemotherapy alone after TURBT, compared with 19.9% for patients who received intravenous chemotherapy combined with intravesical chemotherapy after

Radiotherapy and high-dose chemotherapy in advanced Ewing's tumors

International Nuclear Information System (INIS)

Pape, H.; Glag, M.; Gripp, S.; Wittkamp, M.; Schmitt, G.; Laws, H.J.; Kaik, B. van; Goebel, U.; Burdach, S.; Juergens, H.

1999-01-01

Background: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early ( [de

Treatment of a solid tumor using engineered drug-resistant immunocompetent cells and cytotoxic chemotherapy.

Science.gov (United States)

Dasgupta, Anindya; Shields, Jordan E; Spencer, H Trent

2012-07-01

Multimodal therapy approaches, such as combining chemotherapy agents with cellular immunotherapy, suffers from potential drug-mediated toxicity to immune effector cells. Overcoming such toxic effects of anticancer cellular products is a potential critical barrier to the development of combined therapeutic approaches. We are evaluating an anticancer strategy that focuses on overcoming such a barrier by genetically engineering drug-resistant variants of immunocompetent cells, thereby allowing for the coadministration of cellular therapy with cytotoxic chemotherapy, a method we refer to as drug-resistant immunotherapy (DRI). The strategy relies on the use of cDNA sequences that confer drug resistance and recombinant lentiviral vectors to transfer nucleic acid sequences into immunocompetent cells. In the present study, we evaluated a DRI-based strategy that incorporates the immunocompetent cell line NK-92, which has intrinsic antitumor properties, genetically engineered to be resistant to both temozolomide and trimetrexate. These immune effector cells efficiently lysed neuroblastoma cell lines, which we show are also sensitive to both chemotherapy agents. The antitumor efficacy of the DRI strategy was demonstrated in vivo, whereby neuroblastoma-bearing NOD/SCID/γ-chain knockout (NSG) mice treated with dual drug-resistant NK-92 cell therapy followed by dual cytotoxic chemotherapy showed tumor regression and significantly enhanced survival compared with animals receiving either nonengineered cell-based therapy and chemotherapy, immunotherapy alone, or chemotherapy alone. These data show there is a benefit to using drug-resistant cellular therapy when combined with cytotoxic chemotherapy approaches.

Tumor Therapeutics Work as Stress Inducers to Enhance Tumor Sensitivity to Natural Killer (NK) Cell Cytolysis by Up-regulating NKp30 Ligand B7-H6.

Science.gov (United States)

Cao, Guoshuai; Wang, Jian; Zheng, Xiaodong; Wei, Haiming; Tian, Zhigang; Sun, Rui

2015-12-11

Immune cells are believed to participate in initiating anti-tumor effects during regular tumor therapy such as chemotherapy, radiation, hyperthermia, and cytokine injection. One of the mechanisms underlying this process is the expression of so-called stress-inducible immunostimulating ligands. Although the activating receptor NKG2D has been proven to play roles in tumor therapy through targeting its ligands, the role of NKp30, another key activating receptor, is seldom addressed. In this study, we found that the NKp30 ligand B7-H6 was widely expressed in tumor cells and closely correlated to their susceptibility to NK cell lysis. Further studies showed that treatment of tumor cells with almost all standard tumor therapeutics, including chemotherapy (cisplatin, 5-fluorouracil), radiation therapy, non-lethal heat shock, and cytokine therapy (TNF-α), could up-regulate the expression of B7-H6 in tumor cells and enhance tumor sensitivity to NK cell cytolysis. B7-H6 shRNA treatment effectively dampened sensitization of tumor cells to NK-mediated lysis. Our study not only reveals the possibility that tumor therapeutics work as stress inducers to enhance tumor sensitivity to NK cell cytolysis but also suggests that B7-H6 could be a potential target for tumor therapy in the future. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Anxiety, depression in patients receiving chemotherapy for solid tumors

International Nuclear Information System (INIS)

Mansoor, S.; Jehangir, S.

2015-01-01

To determine the frequency of anxiety and depression in patients undergoing chemotherapy for solid tumors using Hospital Anxiety Depression Scale (HADS). Study Design: Cross sectional descriptive study. Place and Duration of Study: Out-patient department of Armed Forces Institute of Mental Health, Rawalpindi from June 2011 to December 2011. Methodology: Consecutive non probability sampling technique was used to select patients of age (25-70 years), male or female, who had received atleast 03 cycles of chemotherapy for solid tumors. Those with history of prior psychiatric illness, current use of psychotropic medication or psychoactive substance use, and any major bereavement in past one year were excluded from the study. After taking informed consent, relevant socio- demographic data was collected and HADS was administered. HADS-A cut off score of 7 was taken as significant anxiety while a HADS-D cut off score of 7 was taken as significant depression. Results: The total number of participants was 209. The mean age of patients was 42.9 years, with 55.5% males and 44.5% females. Overall 33/209 (15.8%) patients had anxiety while 56/209 (26.8%) were found to have depression. There was a higher frequency of anxiety and depression in younger patients (less than age 40 years), females, patients who were single or divorced, and patients receiving chemotherapy for pancreatic carcinoma. Conclusion: Patients undergoing chemotherapy suffer from considerable levels of anxiety and depression, thus highlighting the need for specialized interventions. (author)

Complete clinical response to neoadjuvant chemotherapy in a 54-year-old male with Askin tumor.

LENUS (Irish Health Repository)

Mulsow, J

2012-02-01

Askin tumor is a tumor of the thoracopulmonary region that most commonly affects children and adolescents. These rare tumors are a form of primitive neuroectodermal tumor and typically carry a poor prognosis. Treatment is multimodal and consists of a combination of neoadjuvant chemotherapy, radical resection, and adjuvant chemo- and radiotherapy or all of the above. Surgery is advocated in most cases. We report a case of Askin tumor in a 54-year-old male who showed rapid and complete response to neoadjuvant chemotherapy. This allowed potentially radical surgery to be avoided. At one-year follow-up he remains disease-free.

Metaplastic carcinoma. Breast. Relapse. Chemotherapy and Radiotherapy

International Nuclear Information System (INIS)

Marquez, A.; Terrasa, J.; Garcia, J.M.; Rifa, J.

1996-01-01

Metaplastic carcinoma of the breast is a rare tumor. The appearance of unexpected mesenchymal elements within the epithelial tumors is the squamous metaplasia. These tumors have a different clinical behaviour that classical breast carcinoma. We present a case of metaplastic mammary carcinoma with multiple relapses treated with a combination of chemotherapy and radiotherapy. The use of chemotherapy after local treatment has enhanced the relapse-free survival. The combined treatment modality seems to produce some benefit in the management of the local relapses of this neoplasms

Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

Directory of Open Access Journals (Sweden)

Yingjen Jeffrey Wu

2009-02-01

Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.

Circulating tumor cells predict survival benefit from chemotherapy in patients with lung cancer.

Science.gov (United States)

Wu, Zhuo-Xuan; Liu, Zhen; Jiang, Han-Ling; Pan, Hong-Ming; Han, Wei-Dong

2016-10-11

This meta-analysis was to explore the clinical significance of circulating tumor cells (CTCs) in predicting the tumor response to chemotherapy and prognosis of patients with lung cancer. We searched PubMed, Embase, Cochrane Database, Web of Science and reference lists of relevant articles. Our meta-analysis was performed by Stata software, version 12.0, with a random effects model. Risk ratio (RR), hazard ratio (HR) and 95% confidence intervals (CI) were used as effect measures. 8 studies, including 453 patients, were eligible for analyses. We showed that the disease control rate (DCR) in CTCs-negative patients was significantly higher than CTCs-positive patients at baseline (RR = 2.56, 95%CI [1.36, 4.82], p chemotherapy (RR = 9.08, CI [3.44, 23.98], p chemotherapy had a worse disease progression than those with CTC-positive to negative or persistently negative (RR = 8.52, CI [1.66, 43.83], p chemotherapy also indicated poor overall survival (OS) (baseline: HR = 3.43, CI [2.21, 5.33], pchemotherapy: HR = 3.16, CI [2.23, 4.48], p chemotherapy: HR = 3.78, CI [2.33, 6.13], p chemotherapy and poor prognosis in patients with lung cancer.

Intratumor partitioning and texture analysis of dynamic contrast-enhanced (DCE)-MRI identifies relevant tumor subregions to predict pathological response of breast cancer to neoadjuvant chemotherapy.

Science.gov (United States)

Wu, Jia; Gong, Guanghua; Cui, Yi; Li, Ruijiang

2016-11-01

To predict pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multiregion analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). In this Institutional Review Board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using 3T DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with high temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast washout were statistically significant (P < 0.05) after correcting for multiple testing, with area under the receiver operating characteristic (ROC) curve (AUC) or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (P = 0.002) in leave-one-out cross-validation. This improved upon conventional imaging predictors such as tumor volume (AUC = 0.53) and texture features based on whole-tumor analysis (AUC = 0.65). The heterogeneity of the tumor subregion associated with fast washout on DCE-MRI predicted pathological response to NAC in breast cancer. J. Magn. Reson. Imaging 2016;44:1107-1115. © 2016 International Society for Magnetic Resonance in Medicine.

TU-D-207B-05: Intra-Tumor Partitioning and Texture Analysis of DCE-MRI Identifies Relevant Tumor Subregions to Predict Early Pathological Response of Breast Cancer to Neoadjuvant Chemotherapy

International Nuclear Information System (INIS)

Wu, J; Gong, G; Cui, Y; Li, R

2016-01-01

Purpose: To predict early pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multi-region analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: In this institution review board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with a high-temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Results: Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast wash-out were statistically significant (p< 0.05) after correcting for multiple testing, with area under the ROC curve or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (p = 0.002) in leave-one-out cross validation. This improved upon conventional imaging predictors such as tumor volume (AUC=0.53) and texture features based on whole-tumor analysis (AUC=0.65). Conclusion: The heterogeneity of the tumor subregion associated with fast wash-out on DCE-MRI predicted early pathological response to neoadjuvant chemotherapy in breast cancer.

TU-D-207B-05: Intra-Tumor Partitioning and Texture Analysis of DCE-MRI Identifies Relevant Tumor Subregions to Predict Early Pathological Response of Breast Cancer to Neoadjuvant Chemotherapy

Energy Technology Data Exchange (ETDEWEB)

Wu, J; Gong, G; Cui, Y; Li, R [Stanford University, Palo Alto, CA (United States)

2016-06-15

Purpose: To predict early pathological response of breast cancer to neoadjuvant chemotherapy (NAC) based on quantitative, multi-region analysis of dynamic contrast enhancement magnetic resonance imaging (DCE-MRI). Methods: In this institution review board-approved study, 35 patients diagnosed with stage II/III breast cancer were retrospectively investigated using DCE-MR images acquired before and after the first cycle of NAC. First, principal component analysis (PCA) was used to reduce the dimensionality of the DCE-MRI data with a high-temporal resolution. We then partitioned the whole tumor into multiple subregions using k-means clustering based on the PCA-defined eigenmaps. Within each tumor subregion, we extracted four quantitative Haralick texture features based on the gray-level co-occurrence matrix (GLCM). The change in texture features in each tumor subregion between pre- and during-NAC was used to predict pathological complete response after NAC. Results: Three tumor subregions were identified through clustering, each with distinct enhancement characteristics. In univariate analysis, all imaging predictors except one extracted from the tumor subregion associated with fast wash-out were statistically significant (p< 0.05) after correcting for multiple testing, with area under the ROC curve or AUCs between 0.75 and 0.80. In multivariate analysis, the proposed imaging predictors achieved an AUC of 0.79 (p = 0.002) in leave-one-out cross validation. This improved upon conventional imaging predictors such as tumor volume (AUC=0.53) and texture features based on whole-tumor analysis (AUC=0.65). Conclusion: The heterogeneity of the tumor subregion associated with fast wash-out on DCE-MRI predicted early pathological response to neoadjuvant chemotherapy in breast cancer.

Effectiveness of chemotherapy in measurable granulosa cell tumors: a retrospective study and review of literature

NARCIS (Netherlands)

van Meurs, Hannah S.; Buist, Marrije R.; Westermann, Anneke M.; Sonke, Gabe S.; Kenter, Gemma G.; van der Velden, Jacobus

2014-01-01

Patients with irresectable granulosa cell tumors (GCTs) often receive chemotherapy. The effectiveness of this approach, however, is uncertain. The aim of our study was to assess the response rate to chemotherapy for residual and recurrent inoperable GCT. All consecutive chemotherapy-naive patients

Ultrasonic RF time series for early assessment of the tumor response to chemotherapy.

Science.gov (United States)

Lin, Qingguang; Wang, Jianwei; Li, Qing; Lin, Chunyi; Guo, Zhixing; Zheng, Wei; Yan, Cuiju; Li, Anhua; Zhou, Jianhua

2018-01-05

Ultrasound radio-frequency (RF) time series have been shown to carry tissue typing information. To evaluate the potential of RF time series for early prediction of tumor response to chemotherapy, 50MCF-7 breast cancer-bearing nude mice were randomized to receive cisplatin and paclitaxel (treatment group; n = 26) or sterile saline (control group; n = 24). Sequential ultrasound imaging was performed on days 0, 3, 6, and 8 of treatment to simultaneously collect B-mode images and RF data. Six RF time series features, slope, intercept, S1, S2, S3 , and S4 , were extracted during RF data analysis and contrasted with microstructural tumor changes on histopathology. Chemotherapy administration reduced tumor growth relative to control on days 6 and 8. Compared with day 0, intercept, S1 , and S2 were increased while slope was decreased on days 3, 6, and 8 in the treatment group. Compared with the control group, intercept, S1, S2, S3 , and S4 were increased, and slope was decreased, on days 3, 6, and 8 in the treatment group. Tumor cell density decreased significantly in the latter on day 3. We conclude that ultrasonic RF time series analysis provides a simple way to noninvasively assess the early tumor response to chemotherapy.

CT findings of hepatoblastoma before and after chemotherapy : correlation with pathologic features

International Nuclear Information System (INIS)

Seo, Joon Beom; Kim, Woo Sun; Kim, In One; Jang, Ja June; Kim, Chong Jai; Ahn, Hyo Seop; Yeon, Kyung Mo

1998-01-01

The purpose of this study was to analyze the CT findings of hepatoblastoma before and after chemotherapy, and to compare them with surgical and pathologic features. Twelve hepatoblastoma patients underwent chemotherapy prior to surgery; in all cases, CT scanning was performed before and after chemotherapy. We reviewed the findings with special attention to changes in tumor volume, the extent and pattern of contrast enhancement, the extent of low-attenuation area in the tumor, the presence of a septum, and calcification or ossification or ossification within the mass before and after chemotherapy. Post-chemotherapy CT findings were compared with operative and pathologic findings. After chemotheapy, the volume of the tumor mass decreased in all patients, and the extent of involved segments decreased in nine (75%), the non-enhancing area within the mass, on the other hand, increased in nine (75 %). On pre-chemotherapy CT, calcifications were detected in seven patients (58%), and on post-chemotherapy CT, in nine (75%); the extent of calcification were detected in seven patients. On the basis of CT findings, viable tumor and necrosis areas could not be distinguished. Massive calcification or osteoid mixed with loose connective tissue was noted in the mesenchymal component of the tumor; the whirling pattern of enhancement within the area of low density seen on CT scanning corresponded to osteoid mixed with loose connective tissue, which contained rich blood vessels. We describe the CT findings of hepatoblastoma both before and after chemotherapy, highlighting the changes which occurred. An understanding of these changes is helpful for the proper management of this condition. (author). 18 refs., 1 tab., 5 figs

Cell-cycle-dependent drug-resistant quiescent cancer cells induce tumor angiogenesis after chemotherapy as visualized by real-time FUCCI imaging

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Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M.

2017-01-01

ABSTRACT We previously demonstrated that quiescent cancer cells in a tumor are resistant to conventional chemotherapy as visualized with a fluorescence ubiquitination cell cycle indicator (FUCCI). We also showed that proliferating cancer cells exist in a tumor only near nascent vessels or on the tumor surface as visualized with FUCCI and green fluorescent protein (GFP)-expressing tumor vessels. In the present study, we show the relationship between cell-cycle phase and chemotherapy-induced tumor angiogenesis using in vivo FUCCI real-time imaging of the cell cycle and nestin-driven GFP to detect nascent blood vessels. We observed that chemotherapy-treated tumors, consisting of mostly of quiescent cancer cells after treatment, had much more and deeper tumor vessels than untreated tumors. These newly-vascularized cancer cells regrew rapidly after chemotherapy. In contrast, formerly quiescent cancer cells decoyed to S/G2 phase by a telomerase-dependent adenovirus did not induce tumor angiogenesis. The present results further demonstrate the importance of the cancer-cell position in the cell cycle in order that chemotherapy be effective and not have the opposite effect of stimulating tumor angiogenesis and progression. PMID:27715464

Rare Presentation of Metastatic Cystic Trophoblastic Tumor in a Patient Without Prior Chemotherapy

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Michael L. Wang

2017-07-01

Full Text Available Cystic trophoblastic tumor (CTT is a rare testicular germ cell tumor (GCT predominantly seen in post-chemotherapy patients. It is prognostically similar to teratoma and requires no additional chemotherapy in the absence of a nonteratomatous GCT component. We report a case of metastatic CTT in a patient with primary testicular teratoma without prior chemotherapy. Retroperitoneal lymph node metastases contained teratoma, embryonal carcinoma, and CTT. The CTT was β-hCG positive and SALL4 negative by immunohistochemistry (IHC. CTT can arise in metastatic testicular GCT in treatment naïve patients. An important differential diagnosis is choriocarcinoma due to treatment implications, and SALL4 IHC may help.

Robotic Stereotactic Radioablation Concomitant With Neo-Adjuvant Chemotherapy for Breast Tumors

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Bondiau, Pierre-Yves; Bahadoran, Phillipe; Lallement, Michel; Birtwisle-Peyrottes, Isabelle; Chapellier, Claire; Chamorey, Emmanuel; Courdi, Adel; Quielle-Roussel, Catherine; Thariat, Juliette; Ferrero, Jean-Marc

2009-01-01

Purpose: Robotic stereotactic radioablation (RSR) allows stereotactic irradiation of thoracic tumors; however, it has never been used for breast tumors and may have a real potential. We conducted a Phase I study, including neoadjuvant chemotherapy (NACT), a two-level dose-escalation study (6.5 Gy x 3 fractions and 7.5 Gy x 3 fractions) using RSR and breast-conserving surgery followed by conventional radiotherapy. Materials and Methods: To define toxicity, we performed a dermatologic exam (DE) including clinical examination by two independent observers and technical examination by colorimetry, dermoscopy, and skin ultrasound. DE was performed before NACT (DE0), at 36 days (DE1), at 56 days (DE2), after the NACT treatment onset, and before surgery (DE3). Surgery was performed 4-8 weeks after the last chemotherapy session. A pathologic examination was also performed. Results: There were two clinical complete responses and four clinical partial responses at D56 and D85. Maximum tolerable dose was not reached. All patients tolerated RSR with no fatigue; 2 patients presented with mild pain after the third fraction of the treatment. There was no significant toxicity measured with ultrasound and dermoscopy tests. Postoperative irradiation (50 Gy) has been delivered without toxicity. Conclusion: The study showed the feasibility of irradiation with RSR combined with chemotherapy and surgery for breast tumors. There was no skin toxicity at a dose of 19.5 Gy or 22.5 Gy delivered in three fractions combined with chemotherapy. Lack of toxicity suggested that the dose could be increased further. Pathologic response was acceptable.

Effects of intra-arterial infusion therapy or systemic chemotherapy with docetaxel for VX2 tumor in rabbit hind limb

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Qian Yuanxin; Wu Xiaomei; He Miao; Liu Tao; Deng Duo

2010-01-01

Objective: To discuss the efficacy and safety of intra-arterial infusion therapy with docetaxel. Methods: Animal model of VX2 tumor in rabbit hind limb was set up. Intra-arterial infusion therapy or systemic chemotherapy with docetaxel was performed. Concentrations of docetaxel in VX2 tumor, wall of stomach, liver, kidney and plasma of rabbits with VX2 tumors in hind limbs were determined. Difference of drug concentrations between intra-arterial infusion therapy and systemic chemotherapy was compared using Student t-test. Results: Concentrations of docetaxel in VX2 tumor and wall of stomach of rabbits with intra-arterial infusion therapy were significantly higher than those with systemic chemotherapy (p<0.05). The drug concentration in VX2 tumor of rabbits with intra-arterial infusion was 14 times higher than that with systemic chemotherapy. Concentration of docetaxel in plasma of rabbits with intra-arterial infusion therapy was not significantly lower than that with systemic chemotherapy (P<0.05). Conclusion: Intra-arterial infusion therapy with docetaxel for tumor is effective. However, there is increased risk of toxicity and the dose should adjusted accordingly. (authors)

CD8+ Tumor-Infiltrating T Cells Are Trapped in the Tumor-Dendritic Cell Network

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Alexandre Boissonnas

2013-01-01

Full Text Available Chemotherapy enhances the antitumor adaptive immune T cell response, but the immunosuppressive tumor environment often dominates, resulting in cancer relapse. Antigen-presenting cells such as tumor-associated macrophages (TAMs and tumor dendritic cells (TuDCs are the main protagonists of tumor-infiltrating lymphocyte (TIL immuno-suppression. TAMs have been widely investigated and are associated with poor prognosis, but the immuno-suppressive activity of TuDCs is less well understood. We performed two-photon imaging of the tumor tissue to examine the spatiotemporal interactions between TILs and TuDCs after chemotherapy. In a strongly immuno-suppressive murine tumor model, cyclophosphamide-mediated chemotherapy transiently enhanced the antitumor activity of adoptively transferred ovalbumin-specific CD8+ T cell receptor transgenic T cells (OTI but barely affected TuDC compartment within the tumor. Time lapse imaging of living tumor tissue showed that TuDCs are organized as a mesh with dynamic interconnections. Once infiltrated into the tumor parenchyma, OTI T cells make antigen-specific and long-lasting contacts with TuDCs. Extensive analysis of TIL infiltration on histologic section revealed that after chemotherapy the majority of OTI T cells interact with TuDCs and that infiltration is restricted to TuDC-rich areas. We propose that the TuDC network exerts antigen-dependent unproductive retention that trap T cells and limit their antitumor effectiveness.

A deterministic and stochastic model for the system dynamics of tumor-immune responses to chemotherapy

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Liu, Xiangdong; Li, Qingze; Pan, Jianxin

2018-06-01

Modern medical studies show that chemotherapy can help most cancer patients, especially for those diagnosed early, to stabilize their disease conditions from months to years, which means the population of tumor cells remained nearly unchanged in quite a long time after fighting against immune system and drugs. In order to better understand the dynamics of tumor-immune responses under chemotherapy, deterministic and stochastic differential equation models are constructed to characterize the dynamical change of tumor cells and immune cells in this paper. The basic dynamical properties, such as boundedness, existence and stability of equilibrium points, are investigated in the deterministic model. Extended stochastic models include stochastic differential equations (SDEs) model and continuous-time Markov chain (CTMC) model, which accounts for the variability in cellular reproduction, growth and death, interspecific competitions, and immune response to chemotherapy. The CTMC model is harnessed to estimate the extinction probability of tumor cells. Numerical simulations are performed, which confirms the obtained theoretical results.

Accuracy of contrast-enhanced spectral mammography for estimating residual tumor size after neoadjuvant chemotherapy in patients with breast cancer: a feasibility study.

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Barra, Filipe Ramos; de Souza, Fernanda Freire; Camelo, Rosimara Eva Ferreira Almeida; Ribeiro, Andrea Campos de Oliveira; Farage, Luciano

2017-01-01

To assess the feasibility of contrast-enhanced spectral mammography (CESM) of the breast for assessing the size of residual tumors after neoadjuvant chemotherapy (NAC). In breast cancer patients who underwent NAC between 2011 and 2013, we evaluated residual tumor measurements obtained with CESM and full-field digital mammography (FFDM). We determined the concordance between the methods, as well as their level of agreement with the pathology. Three radiologists analyzed eight CESM and FFDM measurements separately, considering the size of the residual tumor at its largest diameter and correlating it with that determined in the pathological analysis. Interobserver agreement was also evaluated. The sensitivity, specificity, positive predictive value, and negative predictive value were higher for CESM than for FFDM (83.33%, 100%, 100%, and 66% vs. 50%, 50%, 50%, and 25%, respectively). The CESM measurements showed a strong, consistent correlation with the pathological findings (correlation coefficient = 0.76-0.92; intraclass correlation coefficient = 0.692-0.886). The correlation between the FFDM measurements and the pathological findings was not statistically significant, with questionable consistency (intraclass correlation coefficient = 0.488-0.598). Agreement with the pathological findings was narrower for CESM measurements than for FFDM measurements. Interobserver agreement was higher for CESM than for FFDM (0.94 vs. 0.88). CESM is a feasible means of evaluating residual tumor size after NAC, showing a good correlation and good agreement with pathological findings. For CESM measurements, the interobserver agreement was excellent.

Ball-in-ball ZrO2 nanostructure for simultaneous CT imaging and highly efficient synergic microwave ablation and tri-stimuli-responsive chemotherapy of tumors.

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Long, Dan; Niu, Meng; Tan, Longfei; Fu, Changhui; Ren, Xiangling; Xu, Ke; Zhong, Hongshan; Wang, Jingzhuo; Li, Laifeng; Meng, Xianwei

2017-06-29

Combined thermo-chemotherapy displays outstanding synergically therapeutic efficiency when compared with standalone thermotherapy and chemotherapy. Herein, we developed a smart tri-stimuli-responsive drug delivery system involving X@BB-ZrO 2 NPs (X represents loaded IL, DOX, keratin and tetradecanol) based on novel ball-in-ball-structured ZrO 2 nanoparticles (BB-ZrO 2 NPs). The microwave energy conversion efficiency of BB-ZrO 2 NPs was 41.2% higher than that of traditional single-layer NPs due to the cooperative action of self-reflection and spatial confinement effect of the special two-layer hollow nanostructure. The tri-stimuli-responsive controlled release strategy indicate that integrated pH, redox and microwaves in single NPs based on keratin and tetradecanol could effectively enhance the specific controlled release of DOX. The release of DOX was only 8.1% in PBS with pH = 7.2 and GSH = 20 μM. However, the release could reach about 50% at the tumor site (pH = 5.5, GSH = 13 mM) under microwave ablation. The as-made X@BB-ZrO 2 NPs exhibited perfect synergic therapy effect of chemotherapy and microwave ablation both in subcutaneous tumors (H22 tumor-bearing mice) and deep tumors (liver transplantation VX2 tumor-bearing rabbit model). There was no recurrence and death in the X@BB-ZrO 2 + MW group during the therapy of subcutaneous tumors even on the 42 nd day. The growth rates in the deep tumor of the control, MW and X@BB-ZrO 2 + MW groups were 290.1%, 14.1% and -42% 6 days after ablation, respectively. Dual-source CT was used to monitor the metabolism behavior of the as-made BB-ZrO 2 NPs and traditional CT was utilized to monitor the tumor growth in rabbits. Frozen section examination and ICP results indicated the precise control of drug delivery and enhanced cytotoxicity by the tri-stimuli-responsive controlled release strategy. The ball-in-ball ZrO 2 NPs with high microwave energy conversion efficiency were first developed for synergic microwave ablation and

Correlation of FDG-PET measurements with morphometric tumor response after induction chemotherapy and adjuvant radiotherapy in stage III non-small cell lung cancer (NSCLC)

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Baum, R.P.; Niesen, A.; Griesinger, F.

2002-01-01

Full text: Docetaxel (D) and carboplatin (C) combination chemotherapy (DC) has shown high response rates in advanced NSCLC. Histologic tumor response after chemotherapy or combined modality induction is strongly associated with systemic tumor control and potentially cure. Metabolic tumor response assessed by FDG-PET after induction chemotherapy with etoposide, ifosfamide and cisplatin (VIP) has been shown to be predictive of outcome in NSCLC. Finally, erythropoietin (EPO) may prevent the decrease in hemoglobin levels that was seen in a previous study of DC (median drop 2.7 g/dl) and thus may enhance treatment efficacy. The aim of the present study was to correlate FDG-PET studies with histomorphometric findings after DC induction chemotherapy plus Epo. 33 patients (pts) with NSCLC stage IIIA (7 pts) or IIIB (24 pts) were enrolled and received treatment with D 100 mg/m 2 dl and C AUC 7.5 d2 q21 days for 4 cycles. Epo was given at 10,000 IU s.c. three times a week. All pts received adjuvant radiotherapy. Of 33 enrolled patients, 22 were evaluable for response by CT imaging. 14/22 pts (64 %) achieved PR. Of the 22 responders, 20 were evaluable for repeated FDG-PET studies. 13/20 pts had a decrease of standardized uptake values (SUV) and of the metabolic tumor index (MTI) by >50 %, 9/20 had SUV <2.5 (CR). Seven of these 9 pts underwent tumor resection, and specimens were subjected to morphometric analysis. In 7/7 cases, no vital tumor cells were detected in the specimens. In contrast to our previous study, hemoglobin levels increased by a median of 0.3 g/dl. Morphometric tumor response after induction chemotherapy correlates strongly with metabolic remission by FDG-PET. FDG-PET appears to be a useful non-invasive diagnostic tool to predict pathologic response and potentially long-term outcome in stage III NSCLC. (author)

[A Case with Metastatic Huge Ovarian Tumor from Transverse Colon Cancer, Who Underwent Systemic Chemotherapy after Bilateral Oophorectomy and Right Hemi Colectomy].

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Miyanari, Shun; Nagasaki, Toshiya; Minami, Hironori; Fukuoka, Hironori; Murahashi, Satoshi; Suzuki, Shinsuke; Ushigome, Hajime; Akiyoshi, Takashi; Konishi, Tsuyoshi; Fujimoto, Yoshiya; Nagayama, Satoshi; Fukunaga, Yosuke; Ueno, Masashi

2017-11-01

Metastatic ovarian tumors from colon cancer would be resistant to chemotherapy, and compromising quality of life(QOL) of these patients was caused by acute enlargement of the tumors. A 37-year-old woman with abdominal distension was diagnosed with transverse colon cancer, bilateral ovarian metastases, liver metastases, and peritoneal dissemination at prior hospital. Two courses of chemotherapy(FOLFOX)were administered, but metastaticovarian tumors enlarged. Chemotherapy was discontinued and she was referred to our institution. To achieve symptom relief, improving QOL, and to resume chemotherapy, we planned bilateral oophorectomy and primary tumor resection if other stenotic lesion was not present. As a result, we safely performed open bilateral oophorectomy and right hemi colectomy, and the patient discharged on postoperative day 11 without complications. Chemotherapy was resumed and continued for 7 months up to this time. Even though, curative resection could not be achieved, oophorectomy should be performed in patients with enlarged metastatic ovarian tumor from colon cancer, in spite of administration of chemotherapy.

Accuracy of contrast-enhanced spectral mammography for estimating residual tumor size after neoadjuvant chemotherapy in patients with breast cancer: a feasibility study

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Filipe Ramos Barra

Full Text Available Abstract Objective: To assess the feasibility of contrast-enhanced spectral mammography (CESM of the breast for assessing the size of residual tumors after neoadjuvant chemotherapy (NAC. Materials and methods: In breast cancer patients who underwent NAC between 2011 and 2013, we evaluated residual tumor measurements obtained with CESM and full-field digital mammography (FFDM. We determined the concordance between the methods, as well as their level of agreement with the pathology. Three radiologists analyzed eight CESM and FFDM measurements separately, considering the size of the residual tumor at its largest diameter and correlating it with that determined in the pathological analysis. Interobserver agreement was also evaluated. Results: The sensitivity, specificity, positive predictive value, and negative predictive value were higher for CESM than for FFDM (83.33%, 100%, 100%, and 66% vs. 50%, 50%, 50%, and 25%, respectively. The CESM measurements showed a strong, consistent correlation with the pathological findings (correlation coefficient = 0.76-0.92; intraclass correlation coefficient = 0.692-0.886. The correlation between the FFDM measurements and the pathological findings was not statistically significant, with questionable consistency (intraclass correlation coefficient = 0.488-0.598. Agreement with the pathological findings was narrower for CESM measurements than for FFDM measurements. Interobserver agreement was higher for CESM than for FFDM (0.94 vs. 0.88. Conclusion: CESM is a feasible means of evaluating residual tumor size after NAC, showing a good correlation and good agreement with pathological findings. For CESM measurements, the interobserver agreement was excellent.

Tumor response evaluation after neoadjuvant chemotherapy in locally advanced gastric adenocarcinoma: a prospective, multi-center cohort study

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De Martini, Paolo; Ceresoli, Marco; Mari, Giulio M.; Costanzi, Andrea; Maggioni, Dario; Pugliese, Raffaele; Ferrari, Giovanni

2017-01-01

Background To verify the prognostic value of the pathologic and radiological tumor response after neoadjuvant chemotherapy in the treatment of locally advanced gastric adenocarcinoma. Methods A total of 67 patients with locally advanced gastric cancer (clinical ≥ T2 or nodal disease and without evidence of distant metastases) underwent perioperative chemotherapy (ECF or ECX regimen) from December 2009 through June 2015 in two surgical units. Histopathological and radiological response to chemotherapy were evaluated by using tumor regression grade (TRG) (Becker’s criteria) and volume change assessed by CT. Results Fifty-one (86%) patients completed all chemotherapy scheduled cycles successfully and surgery was curative (R0) in 64 (97%) subjects. The histopathological analysis showed 19 (29%) specimens with TRG1 (less than 10% of vital tumor left) and 25 (37%) patients had partial or complete response (CR) assessed by CT scan. Median disease free survival (DFS) and overall survival (OS) were 25.70 months (range, 14.52–36.80 months) and 36.60 months (range, 24.3–52.9 months), respectively. The median follow up was 27 months (range, 5.00–68.00 months). Radiological response and TRG were found to be a prognostic factor for OS and DFS, while tumor histology was not significantly related to survival. Conclusions Both radiological response and TRG have been shown as promising survival markers in patients treated with perioperative chemotherapy for locally advanced gastric cancer. Other predictive markers of response to chemotherapy are strongly required. PMID:29299362

Drug Repositioning of Proton Pump Inhibitors for Enhanced Efficacy and Safety of Cancer Chemotherapy

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Kenji Ikemura

2017-12-01

Full Text Available Proton pump inhibitors (PPIs, H+/K+-ATPase inhibitors, are the most commonly prescribed drugs for the treatment of gastroesophageal reflux and peptic ulcer diseases; they are highly safe and tolerable. Since PPIs are frequently used in cancer patients, studies investigating interactions between PPIs and anticancer agents are of particular importance to achieving effective and safe cancer chemotherapy. Several studies have revealed that PPIs inhibit not only the H+/K+-ATPase in gastric parietal cells, but also the vacuolar H+-ATPase (V-ATPase overexpressed in tumor cells, as well as the renal basolateral organic cation transporter 2 (OCT2 associated with pharmacokinetics and/or renal accumulation of various drugs, including anticancer agents. In this mini-review, we summarize the current knowledge regarding the impact of PPIs on the efficacy and safety of cancer chemotherapeutics via inhibition of targets other than the H+/K+-ATPase. Co-administration of clinical doses of PPIs protected kidney function in patients receiving cisplatin and fluorouracil, presumably by decreasing accumulation of cisplatin in the kidney via OCT2 inhibition. In addition, co-administration or pretreatment with PPIs could inhibit H+ transport via the V-ATPase in tumor cells, resulting in lower extracellular acidification and intracellular acidic vesicles to enhance the sensitivity of the tumor cells to the anticancer agents. In the present mini-review, we suggest that PPIs enhance the efficacy and safety of anticancer agents via off-target inhibition (e.g., of OCT2 and V-ATPase, rather than on-target inhibition of the H+/K+-ATPase. The present findings should provide important information to establish novel supportive therapy with PPIs during cancer chemotherapy.

Tumor-infiltrating lymphocytes predict response to chemotherapy in patients with advance non-small cell lung cancer.

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Liu, Hui; Zhang, Tiantuo; Ye, Jin; Li, Hongtao; Huang, Jing; Li, Xiaodong; Wu, Benquan; Huang, Xubing; Hou, Jinghui

2012-10-01

Accumulating preclinical evidence suggests that anticancer immune responses contribute to the success of chemotherapy. The predictive significance of tumor-infiltrating lymphocytes (TILs) for response to neoadjuvant chemotherapy in non-small cell lung cancer (NSCLC) remains unknown. The aim of this study was to investigate the prognostic and predictive value of TIL subtypes in patients with advanced NSCLC treated with platinum-based chemotherapy. In total, 159 patients with stage III and IV NSCLC were retrospectively enrolled. The prevalence of CD3(+), CD4(+), CD8(+) and Foxp3(+) TILs was assessed by immunohistochemistry in tumor tissue obtained before chemotherapy. The density of TILs subgroups was treated as dichotomous variables using the median values as cutoff. Survival curves were estimated by the Kaplan-Meier method, and differences in overall survival between groups were determined using the Log-rank test. Prognostic effects of TIL subsets density were evaluated by Cox regression analysis. The presence of CD3(+), CD4(+), CD8(+), and FOXP3(+) TILs was not correlated with any clinicopathological features. Neither the prevalence of TILs nor combined analysis displayed obvious prognostic performances for overall survival in Cox regression model. Instead, higher FOXP3(+)/CD8(+) ratio in tumor sites was an independent factor for poor response to platinum-based chemotherapy in overall cohort. These findings suggest that immunological CD8(+) and FOXP3(+)Tregs cell infiltrate within tumor environment is predictive of response to platinum-based neoadjuvant chemotherapy in advanced NSCLC patients. The understanding of the clinical relevance of the microenvironmental immunological milieu might provide an important clue for the design of novel strategies in cancer immunotherapy.

Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact.

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Murakami, Yoshiaki; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Nakagawa, Naoya; Okada, Kenjiro; Takahashi, Shinya; Sueda, Taijiro

2017-04-01

The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy. Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses. Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis. Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.

Early prediction of the response of breast tumors to neoadjuvant chemotherapy using quantitative MRI and machine learning.

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Mani, Subramani; Chen, Yukun; Arlinghaus, Lori R; Li, Xia; Chakravarthy, A Bapsi; Bhave, Sandeep R; Welch, E Brian; Levy, Mia A; Yankeelov, Thomas E

2011-01-01

The ability to predict early in the course of treatment the response of breast tumors to neoadjuvant chemotherapy can stratify patients based on response for patient-specific treatment strategies. Currently response to neoadjuvant chemotherapy is evaluated based on physical exam or breast imaging (mammogram, ultrasound or conventional breast MRI). There is a poor correlation among these measurements and with the actual tumor size when measured by the pathologist during definitive surgery. We tested the feasibility of using quantitative MRI as a tool for early prediction of tumor response. Between 2007 and 2010 twenty consecutive patients diagnosed with Stage II/III breast cancer and receiving neoadjuvant chemotherapy were enrolled on a prospective imaging study. Our study showed that quantitative MRI parameters along with routine clinical measures can predict responders from non-responders to neoadjuvant chemotherapy. The best predictive model had an accuracy of 0.9, a positive predictive value of 0.91 and an AUC of 0.96.

Glutathione responsive micelles incorporated with semiconducting polymer dots and doxorubicin for cancer photothermal-chemotherapy

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Cai, Zhixiong; Zhang, Da; Lin, Xinyi; Chen, Yunzhu; Wu, Ming; Wei, Zuwu; Zhang, Zhenxi; Liu, Xiaolong; Yao, Cuiping

2017-10-01

Nanoplatform integrated with photothermal therapy (PTT) and chemotherapy has been recognized a promising agent for enhancing cancer therapeutic outcomes, but still suffer from less controllability for optimizing their synergistic effects. We fabricated glutathione (GSH) responsive micelles incorporated with semiconducting polymer dots and doxorubicin (referred as SPDOX NPs) for combining PTT with chemotherapy to enhance cancer therapeutic efficiency. These micelles, with excellent water dispersibility, comprises of three distinct functional components: (1) the monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16), which forms the micelles, can render hydrophobic substances water-soluble and improve the colloidal stability; (2) disulfide linkages can be cleaved in a reductive environment for tumor specific drug release due to the high GSH concentrations of tumor micro-environment; (3) PCPDTBT dots and anti-cancer drug DOX that are loaded inside the hydrophobic core of the micelle can be applied to simultaneously perform PTT and chemotherapy to achieve significantly enhanced tumor killing efficiency both in vitro and in vivo. In summary, our studies demonstrated that our SPDOX NPs with simultaneous photothermal-chemotherapy functions could be a promising platform for a tumor specific responsive drug delivery system.

Combined chemotherapy and radiotherapy in recurrent tumors of the head and neck region

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Tsuji, Hiroshi; Tsujii, Hirohiko; Kamada, Tadashi; Takamura, Akio; Shirato, Hiroki; Matsuoka, Yoshisuke; Irie, Goro

1987-01-01

Over the past four years, 27 patients with recurrent tumors of the head and neck region have been treated with chemotherapy. The regimens used were BCMF (bleomycin 15 mg i.v. for 3 days, cyclophosphamide 500 mg i.v., methotrexate 50 mg i.v. and 5-fluorouracil 500 mg i.v.) and CMU (cyclophosphamide 350 mg/m 2 i.v., methotrexate 30 mg/m 2 i.v. and UFT 600 mg p.o. for 14 days). Of the 27 patients, eight were treated with combined radiation and chemotherapy, and either CR or PR was obtained. Nineteen patients were treated with chemotherapy alone, for which the response (CR + PR) rates were 8 % (1/12) for BCMF and 43 % (3/7) for CMU, respectively. No serious toxicities were observed as a result of these regimens. It was thus demonstrated that the CMU regimen was of great value in terms of improved response and minor toxicity in the treatment of head and neck tumors. (author)

Distribution of 99Tcm-rh-Annexin vin tumor and expression relationship of bcl-2, bax after a single dose of chemotherapy

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Zhang Xin; Li Yaming; Zhang Yanjun; Tao Li; Zhu Yi; Yang Chun; Ji Xiaopeng; Zhao Ming; Tian Aijuan; Zhang Jianying; Zhao Zhenzhen

2007-01-01

The expression of bcl-2 and bax after the single dose of chemotherapy with 99 Tc m -rh-Annexin V as the tracer of tumor apoptosis imaging is studied. tumor cell apoptosis is examined by TUNEL methods, and the expression of bcl-2 and bax in tumor are determined by immunohistochemical methods. Single dose of chemotherapy significantly increased the tumor uptake of 99 Tc m -rh-annexin V and the positive number of TUNEL, as well as the expression of bax (P 99 Tc m -rh-annexin V in tumor reflectes not only the degree of apoptosis of tumor cells, but also the change of bax expression after the single dose of chemotherapy. (authors)

Fluorodeoxyglucose positron emission tomography and chemotherapy-related tumor marker expression in non-small cell lung cancer

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Duan, Xiao-Yi; Wang, Wen; Wang, Jian-Sheng; Shang, Jin; Gao, Jun-Gang; Guo, You-Min

2013-01-01

The chemotherapy resistance of non-small cell lung cancer (NSCLC) remains a clinic challenge and is closely associated with several biomarkers including epidermal growth factor receptor (EGFR) (Drugs 72(Suppl 1):28–36, 012.), p53 (Med Sci Monit 11(6):HY11–HY20, 2005.) and excision repair cross complementing gene 1 (ERCC1) (J Thorac Oncol 8(5):582–586, 2013.). Fluorodeoxyglucose positron emission tomography (FDG–PET) is the best non-invasive surrogate for tumor biology with the maximal standardized uptake values (SUV max ) being the most important paradigm. However, there are limited data correlating FDG-PET with the chemotherapy resistant tumor markers. The purpose of this study was to determine the correlation of chemotherapy related tumor marker expression with FDG–PET SUV max in NSCLC. FDG–PET SUV max was calculated in chemotherapy naïve patients with NSCLC (n = 62) and immunohistochemical analysis was performed for EGFR, p53 or ERCC1 on the intraoperative NSCLC tissues. Each tumor marker was assessed independently by two pathologists using common grading criteria. The SUV max difference based on the histologic characteristics, gender, differentiation, grading and age as well as correlation analysis among these parameters were performed. Multiple stepwise regression analysis was further performed to determine the primary predictor for SUV max and the receiver operating characteristics (ROC) curve analysis was performed to detect the optimized sensitivity and specificity for SUV max in suggesting chemotherapy resistant tumor markers. The significant tumor type (P = 0.045), differentiation (P = 0.021), p53 (P = 0.000) or ERCC1 (P = 0.033) positivity dependent differences of SUV max values were observed. The tumor differentiation is significantly correlated with SUV max (R = -0.327), tumor size (R = -0.286), grading (R = -0.499), gender (R = 0.286) as well as the expression levels for p53 (R = -0.605) and ERCC1 (R = -0.644). The expression level of p53

Enhanced Delivery of Gold Nanoparticles with Therapeutic Potential for Targeting Human Brain Tumors

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Etame, Arnold B.

The blood brain barrier (BBB) remains a major challenge to the advancement and application of systemic anti-cancer therapeutics into the central nervous system. The structural and physiological delivery constraints of the BBB significantly limit the effectiveness of conventional chemotherapy, thereby making systemic administration a non-viable option for the vast majority of chemotherapy agents. Furthermore, the lack of specificity of conventional systemic chemotherapy when applied towards malignant brain tumors remains a major shortcoming. Hence novel therapeutic strategies that focus both on targeted and enhanced delivery across the BBB are warranted. In recent years nanoparticles (NPs) have emerged as attractive vehicles for efficient delivery of targeted anti-cancer therapeutics. In particular, gold nanoparticles (AuNPs) have gained prominence in several targeting applications involving systemic cancers. Their enhanced permeation and retention within permissive tumor microvasculature provide a selective advantage for targeting. Malignant brain tumors also exhibit transport-permissive microvasculature secondary to blood brain barrier disruption. Hence AuNPs may have potential relevance for brain tumor targeting. However, the permeation of AuNPs across the BBB has not been well characterized, and hence is a potential limitation for successful application of AuNP-based therapeutics within the central nervous system (CNS). In this dissertation, we designed and characterized AuNPs and assessed the role of polyethylene glycol (PEG) on the physical and biological properties of AuNPs. We established a size-dependent permeation profile with respect to core size as well as PEG length when AuNPs were assessed through a transport-permissive in-vitro BBB. This study was the first of its kind to systematically examine the influence of design on permeation of AuNPs through transport-permissive BBB. Given the significant delivery limitations through the non

Conventional-Dose versus High-Dose Chemotherapy for Relapsed Germ Cell Tumors

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Deaglan J. McHugh

2018-01-01

Full Text Available The majority of metastatic germ cell tumors (GCTs are cured with cisplatin-based chemotherapy, but 20–30% of patients will relapse after first-line chemotherapy and require additional salvage strategies. The two major salvage approaches in this scenario are high-dose chemotherapy (HDCT with autologous stem cell transplant (ASCT or conventional-dose chemotherapy (CDCT. Both CDCT and HDCT have curative potential in the management of relapsed/refractory GCT. However, due to a lack of conclusive randomized trials, it remains unknown whether sequential HDCT or CDCT represents the optimal initial salvage approach, with practice varying between tertiary institutions. This represents the most pressing question remaining for defining GCT treatment standards and optimizing outcomes. The authors review prognostic factors in the initial salvage setting as well as the major studies assessing the efficacy of CDCT, HDCT, or both, describing the strengths and weaknesses that formed the rationale behind the ongoing international phase III “TIGER” trial.

Cordycepin enhances Epstein-Barr virus lytic infection and Epstein-Barr virus-positive tumor treatment efficacy by doxorubicin.

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Du, Yinping; Yu, Jieshi; Du, Li; Tang, Jun; Feng, Wen-Hai

2016-07-01

The consistent latent presence of Epstein-Barr virus (EBV) in tumor cells offers potential for virus-targeted therapies. The switch from the latent form of EBV to the lytic form in tumor cells can lead to tumor cell lysis. In this study, we report that a natural small molecule compound, cordycepin, can induce lytic EBV infection in tumor cells. Subsequently, we demonstrate that cordycepin can enhance EBV reactivating capacity and EBV-positive tumor cell killing ability of low dose doxorubicin. The combination of cordycepin and doxorubicin phosphorylates CCAAT/enhancer binding protein β (C/EBPβ) through protein kinase C (PKC)-p38 mitogen activated protein kinases (p38 MAPK) signaling pathway, and C/EBPβ is required for the activation of lytic EBV infection. Most importantly, an in vivo experiment demonstrates that the combination of cordycepin and doxorubicin is more effective in inhibiting tumor growth in SCID mice than is doxorubicin alone. Our findings establish that cordycepin can enhance the efficacy of conventional chemotherapy for treatment of EBV-positive tumors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[A Case of Transverse Colon Cancer with Liver Metastasis and Tumor Thrombosis of Portal Vein Effectively Treated with Chemotherapy].

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Aida, Toshiaki; Shiobara, Masayuki; Wakatsuki, Kazuo; Arai, Shuka; Suda, Kosuke; Miyazawa, Kotaro; Miyoshi, Tetsutaro; Takahashi, Yoshihisa; Yoshioka, Shigeru

2018-02-01

The patient was a 70-year-old man. He was diagnosed with advanced transverse colon cancer. A computed tomography (CT)revealed liver metastasis and tumor thrombosis of portal vein. We started combination chemotherapy with capecita- bine/oxaliplatin(CapeOX). Perforation of the tumor was observed 5 days after CapeOX therapy was started. Treatment with abscess drainage and ileostmy, infection was controlled and general condition was improved. After 9 courses of CapeOX, we changed chemotherapy regimen to irinotecan/tegafur-gimeracil-oteracilpotassium (IRIS)due to strong side effects. In CT and FDG-PET examination after 8 courses of IRIS, the tumor of transverse colon, liver metastasis, and the tumor thrombosis of portalvein became unclear. A year and 6 months have passed since chemotherapy was started, recurrence was not observed. For the patients with unresectable colorectal cancer, it is necessary to consider multidisciplinary treatments including chemotherapy while considering the general condition of them.

[Radical Resection of Huge Gastrointestinal Stromal Tumor of the Stomach Following Neoadjuvant Chemotherapy with lmatinib - ACase Report].

Science.gov (United States)

Hiraki, Yoko; Kato, Hiroaki; Shiraishi, Osamu; Tanaka, Yumiko; Iwama, Mitsuru; Yasuda, Atsushi; Shinkai, Masayuki; Kimura, Yutaka; Imano, Motohiro; Imamoto, Haruhiko; Yasuda, Takushi

2017-11-01

The usefulness and safety of imatinibfor neoadjuvant chemotherapy for resectable gastrointestinal stromal tumor(GIST) has not been established. We reported a case of a huge GIST of the stomach that was safely resected following preoperative imatinibtherapy. A 69-year-old man was hospitalized with abdominal fullness which increased rapidly from a month ago. A CT scan showed a huge tumor containing solid and cystic component which was accompanied by an extra-wall nodule. The tumor was strongly suspected to be originated from the stomach and EUS-FNA revealed GIST. We diagnosed GIST of the stomach and initiated preoperative adjuvant chemotherapy with imatinib because there was a risk for the break of tumor capsule and composite resection of the other organs without prior chemotherapy. After the administration of imatinib4 00 mg/day for 6months, the solid component was decreased in size and its' activity by PET-CT had declined, but the size of the cystic component was not changed and the patient's complaint of fullness was not reduced. Then, after a week cessation of imatinib, we performed surgical removal of the tumor with partial gastrectomy without surgical complication during and after the operation. Imatinibwas resumed 2 weeks later postoperatively and 1 year and 8 months has passed since the operation without recurrence. Neoadjuvant chemotherapy with imatinibhas the potential to become an important therapeutic option for the treatment of huge GISTs.

Tumor progression: analysis of the instability of the metastatic phenotype, sensitivity to radiation and chemotherapy

International Nuclear Information System (INIS)

Welch, D.R.

1984-01-01

The major complications for tumor therapy are 1) tumor spread (metastasis); 2) the mixed nature of tumors (heterogeneity); and 3) the capacity of tumors to evolve (progress). To study these tumor characteristics, the rat 13762NF mammary adenocarcinoma was cloned and studied for metastatic properties and sensitivities to therapy (chemotherapy, radiation and hyperthermia). The cell clones were heterogeneous and no correlation between metastatic potential and therapeutic sensitivities was observed. Further, these phenotypes were unstable during pasage in vitro; yet, the changes were clone dependent and reproducible using different cryoprotected cell stocks. To understand the phenotypic instability, subclones were isolated from low and high passage cell clones. The results demonstrated that 1) tumor cells are heterogeneous for multiple phenotypes; 2) tumor cells are unstable for multiple phenotypes; 3) the magnitude, direction and time of occurrence of phenotypic drift is clone dependent; 4) the sensitivity of cell clones to ionizing radiation (γ or heat) and chemotherapy agents is independent of their metastatic potential; 5) shifts in metastatic potential and sensitivity to therapy may occur simultaneously but are not linked; and 6) tumor cells independently diverge to form several subpopulations with unique phenotypic profiles

Radiotherapy and chemotherapy change vessel tree geometry and metastatic spread in a small cell lung cancer xenograft mouse tumor model.

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Thorsten Frenzel

Full Text Available Tumor vasculature is critical for tumor growth, formation of distant metastases and efficiency of radio- and chemotherapy treatments. However, how the vasculature itself is affected during cancer treatment regarding to the metastatic behavior has not been thoroughly investigated. Therefore, the aim of this study was to analyze the influence of hypofractionated radiotherapy and cisplatin chemotherapy on vessel tree geometry and metastasis formation in a small cell lung cancer xenograft mouse tumor model to investigate the spread of malignant cells during different treatments modalities.The biological data gained during these experiments were fed into our previously developed computer model "Cancer and Treatment Simulation Tool" (CaTSiT to model the growth of the primary tumor, its metastatic deposit and also the influence on different therapies. Furthermore, we performed quantitative histology analyses to verify our predictions in xenograft mouse tumor model.According to the computer simulation the number of cells engrafting must vary considerably to explain the different weights of the primary tumor at the end of the experiment. Once a primary tumor is established, the fractal dimension of its vasculature correlates with the tumor size. Furthermore, the fractal dimension of the tumor vasculature changes during treatment, indicating that the therapy affects the blood vessels' geometry. We corroborated these findings with a quantitative histological analysis showing that the blood vessel density is depleted during radiotherapy and cisplatin chemotherapy. The CaTSiT computer model reveals that chemotherapy influences the tumor's therapeutic susceptibility and its metastatic spreading behavior.Using a system biological approach in combination with xenograft models and computer simulations revealed that the usage of chemotherapy and radiation therapy determines the spreading behavior by changing the blood vessel geometry of the primary tumor.

[A case of lung abscess during chemotherapy for testicular tumor].

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Hayashi, Yujiro; Miyago, Naoki; Takeda, Ken; Yamaguchi, Yuichiro; Nakayama, Masashi; Arai, Yasuyuki; Kakimoto, Ken-ichi; Nishimura, Kazuo

2014-05-01

32-year-old man was seen in a clinic because of prolonged cough and slight-fever. Chest X-ray showed multiple pulmonary nodules, and multiple lung and mediastinal lymph node metastases from right testicular tumor was suspected by positron emission tomography/CT (PET/CT) scan. He was diagnosed with right testicular germ cell tumor (embryonal carcinoma + seminoma, pT2N1M1b), and classified into the intermediate risk group according to International Germ Cell Cancer Collaborative Group. He underwent 4 cycles of chemotherapy with bleomycin, etoposide and cisplatin (BEP therapy). During BEP therapy, sputum with foul odor appeared and chest CT scan revealed lung abscess with a necrotic lesion of metastatic tumor. The lung abscess was treated successfully with antibiotics.

The evaluation of the effect of VAB-6 combination chemotherapy by MRI for a germinal cell tumor originating in the anterior mediastinum

International Nuclear Information System (INIS)

Tomioka, Hiromi; Murayama, Takako; Kurasawa, Takuya; Kuze, Fumiyuki; Chihara, Kouji; Wada, Hiromi; Hitomi, Shigeki; Noma, Satoshi.

1988-01-01

A 22-year old man with germinal cell tumor originating in the anterior mediastinum was treated with the VAB-6 chemotherapy. Disappearance of tumor cells and degeneration to fibrous necrotic tissue was revealed by MRI performed after chemotherapy, i.e. change of T 2 weighted image of the tumor from high-intensity to iso-intensity. And this pathological change was confirmed by the histological examination of the resected specimen. MRI was considered to be very useful to evaluate the effect of chemotherapy for germinal cell tumor originating in the anterior mediastinum. (author)

Unusually Located Stroke After Chemotherapy in Testicular Germ Cell Tumors

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Braulio Alexander Martinez MD

2015-06-01

Full Text Available Testicular cancer is a type of malignancy that affects young adults and has high rates of cure; however, as any malignancy, it is associated with an increased risk of ischemic or hemorrhagic cerebrovascular disease, given the systemic tumor effects or side effects of chemotherapy, which in turn increases morbidity, functional impairment, and additional risk of early death.

Low-dose radiation enhances therapeutic HPV DNA vaccination in tumor-bearing hosts.

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Tseng, Chih-Wen; Trimble, Cornelia; Zeng, Qi; Monie, Archana; Alvarez, Ronald D; Huh, Warner K; Hoory, Talia; Wang, Mei-Cheng; Hung, Chien-Fu; Wu, T-C

2009-05-01

Current therapeutic approaches to treatment of patients with bulky cervical cancer are based on conventional in situ ablative modalities including cisplatin-based chemotherapy and radiation therapy. The 5-year survival of patients with nonresectable disease is dismal. Because over 99% of squamous cervical cancer is caused by persistent infection with an oncogenic strain of human papillomavirus (HPV), particularly type 16 and viral oncoproteins E6 and E7 are functionally required for disease initiation and persistence, HPV-targeted immune strategies present a compelling opportunity in which to demonstrate proof of principle. Sublethal doses of radiation and chemotherapeutic agents have been shown to have synergistic effect in combination with either vaccination against cancer-specific antigens, or with passive transfer of tumor-specific cytotoxic T lymphocytes (CTLs). Here, we explored the combination of low-dose radiation therapy with DNA vaccination with calreticulin (CRT) linked to the mutated form of HPV-16 E7 antigen (E7(detox)), CRT/E7(detox) in the treatment of E7-expressing TC-1 tumors. We observed that TC-1 tumor-bearing mice treated with radiotherapy combined with CRT/E7(detox) DNA vaccination generated significant therapeutic antitumor effects and the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of treated mice. Furthermore, treatment with radiotherapy was shown to render the TC-1 tumor cells more susceptible to lysis by E7-specific CTLs. In addition, we observed that treatment with radiotherapy during the second DNA vaccination generated the highest frequency of E7-specific CD8(+) T cells in the tumors and spleens of TC-1 tumor-bearing mice. Finally, TC-1 tumor-bearing mice treated with the chemotherapy in combination with radiation and CRT/E7(detox) DNA vaccination generate significantly enhanced therapeutic antitumor effects. The clinical implications of the study are discussed.

Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors: A Randomized Clinical Trial.

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Pramanik, Raja; Agarwala, Sandeep; Gupta, Yogendra Kumar; Thulkar, Sanjay; Vishnubhatla, Sreenivas; Batra, Atul; Dhawan, Deepa; Bakhshi, Sameer

2017-09-01

Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence. To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy. A double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options. One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression. The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points. A total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than

Computed tomography of mast cell tumors in dogs: assessment before and after chemotherapy; Tomografia computadorizada de mastocitomas em caes: avaliacao pre e pos-tratamento quimioterapico

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Lorigados, Carla A.B.; Matera, Julia Maria; Pinto, Ana Carolina B.C.F.; Macedo, Thais R., E-mail: clorigados@usp.br [Universidade de Sao Paulo (FMVZ/USP), SP (Brazil). Fac. de Medicina Veterinaria e Zootecnia. Dept. de Cirurgia; Coppi, Antonio A.; Ladd, Fernando V.L. [Universidade de Sao Paulo (LSSCA/USP), SP (Brazil). Fac. de Medicina Veterinaria e Zootecnia. Lab. de Estereologia Estocastica e Anatomia Quimica; Souza, Vanessa A.F. de [Faculdades Metropolitanas Unidas (FMU), Sao Paulo, SP (Brazil). Curso de Medicina Veterinaria

2013-11-15

Nineteen dogs with mast cell tumors treated with chemotherapy were evaluated by computed tomography (CT). Were evaluated aspects related to contours, attenuation, postcontrast enhancement and presence of cleavage with adjacent structures. The RECIST criteria and volumetric measurement of lesions were performed to assess the response to treatment. The mast cell tumors presented a homogeneous or heterogeneous attenuation, presented more frequently a well delineated and regular contours and moderate enhancement after intravenous administration of the iodinated contrast media. The methods RECIST and volumetric measurements showed an excellent agreement to the classification of therapeutic response, providing a good parameter of the response to treatment. The CT examination proved to be useful in the delimitation of the tumor and an important tool for planning of surgical margins. (author)

Tumor cell culture on collagen–chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies

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Aziz Mahmoudzadeh

2016-07-01

Full Text Available Tumor cells naturally live in three-dimensional (3D microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen–chitosan scaffold compared with 2D plate cultures. Collagen–chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen–chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies.

Tumor cell culture on collagen-chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies.

Science.gov (United States)

Mahmoudzadeh, Aziz; Mohammadpour, Hemn

2016-07-01

Tumor cells naturally live in three-dimensional (3D) microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D) plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen-chitosan scaffold compared with 2D plate cultures. Collagen-chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen-chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies. Copyright © 2016. Published by Elsevier B.V.

Monitoring of tumor microcirculation during fractionated radiotherapy in patients with rectal carcinomas: a clinical study using contrast enhanced MR imaging

International Nuclear Information System (INIS)

Vries, A. de; Judmaier, W.; Griebel, J.; Kremser, Ch.; Gneiting, T.; Peer, S.; Aichner, F.; Lukas, P.

1996-01-01

Purpose/Objective: Combined radio chemotherapy is a frequently used treatment scheme for malignant neoplasms. The purpose of using chemotherapeutics such as 5-FU during radiotherapy is to enhance the effectiveness of radiation. The effectiveness of this approach depends on the accumulation of the drugs within the tumor, which is governed by micro circulatory parameters. However, to date scheduling of chemotherapy application is based on empirical data. There is no clinical study available monitoring tumor microcirculation during fractionated radiotherapy. Contrast enhanced MR imaging in tumors provides not only a better understanding of tumor micro vascularity but is also a method to characterize the substance accumulation within the tumor matrix during radiotherapy. This could help to optimize the scheduling of chemotherapy application. Materials and Methods: Patients with clinical and histological proven rectal carcinoma underwent a preoperative combined radio chemotherapy up to a total dose of 39,4Gy, hyperfractionated with b.i.d., single dose 1,1Gy. The fields in box-technique included the rectal canal and adjacent lymph nodes. 5-FU (300mg/m 2 per treatment day) was given continuously parallel to irradiation. To evaluate the Gd-DTPA (Magnevist, Schering, Germany) concentration time curve after i.v. constant rate infusion (0,05 mmol/kg Gd-DTPA) we used an ultrafast T1-mapping sequence on a 1,5-T whole body imager (Magneton Vision, Siemens, Germany). The transaxial slice (thickness 5 mm) was chosen so that both tumor and arterial vessels could be clearly identified. Before, during and after the infusion 53 T1 maps were obtained within 40 min in intervals of 14s (35 scans) and 120s (15 scans). Assuming a linear relation between relaxation rate, R1=1/T1, and Gd-DTPA concentration, concentration time curves were evaluated for arterial blood and tumor. The patients underwent MR imaging before and in constant intervals during fractionated radiotherapy. As a first

Nutritional status changes in children with malignant solid tumor before and after chemotherapy

OpenAIRE

Boris Januar; Sri S Nasar; Rulina Suradi; Maria Abdulsalam

2016-01-01

Background Although aggressive multimodal treatment programs in childhood cancer have significantly increased survival rates, the morbidity caused by protein energy malnutrition related to therapy is still high. Objective To describe nutritional status changes in children with malignant solid tumors after 21 days of chemotherapy. Methods A descriptive prospective study with pre- and post-test design in children with malignant solid tumors was conducted in the Departmen...

Alternating current electrical stimulation enhanced chemotherapy: a novel strategy to bypass multidrug resistance in tumor cells

International Nuclear Information System (INIS)

Janigro, Damir; Perju, Catalin; Fazio, Vincent; Hallene, Kerri; Dini, Gabriele; Agarwal, Mukesh K; Cucullo, Luca

2006-01-01

Tumor burden can be pharmacologically controlled by inhibiting cell division and by direct, specific toxicity to the cancerous tissue. Unfortunately, tumors often develop intrinsic pharmacoresistance mediated by specialized drug extrusion mechanisms such as P-glycoprotein. As a consequence, malignant cells may become insensitive to various anti-cancer drugs. Recent studies have shown that low intensity very low frequency electrical stimulation by alternating current (AC) reduces the proliferation of different tumor cell lines by a mechanism affecting potassium channels while at intermediate frequencies interfere with cytoskeletal mechanisms of cell division. The aim of the present study is to test the hypothesis that permeability of several MDR1 over-expressing tumor cell lines to the chemotherapic agent doxorubicin is enhanced by low frequency, low intensity AC stimulation. We grew human and rodent cells (C6, HT-1080, H-1299, SKOV-3 and PC-3) which over-expressed MDR1 in 24-well Petri dishes equipped with an array of stainless steel electrodes connected to a computer via a programmable I/O board. We used a dedicated program to generate and monitor the electrical stimulation protocol. Parallel cultures were exposed for 3 hours to increasing concentrations (1, 2, 4, and 8 μM) of doxorubicin following stimulation to 50 Hz AC (7.5 μA) or MDR1 inhibitor XR9576. Cell viability was assessed by determination of adenylate kinase (AK) release. The relationship between MDR1 expression and the intracellular accumulation of doxorubicin as well as the cellular distribution of MDR1 was investigated by computerized image analysis immunohistochemistry and Western blot techniques. By the use of a variety of tumor cell lines, we show that low frequency, low intensity AC stimulation enhances chemotherapeutic efficacy. This effect was due to an altered expression of intrinsic cellular drug resistance mechanisms. Immunohistochemical, Western blot and fluorescence analysis revealed

Tumor blood flow and systemic shunting in patients receiving intraarterial chemotherapy for head and neck cancer

International Nuclear Information System (INIS)

Wheeler, R.H.; Ziessman, H.A.; Medvec, B.R.; Juni, J.E.; Thrall, J.H.; Keyes, J.W.; Pitt, S.R.; Baker, S.R.

1986-01-01

Radionuclide techniques have been used to estimate the systemic shunt and to quantitate blood flow to the tumor and a reference normal tissue in nine patients undergoing intraarterial chemotherapy for head and neck cancer. The systemic shunt was calculated as the percentage of pulmonary trapping of intraarterially injected /sup 99m/Tc-labeled macroaggregated albumin. The mean systemic shunt in the 12 separate arteries studied was 23 +/- 13% (SE) (range 8-43%). Quantitative blood flow was determined from the slope of the washout curve of intraarterially injected 133 Xe. The mean tumor blood flow was 13.6 +/- 6.7 ml/100 g/min, while the mean blood flow to the scalp was 4.2 +/- 2.1 ml/100 g/min providing a mean tumor/normal tissue ratio of 3.9 +/- 2.7. An estimate of blood flow distribution was obtained by calculating the ratio of counts/pixel in the tumor mass versus the remainder of the head as determined by single photon emission computed tomography following an intraarterial injection of /sup 99m/Tc-labeled macroaggregated albumin. The mean ratio of tumor to normal tissue perfusion by this technique was 5.6 +/- 3.7. These techniques have allowed noninvasive determination of the blood flow parameters associated with intraarterial chemotherapy. At least part of the therapeutic advantage of regional chemotherapy in patients with head and neck cancer is due to a tumor/normal tissue blood flow ratio that favors drug delivery to the tumor contained within the infused volume

Use and duration of chemotherapy in patients with metastatic breast cancer according to tumor subtype and line of therapy.

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Seah, Davinia S E; Luis, Ines Vaz; Macrae, Erin; Sohl, Jessica; Litsas, Georgia; Winer, Eric P; Lin, Nancy U; Burstein, Harold J

2014-01-01

Benefits of chemotherapy vary in patients with metastatic breast cancer (MBC). This article describes the impact of tumor subtype and the line of therapy on the duration of chemotherapy. Clinicopathologic characteristics were extracted from the medical records of 199 consecutive patients with MBC at Dana-Farber Cancer Institute and analyzed according to subtype. Tumor subtypes were classified as hormone receptor (HR)-positive, triple-negative (TNBC), or HER2-amplified breast cancer. Duration of chemotherapy of each line was defined as the start of a chemotherapy regimen to the start of the next line of therapy as a result of progression or toxicity. There were 96, 44, and 59 patients with HR(+), TNBC, and HER2-amplified breast cancer, respectively. Median age at MBC diagnosis was 53 years. Median overall survivals were 32 and 54 months for HER2-amplified disease, 36 months for HR(+) breast cancer, and 17 months for TNBC (Pchemotherapy for every line. The median duration of chemotherapy in HER2-amplified patients remained at more than 4 months even out to sixth-line therapy. Patients with TNBC tended to receive the shortest duration of chemotherapy for every line of therapy. Tumor subtypes influence the number of lines, duration of chemotherapy, and survival. Among patients with HR(+) and HER2-amplified disease who undergo chemotherapy beyond the third line, substantial rates of prolonged therapies suggest clinical benefit. The role of advanced (greater than third) chemotherapy lines in improving survival of all patients with MBC warrants further study.

Longitudinal optical monitoring of blood flow in breast tumors during neoadjuvant chemotherapy

Science.gov (United States)

Cochran, J. M.; Chung, S. H.; Leproux, A.; Baker, W. B.; Busch, D. R.; DeMichele, A. M.; Tchou, J.; Tromberg, B. J.; Yodh, A. G.

2017-06-01

We measure tissue blood flow markers in breast tumors during neoadjuvant chemotherapy and investigate their correlation to pathologic complete response in a pilot longitudinal patient study (n  =  4). Tumor blood flow is quantified optically by diffuse correlation spectroscopy (DCS), and tissue optical properties, blood oxygen saturation, and total hemoglobin concentration are derived from concurrent diffuse optical spectroscopic imaging (DOSI). The study represents the first longitudinal DCS measurement of neoadjuvant chemotherapy in humans over the entire course of treatment; it therefore offers a first correlation between DCS flow indices and pathologic complete response. The use of absolute optical properties measured by DOSI facilitates significant improvement of DCS blood flow calculation, which typically assumes optical properties based on literature values. Additionally, the combination of the DCS blood flow index and the tissue oxygen saturation from DOSI permits investigation of tissue oxygen metabolism. Pilot results from four patients suggest that lower blood flow in the lesion-bearing breast is correlated with pathologic complete response. Both absolute lesion blood flow and lesion flow relative to the contralateral breast exhibit potential for characterization of pathological response. This initial demonstration of the combined optical approach for chemotherapy monitoring provides incentive for more comprehensive studies in the future and can help power those investigations.

Anemia prevalence and treatment practice in patients with non-myeloid tumors receiving chemotherapy

International Nuclear Information System (INIS)

Merlini, Laura; Cartenì, Giacomo; Iacobelli, Stefano; Stelitano, Caterina; Airoldi, Mario; Balcke, Peter; Keil, Felix; Haslbauer, Ferdinand; Belton, Laura; Pujol, Beatriz

2013-01-01

To describe the prevalence and management of anemia in cancer patients. This cross-sectional, observational survey was conducted in Italy and Austria. Centers prespecified one day, during a 4-month enrollment window, to report specific data collected during normal clinical practice for patients with non-myeloid tumors attending for chemotherapy (±radiotherapy) treatment. The primary endpoint was the prevalence of anemia as determined using a prespecified algorithm: hemoglobin (Hb) ≤10 g/dL on/within 3 days prior to visit; ongoing anemia treatment; physician diagnosis of anemia, together with ≥1 anemia symptom. Between November 18, 2010 and March 18, 2011, data for 1412 patients were collected (Italy n = 1130; Austria n = 282). Most patients (n = 1136; 80%) had solid tumors; 809 (57%) had received ≤3 chemotherapy cycles. The prevalence of anemia was 32% (95% confidence interval: 29.4%–34.2%); 196 patients (14%) were deemed anemic based on Hb ≤10 g/dL, 131 (9%) on ongoing anemia treatment, and 121 (9%) on physician diagnosis/anemia symptom. Overall, 1153 patients (82%) had Hb data; mean (standard deviation [SD]) Hb levels were 11.7 (1.7) g/dL. In total, 456 patients (32%) had anemia symptoms: fatigue (n = 392; 28%), depression (n = 122; 9%), and dyspnea (n = 107; 8%) were most common. Fifty-one patients (4%) had had their current chemotherapy cycle delayed due to anemia. On visit day, or ≤28 days prior, 91 (6%), 188 (13%), and 81 patients (6%) had evidence of whole blood/red blood cell transfusion, erythropoiesis-stimulating agent use, or iron use, respectively. On the prespecified study day, one-third of patients with non-myeloid tumors undergoing chemotherapy were found to be anemic and 13% had evidence of erythropoiesis-stimulating agent use then or in the 28 days prior

Study on delineation of tumor volume of primary locally advanced nasopharyngeal carcinoma after induction chemotherapy

International Nuclear Information System (INIS)

Long Jinhua; Dong Shi; Jin Feng; Wu Weili; Gan Jiaying; Chen Haixia; Li Yuanyuan; Gong Xiuyun

2012-01-01

Objective: To investigate the delineation of gross tumor volume (GTV) in locally advanced nasopharyngeal carcinoma (LANC) according to imageological changes before and after induction chemotherapy (IC) in order to decrease high dose area and protect normal tissue better. Methods: Between Mar 2010 to Jan 2011, 11 patients with LANC were enrolled and treated with TPF regimen followed by intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy, target volumes were delineated based on fused CT imaging before and after IC following project determination. Tumor target volumes after and before IC were respectively delineated according to imaging tumor residues and were overlaid by CTV nx in order to ensure radical doses for the imaging tumor volume before IC, the resulting differences of tumor target volumes of IC before and after were measured and analyzed by paired t-test. Results: Before and after IC, the average volumes of GTV nx were respectively 44.72 cm 3 and 28.87 (t=3.89, P=0.003), the average volumes of GTV nd were respectively 32.76 cm 3 and 19.82 cm 3 (t=2.47, P=0.033), the volumes of maximum dose area in brainstem and spinal cord as well as eyeball decreased (t=2.93-4.59, all P<0.05). Conclusions: LANC treated by 3 cycle TPF regimen followed by IMRT with concurrent chemotherapy shows significant shrinkage of tumor volume. The volume of high dose region which caused by normally recovered tissues were decreased by re-delineation of target volume in brainstem and spinal cord as well as eyeball of CT images after IC. (authors)

Neurodevelopmental status of infants and young children treated for brain tumors with preirradiation chemotherapy

International Nuclear Information System (INIS)

Mulhern, R.K.; Horowitz, M.E.; Kovnar, E.H.; Langston, J.; Sanford, R.A.; Kun, L.E.

1989-01-01

In an effort to reduce the severity of late neurotoxicities associated with cranial irradiation, 14 infants and young children with malignant brain tumors were given preirradiation chemotherapy for 2 to 22 months (median, 8 months). Prospective neurodevelopmental evaluations were routinely conducted and now extend from 35 to 60 months (median, 41 months) postdiagnosis, and 10 to 52 months (median, 31 months) postirradiation in the 12 surviving children. At the initiation of chemotherapy, less than one fourth of the patients displayed normal performance status or mental functioning on age-corrected tests; the majority remained stable or declined while receiving chemotherapy. Declining mental development and adaptive behavior were noted in six patients following radiation therapy with only two patients now functioning in the normal range for age. The analysis suggests that neurodevelopmental progress is a function of multiple factors, including neurologic and sensorimotor deficits associated with the tumor, surgical intervention, and chemotherapy that antedated radiation therapy. This implies that delaying irradiation will not necessarily improve the patients' functional status. Whether the interval of postponement of irradiation evidenced in this sample will translate into an ultimately better quality of life remains unknown. Given the probable interaction of multiple risk factors, well-controlled prospective clinical trials are needed to definitively analyze this issue

RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines.

Science.gov (United States)

Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M; Pritzker, Laura B; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

2016-02-24

Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced "RNA disruption" is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3'-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues and is

APOMAB, a La-specific monoclonal antibody, detects the apoptotic tumor response to life-prolonging and DNA-damaging chemotherapy.

Directory of Open Access Journals (Sweden)

Fares Al-Ejeh

Full Text Available BACKGROUND: Antineoplastic therapy may impair the survival of malignant cells to produce cell death. Consequently, direct measurement of tumor cell death in vivo is a highly desirable component of therapy response monitoring. We have previously shown that APOMAB representing the DAB4 clone of a La/SSB-specific murine monoclonal autoantibody is a malignant cell-death ligand, which accumulates preferentially in tumors in an antigen-specific and dose-dependent manner after DNA-damaging chemotherapy. Here, we aim to image tumor uptake of APOMAB (DAB4 and to define its biological correlates. METHODOLOGY/PRINCIPAL FINDINGS: Brisk tumor cell apoptosis is induced in the syngeneic EL4 lymphoma model after treatment of tumor-bearing mice with DNA-damaging cyclophosphamide/etoposide chemotherapy. Tumor and normal organ accumulation of Indium 111 ((111In-labeled La-specific DAB4 mAb as whole IgG or IgG fragments was quantified by whole-body static imaging and organ assay in tumor-bearing mice. Immunohistochemical measurements of tumor caspase-3 activation and PARP-1 cleavage, which are indicators of early and late apoptosis, respectively, were correlated with tumor accumulation of DAB4. Increased tumor accumulation of DAB4 was associated directly with both the extent of chemotherapy-induced tumor cell death and DAB4 binding per dead tumor cell. Tumor DAB4 accumulation correlated with cumulative caspase-3 activation and PARP-1 cleavage as tumor biomarkers of apoptosis and was directly related to the extended median survival time of tumor-bearing mice. CONCLUSIONS/SIGNIFICANCE: Radiolabeled La-specific monoclonal antibody, DAB4, detected dead tumor cells after chemotherapy, rather than chemosensitive normal tissues of gut and bone marrow. DAB4 identified late apoptotic tumor cells in vivo. Hence, radiolabeled DAB4 may usefully image responses to human carcinoma therapy because DAB4 would capture the protracted cell death of carcinoma. We believe that the

Tumor tissue levels of tissue inhibitor of metalloproteinases-I (TIMP-I) and outcome following adjuvant chemotherapy in premenopausal lymph node-positive breast cancer patients

DEFF Research Database (Denmark)

Schrohl, Anne-Sofie; Look, Maxime P.; Gelder, Marion E. Meijer-van

2009-01-01

BACKGROUND: We have previously demonstrated that high tumor tissue levels of TIMP-1 are associated with no or limited clinical benefit from chemotherapy with CMF and anthracyclines in metastatic breast cancer patients. Here, we extend our investigations to the adjuvant setting studying outcome...... an association between shorter survival after treatment in TIMP-1 high patients compared with TIMP-1 low patients, especially in patients receiving anthracycline-based therapy. This suggests that high tumor tissue levels of TIMP-1 might be associated with reduced benefit from classical adjuvant chemotherapy. Our...... after adjuvant chemotherapy in premenopausal lymph node-positive patients. We hypothesize that TIMP-1 high tumors are less sensitive to chemotherapy and accordingly that high tumor tissue levels are associated with shorter survival. METHODS: From our original retrospectively collected tumor samples we...

Tumor vessel normalization by the PI3K inhibitor HS-173 enhances drug delivery.

Science.gov (United States)

Kim, Soo Jung; Jung, Kyung Hee; Son, Mi Kwon; Park, Jung Hee; Yan, Hong Hua; Fang, Zhenghuan; Kang, Yeo Wool; Han, Boreum; Lim, Joo Han; Hong, Soon-Sun

2017-09-10

Tumor vessels are leaky and immature, which causes poor oxygen and nutrient supply to tumor vessels and results in cancer cell metastasis to distant organs. This instability of tumor blood vessels also makes it difficult for anticancer drugs to penetrate and reach tumors. Numerous tumor vessel normalization approaches have been investigated for improving drug delivery into tumors. In this study, we investigated whether phosphoinositide 3-kinase (PI3K) inhibitors are able to improve vascular structure and function over the prolonged period necessary to achieve effective vessel normalization. The PI3K inhibitors, HS-173 and BEZ235 potently suppressed tumor growth and hypoxia, and increased tumor apoptosis in animal models. PI3K inhibitors also induced a regular, flat monolayer of endothelial cells (ECs) in vessels, improving stability of vessel structure, and normalized tumor vessels by increasing vascular maturity, pericyte coverage, basement membrane thickness, and tight-junctions. These effects resulted in a decrease in tumor vessel tortuosity and vessel thinning, and improved vessel function and blood flow. The tumor vessel stabilization effect of the PI3K inhibitor HS-173 also decreased the number of metastatic lung nodules in vivo metastasis model. Furthermore, HS-173 improved the delivery of doxorubicin into the tumor region, enhancing its anticancer effects. Mechanistic studies suggested that PI3K inhibitor HS-173-induced vessel normalization reflected changes in endothelial Notch signaling. Taken together, our findings indicate that vessel normalization by PI3K inhibitors restrained tumor growth and metastasis while improving chemotherapy by enhancing drug delivery into the tumor, suggesting that HS-173 may have a therapeutic value as an enhancer or an anticancer drug. Copyright © 2017 Elsevier B.V. All rights reserved.

Dynamic changes of tumor gene expression during repeated pressurized intraperitoneal aerosol chemotherapy (PIPAC) in women with peritoneal cancer

International Nuclear Information System (INIS)

Rezniczek, Günther A.; Jüngst, Friederike; Jütte, Hendrik; Tannapfel, Andrea; Hilal, Ziad; Hefler, Lukas A.; Reymond, Marc-André; Tempfer, Clemens B.

2016-01-01

Intraperitoneal chemotherapy is used to treat peritoneal cancer. The pattern of gene expression changes of peritoneal cancer during intraperitoneal chemotherapy has not been studied before. Pressurized intraperitoneal aerosol chemotherapy is a new form of intraperitoneal chemotherapy using repeated applications and allowing repeated tumor sampling during chemotherapy. Here, we present the analysis of gene expression changes during pressurized intraperitoneal aerosol chemotherapy with doxorubicin and cisplatin using a 22-gene panel. Total RNA was extracted from 152 PC samples obtained from 63 patients in up to six cycles of intraperitoneal chemotherapy. Quantitative real-time PCR was used to determine the gene expression levels. For select genes, immunohistochemistry was used to verify gene expression changes observed on the transcript level on the protein level. Observed (changes in) expression levels were correlated with clinical outcomes. Gene expression profiles differed significantly between peritoneal cancer and non- peritoneal cancer samples and between ascites-producing and non ascites-producing peritoneal cancers. Changes of gene expression patterns during repeated intraperitoneal chemotherapy cycles were prognostic of overall survival, suggesting a molecular tumor response of peritoneal cancer. Specifically, downregulation of the whole gene panel during intraperitoneal chemotherapy was associated with better treatment response and survival. In summary, molecular changes of peritoneal cancer during pressurized intraperitoneal aerosol chemotherapy can be documented and may be used to refine individual treatment and prognostic estimations. The online version of this article (doi:10.1186/s12885-016-2668-4) contains supplementary material, which is available to authorized users

Ultrawideband Radio Frequency (RF) Enhanced Electroporation for Chemotherapy

National Research Council Canada - National Science Library

Gilgenbach, R. M; Lau, Y. Y; Uhler, M. D; Jordan, D

2005-01-01

Experimental results are presented for a research program in which high voltage, short-pulsed, ultrawideband electric fields have been demonstrated to enhance the effects of chemotherapy upon killing of Jurkat (cancer) cells...

Effect of Kanglaite combined with chemotherapy on myelosuppression, immune function and tumor markers levels in patients with breast cancer

Directory of Open Access Journals (Sweden)

Qi Pan

2017-09-01

Full Text Available Objective: To investigate the effect of Kanglaite combined with chemotherapy on myelosuppression, immune function and tumor markers levels in patients with breast cancer. Methods: A total of 90 breast cancer patients in our hospital were randomly divided into control group (45 cases and observation group (45 cases. The two groups received CAF chemotherapy, and the observation group was additionally given Kanglaite injection (200 mL/d for 2 weeks continuously. Both groups had chemotherapy for 6 courses. The effect on myelosuppression, immune function and tumor markers levels was detected and compared before and after treatment in two groups. Results: After treatment, myelosuppression was found in both groups, and the levels of leukocyte, hemoglobin and platelet decreased significantly compared with before treatment (P0.05, and the levels of immune function indexes (CD3+, CD4+, CD4+/ CD8+ of the observation group were significantly higher than those in the control group （P<0.05） . After treatment, the levels of two tumor markers (CEA, CA15-3 decreased significantly than before treatment in both groups (P<0.05, and the decrease amplitude in the observation group was higher than that in the control group (P<0.05. Conclusions: Kanglaite combined with chemotherapy has evident therapeutic effect on breast cancer. It can alleviate the myelosuppression caused by chemotherapy, improve immune function, and reduce the concentration of tumor markers in patients with breast cancer.

Chemotherapy in combined and multimodality treatment

International Nuclear Information System (INIS)

Anon.

1989-01-01

It is shown that chemotherapy of tumors of various localizations developes intensively in the last few years. It is connected with discovery and adoption of new active antitumoral preparations, such as alkylating preparations, antimetabolites, antitumoral antibiotics, hormonal preparations. To create the rational effective conditions of chemotherapy a study was made on kinetics of tumor gowth, molecular mechanisms of interaction of cytostatics and cells of malignant tumor. Main factors of chemotherapy combination with radiotherapy when treating numerous malignant tumors were considered. Effectiveness of using chemotherapy in combination with other methods of treatment was shown

Solid tumors after chemotherapy or surgery for testicular nonseminoma: a population-based study.

Science.gov (United States)

Fung, Chunkit; Fossa, Sophie D; Milano, Michael T; Oldenburg, Jan; Travis, Lois B

2013-10-20

Increased risks of solid tumors after older radiotherapy strategies for testicular cancer (TC) are well established. Few population-based studies, however, focus on solid cancer risk among survivors of TC managed with nonradiotherapy approaches. We quantified the site-specific risk of solid cancers among testicular nonseminoma patients treated in the modern era of cisplatin-based chemotherapy, without radiotherapy. Standardized incidence ratios (SIRs) for solid tumors were calculated for 12,691 patients with testicular nonseminoma reported to the population-based Surveillance, Epidemiology, and End Results program (1980 to 2008) and treated initially with either chemotherapy (n = 6,013) or surgery (n = 6,678) without radiotherapy. Patients accrued 116,073 person-years of follow-up. Two hundred ten second solid cancers were observed. No increased risk followed surgery alone (SIR, 0.93; 95% CI, 0.76 to 1.14; n = 99 solid cancers), whereas significantly increased 40% excesses (SIR, 1.43; 95% CI, 1.18 to 1.73; n = 111 solid cancers) occurred after chemotherapy. Increased risks of solid cancers after chemotherapy were observed in most follow-up periods (median latency, 12.5 years), including more than 20 years after treatment (SIR, 1.54; 95% CI, 0.96 to 2.33); significantly increased three- to seven-fold risks occurred for cancers of the kidney (SIR, 3.37; 95% CI, 1.79 to 5.77), thyroid (SIR, 4.40; 95% CI, 2.19 to 7.88), and soft tissue (SIR, 7.49; 95% CI, 3.59 to 13.78). To our knowledge, this is the first large population-based series reporting significantly increased risks of solid cancers among patients with testicular nonseminoma treated in the modern era of cisplatin-based chemotherapy. Subsequent analytic studies should focus on the evaluation of dose-response relationships, types of solid cancers, latency patterns, and interactions with other possible factors, including genetic susceptibility.

Tumor reoxygenation by aqueous oxygen solutions and its role in cancer treatment with chemotherapy and radiation therapy

International Nuclear Information System (INIS)

Calderwood, S.K.

2003-01-01

Many tumors contain significant areas of hypoxia which cause resistance to tumor radiation therapy and chemotherapy. We have used perfusion into afferent arteries with super saturated aqueous oxygen solutions (AO) to re-oxygenate the hypoxic areas of experimental tumors with the aim of restoring sensitivity to treatment and enhancing cancer therapy. We first concentrated on examining the ability of AO infusion to reoxygenate the MAT B III 13762 rat carcinoma growing in the thighs of rats. In experiments on 33 AO infused tumors using Eppendorf microelectrode monitoring, we consistently observed a significant decrease in the fraction of tumor domains with O 2 less than 5mmHg before and after AO infusion. Significant tumor reoxygenation was observed in most tumors with a volume less than 2.5 cm 3 . We next examined 15 New Zealand white rabbits transplanted with the VX2 carcinoma. Tissue oxygen studies indicated that intramuscular rabbit VX-2 tumor has a consistently lower hypoxic fraction (O 2 2 <5mm Hg). Significant reoxygenation did occur in these infused tumors although the degree of reoxygenation was slightly less than in the rat MAT B III 13762 perhaps reflecting the lower hypoxic fraction. Further studies showed that AO could also be infused directly into tumors with a reduction of hypoxic fraction of between 60-90% Overall, the experiments show that AO infusion into either arterial or intratumor sites is a viable approach to tumor reoxygenation and preliminary studies indicate increase effectiveness in treatment with cyclophosphamide / AO combination

Expression analysis of genes associated with human osteosarcoma tumors shows correlation of RUNX2 overexpression with poor response to chemotherapy

International Nuclear Information System (INIS)

Sadikovic, Bekim; Thorner, Paul; Chilton-MacNeill, Susan; Martin, Jeff W; Cervigne, Nilva K; Squire, Jeremy; Zielenska, Maria

2010-01-01

Human osteosarcoma is the most common pediatric bone tumor. There is limited understanding of the molecular mechanisms underlying osteosarcoma oncogenesis, and a lack of good diagnostic as well as prognostic clinical markers for this disease. Recent discoveries have highlighted a potential role of a number of genes including: RECQL4, DOCK5, SPP1, RUNX2, RB1, CDKN1A, P53, IBSP, LSAMP, MYC, TNFRSF1B, BMP2, HISTH2BE, FOS, CCNB1, and CDC5L. Our objective was to assess relative expression levels of these 16 genes as potential biomarkers of osteosarcoma oncogenesis and chemotherapy response in human tumors. We performed quantitative expression analysis in a panel of 22 human osteosarcoma tumors with differential response to chemotherapy, and 5 normal human osteoblasts. RECQL4, SPP1, RUNX2, and IBSP were significantly overexpressed, and DOCK5, CDKN1A, RB1, P53, and LSAMP showed significant loss of expression relative to normal osteoblasts. In addition to being overexpressed in osteosarcoma tumor samples relative to normal osteoblasts, RUNX2 was the only gene of the 16 to show significant overexpression in tumors that had a poor response to chemotherapy relative to good responders. These data underscore the loss of tumor suppressive pathways and activation of specific oncogenic mechanisms associated with osteosarcoma oncogenesis, while drawing attention to the role of RUNX2 expression as a potential biomarker of chemotherapy failure in osteosarcoma

Circulating tumor cells in patients with breast cancer: monitoring chemotherapy success.

Science.gov (United States)

Ušiaková, Zuzana; Mikulová, Veronika; Pintérová, Daniela; Brychta, Milan; Valchář, Josef; Kubecová, Martina; Tesařová, Petra; Bobek, Vladimír; Kološtová, Katarína

2014-01-01

Circulating tumor cells (CTCs) are an independent prognostic factor for patients with metastatic breast cancer (MBC). However, the role of CTCs in early breast cancer management is not yet clearly defined. The aim of this study was to assess the CTC-positivity rate in patients undergoing chemotherapy depending on breast cancer stage in the adjuvant and neoadjuvant setting. We evaluated the ability to confirm therapy response by CTC analysis. CTCs isolated from blood by means of immunomagnetic separation were further characterized by means of reverse transcriptase - polymerase chain reaction (RT-PCR) for epithelial cell adhesion molecule (EPCAM), mucin 1 (MUC1) and v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (HER2) transcripts with the AdnaTest™. This prospective study included 179 patients; altogether 419 blood samples were evaluated. Patients with primary tumors were divided into neoadjuvant (n=38), and adjuvant (n=100) groups. Forty-one patients with MBC were evaluated under palliative treatment. CTC positivity was described in 35% of patients with early breast cancer without detected metastases before neoadjuvant chemotherapy; similarly, a 26% positivity rate was found in the adjuvant group. In patients with MBC, we detected CTCs in 43% of them. After completing the therapy, the CTC positivity rate decreased to 5% in the neoadjuvant group, to 13% in the adjuvant group and to 12% in the MBC group. CTC positivity after the therapy may classify a subgroup of patients at high risk of developing metastatic disease. This was even true when a patient was evaluated as being CTC-negative before chemotherapy. The multivariate analysis evaluating the correlation of CTC positivity with clinicopathological characteristics such as tumor size, nodal involvement, hormone receptor status, HER2 expression and number of metastatic sites revealed no statistically significant relationships. CTC status may have a significant impact on early BC management

Catalase-loaded cisplatin-prodrug-constructed liposomes to overcome tumor hypoxia for enhanced chemo-radiotherapy of cancer.

Science.gov (United States)

Zhang, Rui; Song, Xuejiao; Liang, Chao; Yi, Xuan; Song, Guosheng; Chao, Yu; Yang, Yu; Yang, Kai; Feng, Liangzhu; Liu, Zhuang

2017-09-01

Aiming at improved therapeutic efficacies, the combination of chemotherapy and radiotherapy (chemo-radiotherapy) has been widely studied and applied in clinic. However, the hostile characteristics of tumor microenvironment such as hypoxia often limit the efficacies in both types of cancer therapies. Herein, catalase (CAT), an antioxidant enzyme, is encapsulated inside liposomes constituted by cisplatin (IV)-prodrug-conjugated phospholipid, forming CAT@Pt (IV)-liposome for enhanced chemo-radiotherapy of cancer. After being loaded inside liposomes, CAT within CAT@Pt (IV)-liposome shows retained and well-protected enzyme activity, and is able to trigger decomposition of H 2 O 2 produced by tumor cells, so as to produce additional oxygen for hypoxia relief. As the result, treatment of CAT@Pt (IV)-liposome induces the highest level of DNA damage in cancer cells after X-ray radiation compared to the control groups. In vivo tumor treatment further demonstrates a remarkably improved therapeutic outcome in chemo-radiotherapy with such CAT@Pt (IV)-liposome nanoparticles. Hence, an exquisite type of liposome-based nanoparticles is developed in this work by integrating cisplatin-based chemotherapy and catalase-induced tumor hypoxia relief together for combined chemo-radiotherapy with great synergistic efficacy, promising for clinical translation in cancer treatment. Copyright © 2017. Published by Elsevier Ltd.

[A prospective study of adenosine triphosphate-tumor chemosensitivity assay directed chemotherapy in patients with recurrent ovarian cancer].

Science.gov (United States)

Gao, Yu-tao; Wu, Ling-ying; Zhang, Wei; Zhao, Dan; Li, Ning; Tian, Hai-mei; Wang, Xiao-bing; Li, Mo; Sun, Yang-chun; Li, Nan; Li, Xiao-guang

2013-05-01

To investigate the efficacy of adenosine triphosphate (ATP)-tumor chemosensitivity assay (TCA) directed chemotherapy in patients with recurrent epithelial ovarian cancer. From August 2010 to June 2012, recurrent epithelial ovarian cancer patients were prospectively enrollmented in Cancer Hospital, Peking Union Medical College,Chinese Academy of Medical Sciences.The entry criteria are as follows: (1) Histologically proven to be epithelial ovarian cancer. (2) Patients of recurrent ovarian cancer with bidimensionally measurable tumor, or ascitic or pleural fluid for testing. (3) Karnofsky performance status > 60. (4) A life expectancy of at least more than 6 months.According to patients desires, they were assigned into two groups: assay-directed therapy group and physician's-choice therapy group, patients' clinical and pathological characteristics, response rate to chemotherapy and progression-free survival (PFS) were compared between two groups. A total of 113 patients with recurrent epithelial ovarian cancer were prospectively enrollmented to assay-directed chemotherapy (n = 56) or physician's-choice chemotherapy (n = 57).There was no difference in median age,types of recurrence, surgical-pathological stage, pathological type, tumor grade, times of recurrence, residual disease at secondary cytoreductive surgery between assay-directed group and physician's-choice group. The overall response rate (ORR) and median PFS in the ATP-TCA group was 66% (37/56) and 7 months, while the ORR in the control group was 46% (26/57, P = 0.037), the median PFS was 4 months (P = 0.040). For platinum-resistant patients, the ORR between ATP-TCA directed chemotherapy 59% (16/27) and control group 25% (7/28) were significantly different (P = 0.010), and the median PFS between two groups were also significantly different (5 months and 2 months, respectively, P = 0.003). ATP-TCA directed chemotherapy could improve ORR and PFS in patients with recurrent epithelial ovarian cancer, especially

Chemotherapy Toxicity Risk Score for Treatment Decisions in Older Adults with Advanced Solid Tumors.

Science.gov (United States)

Nishijima, Tomohiro F; Deal, Allison M; Williams, Grant R; Sanoff, Hanna K; Nyrop, Kirsten A; Muss, Hyman B

2018-05-01

The decision whether to treat older adults with advanced cancer with standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. We assessed the potential utility of the chemotherapy toxicity risk score (CTRS) [J Clin Oncol 2011;29:3457-3465] for treatment decisions in older adults. This was a prospective observational study of patients aged ≥65 years receiving first-line chemotherapy for advanced cancer for which combination chemotherapy is the standard of care. Patients were categorized as high risk (CTRS ≥10), for whom RT (dose-reduced combination or single-agent chemotherapy) is deemed appropriate, or nonhigh risk (CTRS statistic. Fifty-eight patients (median age, 71 years) were enrolled. Thirty-eight patients received ST (21 had CTRS advanced solid tumors receiving first-line chemotherapy was assessed. Little agreement was found between chemotherapy treatment decisions based on the clinical impression versus what was recommended based on the CTRS. Among patients treated with standard-dose combination chemotherapy, patients with CTRS ≥10 had a very high incidence of grade 3-4 toxicities and hospitalization, which was significantly greater than that of patients with a low CTRS (<10). These findings suggest that the addition of CTRS to the clinical impression has a potential to improve treatment decisions. © AlphaMed Press 2018.

CXCR4 Protein Epitope Mimetic Antagonist POL5551 Disrupts Metastasis and Enhances Chemotherapy Effect in Triple-Negative Breast Cancer.

Science.gov (United States)

Xiang, Jingyu; Hurchla, Michelle A; Fontana, Francesca; Su, Xinming; Amend, Sarah R; Esser, Alison K; Douglas, Garry J; Mudalagiriyappa, Chidananda; Luker, Kathryn E; Pluard, Timothy; Ademuyiwa, Foluso O; Romagnoli, Barbara; Tuffin, Gérald; Chevalier, Eric; Luker, Gary D; Bauer, Michael; Zimmermann, Johann; Aft, Rebecca L; Dembowsky, Klaus; Weilbaecher, Katherine N

2015-11-01

The SDF-1 receptor CXCR4 has been associated with early metastasis and poorer prognosis in breast cancers, especially the most aggressive triple-negative subtype. In line with previous reports, we found that tumoral CXCR4 expression in patients with locally advanced breast cancer was associated with increased metastases and rapid tumor progression. Moreover, high CXCR4 expression identified a group of bone marrow-disseminated tumor cells (DTC)-negative patients at high risk for metastasis and death. The protein epitope mimetic (PEM) POL5551, a novel CXCR4 antagonist, inhibited binding of SDF-1 to CXCR4, had no direct effects on tumor cell viability, but reduced migration of breast cancer cells in vitro. In two orthotopic models of triple-negative breast cancer, POL5551 had little inhibitory effect on primary tumor growth, but significantly reduced distant metastasis. When combined with eribulin, a chemotherapeutic microtubule inhibitor, POL5551 additively reduced metastasis and prolonged survival in mice after resection of the primary tumor compared with single-agent eribulin. Hypothesizing that POL5551 may mobilize tumor cells from their microenvironment and sensitize them to chemotherapy, we used a "chemotherapy framing" dosing strategy. When administered shortly before and after eribulin treatment, three doses of POL5551 with eribulin reduced bone and liver tumor burden more effectively than chemotherapy alone. These data suggest that sequenced administration of CXCR4 antagonists with cytotoxic chemotherapy synergize to reduce distant metastases. ©2015 American Association for Cancer Research.

Therapeutic Silencing of Bcl-2 by Systemically Administered siRNA Nanotherapeutics Inhibits Tumor Growth by Autophagy and Apoptosis and Enhances the Efficacy of Chemotherapy in Orthotopic Xenograft Models of ER (− and ER (+ Breast Cancer

Directory of Open Access Journals (Sweden)

Ibrahim Tekedereli

2013-01-01

Full Text Available Bcl-2 is overexpressed in about a half of human cancers and 50–70% of breast cancer patients, thereby conferring resistance to conventional therapies and making it an excellent therapeutic target. Small interfering RNA (siRNA offers novel and powerful tools for specific gene silencing and molecularly targeted therapy. Here, we show that therapeutic silencing of Bcl-2 by systemically administered nanoliposomal (NL-Bcl-2 siRNA (0.15 mg siRNA/kg, intravenous twice a week leads to significant antitumor activity and suppression of growth in both estrogen receptor-negative (ER(− MDA-MB-231 and ER-positive (+ MCF7 breast tumors in orthotopic xenograft models (P < 0.05. A single intravenous injection of NL-Bcl-2-siRNA provided robust and persistent silencing of the target gene expression in xenograft tumors. NL-Bcl-2-siRNA treatment significantly increased the efficacy of chemotherapy when combined with doxorubicin in both MDA-MB-231 and MCF-7 animal models (P < 0.05. NL-Bcl-2-siRNA treatment-induced apoptosis and autophagic cell death, and inhibited cyclin D1, HIF1α and Src/Fak signaling in tumors. In conclusion, our data provide the first evidence that in vivo therapeutic targeting Bcl-2 by systemically administered nanoliposomal-siRNA significantly inhibits growth of both ER(− and ER(+ breast tumors and enhances the efficacy of chemotherapy, suggesting that therapeutic silencing of Bcl-2 by siRNA is a viable approach in breast cancers.

RNA disruption is associated with response to multiple classes of chemotherapy drugs in tumor cell lines

International Nuclear Information System (INIS)

Narendrula, Rashmi; Mispel-Beyer, Kyle; Guo, Baoqing; Parissenti, Amadeo M.; Pritzker, Laura B.; Pritzker, Ken; Masilamani, Twinkle; Wang, Xiaohui; Lannér, Carita

2016-01-01

Cellular stressors and apoptosis-inducing agents have been shown to induce ribosomal RNA (rRNA) degradation in eukaryotic cells. Recently, RNA degradation in vivo was observed in patients with locally advanced breast cancer, where mid-treatment tumor RNA degradation was associated with complete tumor destruction and enhanced patient survival. However, it is not clear how widespread chemotherapy induced “RNA disruption” is, the extent to which it is associated with drug response or what the underlying mechanisms are. Ovarian (A2780, CaOV3) and breast (MDA-MB-231, MCF-7, BT474, SKBR3) cancer cell lines were treated with several cytotoxic chemotherapy drugs and total RNA was isolated. RNA was also prepared from docetaxel resistant A2780DXL and carboplatin resistant A2780CBN cells following drug exposure. Disruption of RNA was analyzed by capillary electrophoresis. Northern blotting was performed using probes complementary to the 28S and 18S rRNA to determine the origins of degradation bands. Apoptosis activation was assessed by flow cytometric monitoring of annexin-V and propidium iodide (PI) binding to cells and by measuring caspase-3 activation. The link between apoptosis and RNA degradation (disruption) was investigated using a caspase-3 inhibitor. All chemotherapy drugs tested were capable of inducing similar RNA disruption patterns. Docetaxel treatment of the resistant A2780DXL cells and carboplatin treatment of the A2780CBN cells did not result in RNA disruption. Northern blotting indicated that two RNA disruption bands were derived from the 3’-end of the 28S rRNA. Annexin-V and PI staining of docetaxel treated cells, along with assessment of caspase-3 activation, showed concurrent initiation of apoptosis and RNA disruption, while inhibition of caspase-3 activity significantly reduced RNA disruption. Supporting the in vivo evidence, our results demonstrate that RNA disruption is induced by multiple chemotherapy agents in cell lines from different tissues

Delayed enhanced MRI in intraparenchymal tumors

International Nuclear Information System (INIS)

Eguchi, Takahiko; Morimoto, Tetsuya; Takeshima, Toshikazu

1991-01-01

Delayed enhanced MRI was performed on 20 intraparenchymal tumors, and these findings were compared with those of early enhanced MRI. Using the spin-echo technique (SE: 400-500/20 msec), early scans were obtained 5 minutes, and delayed scans were obtained 60 minutes, after the intravenous injection of 0.1 nmol of gadolinium-DTPA/Kg. We discussed the changes in the delayed scan with regard to the change in the pattern of enhancement and the boundary of enhancement. In these twenty intraparenchymal tumors, there were three low-grade astrocytomas, two anaplastic astrocytomas, seven glioblastomas, and eight metastatic tumors. The changes in the enhanced pattern showed three types as follows: Type I: heterogeneous enhancement in both early and delayed scans; Type II: heterogeneous enhancement in early scan and homogeneous enhancement in delayed scan; Type III: homogeneous enhancement in both early and delayed scans. Most malignant tumors, such as glioblastomas (6/8), anaplastic astrocytomas (2/2), and metastatic tumors (7/8), revealed Type I, although low-grade astrocytomas showed Type II (3/2) and Type III (1/3). The heterogeneous enhancement in delayed scan was found in malignant tumors and in low-grade astrocytoma; even if the early scan revealed heterogeneous enhancement, the delayed scan showed homogeneous enhancement. In the delayed scan, most enhanced boundaries spread out of the boundaries in the early scan. Glioblastomas spread markedly in the delayed scan, although none of the low-grade astrocytomas, anaplastic astrocytomas, or metastases revealed marked spreading. We called these marked increases in the delayed scan a 'spreading sign' and thought that this sign was specific to glioblastomas. Recently some authors have emphasized the usefulness of serial scans. Delayed enhanced MRI 60 minutes after the administration of a contrast medium was here found also to be useful for the accurate diagnosis for brain tumors. (author)

Metronomic chemotherapy.

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Mutsaers, Anthony J

2009-08-01

Chemotherapy drugs are usually administered at doses that are high enough to result in an obligatory break period to allow for the observation of potential side effects and institution of supportive care, if required. In recent years, efforts to administer chemotherapy on a more continuous basis, with a much shorter break period, or none at all, have received increased interest, and the practice has come to be known as metronomic chemotherapy. The basis for success with this currently investigational approach may be rooted in continuous drug exposure to susceptible cancer cells, inhibition of tumor blood vessel growth-a process known as tumor angiogenesis, and/or alterations in tumor immunology. Increased benefit also appears to occur when metronomic chemotherapy is used in combination with newer, targeted antiangiogenic agents, and therefore represents a promising approach to combination therapy, particularly as targeted oncology drugs make their way into veterinary oncology applications. There is still much to be learned in this field, especially with regard to optimization of the proper drugs, dose, schedule, and tumor applications. However, the low cost, ease of administration, and acceptable toxicity profiles potentially associated with this therapeutic strategy make metronomic chemotherapy protocols attractive and suitable to veterinary applications. Preliminary clinical trial results have now been reported in both human and veterinary medicine, including adjuvant treatment of canine splenic hemangiosarcoma and incompletely resected soft tissue sarcoma, and, further, more powerful studies are currently ongoing.

Infusion MR arteriography during hepatic arterial infusion chemotherapy. Evaluation of clinical usefulness

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Uchino, Minako; Takizawa, Kenji

2003-01-01

We developed a new method of infusion MR arteriography (IMRA) via an implantable port system using an infusion pump for the evaluation of drug distribution during hepatic arterial infusion chemotherapy. The purposes of this study were to optimize the method and evaluate its clinical usefulness. We used 3D-T1 turbo field echo (TFE) as the most suitable sequence for IMRA according to the results of a phantom model experiment. We examined 33 cases of liver cancer that had been treated by arterial infusion chemotherapy via the port system. The following investigations were performed: degree of tumor enhancement, intra- and extra- hepatic perfusion abnormality, and related toxicity. The evaluation of images was performed separately by two radiologists. IMRA provided good images of contrast enhancement, to reveal the perfusion patterns. The treatment response rate in the tumor group with well enhancement was higher than that of the group with poor enhancement (p<0.0001). Extrahepatic perfusion was well visualized and was correlated with toxicity (p<0.0001). IMRA is a useful method to evaluate drug perfusion for the optimization of arterial infusion chemotherapy. (author)

Role of vascular normalization in benefit from metronomic chemotherapy.

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Mpekris, Fotios; Baish, James W; Stylianopoulos, Triantafyllos; Jain, Rakesh K

2017-02-21

Metronomic dosing of chemotherapy-defined as frequent administration at lower doses-has been shown to be more efficacious than maximum tolerated dose treatment in preclinical studies, and is currently being tested in the clinic. Although multiple mechanisms of benefit from metronomic chemotherapy have been proposed, how these mechanisms are related to one another and which one is dominant for a given tumor-drug combination is not known. To this end, we have developed a mathematical model that incorporates various proposed mechanisms, and report here that improved function of tumor vessels is a key determinant of benefit from metronomic chemotherapy. In our analysis, we used multiple dosage schedules and incorporated interactions among cancer cells, stem-like cancer cells, immune cells, and the tumor vasculature. We found that metronomic chemotherapy induces functional normalization of tumor blood vessels, resulting in improved tumor perfusion. Improved perfusion alleviates hypoxia, which reprograms the immunosuppressive tumor microenvironment toward immunostimulation and improves drug delivery and therapeutic outcomes. Indeed, in our model, improved vessel function enhanced the delivery of oxygen and drugs, increased the number of effector immune cells, and decreased the number of regulatory T cells, which in turn killed a larger number of cancer cells, including cancer stem-like cells. Vessel function was further improved owing to decompression of intratumoral vessels as a result of increased killing of cancer cells, setting up a positive feedback loop. Our model enables evaluation of the relative importance of these mechanisms, and suggests guidelines for the optimal use of metronomic therapy.

Systemic co-delivery of doxorubicin and siRNA using nanoparticles conjugated with EGFR-specific targeting peptide to enhance chemotherapy in ovarian tumor bearing mice

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Liu, C. W.; Lin, W. J., E-mail: wjlin@ntu.edu.tw [National Taiwan University, Graduate Institute of Pharmaceutical Sciences, School of Pharmacy (China)

2013-10-15

This aim of this study was to develop peptide-conjugated nanoparticles (NPs) for systemic co-delivery of siRNA and doxorubicin to enhance chemotherapy in epidermal growth factor receptor (EGFR) high-expressed ovarian tumor bearing mice. The active targeting NPs were prepared using heptapeptide-conjugated poly(d,l-lactic-co-glycolic acid)-poly(ethylene glycol). The particle sizes of peptide-free and peptide-conjugated NPs were 159.3 {+-} 32.5 and 184.0 {+-} 52.9 nm, respectively, with zeta potential -21.3 {+-} 3.8 and -15.3 {+-} 2.8 mV. The peptide-conjugated NPs uptake were more efficient in EGFR high-expressed SKOV3 cells than in EGFR low-expressed HepG2 cells due to heptapeptide specificity. The NPs were used to deliver small molecule anticancer drug (e.g., doxorubicin) and large molecule genetic agent (e.g., siRNA). The IC{sub 50} of doxorubicin-loaded peptide-conjugated NPs (0.09 {+-} 0.06 {mu}M) was significantly lower than peptide-free NPs (5.72 {+-} 2.64 {mu}M). The similar result was observed in siRNA-loaded NPs. The peptide-conjugated NPs not only served as a nanocarrier to efficiently deliver doxorubicin and siRNA to EGFR high-expressed ovarian cancer cells but also increased the intracellular accumulation of the therapeutic agents to induce assured anti-tumor growth effect in vivo.

Prevalence and rupture rate of cerebral aneurysms discovered during intra-arterial chemotherapy of brain tumors.

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Bourekas, E C; Newton, H B; Figg, G M; Slone, H W

2006-02-01

During the administration of intra-arterial (IA) chemotherapy for the treatment of brain tumors (BTs), angiography may demonstrate asymptomatic, incidental cerebral aneurysms. The prevalence and complication rate of incidental aneurysms in patients undergoing IA chemotherapy remains unknown. It remains unclear whether the presence of an aneurysm represents an increased risk or a contraindication to this form of treatment. We performed a chart and angiography review of BT patients receiving IA chemotherapy over the previous 16 months. Seventy-eight patients were identified with primary (39) and metastatic (39) BTs. The cohort consisted of 40 men and 38 women, with a mean age of 47.8 years (range, 22-80 years). During initial angiography, 8 patients (10.3%) were identified with incidental cerebral aneurysms. The aneurysms were saccular and varied in size from 2-4 mm (mean, 3 mm). Seven of the 8 patients continued IA chemotherapy after detection of the aneurysm, for a total of 35 IA procedures. Of these 7 patients, 5 expired from nonaneurysmal complications (mean survival, 5.4 months; range, 2-10 months); 4 from the primary tumor, and one from an infected craniotomy site. Two patients continue to survive; one remains in treatment, and the other has completed 12 months of IA therapy. There were no aneurysmal complications during or after IA treatment in any of the BT patients. Incidental aneurysms may be more common in patients with BTs than the general population. In our patient population, there was no indication that an incidental aneurysm was reason to preclude or delay the use of IA chemotherapy.

Enhanced tumor responses through therapies combining CCNU, MISO and radiation

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Siemann, D.W.; Hill, S.A.

1984-01-01

Studies were performed to determine whether the radiation sensitizer misonidazole (MISO) could enhance the tumor control probability in a treatment strategy combining radiation and the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU). In initial experiments KHT sarcoma-bearing mice were injected with 1.0 mg/g of MISO simultaneously with a 20 mg/kg dose of CCNU 30-40 min prior to irradiation (1500 rad). With this treatment protocol approximately 60% of the mice were found to be tumor-free 100 days post treatment. By comparison all 2 agent combinations led to 0% cures. To evaluate the relative importance of chemopotentiation versus radiosensitization in the 3 agent protocol, tumors were treated with MISO plus one anti-tumor agent (either radiation of CCNU) and then at times ranging from 0 to 24 hr later exposed to the other agent. When the time between treatments was 0 to 6 hr, a 60 to 80% tumor control rate was achieved for both MISO plus radiation followed by CCNU and MISO plus CCNU followed by radiation. However if the time interval was increased to 18 or 24 hr, the cure rate in the former treatment regimen dropped to 10% while that of the latter remained high at 40%. The data therefore indicate that (1) improved tumor responses may be achieved when MISO is added to a radiation-chemotherapy combination and (2) MISO may be more effective in such a protocol when utilized as a chemopotentiator

Contrast-enhanced ultrasonography depicts small tumor vessels for the evaluation of pancreatic tumors

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Okamoto, Yuko; Kawamoto, Hirofumi; Takaki, Akinobu; Ishida, Etsuji; Ogawa, Tsuneyoshi; Kuwaki, Kenji; Kobayashi, Yoshiyuki; Sakaguchi, Kohsaku; Shiratori, Yasushi

2007-01-01

Objective: The aim of this study is to evaluate the efficacy of contrast-enhanced ultrasonography for the diagnosis of pancreatic tumors. Materials and methods: Contrast-enhanced ultrasonography with Levovist was performed on 62 consecutive patients (53 with pancreatic cancer, 4 with islet cell tumor, 3 with inflammatory pancreatic tumor, and 2 with metastatic tumor). The vascular and perfusion image phases of the tumors were evaluated and compared with the findings of contrast-enhanced computed tomography. Results: Contrast-enhanced ultrasonography showed tumor vessels around and/or in the tumor at the vascular image phase in 79% of pancreatic cancer patients (42/53). At the perfusion image phase, 96% of pancreatic cancers (51/53) were classified as hypo-enhancement type. However, tiny spotty or irregular heterogeneous enhanced lesions were found in 84% of hypo-enhanced pancreatic cancer patients (43/51). The presence of small vessels at the vascular image phase was closely correlated with the presence of these intratumor regional enhanced lesions at the perfusion image phase (κ coefficient = 0.42). The sensitivity of contrast-enhanced ultrasonography (100%) for pancreatic cancer was superior to that of contrast-enhanced computed tomography (91%), but no significant difference was observed between the two (McNemar test: p = 0.063). Conclusion: Contrast-enhanced ultrasonography with Levovist successfully visualizes fine vessels and enhancement in pancreatic tumors, and is useful for evaluating pancreatic tumors

Treatment of Extra — Abdominal Desmoid Tumors with Chemotherapy

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Montgomery, Corey; Emory, Cynthia; Adams, Sheila; Cohen, Jonathan; Pitcher, John David; Potter, Benjamin Kyle; Temple, H. Thomas

2011-01-01

Fibromatosis, or extra-abdominal desmoid tumor, is a benign disease which often has an aggressive clinical course that can be difficult to treat. We performed a retrospective review of 16 patients (12 females and four males) with a mean age of 34.2 years treated with methotrexate and vinblastine for newly diagnosed or recurrent extra-abdominal desmoid tumor. The mean age of our patient cohort was 34.2 years (range 11–70), and the mean tumor size was 11.5 cm (range 2.5–21.2 cm). The mean duration of therapy was 12 months with an average follow-up of 43 months (range 1–149 months). Fourteen of 16 patients demonstrated a clinical response to treatment. Eight of 14 patients demonstrated a radiologic decrease in tumor size. Only one patient progressed on therapy. Six patients developed recurrent symptoms after discontinuation of treatment. Chemotherapy-related symptoms including neutropenia, nausea, and vomiting were common and observed in most patients, however these side effects were mild and transient. Five patients developed peripheral neuropathy that prompted a change from vinblastine to vinorelbine during treatment. One potentially life-threatening complication (pneumocystis pneumonia) occurred which was diagnosed early and successfully treated. The use of methotrexate and vinblastine/vinorelbine in the management of fibromatosis appears to be an effective treatment with minimal treatment-related side effects

Treatment of Extra — Abdominal Desmoid Tumors with Chemotherapy

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Montgomery, Corey [Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72211 (United States); Emory, Cynthia [Wake Forest School of Medicine, Medical Center Blvds, Winston-Salem, NC 27157 (United States); Adams, Sheila [Department of Orthopaedics and Rehabilitation, University of Miami Miller School of Medicine, Cedars Medical Center, 1400 NW 12th Avenue (R-12), Miami, FL 33136 (United States); Cohen, Jonathan [Division of Psychology, University of Miami Miller School of Medicine, 1695 N.W. 9th Ave. (D-29), Miami, FL 33136 (United States); Pitcher, John David [Department of Orthopaedics and Rehabilitation, University of Miami School of Medicine, 1400 NW 12th Avenue (R-12), Miami, FL 33136 (United States); Potter, Benjamin Kyle [Department of Orthopaedic Surgery, Walter Reed Army Medical Center, 6900 Georgia Avenue North West, Washington, D.C., 20307 (United States); Temple, H. Thomas [Department of Orthopaedic Surgery, University of Miami Miller School of Medicine, 1600 N.W. 10th Avenue (R-12), Miami, FL 33136 (United States)

2011-08-25

Fibromatosis, or extra-abdominal desmoid tumor, is a benign disease which often has an aggressive clinical course that can be difficult to treat. We performed a retrospective review of 16 patients (12 females and four males) with a mean age of 34.2 years treated with methotrexate and vinblastine for newly diagnosed or recurrent extra-abdominal desmoid tumor. The mean age of our patient cohort was 34.2 years (range 11–70), and the mean tumor size was 11.5 cm (range 2.5–21.2 cm). The mean duration of therapy was 12 months with an average follow-up of 43 months (range 1–149 months). Fourteen of 16 patients demonstrated a clinical response to treatment. Eight of 14 patients demonstrated a radiologic decrease in tumor size. Only one patient progressed on therapy. Six patients developed recurrent symptoms after discontinuation of treatment. Chemotherapy-related symptoms including neutropenia, nausea, and vomiting were common and observed in most patients, however these side effects were mild and transient. Five patients developed peripheral neuropathy that prompted a change from vinblastine to vinorelbine during treatment. One potentially life-threatening complication (pneumocystis pneumonia) occurred which was diagnosed early and successfully treated. The use of methotrexate and vinblastine/vinorelbine in the management of fibromatosis appears to be an effective treatment with minimal treatment-related side effects.

Enhancement in blood-tumor barrier permeability and delivery of liposomal doxorubicin using focused ultrasound and microbubbles: evaluation during tumor progression in a rat glioma model

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Aryal, Muna; Park, Juyoung; Vykhodtseva, Natalia; Zhang, Yong-Zhi; McDannold, Nathan

2015-03-01

Effective drug delivery to brain tumors is often challenging because of the heterogeneous permeability of the ‘blood tumor barrier’ (BTB) along with other factors such as increased interstitial pressure and drug efflux pumps. Focused ultrasound (FUS) combined with microbubbles can enhance the permeability of the BTB in brain tumors, as well as the blood-brain barrier in the surrounding tissue. In this study, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to characterize the FUS-induced permeability changes of the BTB in a rat glioma model at different times after implantation. 9L gliosarcoma cells were implanted in both hemispheres in male rats. At day 9, 14, or 17 days after implantation, FUS-induced BTB disruption using 690 kHz ultrasound and definity microbubbles was performed in one tumor in each animal. Before FUS, liposomal doxorubicin was administered at a dose of 5.67 mg kg-1. This chemotherapy agent was previously shown to improve survival in animal glioma models. The transfer coefficient Ktrans describing extravasation of the MRI contrast agent Gd-DTPA was measured via DCE-MRI before and after sonication. We found that tumor doxorubicin concentrations increased monotonically (823  ±  600, 1817  ±  732 and 2432  ±  448 ng g-1) in the control tumors at 9, 14 and 17 d. With FUS-induced BTB disruption, the doxorubicin concentrations were enhanced significantly (P benefit from FUS-induced drug enhancement. Corresponding enhancements in Ktrans were found to be variable in large/late-stage tumors and not significantly different than controls, perhaps reflecting the size mismatch between the liposomal drug (~100 nm) and Gd-DTPA (molecular weight: 938 Da; hydrodynamic diameter: ≃2 nm). It may be necessary to use a larger MRI contrast agent to effectively evaluate the sonication-induced enhanced permeabilization in large/late-stage tumors when a large drug carrier such as a liposome is used.

Carbogen Breathing Differentially Enhances Blood Plasma Volume and 5-Fluorouracil Uptake in Two Murine Colon Tumor Models with a Distinct Vascular Structure

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Hanneke W.M. van Laarhoven

2006-06-01

Full Text Available For the systemic treatment of colorectal cancer, 5-fluorouracil (FU-based chemotherapy is the standard. However, only a subset of patients responds to chemotherapy. Breathing of carbogen (95% O2 and 5% CO2 may increase the uptake of FU through changes in tumor physiology. This study aims to monitor in animal models in vivo the effects of carbogen breathing on tumor blood plasma volume, pH, and energy status, and on FU uptake and metabolism in two colon tumor models C38 and C26a, which differ in their vascular structure and hypoxic status. Phosphorus-31 magnetic resonance spectroscopy (MRS was used to assess tumor pH and energy status, and fluorine-19 MRS was used to follow FU uptake and metabolism. Advanced magnetic resonance imaging methods using ultrasmall particles of iron oxide were performed to assess blood plasma volume. The results showed that carbogen breathing significantly decreased extracellular pH and increased tumor blood plasma volume and FU uptake in tumors. These effects were most significant in the C38 tumor line, which has the largest relative vascular area. In the C26a tumor line, carbogen breathing increased tumor growth delay by FU. In this study, carbogen breathing also enhanced systemic toxicity by FU.

Cells responsible for tumor surveillance in man: effects of radiotherapy, chemotherapy, and biologic response modifiers

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Reizenstein, P.; Ogier, C.; Blomgren, H.; Petrini, B.; Wasserman, J.

1985-01-01

Currently, the most probable theory of tumor surveillance is neither the existence of any tumor-specific, antigen-dependent, T-cell-mediated cytotoxic effect that could eliminate spontaneous tumors in man and that could be used for some kind of vaccination against tumors, nor the complete absence of any surveillance or defense systems against tumors. What is probable is the cooperation of a number of antigen-independent, relatively weakly cytotoxic or possibly only cytostatic humoral and cellular effects, including nutritional immunity, tumor necrosis factor, certain cytokines, and the cytotoxic effects mediated by macrophages, NK cells, NK-like cells, and certain stimulated T-cells. One question remaining to be solved is why these antigen-independent effects do not attack normal cells. A number of plausible hypotheses are discussed. The hypothetical surveillance system is modulated both by traditional cancer treatment and by attempts at immunomodulation. Radiotherapy reduced the T-helper cell function for almost a decade, but not those of macrophages or NK cells. T-cell changes have no prognostic implication, supporting, perhaps, the suggestion of a major role for macrophages and NK cells. Cyclic adjuvant chemotherapy reduces the peripheral lymphocyte population and several lymphocyte functions but not NK activity. Most of the parameters were normalized some years following treatment, but NK activity remained elevated and Th/Ts cell ratio was still decreased. This might possibly be taken to support the surveillance role of NK cells. Bestatin increases the frequency of lymphocytes forming rosettes with sheep red blood cells (but not their mitogenic responses), enhances NK activity, and augments the phagocytic capacity of granulocytes and monocytes (but not their cytotoxic activity). 154 references

Retinoblastoma: Achieving new standards with methods of chemotherapy

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Swathi Kaliki

2015-01-01

Full Text Available The management of retinoblastoma (RB has dramatically changed over the past two decades from previous radiotherapy methods to current chemotherapy strategies. RB is a remarkably chemotherapy-sensitive tumor. Chemotherapy is currently used as a first-line approach for children with this malignancy and can be delivered by intravenous, intra-arterial, periocular, and intravitreal routes. The choice of route for chemotherapy administration depends upon the tumor laterality and tumor staging. Intravenous chemotherapy (IVC is used most often in bilateral cases, orbital RB, and as an adjuvant treatment in high-risk RB. Intra-arterial chemotherapy (IAC is used in cases with group C or D RB and selected cases of group E tumor. Periocular chemotherapy is used as an adjunct treatment in eyes with group D and E RB and those with persistent/recurrent vitreous seeds. Intravitreal chemotherapy is reserved for eyes with persistent/recurrent vitreous seeds. In this review, we describe the various forms of chemotherapy used in the management of RB. A database search was performed on PubMed, using the terms "RB," and "treatment," "chemotherapy," "systemic chemotherapy," "IVC," "IAC," "periocular chemotherapy," or "intravitreal chemotherapy." Relevant English language articles were extracted, reviewed, and referenced appropriately.

High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors.

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Spugnini, Enrico P; Buglioni, Sabrina; Carocci, Francesca; Francesco, Menicagli; Vincenzi, Bruno; Fanciulli, Maurizio; Fais, Stefano

2014-08-21

The treatment of human cancer has been seriously hampered for decades by resistance to chemotherapeutic drugs. A very efficient mechanism of tumor resistance to drugs is the proton pumps-mediated acidification of tumor microenvironment. Metronomic chemotherapy has shown efficacy in adjuvant fashion as well as in the treatment of pets with advanced disease. Moreover, we have shown in veterinary clinical settings that pre-treatment with proton-pumps inhibitors (PPI) increases tumor responsiveness to chemotherapeutics. In this study pet with spontaneously occurring cancer have been recruited to be treated by a combination of metronomic chemotherapy and high dose PPIs and their responses have been matched to those of a historical control of ten patients treated with metronomic chemotherapy alone. Single arm, non randomized phase II open study, with historical control group, evaluating safety and efficacy of the combination of metronomic chemotherapy and alkalization. Twenty-four companion animals (22 dogs and 2 cats) were treated adding to their metronomic chemotherapy protocol the pump inhibitor lansoprazole at high dose, and a water alkalizer. Their responses have been evaluated by clinical and instrumental evaluation and matched to those of the control group. The protocol was overall well tolerated, with only two dogs experiencing side effects due to gastric hypochlorhydria consisting with vomiting and or diarrhea. In terms of overall response, in the alkalized cohort, 18 out of 24 had partial or complete responses (75%), two patients had a stable disease and the remaining patients experienced no response or progressive disease. On the other hand, only one patient in the control group experienced a complete response (10%) and three other experienced short lived responses. Median time to terminal event was 34 weeks for the experimental group versus 2 weeks in the controls (p= 0.042). Patient alkalization has shown to be well tolerated and to increase tumor response

Clinical application of radiotherapy combined with chemotherapy

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Morita, Kozo

1978-01-01

In clinical application of radiation therapy combined with chemotherapy, it is important to gain the maximal therapeutic benefit. At present we have no agents that improve the therapeutic ratio by enhancing the effect of radiation on the tumor cell selectively. Therefore, it is necessary to use combining some or all of following procedures: (1) the intraarterial infusion of the agents, (2) the selective localization by reason of the biological affinity of the agents, (3) the surgical removal of the non-sensitized tumor residue and (4) the selective sensitization of the tumor due to its shorter cell cycle. (author)

Decreased background parenchymal enhancement of the contralateral breast after two cycles of neoadjuvant chemotherapy is associated with tumor response in HER2-positive breast cancer.

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You, Chao; Gu, Yajia; Peng, Wen; Li, Jianwei; Shen, Xuxia; Liu, Guangyu; Peng, Weijun

2018-07-01

Background Several recent studies have focused on the association between background parenchymal enhancement (BPE) and tumor response to neoadjuvant chemotherapy (NAC), but early prediction of tumor response based on BPE has yet not been investigated. Purpose To retrospectively investigate whether changes in the BPE of the contralateral breast following NAC could help predict tumor response in early stage HER2-positive breast cancer. Material and Methods Data from 71 patients who were diagnosed with unilateral HER2 positive breast cancer and then underwent NAC with trastuzumab before surgery were analyzed retrospectively. Two experienced radiologists independently categorized the patients' levels of BPE of the contralateral breast into four categories (1 = minimal, 2 = mild, 3 = moderate, 4 = marked) at baseline and after the second cycle of NAC. After undergoing surgery, 34 patients achieved pathologic complete response (pCR) and 37 patients had residual disease (non-pCR). The association between BPE and histopathologic tumor response was analyzed. Result The level of BPE was higher in premenopausal than post-menopausal women both at baseline and after the second cycle of NAC ( P < 0.005). A significant reduction in BPE ( P < 0.001) was observed after the second NAC cycle; however, a more obvious decrease in BPE was identified in premenopausal relative to post-menopausal women ( P = 0.041). No significant association was identified between pCR and baseline BPE ( P = 0.287). However, after the second NAC cycle, decreased BPE was significantly associated with pCR ( P = 0.003). Conclusion For HER2-positive patients, changes in BPE may serve as an additional imaging biomarker of treatment response at an early stage.

Supercritical-Carbon Dioxide Fluid Extract from Chrysanthemum indicum Enhances Anti-Tumor Effect and Reduces Toxicity of Bleomycin in Tumor-Bearing Mice

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Hong-Mei Yang

2017-02-01

Full Text Available Bleomycin (BLM, a family of anti-tumor drugs, was reported to exhibit severe side effects limiting its usage in clinical treatment. Therefore, finding adjuvants that enhance the anti-tumor effect and reduce the detrimental effect of BLM is a prerequisite. Chrysanthemum indicum, an edible flower, possesses abundant bioactivities; the supercritical-carbon dioxide fluid extract from flowers and buds of C. indicum (CISCFE have strong anti-inflammatory, anti-oxidant, and lung protective effects. However, the role of CISCFE combined with BLM treatment on tumor-bearing mice remains unclear. The present study aimed to investigate the potential synergistic effect and the underlying mechanism of CISCFE combined with BLM in the treatment of hepatoma 22 (H22 tumor-bearing mice. The results suggested that the oral administration of CISCFE combined with BLM could markedly prolong the life span, attenuate the BLM-induced pulmonary fibrosis, suppress the production of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-α, activities of myeloperoxidase, and malondiadehyde. Moreover, CISCFE combined with BLM promoted the ascites cell apoptosis, the activities of caspases 3 and 8, and up-regulated the protein expression of p53 and down-regulated the transforming growth factor-β1 by activating the gene expression of miR-29b. Taken together, these results indicated that CISCFE could enhance the anti-cancer activity of BLM and reduce the BLM-induced pulmonary injury in H22 tumor-bearing mice, rendering it as a potential adjuvant drug with chemotherapy after further investigation in the future.

Response to neoadjuvant chemotherapy in locally advanced breast cancer according to tumor subtypes

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Tabassum, S.; Zahid, N.

2017-01-01

To compare the pathological response to neoadjuvant chemotherapy in different molecular subtypes of breast cancer Study Design: Prospective cohort study. Place and Duration of Study: Department of Oncology Liaquat National Hospital Karachi from Jan 2013 to Dec 2014. Material and Methods: A total of 119 patients received neo-adjuvant chemotherapy for locally advanced breast cancer followed by definitive surgery. Demographic, clinical and pathological data of 101 patients were available for analysis. Tumors were divided into different molecular subtypes, luminal A, luminal B human epidermal growth factor receptor 2 (HER 2) was negative, luminal B (HER 2 positive), HER 2 over expressed and triple negative. Neoadjuvant chemotherapy was given for total of eight cycles. Primary end point was pathological response [pathological complete response (PCR) versus no PCR] after surgery. Results: A total of 101 patients data were analyzed. Seventeen (16.8%) were luminal A, thirty eight (37.6%) were luminal B, out of 38 luminal B patients, twenty one (55.2%) were HER 2 + and seventeen (44.7%) were HER 2 -ve. Sixteen (15.8%) patients were HER 2 over expressed and thirty (29.7%) were triple negative. Out of 101 patients, twenty eight (27.72%) achieved PCR. A total of 5.9% achieved PCR in luminal A, 4.8% had PCR in luminal B (HER 2 -ve type), 23.5% had in luminal B (HER 2 +ve type), 50% achieved PCR in HER-2 over expressed type and 46.7% had PCR in triple negative subtype, (p=0.001). There was no significant association of PCR with age, tumor size, lymph node status, histology or grade. Conclusion: Molecular subtypes of breat cancer were found to be statistically significant predictor of PCR after neoadjuvant chemotherapy. (author)

Percentage tumor necrosis following chemotherapy in neuroblastoma correlates with MYCN status but not survival.

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Bomken, Simon; Davies, Beverley; Chong, Leeai; Cole, Michael; Wood, Katrina M; McDermott, Michael; Tweddle, Deborah A

2011-03-01

The percentage of chemotherapy-induced necrosis in primary tumors corresponds with outcome in several childhood malignancies, including high-risk metastatic diseases. In this retrospective pilot study, the authors assessed the importance of postchemotherapy necrosis in high-risk neuroblastoma with a histological and case notes review of surgically resected specimens. The authors reviewed all available histology of 31 high-risk neuroblastoma cases treated with COJEC (dose intensive etoposide and vincristine with either cyclophosphamide, cisplatin or carboplatin) or OPEC/OJEC (etoposide, vincristine and cyclophosphamide with alternating cisplatin [OPEC] or carboplatin [OJEC]) induction chemotherapy in 2 Children's Cancer & Leukaemia Group (CCLG) pediatric oncology centers. The percentage of postchemotherapy necrosis was assessed and compared with MYCN amplification status and overall survival. The median percentage of postchemotherapy tumor necrosis was 60%. MYCN status was available for 28 cases, of which 12 were amplified (43%). Survival in cases with ≥ 60% necrosis or ≥ 90% necrosis was not better than those with less necrosis, nor was percentage necrosis associated with survival using Cox regression. However, MYCN-amplified tumors showed a higher percentage of necrosis than non-MYCN-amplified tumors, 71.3% versus 37.2% (P = .006). This effect was not related to prechemotherapy necrosis and did not confer improved overall survival. Postchemotherapy tumor necrosis is higher in patients with MYCN amplification. In this study, postchemotherapy necrosis did not correlate with overall survival and should not lead to modification of postoperative treatment. However, these findings need to be confirmed in a larger prospective study of children with high-risk neuroblastoma.

Expression of the BRCA1 gene in a breast tumor: Correlation with the effect of neoadjuvant chemotherapy

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Tsyganov, M. M.; Ibragimova, M. K.; Deryusheva, I. V.; Slonimskaya, E. M.; Litviakov, N. V.

2017-09-01

Most current research is limited by only germinal mutations of the BRCA1 gene (more often 5382insC) and the number of studies, which characterize various somatic alterations of the BRCA1 gene in a tumor, namely the expression of this gene and its correlation with the efficiency of chemotherapy, which is scarce. Taking into account the data on the connection between the genetic mutation of BRCA1 with the high efficiency of the platinum medication one may suggest that the expression of the BRCA1 gene is also associated with the high sensitivity of the tumor to the platinum medication. Aim: to evaluate the correlation between the expression of the BRCA1 gene in a breast tumor with the neoadjuvant chemotherapy (NACT) efficiency. The research included 86 patients with BC. We evaluated the expression of BRCA1 in the tumor material before and after NACT. We established that objective response to NACT is connected with a high level of BRCA1 in the general group of patients (p = 0.01) and in case of docetaxel monotherapy (p < 0.05).

Non-tumor enhancement at the surgical margin on CT after the removal of brain tumors

International Nuclear Information System (INIS)

Adachi, Michito; Hosoya, Takaaki; Yamaguchi, Kohichi; Yamada, Kiyotada

1992-01-01

Marginal enhancement is occasionally seen at the surgical margin on CT after the total removal of brain tumors. This enhancement disappears in due time, and therefore we call it non-tumor enhancement. It is often difficult, however, to differentiate non-tumor enhancement from tumor recurrence. In this study, we attempted to determine the characteristics of non-tumor enhancement. The subjects of the study consisted of 15 patients with astrocytoma and one with metastatic tumor in whom sequential CT scans had been performed after total removal of the tumor. Based on the observation of these sequential CT scans, the characteristics of non-tumor enhancement were presumed to be as follows: (1) In four cases, enhancement at the surgical margin persisted more than four months after surgery and then disappeared. Therefore, these cases were considered non-tumor enhancement. Prolonged duration of enhancement such as that in these cases is not necessarily due to recurrence. Marginal enhancement within 3 mm in thickness and with a well-demarcated border like that of a flax is likely to be non-tumor enhancement. (author)

Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

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Bo Zhang

2017-12-01

Full Text Available Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents.

Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

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Zhang, Bo; Hu, Yu; Pang, Zhiqing

2017-01-01

Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR) effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents. PMID:29311946

Tumor metabolism, the ketogenic diet and β-hydroxybutyrate: novel approaches to adjuvant brain tumor therapy

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Eric C. Woolf

2016-11-01

Full Text Available Malignant brain tumors are devastating despite aggressive treatments such as surgical resection, chemotherapy and radiation therapy. The average life expectancy of patients with newly diagnosed glioblastoma is approximately ~18 months. It is clear that increased survival of brain tumor patients requires the design of new therapeutic modalities, especially those that enhance currently available treatments and/or limit tumor growth. One novel therapeutic arena is the metabolic dysregulation that results in an increased need for glucose in tumor cells. This phenomenon suggests that a reduction in tumor growth could be achieved by decreasing glucose availability, which can be accomplished through pharmacological means or through the use of a high-fat, low-carbohydrate ketogenic diet (KD. The KD, as the name implies, also provides increased blood ketones to support the energy needs of normal tissues. Preclinical work from a number of laboratories has shown that the KD does indeed reduce tumor growth in vivo. In addition, the KD has been shown to reduce angiogenesis, inflammation, peri-tumoral edema, migration and invasion. Furthermore, this diet can enhance the activity of radiation and chemotherapy in a mouse model of glioma, thus increasing survival. Additional studies in vitro have indicated that increasing ketones such as β-hydroxybutyrate in the absence of glucose reduction can also inhibit cell growth and potentiate the effects of chemotherapy and radiation. Thus, while we are only beginning to understand the pluripotent mechanisms through which the KD affects tumor growth and response to conventional therapies, the emerging data provide strong support for the use of a KD in the treatment of malignant gliomas. This has led to a limited number of clinical trials investigating the use of a KD in patients with primary and recurrent glioma.

Effect of Chemotherapy Bleomycin, Vincristin, Mitomycin and Carboplatin by Tumor Mass and Infiltration Parametrial for Cervical Cancer Patients: Case Study in Sanglah General Hospital, Denpasar

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Rini Noviyani

2017-09-01

Full Text Available BOM-cisplatin regimen for chemotherapy for cervical cancer patients has not resulted high efficacy, hence a replacement of cisplatin with carboplatin is proposed. BOM-carboplatin chemotherapy is at present a treatment for cervical cancer patients in Sanglah Hospital in Denpasar. Information about the efficacy of using the BOM-carboplatin for cervical cancer chemotherapy is not provided, therefore this research performed by observing tumor mass and parametrial infiltration. This research was carried out using case study method on 9 patients with squamous cell cervical cancer stage IIB–IIIB before and after BOM-carboplatin chemotherapy at Sanglah Hospital from February until August 2015. Examination of tumor mass and parametrial infiltration (%CFS conducted prior to chemotherapy series I and after chemotherapy series III. Sampling was done consecutively. The research data were analyzed using the normal distribution Shapiro-Wilk test continued by paired t-test with 95% confidence level, while data that is classified otherwise is transformed to logarithmic function and were analyzed using the Wilcoxon test. Based on statistical analysis there is significant reduction in tumor mass and left parametrial infiltration after the third chemotherapy with (p0.05 that is p>0,083.

Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

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Machiavelli, M R; Romero, A O; Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Ortiz, E H; Vallejo, C T; Leone, B A

1998-01-01

The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes

The role of preoperative chemotherapy in the management of Wilms' tumor. The SIOP studies. International Society of Pediatric Oncology

NARCIS (Netherlands)

Graf, N.; Tournade, M. F.; de Kraker, J.

2000-01-01

More than 25 years after introducing preoperative chemotherapy for Wilms' tumor, the benefits of this approach are well known. The preoperative protocol results in easier operations with significantly fewer tumor ruptures during surgery and a favorable stage distribution. Acute toxicity and late

SUVmax of 18F-FDG PET/CT correlates to expression of major chemotherapy-related tumor markers and serum tumor markers in gastric adenocarcinoma patients.

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Bai, Lu; Guo, Chi-Hua; Zhao, Yan; Gao, Jun-Gang; Li, Miao; Shen, Cong; Guo, You-Min; Duan, Xiao-Yi

2017-06-01

The expression of P53 was previously found by us significantly correlated with maximal standardized uptake value (SUVmax) in non-small cell lung cancer (NSCLC) patients. Hence, the aim of this study was to clarify the relationship between SUVmax and the status of the chemotherapy-related tumor marker expression or serum tumor markers in gastric adenocarcinoma patients. Sixty-four gastric adenocarcinoma patients who underwent 18F-FDG PET/CT prior to treatment were enrolled in this study. Immunohistochemistry was performed to detect changes of Her-2, P53 and Survivin in lesions, and electrochemiluminescence (ECL) method was used to quantify expression of serum CA72-4, CA19-9 and CEA of these patients. Then, the relationships between these parameters above were assessed by Spearman correlation analysis. Also, receiver-operating characteristic (ROC) curve was performed to determine the best cut-off value of SUVmax for suggesting chemotherapy resistant tumor markers. Besides, we identified a linear correlation to estimate the equations between SUVmax and the serum tumor markers. Our results showed that higher SUVmax was detected in patients with positive expression of Her-2 and P53, compared with negative groups. The Spearman correlation analysis showed that SUVmax was associated with Her-2 or P53 with the moderate relevant Pearson correlation coefficient. ROC curve analysis showed that the sensitivity and specificity of SUVmax for suggesting Her-2 or P53-positive, when the cut-off value of SUVmax was set at 3.25 or 5.45, respectively. Moreover, the relationship between SUVmax and serum tumor markers were analyzed by linear correlation analysis, and serum CA72-4 and CA19-9 could be used as independent parameters to establish an equation for SUVmax by the linear regression models. These results suggested that SUVmax of 18F-FDG PET/CT could be used to predict and evaluate Her-2 or P53 related chemotherapy resistance of gastric adenocarcinoma patients. However, before PET

Hypoxia and anemia: factors in decreased sensitivity to radiation therapy and chemotherapy?

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Harrison, Louis; Blackwell, Kimberly

2004-01-01

Hypoxia is a common feature of solid tumors that occurs across a wide variety of malignancies. Hypoxia and anemia (which contributes to tumor hypoxia) can lead to ionizing radiation and chemotherapy resistance by depriving tumor cells of the oxygen essential for the cytotoxic activities of these agents. Hypoxia may also reduce tumor sensitivity to radiation therapy and chemotherapy through one or more indirect mechanisms that include proteomic and genomic changes. These effects, in turn, can lead to increased invasiveness and metastatic potential, loss of apoptosis, and chaotic angiogenesis, thereby further increasing treatment resistance. Investigations of the prognostic significance of pretreatment tumor oxygenation status have shown that hypoxia (oxygen tension [pO(2)] value effect of hypoxia on standard cancer treatment, a variety of hypoxia- and anemia-targeted therapies have been studied in an effort to improve therapeutic effectiveness and patient outcomes. Early evidence from experimental and clinical studies suggests the administration of recombinant human erythropoietin (rHuEPO) may enhance the effectiveness of radiation therapy and chemotherapy by increasing hemoglobin levels and ameliorating anemia in patients with disease- or treatment-related anemia. However, further research is needed in the area of hypoxia-related treatment resistance and its reversal.

Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery.

Science.gov (United States)

Gao, Ning; Bozeman, Erica N; Qian, Weiping; Wang, Liya; Chen, Hongyu; Lipowska, Malgorzata; Staley, Charles A; Wang, Y Andrew; Mao, Hui; Yang, Lily

2017-01-01

The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.

Diltiazem enhances tumor blood flow: MRI study in a murine tumor

International Nuclear Information System (INIS)

Muruganandham, M.; Kasiviswanathan, A.; Jagannathan, N.R.; Raghunathan, P.; Jain, P.C.; Jain, V.

1999-01-01

Purpose: Diltiazem, a calcium-channel blocker, is known to differentially influence the radiation responses of normal and murine tumor tissues. To elucidate the underlying mechanisms, the effects of diltiazem on the radiation response of Ehrlich ascites tumor (EAT) in mice have been investigated, and the hemodynamic changes induced by diltiazem in tumor and normal muscle have been studied using magnetic resonance imaging (MRI) techniques. Methods and Materials: Ehrlich ascites tumors were grown subcutaneously in Swiss albino strain A mice. Dynamic gadodiamide and blood oxygen level dependent (BOLD) contrast enhanced 1 H MR imaging studies of EAT and normal muscle were performed after administration of diltiazem in mice using a 4.7 Tesla MR scanner. Tumor radiotherapy experiments (total dose = 10 Gy, 0.4-0.5 Gy/min, single fraction) were carried out with 30 min preadministration of diltiazem (27.5 or 55 mg/kg i.p.) to EAT-bearing mice using a teletherapy machine. Results: The diltiazem+ radiation treated group showed significant tumor regression (in congruent with 65% of the animals) and enhanced animal survival. MR-gadodiamide contrast kinetics revealed a higher magnitude of signal enhancement in diltiazem treated groups as compared to the controls. The observed changes in the magnitude of kinetic parameters were the same for both tumor and normal muscle. BOLD-MR images at 30 min after diltiazem administration showed a 25% and 8% (average) intensity enhancement from their basal values in tumor and normal muscle regions, respectively. The control group showed no significant changes. Conclusion: The present studies demonstrate the radiosensitization potential of diltiazem in the mice EAT model. The enhanced radiation response observed with diltiazem correlates with the diltiazem-induced increase in tumor blood flow (TBF) and tumor oxygenation. The present results also demonstrate the applications of BOLD-MR measurements in investigating the alterations in tumor

Early prediction of therapy response and disease free survival after induction chemotherapy in stage III non-small cell lung cancer by FDG-PET: Correlation between tumor FDG-metabolism and morphometric tumor response

International Nuclear Information System (INIS)

Baum, R.P.; Schmuecking, M.; Niesen, A.; Przetak, C.; Griesinger, F.

2002-01-01

Aim: Chemotherapy with Docetaxel and Carboplatin (DC) has shown high response rates in advanced non-small cell lung cancer (NSCLC). Histologic tumor response after chemotherapy or combined chemoradiotherapy is strongly associated with systemic tumor control and potentially cure. Metabolic tumor response assessed by FDG-PET after induction VIP-chemotherapy has been shown to be predictive of outcome in NSCLC. The aim of the present study was to correlate the tumor FDG metabolism as measured by F-18 FDG-PET with morphometric findings after DC induction chemotherapy plus Erythropoietin (10,000 IU Epo s.c. three times a week). Material and Methods: In this prospective multicenter study, 54 patients with NSCLC stage IIIA (9 patients) or IIIB (45 patients) were enrolled and received neoadjuvant treatment with D 100 mg/m 2 d1 and C AUC 7.5 d2 q21 days for 4 cycles prior to surgery. Postoperatively, all patients received adjuvant radiotherapy. WB-PET-studies (ECAT Exact 47) were obtained p.i. of 400 MBq F-18 FDG. Standardized uptake values (SUV), metabolic tumor diameter (MTD) and metabolic tumor index (MTI SUV x MTD) were assessed. Image fusion of PET and CT data was applied on a HERMES computer. Results: Of 54 enrolled patients, 46 were evaluable for response by CT. 30/46 patients (65%) achieved complete remission (CR, 1 patient) or partial remission (PR 29 patients.). Of the 46 patients, 37 patients completed neoadjuvant chemotherapy (Chx) and were studied before and after Chx by FDG-PET. 14 (30% of the 46 evaluable patients) had SUV < 2.5, corresponding to metabolic complete remission (mCR), 23 had PR or stable disease (non-mCR); in 9 patients, PET was not performed because of progressive disease demonstrated by CT. The R0-resection rate was 56% (27/48 evaluable patients). Of the 14 patients with metabolic CR, 9 were evaluated by morphometry. All had regression grades III (no vital tumor cells) or grade IIB (< 10% vital tumor cells and induced apoptosis). With a median

Inhibition of human esophageal squamous cell carcinomas by targeted silencing of tumor enhancer genes: an overview

International Nuclear Information System (INIS)

Islamian, Jalil Pirayesh; Mohammadi, Mohsen; Baradaran, Behzad

2014-01-01

Esophageal cancer has been reported as the ninth most common malignancy and ranks as the sixth most frequent cause of death worldwide. Esophageal cancer treatment involves surgery, chemotherapy, radiation therapy, or combination therapy. Novel strategies are needed to boost the oncologic outcome. Recent advances in the molecular biology of esophageal cancer have documented the role of genetic alterations in tumorigenesis. Oncogenes serve a pivotal function in tumorigenesis. Targeted therapies are directed at the unique molecular signature of cancer cells for enhanced efficacy with low toxicity. RNA interference (RNAi) technology is a powerful tool for silencing endogenous or exogenous genes in mammalian cells. Related results have shown that targeting oncogenes with siRNAs, specifically the mRNA, effectively reduces tumor cell proliferation and induces apoptotic cell death. This article will briefly review studies on silencing tumor enhancer genes related to the induction of esophageal cancer

Timed sequential chemotherapy of cytoxan-refractory multiple myeloma with cytoxan and adriamycin based on induced tumor proliferation.

Science.gov (United States)

Karp, J E; Humphrey, R L; Burke, P J

1981-03-01

Malignant plasma cell proliferation and induced humoral stimulatory activity (HSA) occur in vivo at a predictable time following drug administration. Sequential sera from 11 patients with poor-risk multiple myeloma (MM) undergoing treatment with Cytoxan (CY) 2400 mq/sq m were assayed for their in vitro effects on malignant bone marrow plasma cell tritiated thymidine (3HTdR) incorporation. Peak HSA was detected day 9 following CY. Sequential changes in marrow malignant plasma cell 3HTdR-labeling indices (LI) paralleled changes in serum activity, with peak LI occurring at the time of peak HS. An in vitro model of chemotherapy demonstrated that malignant plasma cell proliferation was enhanced by HSA, as determined by 3HTdR incorporation assay, 3HTdR LI, and tumor cells counts, and that stimulated plasma cells were more sensitive to cytotoxic effects of adriamycin (ADR) than were cells cultured in autologous pretreatment serum. Based on these studies, we designed a clinical trial to treat 12 CY-refractory poor-risk patients with MM in which ADR (60 mg/sq m) was administered at the time of peak HSA and residual tumor cell LI (day 9) following initial CY, 2400 mg/m (CY1ADR9). Eight of 12 (67%) responded to timed sequential chemotherapy with a greater than 50% decrement in monoclonal protein marker and a median survival projected to be greater than 8 mo duration (range 4-21+ mo). These clinical results using timed sequential CY1ADR9 compare favorably with results obtained using ADR in nonsequential chemotherapeutic regimens.

Cancer cell adaptation to chemotherapy

International Nuclear Information System (INIS)

Di Nicolantonio, Federica; Johnson, Penny; Somers, Shaw S; Toh, Simon; Higgins, Bernie; Lamont, Alan; Gulliford, Tim; Hurren, Jeremy; Yiangou, Constantinos; Cree, Ian A; Mercer, Stuart J; Knight, Louise A; Gabriel, Francis G; Whitehouse, Pauline A; Sharma, Sanjay; Fernando, Augusta; Glaysher, Sharon; Di Palma, Silvana

2005-01-01

Tumor resistance to chemotherapy may be present at the beginning of treatment, develop during treatment, or become apparent on re-treatment of the patient. The mechanisms involved are usually inferred from experiments with cell lines, as studies in tumor-derived cells are difficult. Studies of human tumors show that cells adapt to chemotherapy, but it has been largely assumed that clonal selection leads to the resistance of recurrent tumors. Cells derived from 47 tumors of breast, ovarian, esophageal, and colorectal origin and 16 paired esophageal biopsies were exposed to anticancer agents (cisplatin; 5-fluorouracil; epirubicin; doxorubicin; paclitaxel; irinotecan and topotecan) in short-term cell culture (6 days). Real-time quantitative PCR was used to measure up- or down-regulation of 16 different resistance/target genes, and when tissue was available, immunohistochemistry was used to assess the protein levels. In 8/16 paired esophageal biopsies, there was an increase in the expression of multi-drug resistance gene 1 (MDR1) following epirubicin + cisplatin + 5-fluorouracil (ECF) chemotherapy and this was accompanied by increased expression of the MDR-1 encoded protein, P-gp. Following exposure to doxorubicin in vitro, 13/14 breast carcinomas and 9/12 ovarian carcinomas showed >2-fold down-regulation of topoisomerase IIα (TOPOIIα). Exposure to topotecan in vitro, resulted in >4-fold down-regulation of TOPOIIα in 6/7 colorectal tumors and 8/10 ovarian tumors. This study suggests that up-regulation of resistance genes or down-regulation in target genes may occur rapidly in human solid tumors, within days of the start of treatment, and that similar changes are present in pre- and post-chemotherapy biopsy material. The molecular processes used by each tumor appear to be linked to the drug used, but there is also heterogeneity between individual tumors, even those with the same histological type, in the pattern and magnitude of response to the same drugs. Adaptation

Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

Directory of Open Access Journals (Sweden)

Thamm Reinhard

2006-06-01

Full Text Available Abstract Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical

Integration of chemotherapy into current treatment strategies for brain metastases from solid tumors

International Nuclear Information System (INIS)

Nieder, Carsten; Grosu, Anca L; Astner, Sabrina; Thamm, Reinhard; Molls, Michael

2006-01-01

Patients with brain metastases represent a heterogeneous group where selection of the most appropriate treatment depends on many patient- and disease-related factors. Eventually, a considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. Whole-brain radiotherapy in combination with chemotherapy has recently gained increasing attention and is hoped to augment the palliative effect of whole-brain radiotherapy alone and to extend survival in certain subsets of patients with controlled extracranial disease and good performance status. The randomized trials of whole-brain radiotherapy vs. whole-brain radiotherapy plus chemotherapy suggest that this concept deserves further study, although they failed to improve survival. However, survival might not be the most relevant endpoint in a condition, where most patients die from extracranial progression. Sometimes, the question arises whether patients with newly detected brain metastases and the indication for systemic treatment of extracranial disease can undergo standard systemic chemotherapy with the option of deferred rather than immediate radiotherapy to the brain. The literature contains numerous small reports on this issue, mainly in malignant melanoma, breast cancer, lung cancer and ovarian cancer, but very few sufficiently powered randomized trials. With chemotherapy alone, response rates were mostly in the order of 20–40%. The choice of chemotherapy regimen is often complicated by previous systemic treatment and takes into account the activity of the drugs in extracranial metastatic disease. Because the blood-brain barrier is partially disrupted in most macroscopic metastases, systemically administered agents can gain access to such tumor sites. Our systematic literature review suggests that both chemotherapy and radiochemotherapy for newly diagnosed brain metastases need further critical evaluation before standard clinical implementation. A potential chemotherapy

Gold namoprtices enhance anti-tumor effect of radiotherapy to hypoxic tumor

Energy Technology Data Exchange (ETDEWEB)

Kim, Mi Sun; Lee, Eun Jung; Kim, Jae Won; Keum, Ki Chang; Koom, Woong Sub [Dept. of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Chung, Ui Seok; Koh, Won Gun [Dept. of Chemical and Biomolecular Engineering, Yonsei University, Seoul (Korea, Republic of)

2016-09-15

Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible factor-1α (HIF-1α) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors.

Gold namoprtices enhance anti-tumor effect of radiotherapy to hypoxic tumor

International Nuclear Information System (INIS)

Kim, Mi Sun; Lee, Eun Jung; Kim, Jae Won; Keum, Ki Chang; Koom, Woong Sub; Chung, Ui Seok; Koh, Won Gun

2016-01-01

Hypoxia can impair the therapeutic efficacy of radiotherapy (RT). Therefore, a new strategy is necessary for enhancing the response to RT. In this study, we investigated whether the combination of nanoparticles and RT is effective in eliminating the radioresistance of hypoxic tumors. Gold nanoparticles (GNPs) consisting of a silica core with a gold shell were used. CT26 colon cancer mouse model was developed to study whether the combination of RT and GNPs reduced hypoxia-induced radioresistance. Hypoxia inducible factor-1α (HIF-1α) was used as a hypoxia marker. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were conducted to evaluate cell death. Hypoxic tumor cells had an impaired response to RT. GNPs combined with RT enhanced anti-tumor effect in hypoxic tumor compared with RT alone. The combination of GNPs and RT decreased tumor cell viability compare to RT alone in vitro. Under hypoxia, tumors treated with GNPs + RT showed a higher response than that shown by tumors treated with RT alone. When a reactive oxygen species (ROS) scavenger was added, the enhanced antitumor effect of GNPs + RT was diminished. In the present study, hypoxic tumors treated with GNPs + RT showed favorable responses, which might be attributable to the ROS production induced by GNPs + RT. Taken together, GNPs combined with RT seems to be potential modality for enhancing the response to RT in hypoxic tumors

Enhanced therapeutic effect of APAVAC immunotherapy in combination with dose-intense chemotherapy in dogs with advanced indolent B-cell lymphoma.

Science.gov (United States)

Marconato, L; Stefanello, D; Sabattini, S; Comazzi, S; Riondato, F; Laganga, P; Frayssinet, P; Pizzoni, S; Rouquet, N; Aresu, L

2015-09-22

The aim of this non-randomized controlled trial was to compare time to progression (TTP), lymphoma-specific survival (LSS), and safety of an autologous vaccine (consisting of hydroxyapatite ceramic powder and Heat Shock Proteins purified from the dogs' tumors, HSPPCs-HA) plus chemotherapy versus chemotherapy alone in dogs with newly diagnosed, clinically advanced, histologically confirmed, multicentric indolent B-cell lymphoma. The vaccine was prepared from dogs' resected lymph nodes and administered as an intradermal injection. Forty-five client-owned dogs were enrolled: 20 dogs were treated with dose-intense chemotherapy, and 25 received concurrent immunotherapy. Both treatment arms were well tolerated, with no exacerbated toxicity in dogs also receiving the vaccine. TTP was significantly longer for dogs treated with chemo-immunotherapy versus those receiving chemotherapy only (median, 209 versus 85 days, respectively, P=0.015). LSS was not significantly different between groups: dogs treated with chemo-immunotherapy had a median survival of 349 days, and those treated with chemotherapy only had a median survival of 200 days (P=0.173). Among vaccinated dogs, those mounting an immune response had a significantly longer TTP and LSS than those with no detectable response (P=0.012 and P=0.003, respectively). Collectively these results demonstrate that vaccination with HSPPCs-HA may produce clinical benefits with no increased toxicity, thereby providing a strategy for enhancing chemotherapy in dogs with advanced indolent lymphoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemotherapy-induced Spontaneous Pneumothorax: Case Series

Directory of Open Access Journals (Sweden)

Een Hendarsih

2016-09-01

The mechanism of pneumothorax following chemotherapy is not clearly understood yet, however, several hypotheses have been considered: 1 the rupture of a subpleural bulla after chemotherapy; 2 the rupture of an emphysematous bulla in an over expanded portion of the lung which is partially obstructed by a neoplasm; 3 tumor lyses or necrosis due to cytotoxic chemotherapy directly induces the formation of fistula. Dyspnea and chest pain suddenly appear during successful chemotherapy for metastatic chemosensitive tumors should alert the physician to the possibility of SP. The treatment is directed toward lung re-expansion. Chemotherapy induced pneumothorax should be considered as oncologic emergency.

Tumor Lysis Syndrome (TLS following intrathecal chemotherapy in a child with acute myelogenous leukemia (AML

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Chana L. Glasser, MD

2017-01-01

Full Text Available Tumor Lysis Syndrome (TLS is a well-known complication of induction therapy for hematologic malignancies. It is characterized by rapid breakdown of malignant white blood cells (WBCs leading to metabolic derangements and serious morbidity if left untreated. Most commonly, TLS is triggered by systemic chemotherapy, however, there have been case reports of TLS following intrathecal (IT chemotherapy, all in patients with acute lymphoblastic leukemia (ALL/lymphoma. Here, we report the first case of a patient with acute myelogenous leukemia (AML who developed TLS following a single dose of IT cytosine arabinoside (Ara-C.

Dramatic Tumor Shrinkage of Locally Advanced and Inoperable Adenoid Cystic Carcinoma after Intra-arterial Chemotherapy

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Fu-Jen Hsueh

2015-06-01

Full Text Available Adenoid cystic carcinoma is rare and usually arises in the salivary glands. It grows slowly, but is characterized by easy perineural invasion with local infiltration and distant metastasis. In metastatic setting, the efficacy of intravenous chemotherapy is limited. Herein, we report one male patient who had a advanced, inoperable adenoid cystic carcinoma with lung metastasis, presenting with right buccal unhealed ulcer, pain and poor intake, whose loco-regional tumors responded dramatically after intra-arterial chemotherapy and his symptoms were almost completely relieved. We also make a literature review for treatment of adenoid cystic carcinoma.

Oral mucositis in patients treated with chemotherapy for solid tumors: a retrospective analysis of 150 cases

NARCIS (Netherlands)

Raber-Durlacher, J. E.; Weijl, N. I.; Abu Saris, M.; de Koning, B.; Zwinderman, A. H.; Osanto, S.

2000-01-01

The incidence and the severity of chemotherapy-associated oral mucositis were determined in a retrospective analysis of 150 patients with various solid tumors. In addition, possible risk factors for the development of mucositis were identified. Patients were treated with chemotherapeutic regimens

Novel formulations and new mechanisms of delivering chemotherapy.

Science.gov (United States)

Stinchcombe, Thomas E

2014-01-01

The identification of epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangements and the development of targeted therapy for patients with these molecular alterations has been a tremendous advance in the treatment of advanced stage or metastatic non-small cell lung cancer (NSCLC). However, the majority of patients with advanced stage NSCLC will not have one of these molecular alterations and will receive chemotherapy as their primary therapy. Chemotherapy remains a critical component of therapy for resected and locally advanced NSCLC, as well as for patients with limited-stage and extensive stage small cell lung cancer (SCLC). A significant unmet need exists to develop novel chemotherapy agents and to improve the efficacy and toxicity of currently available agents. Several novel formulations of currently available chemotherapy agents are in development for NSCLC and SCLC. Antibody conjugates are therapeutic agents that employ a tumor-specific monoclonal antibody conjugated to a cytotoxic or radionuclide agent. After the monoclonal antibody binds to the tumor antigen, these agents are internalized, and the link between the antibody and the therapeutic agent is dissolved and the cytotoxic agent is release intracellularly. This enhanced delivery of chemotherapy to malignant tissues has the potential to improve efficacy and reduce toxicity. Antibody conjugates to therapeutic agents are currently available for other malignancies and are in development for NSCLC and SCLC.

Ring enhancement in recurrent gliomas

International Nuclear Information System (INIS)

Ogashiwa, Motohide; Takeuchi, Kazuo; Akai, Keiichiro

1981-01-01

The clinical courses,CT scans, and postmortem reports for 6 glioma patients treated by surgery, radiation, and chemotherapy were reviewed. They underwent reoperation and/or retreatment with radiation or chemotherapy for recurrent tumors. CT scans taken at the time of recurrence or about one month prior to death showed ring enhancement of varied size and form after intensive treatment. The cases were examined histologically in correlation with the CT features and divided into two groups based on the pathological findings in the centers surrounded by areas of ring enhancement. The 1st group demonstrated a large necrotic area in the center, and the 2nd group, a cystic tumor. Tumor cells were found to have spread throughout the high-density areas around the necrotic area or cyst. However, gross differentiation between tumor and necrosis was difficult. In addition to an increase in cellularity, all cases demonstrated vascular proliferation, and dilatation of vessels in the sulci or sulci adjacent to gyri invaded by the tumor. The contrast enhancement corresponded well with the vascular proliferation in these areas. It is concluded that vascular proliferation or dilatation of vessels in and around the tumor is an important factor in demonstrating high-density areas in ring enhancement, while a cyst or necrosis in the tumor center is revealed as a low-density area in the CT scan of recurrent gliomas. (author)

Ring enhancement in recurrent gliomas

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Ogashiwa, M; Takeuchi, K; Akai, K [Kyorin Univ., Mitaka, Tokyo (Japan). School of Medicine

1981-08-01

The clinical courses,CT scans, and postmortem reports for 6 glioma patients treated by surgery, radiation, and chemotherapy were reviewed. They underwent reoperation and/or retreatment with radiation or chemotherapy for recurrent tumors. CT scans taken at the time of recurrence or about one month prior to death showed ring enhancement of varied size and form after intensive treatment. The cases were examined histologically in correlation with the CT features and divided into two groups based on the pathological findings in the centers surrounded by areas of ring enhancement. The 1st group demonstrated a large necrotic area in the center, and the 2nd group, a cystic tumor. Tumor cells were found to have spread throughout the high-density areas around the necrotic area or cyst. However, gross differentiation between tumor and necrosis was difficult. In addition to an increase in cellularity, all cases demonstrated vascular proliferation, and dilatation of vessels in the sulci or sulci adjacent to gyri invaded by the tumor. The contrast enhancement corresponded well with the vascular proliferation in these areas. It is concluded that vascular proliferation or dilatation of vessels in and around the tumor is an important factor in demonstrating high-density areas in ring enhancement, while a cyst or necrosis in the tumor center is revealed as a low-density area in the CT scan of recurrent gliomas.

Increased Tumor Oxygenation and Drug Uptake During Anti-Angiogenic Weekly Low Dose Cyclophosphamide Enhances the Anti-Tumor Effect of Weekly Tirapazamine

Science.gov (United States)

Doloff, J.C.; Khan, N.; Ma, J.; Demidenko, E.; Swartz, H.M.; Jounaidi, Y.

2010-01-01

Metronomic cyclophosphamide treatment is associated with anti-angiogenic activity and is anticipated to generate exploitable hypoxia using hypoxia-activated prodrugs. Weekly administration of tirapazamine (TPZ; 5 mg/kg body weight i.p.) failed to inhibit the growth of 9L gliosarcoma tumors grown s.c. in scid mice. However, the anti-tumor effect of weekly cyclophosphamide (CPA) treatment (140 mg/kg BW i.p.) was substantially enhanced by weekly TPZ administration. An extended tumor free period and increased frequency of tumor eradication without overt toxicity were observed when TPZ was given 3, 4 or 5 days after each weekly CPA treatment. Following the 2nd CPA injection, Electron Paramagnetic Resonance (EPR) Oximetry indicated significant increases in tumor pO2, starting at 48 hr, which further increased after the 3rd CPA injection. pO2 levels were, however, stable in growing untreated tumors. A strong negative correlation (−0.81) between tumor pO2 and tumor volume during 21 days of weekly CPA chemotherapy was observed, indicating increasing tumor pO2 with decreasing tumor volume. Furthermore, CPA treatment resulted in increased tumor uptake of activated CPA. CPA induced increases in VEGF RNA, which reached a maximum on day 1, and in PLGF RNA which was sustained throughout the treatment, while anti-angiogenic host thrombospondin-1 increased dramatically through day 7 post-CPA treatment. Weekly cyclophosphamide treatment was anticipated to generate exploitable hypoxia. However, our findings suggest that weekly CPA treatment induces a functional improvement of tumor vasculature, which is characterized by increased tumor oxygenation and drug uptake in tumors, thus counter-intuitively, benefiting intratumoral activation of TPZ and perhaps other bioreductive drugs. PMID:19754361

Impact of adjuvant chemotherapy for gliomatosis cerebri

International Nuclear Information System (INIS)

Kong, Doo-Sik; Nam, Do-Hyun; Kim, Sung Tae; Lee, Jung-Il; Suh, Yeon-Lim; Lim, Do Hoon; Kim, Won Seog; Kwon, Ki-Hoon; Park, Kwan; Kim, Jong Hyun

2010-01-01

Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC. Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy. Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008). Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC

Salmonella Immunotherapy Improves the Outcome of CHOP Chemotherapy in Non-Hodgkin Lymphoma-Bearing Mice

Science.gov (United States)

Bascuas, Thais; Moreno, María; Grille, Sofía; Chabalgoity, José A.

2018-01-01

We have previously shown that Salmonella immunotherapy is effective to treat B-cell non-Hodgkin lymphoma (B-NHL) in mice. However, this model involves animals with high tumor burden, whereas in the clinics B-NHL patients are usually treated with chemotherapy (CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone) as first-line therapy prior to immunotherapy. Recently, we have described a NHL-B preclinical model using CHOP chemotherapy to achieve MRD in immunocompetent animals that closely resemble patients’ conditions. In this work, we assessed the efficacy of Salmonella immunotherapy in B-NHL-bearing mice undergoing chemotherapy. Salmonella administration significantly delayed tumor growth and prolonged survival of chemotherapy-treated NHL-bearing animals. Mice receiving the CHOP–Salmonella combined therapy showed increased numbers of tumor-infiltrating leukocytes and a different profile of cytokines and chemokines expressed in the tumor microenvironment. Further, Salmonella immunotherapy in CHOP-treated animals also enhanced NK cells cytotoxic activity as well as induced systemic lymphoma-specific humoral and cellular responses. Chemotherapy treatment profoundly impacted on the general health status of recipient animals, but those receiving Salmonella showed significantly better overall body condition. Altogether, the results clearly demonstrated that Salmonella immunotherapy could be safely used in individuals under CHOP treatment, resulting in a better prognosis. These results give strong support to consider Salmonella as a neoadjuvant therapy in a clinical setting. PMID:29410666

A model to describe potential effects of chemotherapy on critical radiobiological treatments

Science.gov (United States)

Rodríguez-Pérez, D.; Desco, M. M.; Antoranz, J. C.

2016-08-01

Although chemo- and radiotherapy can annihilate tumors on their own. they are also used in coadjuvancy: improving local effects of radiotherapy using chemotherapy as a radiosensit.izer. The effects of radiotherapy are well described by current radiobiological models. The goal of this work is to describe a discrete radiotherapy model, that has been previously used describe high radiation dose response as well as unusual radio-responses of some types of tumors (e.g. prostate cancer), to obtain a model of chemo+radiotherapy that can describe how the outcome of their combination is a more efficient removal of the tumor. Our hypothesis is that, although both treatments haven different mechanisms, both affect similar key points of cell metabolism and regulation, that lead to cellular death. Hence, we will consider a discrete model where chemotherapy may affect a fraction of the same targets destroyed by radiotherapy. Although radiotherapy reaches all cells equally, chemotherapy diffuses through a tumor attaining lower concentration in its center and higher in its surface. With our simulations we study the enhanced effect of combined therapy treatment and how it depends on the tissue critical parameters (the parameters of the lion-extensive radiobiological model), the number of “targets” aimed at by chemotherapy, and the concentration and diffusion rate of the drug inside the tumor. The results show that an equivalent, cliemo-radio-dose can be computed that allows the prediction of the lower radiation dose that causes the same effect than a radio-only treatment.

Chemotherapy disruption of efficient radiotherapy

International Nuclear Information System (INIS)

Nervi, C.; Friedman, M.

1974-01-01

Studies on the use of chemotherapy in combination with radiotherapy are reviewed. Some topics discussed are: indications for the use of combined chemotherapy and radiotherapy; improvement of the therapeutic ratio following the use of methotrexate; advantages of preirradiation and postirradiation chemotherapy; side effects following simultaneous chemotherapy and radiotherapy; and effects of chemotherapy on cure rate of radiosensitive and radioresistant tumors. (U.S.)

Inflammatory markers in blood and serum tumor markers predict survival in patients with epithelial appendiceal neoplasms undergoing surgical cytoreduction and intraperitoneal chemotherapy.

Science.gov (United States)

Chua, Terence C; Chong, Chanel H; Liauw, Winston; Zhao, Jing; Morris, David L

2012-08-01

The study examines the role inflammatory and tumor markers as biomarkers to preoperatively predict outcome in patients with epithelial appendiceal neoplasm undergoing cytoreduction and intraperitoneal chemotherapy. Associations between baseline variables, tumor markers [CEA (carcinoembyronic antigen], CA125, CA199), inflammatory markers including neutrophils-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-reactive protein (CRP) with progression-free survival (PFS) and overall survival (OS) were examined in patients undergoing surgical cytoreduction and intraperitoneal chemotherapy for epithelial appendiceal neoplasm. A total of 174 patients with epithelial appendiceal neoplasm (low-grade pseudomyxoma, n = 117; appendiceal cancer, n = 57) underwent cytoreduction. On univariate analysis, all 3 inflammatory and tumor markers predicted for both PFS and OS, respectively; NLR ≤ 2.6 (P = 0.01, P = 0.002), PLR ≤ 166 (P = 0.006, P = 0.016), CRP ≤ 12.5 (P = 0.001, P = 0.008), CEA (P 37 (P = 0.003), and a CRP > 12.5 (P = 0.013). A higher peritoneal cancer index (PCI > 24) was associated with elevation in CEA > 12, CA125 > 39, CA199 > 37, PLR > 166 and CRP > 12. The tumor histologic subtype was associated with CA 199 levels. The results from this investigation suggest that preoperative inflammatory markers in blood and serologic tumor markers may predict outcomes and are associated with tumor biology in patients with epithelial appendiceal neoplasm undergoing cytoreduction and intraperitoneal chemotherapy treatment.

Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice

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Kim Sung-Ho

2009-03-01

Full Text Available Abstract Background Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. Methods HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. Results In melanoma-bearing mice, cisplatin (4 mg/kg B.W. reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-γ secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. Conclusion HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.

Integrated genomics of ovarian xenograft tumor progression and chemotherapy response

International Nuclear Information System (INIS)

Stuckey, Ashley; Brodsky, Alexander S; Fischer, Andrew; Miller, Daniel H; Hillenmeyer, Sara; Kim, Kyu K; Ritz, Anna; Singh, Rakesh K; Raphael, Benjamin J; Brard, Laurent

2011-01-01

can identify genes that are likely important for chemotherapy response. Our findings suggest a new approach to identify candidate genes that are critical for anti-tumor therapy

Dysphagia is not a Valuable Indicator of Tumor Response after Preoperative Chemotherapy for R0 Resected Patients with Adenocarcinoma of the Gastroesophageal Junction

DEFF Research Database (Denmark)

Strandby, Rune B; Svendsen, Lars Bo; Bæksgaard, Lene

2016-01-01

was to evaluate dysphagia as a predictor of tumor response after preoperative chemotherapy and as a predictor of recurrence and survival. METHODS: Patients with adenocarcinoma of the gastroesophageal junction, treated between 2010 and 2012, were retrospectively reviewed. Dysphagia scores (Mellow-Pinkas) were...... obtained before and after three cycles of perioperative chemotherapy together with clinicopathological patient characteristics. A clinical response was defined as improvement of dysphagia by at least 1 score from the baseline. The tumor response was defined as down staging of T-stage from initial computer...... tomography (CT) scan (cT-stage) to pathologic staging of surgical specimen (pT-stage). Patients were followed until death or censored on June 27th, 2014. RESULTS: Of the 110 included patients, 59.1% had improvement of dysphagia after three cycles of perioperative chemotherapy, and 31.8% had a chemotherapy...

[A case of polymyositis associated with transverse colon cancer that responded to tumor resection and chemotherapy].

Science.gov (United States)

Uchida, Yuichiro; Okabe, Michio; Kawamoto, Yusuke; Tsukumo, Yuta; Ito, Tadashi

2015-04-01

A 72-year-old woman was admitted to our hospital because of muscle weakness and was diagnosed as having polymyositis. Whole-body evaluation revealed advanced transverse colon cancer, and we therefore considered it likely that the patient had paraneoplastic myositis. We performed a curative surgical resection for colon cancer, after which her serum creatine phosphokinase(CPK)level greatly decreased. Steroid therapy was administered postoperatively. However, her CPK levels remained persistently high, even after steroid pulse therapy, and we considered that this was due to steroid-resistance myositis. We administered chemotherapy for colon cancer using 5-fluorouracil plus Leucovorin(5-FU/LV), after which the CPK levels gradually decreased. There have been few previous reports of polymyositis associated with colon cancer and a standard treatment for paraneoplastic myositis has not been established. Most clinicians believe that treatment of the primary tumor may contribute to an improvement of myositis, and in our case, tumor resection and chemotherapy were effective.

Tumor residual pós-quimioterapia neoadjuvante para câncer de mama: impacto sobre o tratamento cirúrgico conservador Residual tumor after neoadjuvant chemotherapy for breast cancer: impact on conservative surgical treatment

Directory of Open Access Journals (Sweden)

Edison Mantovani Barbosa

1999-05-01

Full Text Available Objetivo: analisar as alterações histopatológicas provocadas pela ação da quimioterapia neoadjuvante (fluoracil, epirrubicina e ciclofosfamida; FEC -- 4 ciclos na área tumoral, no tecido mamário adjacente e nos linfonodos homolaterais, em peças cirúrgicas obtidas de pacientes portadoras de carcinomas primários da mama. Método: estudo histológico detalhado de 30 peças cirúrgicas obtidas por mastectomia radical (Patey de pacientes portadoras de carcinomas primários da mama, previamente submetidas a esse tipo de terapêutica sistêmica. Resultados: observamos regressão tumoral, de grau variável, em todas as peças analisadas. Esta regressão ocorreu de forma irregular, restando inúmeros focos refratários na área ocupada pelo tumor primário. Observamos focos celulares resistentes independentes do tumor primário no tecido mamário. Detalhamos outros achados histopatológicos decorrentes da ação quimioterápica nos tecidos tumoral e mamário, como calcificações e fibrose, e nos linfonodos axilares homolaterais. Conclusão: concluímos que a ação da quimioterapia neoadjuvante não é uniforme, restando focos tumorais refratários, tanto na área do tumor inicial, quanto à distância. A regressão do tumor independe da resposta de regressão dos linfonodos axilares metastáticos. A utilização da cirurgia conservadora pós-quimioterapia neoadjuvante (FEC deve ser evitada.Purpose: analysis of histopathologic alterations caused by neoadjuvant chemotherapy (fluorouracil, epirubicine, cyclophosphamide; FEC - 4 cycles at the tumor site, adjacent mammary tissue and homolateral lymph nodes, as observed in sections of patients with primary breast carcinomas. Method: histological studies performed on 30 surgical sections obtained from radical mastectomy (Patey of patients with primary breast carcinomas, who underwent prior neoadjuvant systemic therapy. Results: all sections showed tumor regression with variable intensity. This

WE-D-BRE-04: Modeling Optimal Concurrent Chemotherapy Schedules

International Nuclear Information System (INIS)

Jeong, J; Deasy, J O

2014-01-01

Purpose: Concurrent chemo-radiation therapy (CCRT) has become a more common cancer treatment option with a better tumor control rate for several tumor sites, including head and neck and lung cancer. In this work, possible optimal chemotherapy schedules were investigated by implementing chemotherapy cell-kill into a tumor response model of RT. Methods: The chemotherapy effect has been added into a published model (Jeong et al., PMB (2013) 58:4897), in which the tumor response to RT can be simulated with the effects of hypoxia and proliferation. Based on the two-compartment pharmacokinetic model, the temporal concentration of chemotherapy agent was estimated. Log cell-kill was assumed and the cell-kill constant was estimated from the observed increase in local control due to concurrent chemotherapy. For a simplified two cycle CCRT regime, several different starting times and intervals were simulated with conventional RT regime (2Gy/fx, 5fx/wk). The effectiveness of CCRT was evaluated in terms of reduction in radiation dose required for 50% of control to find the optimal chemotherapy schedule. Results: Assuming the typical slope of dose response curve (γ50=2), the observed 10% increase in local control rate was evaluated to be equivalent to an extra RT dose of about 4 Gy, from which the cell-kill rate of chemotherapy was derived to be about 0.35. Best response was obtained when chemotherapy was started at about 3 weeks after RT began. As the interval between two cycles decreases, the efficacy of chemotherapy increases with broader range of optimal starting times. Conclusion: The effect of chemotherapy has been implemented into the resource-conservation tumor response model to investigate CCRT. The results suggest that the concurrent chemotherapy might be more effective when delayed for about 3 weeks, due to lower tumor burden and a larger fraction of proliferating cells after reoxygenation

MRI of cervical carcinoma: before and after chemotherapy

International Nuclear Information System (INIS)

Kim, Jung Sik; Suh, Soo Jhi; Choi, Tae Jin; Lee, Tae Sung; Suh, Young Wook

1992-01-01

To evaluate usefulness of MR in assessment of tumor response to the chemotherapy, we prospectively studied cases of cervical carcinoma with more than 2.5cm in diameter or stage IIb or more. Three courses of chemotherapy were performed with cisplatin and 5 F-U. MR images were obtained both before and after chemotherapy. Nine of 13 patients were undertaken radical hysterectomy after chemotherapy and MR amination. MR volumetry, stage and depth of stromal invasion were compared before and after chemotherapy. And in 9 patients who underwent radical hysterectomy, comparison of pathologic and MR imaging findings were also done. The results were following. 1) All tumors dectrased in volume (m = 80.5%). 2) Five tumors (38.5%) reduced in stage, IB → CIS (1); IIA → CIS (1), IIA → IB (2), IIB → IB (1). 3) Depth of stromal invasion in MRI correlated well with that of histopathologic specimen in 7 of the 9 patients. Conclusively MR imaging is useful in assessment of tumor response to chemotherapy

Effect of Xiao Chaihu Tang combined with intravenous chemotherapy on tumor markers and immune function in patients with advanced breast cancer

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Jian-Ping Zhong

2017-05-01

Full Text Available Objective: To study the effect of Xiao Chaihu Tang combined with intravenous chemotherapy on tumor markers and immune function in patients with advanced breast cancer. Methods: 76 patients with advanced breast cancer treated in our hospital between May 2012 and November 2015 were collected and divided into the combined treatment group (n=34 who accepted Xiao Chaihu Tang combined with intravenous chemotherapy and the control group (n=42 who accepted intravenous chemotherapy alone according to different treatment, and the treatment cycle was 3 months for both groups. Before treatment and 3 months after treatment, ELISA method was used to detect serum levels of broad-spectrum tumor markers and breast cancerspecific tumor markers; flow cytometer was used to detect cellular immune function index levels, and turbidimetric immunoassay was used to detect humoral immune function index levels in peripheral blood. Results: Before treatment, differences in serum tumor marker levels as well as cellular immunity and humoral immunity index levels in peripheral blood were not statistically significant between two groups of patients (P>0.05; after 3 months of treatment, broad-spectrum tumor markers carcinoembryonic antigen (CEA, carbohydrate antigen 153 (CA153 and carbohydrate antigen 125 (CA125 levels in serum of combined treatment group were lower than those of control group, and breast cancer-specific tumor markers insulin-like growth factor-1 (IGF-1, midkine (MK, soluble E-cadherin (sEC and thymidine kinase 1 (TK1 levels were lower than those of control group (P<0.05; CD3+ and CD4+ T lymphocyte levels as well as CD4+/CD8+ ratio in peripheral blood of combined treatment group were higher than those of control group while CD8+ T lymphocyte level was lower than that of control group, and immunoglobulin G (IgG, immunoglobulin A (IgA and immunoglobulin M (IgM levels in peripheral blood were higher than those of control group (P<0.05. Conclusions: Xiao Chaihu Tang

A model to describe potential effects of chemotherapy on critical radiobiological treatments

International Nuclear Information System (INIS)

Rodríguez-Pérez, D.; Desco, M.M.; Antoranz, J.C.

2016-01-01

Although chemo- and radiotherapy can annihilate tumors on their own. they are also used in coadjuvancy: improving local effects of radiotherapy using chemotherapy as a radiosensit.izer. The effects of radiotherapy are well described by current radiobiological models. The goal of this work is to describe a discrete radiotherapy model, that has been previously used describe high radiation dose response as well as unusual radio-responses of some types of tumors (e.g. prostate cancer), to obtain a model of chemo+radiotherapy that can describe how the outcome of their combination is a more efficient removal of the tumor. Our hypothesis is that, although both treatments haven different mechanisms, both affect similar key points of cell metabolism and regulation, that lead to cellular death. Hence, we will consider a discrete model where chemotherapy may affect a fraction of the same targets destroyed by radiotherapy. Although radiotherapy reaches all cells equally, chemotherapy diffuses through a tumor attaining lower concentration in its center and higher in its surface. With our simulations we study the enhanced effect of combined therapy treatment and how it depends on the tissue critical parameters (the parameters of the lion-extensive radiobiological model), the number of “targets” aimed at by chemotherapy, and the concentration and diffusion rate of the drug inside the tumor. The results show that an equivalent, cliemo-radio-dose can be computed that allows the prediction of the lower radiation dose that causes the same effect than a radio-only treatment. (paper)

Chemotherapy alters monocyte differentiation to favor generation of cancer-supporting M2 macrophages in the tumor microenvironment

NARCIS (Netherlands)

Dijkgraaf, Eveline M.; Heusinkveld, Moniek; Tummers, Bart; Vogelpoel, Lisa T. C.; Goedemans, Renske; Jha, Veena; Nortier, Johan W. R.; Welters, Marij J. P.; Kroep, Judith R.; van der Burg, Sjoerd H.

2013-01-01

Current therapy of gynecologic malignancies consists of platinum-containing chemotherapy. Resistance to therapy is associated with increased levels of interleukin (IL)-6 and prostaglandin E2 (PGE(2)), 2 inflammatory mediators known to skew differentiation of monocytes to tumor-promoting M2

Bladder cancer: The combination of chemotherapy and irradiation in the treatment of patients with muscle-invading tumors

International Nuclear Information System (INIS)

Shipley, William U.; Zietman, Anthony L.

1996-01-01

In the USA the recommended treatment for patients with muscle-invading transitional cell cancer of the bladder is usually radical cystectomy. Conservative surgery irradiation, and cisplatin-based systemic chemotherapy are, however, each effective for some patients. Although they provide the opportunity for bladder preservation, each modality, when used alone, is inferior to radical cystectomy in terms of local control and, perhaps, survival. Many recent publications have now documented the efficacy of combined modality treatment protocols employing all three of these modalities together. All employ a selective approach in which the patients only receive full-dose radiation if they have had a complete response to induction CMT. Overall survival data for T2-T3a patients are certainly as good as any reported cystectomy series of similarly clinically staged and similar aged patients. Radiation adds very significantly to the transurethral resection and systemic chemotherapy to maintain the bladder free of tumor. Substantially higher rates of pathologic confirmation of complete response are found following transurethral surgery and chemoradiation when compared with transurethral surgery and chemotherapy omitting the radiation. Overall survival is as good as cystectomy based approaches at 48-54% and over 80% of these long-term survivors keep their bladders. Following such therapies, 20-30% will subsequently develop superficial tumors. These patients may still be well treated by standard methods using transurethral resection and intravesical drugs. The concern of urologists that the conserved irradiated bladder functions poorly has also been answered by recent reports using modern radiation techniques. The instance of cystectomy for bladder shrinkage is repeatedly below 2%. Furthermore, sexual function is commonly preserved. The systemic morbidity of the chemotherapy is relatively high, but new approached using anti-emetics and GCSF now allow this to be reduced. In many

Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types.

Science.gov (United States)

Iliopoulos, Dimitrios; Hirsch, Heather A; Struhl, Kevin

2011-05-01

Metformin, the first-line drug for treating diabetes, selectively kills the chemotherapy resistant subpopulation of cancer stem cells (CSC) in genetically distinct types of breast cancer cell lines. In mouse xenografts, injection of metformin and the chemotherapeutic drug doxorubicin near the tumor is more effective than either drug alone in blocking tumor growth and preventing relapse. Here, we show that metformin is equally effective when given orally together with paclitaxel, carboplatin, and doxorubicin, indicating that metformin works together with a variety of standard chemotherapeutic agents. In addition, metformin has comparable effects on tumor regression and preventing relapse when combined with a four-fold reduced dose of doxorubicin that is not effective as a monotherapy. Finally, the combination of metformin and doxorubicin prevents relapse in xenografts generated with prostate and lung cancer cell lines. These observations provide further evidence for the CSC hypothesis for cancer relapse, an experimental rationale for using metformin as part of combinatorial therapy in a variety of clinical settings, and for reducing the chemotherapy dose in cancer patients.

Gd-DTPA MR imaging enhancement of spinal cord tumors

International Nuclear Information System (INIS)

Dillon, W.P.; Bolla, K.; Mark, A.S.; Tsudura, J.S.; Norman, D.; Newton, T.H.

1987-01-01

Nineteen patients with suspected spinal cord tumors were imaged with T1- and T2-weighted sequences before and after the administration of Gd-DTPA (0.1 mmol/kg). Eleven of the 19 patients had spinal cord tumors (three unproven). Eight of 11 patients had intramedullary tumors (four astrocytomas, two ependymomas) and two had extra-medullary tumors (one meningioma, one metastatic melanoma). Other lesions studied include idiopathic syringomyelia (two), spinal arteriovenous malformation (AVM) (one), posttraumatic arachnoiditis (one), and cord infarct (one). All of the tumors enhanced after the administration of Gd-DTPA. Spinal cord enhancement was also noted in association with a spinal cord AVM, a suspected cord infarct, and in the patient with severe arachnoiditis. No enhancement was present in patients with idiopathic or posttraumatic syringomyelia or in the three normal patients. In six of the patients, enhancement was critical in confirming disease that was questionable on the precontrast MR images. Gadolinium enhancement allowed differentiation of tumor from postoperative changes in two patients with spinal cord tumors. Enhanced images localized the lesion more accurately than precontrast MR images in eight patients. In four patients a lesion could only be detected after the administration of contrast. The postcontrast images better defined the margin of tumor from surrounding edema, operative scarring, and cord cavitation. The AVM case had enhancement of slowly flowing veins with Gd-DTPA posterior to an ischemic cord segment. Gd-DTPA enhancement is extremely useful in the detection and therapeutic assessment of spinal cord tumors; however, enhancement is not specific for tumors and should be interpreted in light of the clinical setting

Enhanced antitumor efficacy of cisplatin in combination with HemoHIM in tumor-bearing mice.

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Park, Hae-Ran; Ju, Eun-Jin; Jo, Sung-Kee; Jung, Uhee; Kim, Sung-Ho; Yee, Sung-Tae

2009-03-17

Although cisplatin is one of the most effective chemotherapeutic agents, cisplatin alone does not achieve a satisfactory therapeutic outcome. Also cisplatin accumulation shows toxicity to normal tissues. In this study, we examined the possibility of HemoHIM both to enhance anticancer effect with cisplatin and to reduce the side effects of cisplatin in melanoma-bearing mice. HemoHIM was prepared by adding the ethanol-insoluble fraction to the total water extract of a mixture of 3 edible herbs, Angelica Radix, Cnidium Rhizoma and Paeonia Radix. Anticancer effects of HemoHIM with cisplatin were evaluated in melanoma-bearing mice. We used a Cr51-release assay to measure the activity of NK/Tc cell and ELISA to evaluate the production of cytokines. In melanoma-bearing mice, cisplatin (4 mg/kg B.W.) reduced the size and weight of the solid tumors, and HemoHIM supplementation with cisplatin enhanced the decrease of both the tumor size (p HemoHIM itself did not inhibit melanoma cell growth in vitro, and did not disturb the effects of cisplatin in vitro. However HemoHIM administration enhanced both NK cell and Tc cell activity in mice. Interestingly, HemoHIM increased the proportion of NK cells in the spleen. In melanoma-bearing mice treated with cisplatin, HemoHIM administration also increased the activity of NK cells and Tc cells and the IL-2 and IFN-gamma secretion from splenocytes, which seemed to contribute to the enhanced efficacy of cisplatin by HemoHIM. Also, HemoHIM reduced nephrotoxicity as seen by tubular cell of kidney destruction. HemoHIM may be a beneficial supplement during cisplatin chemotherapy for enhancing the anti-tumor efficacy and reducing the toxicity of cisplatin.

Large germinoma in basal ganglia treated by intraarterial chemotherapy with ACNU following osmotic blood-brain barrier disruption and radiation therapy

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Miyagami, Mitsusuke; Tsubokawa, Takashi; Kobayashi, Makio.

1988-10-01

A rare case of large germinoma in the basal ganglia is reported which was effectively treated by intracarotid chemotherapy with ACNU following osmotic blood-brain barrier disruption using 20 % mannitol and radiation therapy. A 19-year-old man displayed slowly progressive right hemiparesis, motor aphasia and predementia on admission. Plain CT demonstrated a tumor which had a slightly high density with intratumoral calcification and a small cyst, and slight to moderate enhancement was observed following intravenous injection of contrast medium, but there was no unilateral ventricular enlargement. Cerebral angiography revealed hypervascular tumor staining with early draining veins. After biopsy, and as a result of intracarotid chemotherapy with ACNU following osmotic blood-brain barrier disruption and radiation therapy, the tumor decreased rapidly to about 20 % of its original mass. After discharge, tumor progression was observed. However, the enlarged tumor mass almost disappeared (except for calcification) on CT with clinical improvement in response to intracarotid chemotherapy with ACNU following 20 % mannitol.

  Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and survival following adjuvant chemotherapy in pre-menopausal lymph node-positive breast cancer patients (N=525)

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Rasmussen, Anne-Sofie Schrohl; Look, Maxime P.; Meijer-van Gelder, Marion E.

tumor tissue TIMP-1 concentrations are associated with decreased benefit from adjuvant chemotherapy. Especially in the group treated with anthracycline-based therapy, there is a strong tendency for TIMP-1 high tumors to be less sensitive to the treatment. The anthracycline-treated group, however...... Predictive markers are needed to guide planning of adjuvant therapy for patients with breast cancer. We have recently shown that high tumor tissue levels of TIMP-1 are associated with decreased response to chemotherapy in metastatic breast cancer patients (Schrohl et al, Clin Cancer Res, 2006......) suggesting that TIMP-1 may be a predictive marker in breast cancer patients. Purpose: This study investigates the association of tumor tissue TIMP-1 levels with response to adjuvant chemotherapy with CMF (cyclophosphamide/methotrexate/5-fluorouracil) or an anthracycline-containing regimen. Patients...

Influence of radiation on the blood-brain barrier and optimum time of chemotherapy

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Qin, D.X.; Zheng, R.; Tang, J.; Li, J.X.; Hu, Y.H.

1990-01-01

A pilot study of the destructive effects of radiation on the blood-brain barrier (BBB) was made on 14 patients with localized and limited brain tumors by 99MTc-GH imaging from August 1988 to November 1989. Count/pixel data were obtained from the unirradiated, irradiated, and tumor areas before and after radiotherapy of 30-40 Gy. It was observed that the BBB in the unirradiated area outside the radiation portal was not changed and the degree of destructive effect on the BBB in the irradiated normal area was directly proportional to the radiation dose. For 30-40 Gy, the count/pixel change enhances to average 24.7% [(147.6-118.4)/118.4], and (c) the BBB in the tumor area is partially destroyed on an average of 22.1% [(206.8-169.4)/169.4] by the tumor. The radiotherapy further enhances this effect to an average of 74.7% [(206.8-118.4)/118.4]. Case 3 showed that before radiation, the degree of destructive effect on the BBB in the tumor area was 22% [(167-137)/137] higher than normal brain tissue. After a dose of 30 Gy of irradiation, it increased to 76.7% [(242-137)/137]; 8 months later it decreased to 17% [(160.3-137)/137]. It has been proven that the BBB can recover at least partially. Based on these observations, the authors believe that in the combined treatment of operated brain tumors, radiotherapy should precede chemotherapy so as to enhance the destruction of the BBB, facilitating the incorporation of drugs into the tumor. The dose at which to start chemotherapy is 20-30 Gy

Contrast-enhanced CISS imaging of cerebellopontine angle tumors

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Tozaki, Mitsuhiro; Toyoda, Keiko; Hata, Yuichi; Fukuda, Yasushi; Fukuda, Kunihiko [Jikei Univ., Tokyo (Japan). School of Medicine; Katano, Shuichi

1999-10-01

Our purpose of this study was to evaluate the clinical usefulness of contrast-enhanced CISS-3DFT MR imaging for the diagnosis of CP angle tumors. CISS-3DFT MR imaging is expected for screening procedure of acoustic schwannoma because of excellent spatial resolution. Recently, we discovered contrast enhancement effect on CISS sequence in spite of heavily T{sub 2}-weighted images. Fourteen patients with CP angle tumors were performed on a 1.0 T MR unit. Transaxial CISS-3DFT MRI was obtained both before and after intravenous injections of Gd-DTPA. Multiplanar reconstructions (MPRs) were performed in all cases. Contrast enhancement effect of CP angle tumors, and the relationship between tumors and the adjacent cranial nerves were evaluated. Contrast enhancement effect of the tumors was present in all cases in spite of heavily T{sub 2}-weighted images of CISS sequences. In the internal auditory canal, relationship between the tumors and the cranial nerves was demonstrated in 6 cases (6/9). In the cerebellopontine cistern, all cases were demonstrated (11/11). Contrast-enhanced CISS-3DFT MR imaging with a good contrast resolution and an excellent spatial resolution is useful for the diagnosis of CP angle tumors. (author)

Chemotherapy-induced hypocalcemia.

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Ajero, Pia Marie E; Belsky, Joseph L; Prawius, Herbert D; Rella, Vincent

2010-01-01

To present a unique case of transient, asymptomatic chemotherapy-induced hypocalcemia not attributable to hypomagnesemia or tumor lysis syndrome and review causes of hypocalcemia related to cancer with and without use of chemotherapy. We present a case detailing the clinical and laboratory findings of a patient who had severe hypocalcemia during chemotherapy and discuss causes of hypocalcemia with an extensive literature review of chemotherapeutic agents associated with this biochemical abnormality. In a 90-year-old man, hypocalcemia developed during 2 courses of chemotherapy for Hodgkin lymphoma, with partial recovery between courses and normal serum calcium 10 months after completion of treatment. Magnesium, vitamin D, and parathyroid hormone levels were low normal. There was no evidence of tumor lysis syndrome. Of the various agents administered, vinca alkaloids seemed the most likely cause. Serial testing suggested that the underlying mechanism may have been acquired, reversible hypoparathyroidism. No other similar case was found in the published literature. The severe hypocalcemia in our patient could not be attributed to hypomagnesemia or tumor lysis syndrome, and it was clearly associated with the timing of his chemotherapeutic regimen. Possibilities include direct parathyroid hormone suppression or alteration of calcium sensing by the chemotherapeutic drugs. Serum calcium surveillance before and during chemotherapeutic management of cancer patients may reveal more instances and provide insight into the exact mechanism of this lesser known yet striking complication.

Differential diagnosis of metastases in bone scans: chemotherapy induced bone necrosis

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Reuland, P.

1999-01-01

Aim: Influenced by the incorrect diagnosis of a bone metastasis caused by bone necrosis we evaluated reasons and frequency of bone necrosis in patients referred for bone scanning in follow-up of tumors. Methods: Bone scans performed within two years on patients with primary bone tumors or tumors metastatic to bone were reviewed in respect to the final diagnosis bone necrosis. Results: We found the cases of three young patients who presented the appearance of hot spots on bone scintigrams which were finally diagnosed as bone necrosis. In two cases the diagnosis was based on histological findings, in one case the diagnosis was made evident by follow-up. All the three patients had been treated by chemotherapy and presented no other reason for the development of bone necrosis. Enhanced tracer uptake in all sites decreased within eight weeks up to two years without therapy. Conclusion: Single and multiple hot spots after chemotherapy may be originated by bone necrosis but mimikry metastases. (orig.) [de

Super-selective interventional chemotherapy combined with systemic chemotherapy for the treatment of postoperative gliomas:a clinical study

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Chen Jian; Hu Qinglei; Sun Yanchun; Feng Lei; Liu Yunzhen; Liu Ju; Kong Ruifen

2010-01-01

Objective: To evaluate super-selective interventional chemotherapy combined with systemic chemotherapy in treating postoperative gliomas. Methods: During the period of 2005-2009, a total of 46 patients with glioma were encountered in our hospital. According to the principle of patient's free will the involved patients were divided into two groups. Study group (n = 25): after operation the patients received routine radiotherapy, which was followed by super-selective interventional chemotherapy combined simultaneously with systemic chemotherapy. Control group (n = 21): after operation the patients received routine radiotherapy, which was followed by systemic chemotherapy only. The patients were regularly followed up. Cranial CT checkups were made to determine the tumor size, and the results were evaluated with Karnofsky scores. The clinical data were analyzed and compared between two groups. Results: In the study group, the side-effects and complications included epileptic seizures (n = 3), eye pain (n = 5), headache (n = 9), nausea and vomiting (n = 8) and thrombopenia (n = 1). In the control group,the side-effects and complications were as follows: epileptic seizures (n = 1), headache (n = 7), nausea and vomiting (n = 6) and thrombopenia(n = 3). No death occurred in either of the two groups. The patients were followed up for an average period of 2.3 years. Before chemotherapy no statistically significant difference in tumor size existed between two groups (P > 0.05). One year after the chemotherapy, the tumor volume in study group was reduced by 67.11%, while it was 45.79% in control group. By using independent sample t test analysis, the difference between two groups was of statistical significance (P < 0.05). Wilcoxon rank sum test and Karnofsky prognostic score analysis indicated that the prognosis of study group was much better than that of control group (P < 0.05). Conclusion: In comparison with routine radiotherapy plus simple systemic chemotherapy, routine

Chemotherapy for intracranial ependymoma in adults

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Gramatzki, Dorothee; Roth, Patrick; Felsberg, Jörg; Hofer, Silvia; Rushing, Elisabeth J.; Hentschel, Bettina; Westphal, Manfred; Krex, Dietmar; Simon, Matthias; Schnell, Oliver; Wick, Wolfgang; Reifenberger, Guido; Weller, Michael

2016-01-01

Ependymal tumors in adults are rare, accounting for less than 4 % of primary tumors of the central nervous system in this age group. The low prevalence of intracranial ependymoma in adults limits the ability to perform clinical trials. Therefore, treatment decisions are based on small, mostly retrospective studies and the role of chemotherapy has remained unclear. We performed a retrospective study on 17 adult patients diagnosed with intracranial World Health Organisation grade II or III ependymoma, who were treated with chemotherapy at any time during the disease course. Benefit from chemotherapy was estimated by applying Macdonald criteria. Progression-free (PFS) and overall survival (OS) were calculated from start of chemotherapy, using the Kaplan-Meier method. Eleven patients had supratentorial and 6 infratentorial tumors. Ten patients were treated with temozolomide (TMZ), 3 with procarbazine/lomustine/vincristine (PCV), 3 with platinum-based chemotherapy and 1 patient received epirubicin/ifosfamide. Response rates were as follows: TMZ 8/10 stable disease; PCV 3/3 stable disease; platinum-based chemotherapy 1/3 partial response; epirubicin/ifosfamide 1/1 complete response. PFS rates at 6, 12 and 24 months were 52.9, 35.3 and 23.5 %. OS rates at 6, 12 and 24 months were 82.4, 82.4 and 70.1 %. There was no indication for a favourable prognostic role of O 6 -methylguanyl-DNA-methyltransferase (MGMT) promoter methylation which was detected in 3/12 investigated tumors. Survival outcomes in response to chemotherapy in adult intracranial ependymoma patients vary substantially, but individual patients may respond to any kind of chemotherapy. There were too few patients to compare survival data between chemotherapeutic subgroups. The online version of this article (doi:10.1186/s12885-016-2323-0) contains supplementary material, which is available to authorized users

The interplay of immunotherapy and chemotherapy: harnessing potential synergies.

Science.gov (United States)

Emens, Leisha A; Middleton, Gary

2015-05-01

Although cancer chemotherapy has historically been considered immune suppressive, it is now accepted that certain chemotherapies can augment tumor immunity. The recent success of immune checkpoint inhibitors has renewed interest in immunotherapies, and in combining them with chemotherapy to achieve additive or synergistic clinical activity. Two major ways that chemotherapy promotes tumor immunity are by inducing immunogenic cell death as part of its intended therapeutic effect and by disrupting strategies that tumors use to evade immune recognition. This second strategy, in particular, is dependent on the drug, its dose, and the schedule of chemotherapy administration in relation to antigen exposure or release. In this Cancer Immunology at the Crossroads article, we focus on cancer vaccines and immune checkpoint blockade as a forum for reviewing preclinical and clinical data demonstrating the interplay between immunotherapy and chemotherapy. ©2015 American Association for Cancer Research.

MR imaging of gestational trophoblastic tumor: role of gadolinium enhancement

International Nuclear Information System (INIS)

Choi, Si Young; Byun, Jae Young; Kim, Bum Su; Yun, Young Hyun; Mun, Kyung Mi; Park, Kyung Sin; Kim, Byung Kee; Bae, Seog Nyeon; Shinn, Kyung Sub.

1997-01-01

The purpose of this study is to investigate the role of gadolinium enhanced MR imaging in the evaluation of gestational trophoblastic tumors (invasive mole and choriocarcinoma). Pre-enhanced T1-and T2-weighted images and gadolinium enhanced T1-weighted images of 34 gestational trophoblastic tumors (15 choriocarcinomas, 19 invasive moles) were retrospectively evaluated and enhancement patterns were analyzed. Morphologica differences and structural characteristics were analyzed by the evaluation of tumor margin, patterns of hemorrhagic necroses, the development of intratumoral vascularity, and molar villi. Graded scores of MR findings between pre- and gadolinium enhanced images were based on the following criteria : 1) visualization of tumor margin 2) distinction between tumor necrosis and zone of trophoblastic proliferation ; and 3) molar villi. Statistical differences between graded scores of pre- and post-enhanced images were analyzed. Gadolinium enhanced MR imaging was helpful for the visualization of tumor characteristics in gestational trophoblastic tumors and in differential diagnosis between invasive mole and choriocarcinoma. (author). 16 refs., 4 tabs., 4 figs

Anemia prevalence and treatment practice in patients with non-myeloid tumors receiving chemotherapy

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Merlini L

2013-08-01

Full Text Available Laura Merlini,1 Giacomo Cartenì,2 Stefano Iacobelli,3 Caterina Stelitano,4 Mario Airoldi,5 Peter Balcke,6 Felix Keil,7 Ferdinand Haslbauer,8 Laura Belton,9 Beatriz Pujol10 1Department of Medical Oncology, Ospedale Civile S, Bortolo, Vicenza, 2Department of OncoHematology, Azienda Ospedaliera di Rilievo Nazionale "Antonio Cardarelli", Napoli, 3Department of Medical Oncology, Ospedale Clinicizzato SS Annunziata, Chieti, 4Department of Hematology, Azienda Ospedaliera "Bianchi Melacrino Morelli", Reggio Calabria, 5Department of Medical Oncology, Azienda Ospedaliero Universitaria Le Molinette, Torino, Italy; 61st Medical Department, General Hospital St Pölten and Karl Landsteiner Institute of Oncology, St Pölten, 73rd Medical Department (Hematology and Oncology, Hanusch Krankenhaus der Wiener Gebietskrankenkasse, Vienna, 8Department of Oncology, Landeskrankenhaus Vöcklabruck, Vöcklabruck, Austria; 9Contract biostatistician, Amgen Ltd, Uxbridge, UK; 10Research and Development Haematology/Oncology, Amgen Europe, Zug, Switzerland Purpose: To describe the prevalence and management of anemia in cancer patients. Methods: This cross-sectional, observational survey was conducted in Italy and Austria. Centers prespecified one day, during a 4-month enrollment window, to report specific data collected during normal clinical practice for patients with non-myeloid tumors attending for chemotherapy (±radiotherapy treatment. The primary endpoint was the prevalence of anemia as determined using a prespecified algorithm: hemoglobin (Hb ≤10 g/dL on/within 3 days prior to visit; ongoing anemia treatment; physician diagnosis of anemia, together with ≥1 anemia symptom. Results: Between November 18, 2010 and March 18, 2011, data for 1412 patients were collected (Italy n = 1130; Austria n = 282. Most patients (n = 1136; 80% had solid tumors; 809 (57% had received ≤ 3 chemotherapy cycles. The prevalence of anemia was 32% (95% confidence interval: 29.4%–34

The role of chemotherapy in the treatment of patients with brain metastases from solid tumors

International Nuclear Information System (INIS)

Walbert, T.; Gilbert, M.R.

2009-01-01

Brain metastases are the most frequent cancer in the central nervous system, being ten times more common than primary brain tumors. Patients generally have a poor outcome with a median survival of 4 months after diagnosis of the metastases. Therapeutic options include surgery, stereotactic, radiosurgery, whole-brain radiotherapy (WBRT), and chemotherapy. Patients with a limited number of brain metastases and well-controlled systemic cancer benefit from brain metastases-specific therapies, including surgery, radiosurgery, and conventional radiation. The role of chemotherapy for brain metastases remains limited. There is concern about drug delivery because of the blood-brain barrier. However, higher response rates are noted with initial therapies, suggesting that part of the poor response rate may be related to the late onset of brain metastases and the use of second- and third-line regimens. Recent studies have demonstrated objective responses with systemic therapy in a variety of cancer types, especially when combined with WBRT. Individual therapeutic strategies for central nervous system metastases must be chosen based on performance status, the extent of intracranial disease, and the chemosensitivity of the underlying tumor, as well as the control of the systemic cancer. In this article we review important prognostic factors and challenges in using chemotherapy. We specifically review recent advances in the treatment of brain metastases from breast and lung cancer as well as melanoma. Future treatment advances will require a multidisciplinary approach integrating surgical, radiation, and chemotherapeutic options to improve neurological function and quality of life, rather than just focusing on survival endpoints. (author)

Primary tumor levels of tissue inhibitor of metalloproteinases-1 are predictive of resistance to chemotherapy in patients with metastatic breast cancer

DEFF Research Database (Denmark)

Rasmussen, Anne-Sofie Schrohl; Meijer-van Gelder, Marion E.; Holten-Andersen, Mads N.

2006-01-01

/methotrexate/5-fluorouracil and anthracycline-based chemotherapy (P = 0.01; odds ratio, 2.0; 95% confidence interval, 1.1-3.3). In a multivariate model, including lymph node status, steroid hormone receptor status, menopausal status, dominant metastases site, type of chemotherapy, and disease-free interval, TIMP......PURPOSE: Only about 50% of metastatic breast cancer patients benefit from cytotoxic chemotherapy. Today, no validated markers exist for prediction of chemotherapy sensitivity/resistance in this patient group. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been shown to protect against...... tumor expression levels of TIMP-1 protein and objective response to first-line chemotherapy in 173 patients with metastatic breast cancer. RESULTS: When analyzed as a continuous log-transformed variable, increasing TIMP-1 levels were significantly associated with lack of response to cyclophosphamide...

99mTc-MIBI SPECT in small call lung cancer patients before chemotherapy and after unresponsive chemotherapy

International Nuclear Information System (INIS)

Yamamoto, Yuka; Nishiyama, Yoshihiro; Fukunaga, Kotaro; Satoh, Katashi; Fujita, Jiro; Ohkawa, Motoomi

2001-01-01

We evaluated the accumulation of 99m Tc-MIBI in small cell lung cancer patients before chemotherapy and after unresponsive chemotherapy. The pre-chemotherapeutic group included 22 newly diagnosed patients. These patients underwent a 99m Tc-MIBI SPECT study before starting chemotherapy. After chemotherapy, based on changes in tumor size, three different patterns of response (complete remission: CR, partial remission: PR and no change: NC) were defined. The post-chemotherapeutic group included 11 patients after chemotherapy who did not respond to chemotherapy. These patients underwent a 99m Tc-MIBI SPECT study after completion of chemotherapy. SPECT images were acquired 15 min (early) and 2 hr (delayed) after injection of 99m Tc-MIBI. With a region of interest technique, the early ratio, delayed ratio and retention index were calculated. Early and delayed ratios in pre-chemotherapeutic patients were significantly higher than those in post-chemotherapeutic patients. There were no significant differences between the pre-chemotherapeutic and post-chemotherapeutic patients in the retention index. In the pre-chemotherapeutic patients, early and delayed ratios for the CR and PR groups were significantly higher than those for the NC group. There were no significant differences in the retention index with respect to the tumor response. 99m Tc-MIBI might be useful for evaluating the tumor chemosensitivity in patients with small cell lung cancer. (author)

Metabolically stable bradykinin B2 receptor agonists enhance transvascular drug delivery into malignant brain tumors by increasing drug half-life

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Glen Daniel

2009-05-01

Full Text Available Abstract Background The intravenous co-infusion of labradimil, a metabolically stable bradykinin B2 receptor agonist, has been shown to temporarily enhance the transvascular delivery of small chemotherapy drugs, such as carboplatin, across the blood-brain tumor barrier. It has been thought that the primary mechanism by which labradimil does so is by acting selectively on tumor microvasculature to increase the local transvascular flow rate across the blood-brain tumor barrier. This mechanism of action does not explain why, in the clinical setting, carboplatin dosing based on patient renal function over-estimates the carboplatin dose required for target carboplatin exposure. In this study we investigated the systemic actions of labradimil, as well as other bradykinin B2 receptor agonists with a range of metabolic stabilities, in context of the local actions of the respective B2 receptor agonists on the blood-brain tumor barrier of rodent malignant gliomas. Methods Using dynamic contrast-enhanced MRI, the pharmacokinetics of gadolinium-diethyltriaminepentaacetic acid (Gd-DTPA, a small MRI contrast agent, were imaged in rodents bearing orthotopic RG-2 malignant gliomas. Baseline blood and brain tumor tissue pharmacokinetics were imaged with the 1st bolus of Gd-DTPA over the first hour, and then re-imaged with a 2nd bolus of Gd-DTPA over the second hour, during which normal saline or a bradykinin B2 receptor agonist was infused intravenously for 15 minutes. Changes in mean arterial blood pressure were recorded. Imaging data was analyzed using both qualitative and quantitative methods. Results The decrease in systemic blood pressure correlated with the known metabolic stability of the bradykinin B2 receptor agonist infused. Metabolically stable bradykinin B2 agonists, methionine-lysine-bradykinin and labradimil, had differential effects on the transvascular flow rate of Gd-DTPA across the blood-brain tumor barrier. Both methionine

Intratumoral chemotherapy for lung cancer: re-challenge current targeted therapies

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Hohenforst-Schmidt W

2013-07-01

Full Text Available Wolfgang Hohenforst-Schmidt,1 Paul Zarogoulidis,2,3 Kaid Darwiche,3 Thomas Vogl,4 Eugene P Goldberg,5 Haidong Huang,6 Michael Simoff,7 Qiang Li,6 Robert Browning,8 J Francis Turner,9 Patrick Le Pivert,10 Dionysios Spyratos,2 Konstantinos Zarogoulidis,2 Seyhan I Celikoglu,11 Firuz Celikoglu,11 Johannes Brachmann11II Medical Clinic, Coburg Hospital, University of Wuerzburg, Coburg, Germany; 2Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece; 3Department of Interventional Pneumology, Ruhrlandklinik, West German Lung Center, University Hospital, University Duisburg-Essen, Essen, Germany; 4Department of Diagnostic and Interventional Radiology, Goethe University of Frankfurt, Frankfurt, Germany; 5Biomaterials Science and Engineering, Department of Materials Science and Engineering, University of Florida, FL, USA; 6Department of Respiratory Diseases, Changhai Hospital/First Affiliated Hospital of the Second Military Medical University, Shanghai, People's Republic of China; 7Bronchoscopy and Interventional Pulmonology, Pulmonary and Critical Care Medicine, Henry Ford Hospital, Wayne State University, School of Medicine, MI, USA; 8Pulmonary and Critical Care Medicine, Interventional Pulmonology, National Naval Medical Center, Walter Reed Army Medical Center, Bethesda, USA; 9Pulmonary Medicine, University of Nevada School of Medicine, National Supercomputing Center for Energy and the Environment University of Nevada, Las Vegas, USA; 10Interventional Drug Delivery Systems and Strategies (ID2S2, Medical Cryogenics, Jupiter, FL, USA; 11Pulmonary Department, Cerrahpasa Medical Faculty, University of Istanbul, Istanbul, TurkeyAbstract: Strategies to enhance the already established doublet chemotherapy regimen for lung cancer have been investigated for more than 20 years. Initially, the concept was to administer chemotherapy drugs locally to the tumor site for efficient diffusion

Response of the primary tumor in symptomatic and asymptomatic stage IV colorectal cancer to combined interventional endoscopy and palliative chemotherapy

International Nuclear Information System (INIS)

Cameron, Silke; Hünerbein, Diana; Mansuroglu, Tümen; Armbrust, Thomas; Scharf, Jens-Gerd; Schwörer, Harald; Füzesi, László; Ramadori, Giuliano

2009-01-01

The treatment of the primary tumor in advanced metastatic colorectal cancer (CRC) is still a matter of discussion. Little attention has thus far been paid to the endoscopically observable changes of the primary in non-curatively resectable stage IV disease. 20 patients [14 men, 6 women, median age 67 (39–82) years] were observed after initial diagnosis of non-curatively resectable metastasized symptomatic (83%) or asymptomatic (17%) CRC, from June 2002 to April 2009. If necessary, endoscopic tumor debulking was performed. 5-FU based chemotherapy was given immediately thereafter. In 10 patients, chemotherapy was combined with antibody therapy. Response of the primary was observed in all patients. Local symptoms were treated endoscopically whenever necessary (obstruction or bleeding), and further improved after chemotherapy was started: Four patients showed initial complete endoscopic disappearance of the primary. In an additional 6 patients, only adenomatous tissue was histologically detected. In both these groups, two patients revealed local tumor relapse after interruption of therapy. Local tumor regression or stable disease was achieved in the remaining 10 patients. 15 patients died during the observation time. In 13 cases, death was related to metastatic disease progression. The mean overall survival time was 19.6 (3–71) months. No complications due to the primary were observed. This study shows that modern anti-cancer drugs combined with endoscopic therapy are an effective and safe treatment of the symptomatic primary and ameliorate local complaints without the need for surgical intervention in advanced UICC stage IV CRC

The role of adjuvant platinum-based chemotherapy in esophagogastric cancer patients who received neoadjuvant chemotherapy prior to definitive surgery.

Science.gov (United States)

Saunders, John H; Bowman, Christopher R; Reece-Smith, Alex M; Pang, Vincent; Dorrington, Matthew S; Mumtaz, Errum; Soomro, Irshad; Kaye, Philip; Madhusudan, Srinivasan; Parsons, Simon L

2017-06-01

For patients with operable esophagogastric cancer, peri-operative chemotherapy confers a significant overall survival benefit compared to surgery alone, however only 30-40% of patients demonstrate histopathological response. It is unclear whether those with no neoadjuvant chemotherapy response should go onto receive adjuvant chemotherapy, as no further benefit may be conferred. Esophagogastric cancers were prospectively captured with associated histopathological tumor regression grades following neoadjuvant chemotherapy. This cohort was then interrogated for clinico-pathological and survival outcomes. Following neoadjuvant chemotherapy and surgery, patients with chemotherapy responsive cancers, who were administered adjuvant chemotherapy gained a significant overall survival benefit. Multivariate Cox analysis, demonstrated a final adjusted hazard ratio for adjuvant therapy of 0.509; (95%CI 0.28-0.93); P = 0.028. In contrast, patients with non-responsive tumors, who underwent adjuvant chemotherapy, did not show any survival benefit. Chemotherapy toxicity was prevalent and contributed to only half of patients receiving adjuvant chemotherapy. These results suggest the benefit of the adjuvant portion of chemotherapy is limited to those who demonstrate a histopathological response to neoadjuvant chemotherapy. The administration of the adjuvant portion of chemotherapy to patients without a response to neoadjuvant chemotherapy may not provide any survival benefit, while potentially causing increased morbidity. © 2017 Wiley Periodicals, Inc.

Audiological findings in patients treated with radio- and concomitant chemotherapy for head and neck tumors

International Nuclear Information System (INIS)

Dell'Aringa, Ana Helena B; Isaac, Myrian L; Arruda, Gustavo V; Esteves, Maria Carolina BN; Dell'Aringa, Alfredo Rafael; Júnior, José Luis S; Rodrigues, Alexandre F

2009-01-01

To evaluate the functionality of the auditory system in patients who underwent radiotherapy and chemotherapy treatment with cisplatin to treat head and neck tumors. Case series with planned data collection. From May 2007 to May 2008 by the Department of Otorhinolaryngology and the Department of Oncology/Radiotherapy at Faculdade de Medicina de Marília. Audiological evaluation (Pure Tone Audiometry (air and bone conduction), Speech Audiometry, Tympanometry, Acoustic Reflex testing and Distortion Product Otoacoustic Emissions) was performed in 17 patients diagnosed with head and neck neoplasia and treated with chemotherapy, using cisplatin, and radiotherapy. 12 left ears (70.5%) and 11 right ears (64.7%) presented bilateral decreased hearing soon after the treatment for the frequency 1 kHz (mild auditory damage) and for the frequency 8 kHz (more significant auditory damage). Patients with head and neck cancer submitted to the conventional radiotherapy treatment, combined with the chemotherapy with cisplatin, presented a high incidence of decreased hearing by the end of treatment. Strong evidence was observed linking auditory alteration to the amount of radiotherapy treatment

Selective alpha-particle mediated depletion of tumor vasculature with vascular normalization.

Directory of Open Access Journals (Sweden)

Jaspreet Singh Jaggi

2007-03-01

Full Text Available Abnormal regulation of angiogenesis in tumors results in the formation of vessels that are necessary for tumor growth, but compromised in structure and function. Abnormal tumor vasculature impairs oxygen and drug delivery and results in radiotherapy and chemotherapy resistance, respectively. Alpha particles are extraordinarily potent, short-ranged radiations with geometry uniquely suitable for selectively killing neovasculature.Actinium-225 ((225Ac-E4G10, an alpha-emitting antibody construct reactive with the unengaged form of vascular endothelial cadherin, is capable of potent, selective killing of tumor neovascular endothelium and late endothelial progenitors in bone-marrow and blood. No specific normal-tissue uptake of E4G10 was seen by imaging or post-mortem biodistribution studies in mice. In a mouse-model of prostatic carcinoma, (225Ac-E4G10 treatment resulted in inhibition of tumor growth, lower serum prostate specific antigen level and markedly prolonged survival, which was further enhanced by subsequent administration of paclitaxel. Immunohistochemistry revealed lower vessel density and enhanced tumor cell apoptosis in (225Ac-E4G10 treated tumors. Additionally, the residual tumor vasculature appeared normalized as evident by enhanced pericyte coverage following (225Ac-E4G10 therapy. However, no toxicity was observed in vascularized normal organs following (225Ac-E4G10 therapy.The data suggest that alpha-particle immunotherapy to neovasculature, alone or in combination with sequential chemotherapy, is an effective approach to cancer therapy.

Intraoperative Spillage of Favorable Histology Wilms Tumor Cells: Influence of Irradiation and Chemotherapy Regimens on Abdominal Recurrence. A Report From the National Wilms Tumor Study Group

International Nuclear Information System (INIS)

Kalapurakal, John A.; Li, Sierra M.; Breslow, Norman E.; Beckwith, J. Bruce; Ritchey, Michael L.; Shamberger, Robert C.; Haase, Gerald M.; Thomas, Patrick R.M.; Grundy, Paul; Green, Daniel M.; D'Angio, Giulio J.

2010-01-01

Purpose: We undertook this study to determine (1) the frequency with which spilled tumor cells of favorable histology produced intra-abdominal disease in patients treated with differing chemotherapy regimens and abdominal radiation therapy (RT) and (2) the patterns of relapse and outcomes in such patients. Methods and Materials: The influence of RT dose (0, 10, and 20 Gy), RT fields (flank, whole abdomen), and chemotherapy with dactinomycin and vincristine (2 drugs) vs. added doxorubicin (three drugs) on intra-abdominal tumor recurrence rates was analyzed by logistic regression in 450 patients. Each patient was considered at risk for two types of failure: flank and subdiaphragmatic beyond-flank recurrence, with the correlation between the two outcomes accounted for in the analyses. Results: The crude odds ratio for the risk of recurrence relative to no RT was 0.35 (0.15-0.78) for 10Gy and 0.08 (0.01-0.58) for 20Gy. The odds ratio for the risk of recurrence for doxorubicin to two drugs after adjusting for RT was not significant. For Stage II patients (NWTS-4), the 8-year event rates with and without spillage, respectively, were 79% and 87% for relapse-free survival (p = 0.07) and 90% and 95% for overall survival (p = 0.04). Conclusions: Irradiation (10 Gy or 20 Gy) reduced abdominal tumor recurrence rates after tumor spillage. Tumor spillage in Stage II patients reduced relapse-free survival and overall survival, but only the latter was of statistical significance. These data provide a basis for assessing the risks vs. benefits when considering treatment for children with favorable histology Wilms tumor and surgical spillage.

Neoadjuvant Chemotherapy for Facilitating Surgical Resection of Infantile Massive Intracranial Immature Teratoma.

Science.gov (United States)

Kitahara, Takahiro; Tsuji, Yoshihito; Shirase, Tomoyuki; Yukawa, Hiroyuki; Takeichi, Yasuhiro; Yamazoe, Naohiro

2016-04-01

Immature teratoma (IMT) is the most frequent histological subtype of infantile intracranial teratoma, the most common congenital brain tumor. IMT contains incompletely differentiated components resembling fetal tissues. Infantile intracranial IMT has a dismal prognosis, because it is often inoperable due to its massive size and high vascularity. Neoadjuvant chemotherapy has been shown to be effective in decreasing tumor volume and vascularity to facilitate surgical resection in other types of infantile brain tumors. However, only one recent case report described the effectiveness of neoadjuvant chemotherapy for infantile intracranial IMT in the literature, even though it is common entity with a poor prognosis in infants. Here, we describe the case of a 2-month-old male infant with a very large intracranial IMT. Maximal surgical resection was first attempted but was unsuccessful because of severe intraoperative hemorrhage. Neoadjuvant carboplatin and etoposide (CARE) chemotherapy was then administered with the aim of shrinking and devascularizing the tumor. After neoadjuvant chemotherapy, tumor size did not decrease, but intraoperative blood loss significantly decreased and near-total resection was achieved by the second and third surgery. The patient underwent adjuvant CARE chemotherapy and has been alive for 3 years after surgery without tumor regrowth. Even when neoadjuvant chemotherapy does not decrease tumor volume of infantile intracranial IMT, surgical resection should be tried because chemotherapy can facilitate surgical resection and improve clinical outcome by reducing tumor vascularity.

Preoperative chemotherapy of bone and soft tissue sarcomas. Evaluation with dynamic MR imaging

International Nuclear Information System (INIS)

Ando, Yoko; Fukatsu, Hiroshi; Isomura, Takayuki; Itoh, Shigeki; Ishigaki, Takeo; Yamamura, Shigeki; Sugiura, Hideshi; Satoh, Keiji.

1995-01-01

Dynamic MR imaging and conventional angiography were performed in eleven patients with musculoskeletal malignant tumors before and after preoperative chemotherapy in order to evaluate its effect. Dynamic MRI was obtained with GRASS (TR/TE/FA=50/10-13/30) or SE (TR/TE=150-350/20). Although resected specimen in one case of osteosarcoma had the necrotic ratio of more than 90%, it had marked early enhancement in dynamic MRI, and microscopic examination revealed fibrotic necrosis with many capillaries. In soft tissue sarcomas with hemorrhage and/or cystic change, dynamic MRI findings did not necessarily correlate with the chemotherapy effect. Dynamic MRI was more useful than angiography because of its ability to show tumor vascularity and of its non-invasiveness. (author)

The effect of hyperthermia in the preoperative combined treatment of radiation, hyperthermia and chemotherapy for rectal carcinoma

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Konishi, Fumio; Furuta, Kazuhiro; Saito, Yukio; Kataoka, Takashi; Kashiwagi, Hiroshi; Okada, Masaki; Kanazawa, Kyotaro; Sugahara, Tadashi; Shinohara, Naohiro (Jichi Medical School, Minamikawachi, Tochigi (Japan))

1994-03-01

To investigate the effectiveness of hyperthermia in the preoperative combined treatment of radiation, chemotherapy and hyperthermia for rectal carcinoma, two groups were compared. Group A consisted of 18 patients in whom hyperthermia, radiation and chemotherapy were performed. Group B consisted of 18 patients in whom only chemotherapy and radiation were performed. The total dose of radiation in both of the two groups was 40.5 Gy, and a radiation field covering the whole pelvis was used. Hyperthermia was performed using 8 MHz radiofrequency waves (Thermotron RF8, Yamamoto Vinyter, Japan), and tumors were heated at about 42 degrees C for 50 minutes. Hyperthermia was repeated five times during the preoperative treatment. Chemotherapy was performed by giving 5-fluorouracil suppositories to a total dose of 3400 mg. Mean tumor reduction rates on barium enema were 31.8% in group A and 18.2% in group B. The difference was statistically significant. The result of the histological assessment of tumor necrosis showed that there was a significantly higher degree of necrosis in group A than in group B. These results showed that the addition of hyperthermia enhanced tumor necrosis. It was concluded that the addition of hyperthermia would be an effective preoperative treatment of rectal carcinoma. (author).

The effect of hyperthermia in the preoperative combined treatment of radiation, hyperthermia and chemotherapy for rectal carcinoma

International Nuclear Information System (INIS)

Konishi, Fumio; Furuta, Kazuhiro; Saito, Yukio; Kataoka, Takashi; Kashiwagi, Hiroshi; Okada, Masaki; Kanazawa, Kyotaro; Sugahara, Tadashi; Shinohara, Naohiro

1994-01-01

To investigate the effectiveness of hyperthermia in the preoperative combined treatment of radiation, chemotherapy and hyperthermia for rectal carcinoma, two groups were compared. Group A consisted of 18 patients in whom hyperthermia, radiation and chemotherapy were performed. Group B consisted of 18 patients in whom only chemotherapy and radiation were performed. The total dose of radiation in both of the two groups was 40.5 Gy, and a radiation field covering the whole pelvis was used. Hyperthermia was performed using 8 MHz radiofrequency waves (Thermotron RF8, Yamamoto Vinyter, Japan), and tumors were heated at about 42 degrees C for 50 minutes. Hyperthermia was repeated five times during the preoperative treatment. Chemotherapy was performed by giving 5-fluorouracil suppositories to a total dose of 3400 mg. Mean tumor reduction rates on barium enema were 31.8% in group A and 18.2% in group B. The difference was statistically significant. The result of the histological assessment of tumor necrosis showed that there was a significantly higher degree of necrosis in group A than in group B. These results showed that the addition of hyperthermia enhanced tumor necrosis. It was concluded that the addition of hyperthermia would be an effective preoperative treatment of rectal carcinoma. (author)

Hyperfractionated craniospinal radiotherapy and adjuvant chemotherapy for children with newly diagnosed medulloblastoma and other primitive neuroectodermal tumors

International Nuclear Information System (INIS)

Allen, Jeffrey C.; Donahue, Bernadine; DaRosso, Robert; Nirenberg, Anita

1996-01-01

Purpose: This single-institution Phase I/II study conducted from 1989 to 1995 evaluates the feasibility of a multi-modality protocol combining hyperfractionated craniospinal radiotherapy (HFRT) followed by adjuvant chemotherapy in 23 patients with newly diagnosed primitive neuroectodermal tumors (PNET) arising in the central nervous system. Methods and Materials: All 23 patients had a histologically confirmed PNET and were over 3 years of age at diagnosis. The eligibility criteria for PNET patients with cerebellar primaries (medulloblastoma) included either a high T stage (T3b or 4) or high M stage (M1-3). All patients with noncerebellar primaries were eligible regardless of T or M stage. The median age of the 23 patients was 9 years (mean 3-25); 11 were female. The primary tumor arose in the cerebellum in 19. Of these medulloblastoma patients, 15 had high T stages (T3b or T4) with large locally invasive tumors and no evidence of metastases (M0), constituting Group 1. Thirteen (86%) of these patients had gross total resections. Four other medulloblastoma patients had both high T and high M stages, constituting Group 2. Group 3 consisted of four other patients with exocerebellar primaries (two brain, one brain stem, and one cauda equina), three of whom were M3. Hyperfractionated radiotherapy was administered within 4 weeks of surgery. Twice-daily 1-Gy fractions were administered separated by 4-6 h. The total dose to the primary intracranial tumor and other areas of measurable intracranial disease was 72 Gy. The prophylactic craniospinal axis dose was 36 Gy, and boosts of 44-56 Gy were administered to metastatic spinal deposits. Following radiotherapy, monthly courses of multiagent chemotherapy were administered sequentially (cyclophosphamide-vincristine followed by cisplatin-etoposide followed by carboplatin-vincristine) for a total of 9 months. Results: All patients completed radiotherapy as planned. Only three patients lost >10% of their body weight. One patient

Tumor markers CEA and CA 19-9 correlate with radiological imaging in metastatic colorectal cancer patients receiving first-line chemotherapy.

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Michl, M; Koch, J; Laubender, R P; Modest, D P; Giessen, C; Schulz, Ch; Heinemann, V

2014-10-01

In patients with metastatic colorectal cancer (mCRC), radiological imaging represents the current standard to evaluate the efficacy of chemotherapy. However, with growing knowledge about tumor biology, other diagnostic tools become of interest which can supplement radiology. The aim of the present study was to examine the correlation of tumor and serum markers with radiological imaging in patients with mCRC receiving first-line therapy. Patients were included if tumor (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9)) and serum marker (lactatdehydrogenase (LDH), γ-glutamyltransferase (γGT), alkaline phosphatase (AP), C-reactive protein (CRP), leucocyte count (WBC), hemoglobin (Hb)) levels were available at baseline and at least two times during treatment. The decline and increase of tumor and serum markers over time were approximated for each patient by estimating slopes depending on the radiological assessment. A linear mixed effects multiple regression model for each subject was used to evaluate the intra-class correlation of these slopes modeling tumor and serum marker changes with radiological imaging. Data of 124 patients (41 female, 83 male; median age 62.9 years, range 27-85) who received first-line chemotherapy for mCRC from 11/2007 to 04/2010 were analyzed retrospectively. CEA level slopes (n = 49; slopes = 102) differed between radiologically determined progressive disease (PD) and partial response (PR) (p = 0.005) and between PD and stable disease (SD) (p = 0.042). CA 19-9 level slopes (n = 57; slopes = 127) also showed a significant difference between PD and PR (p = 0.002) and PD and SD (p = 0.058). Furthermore, CRP slopes (n = 62; slopes = 134) differed significantly between PD and PR (p = 0.009). For LDH, ALP, γGT, Hb, and WBC, no correlations were observed. The results indicate the correlation of the tumor markers CEA, CA 19-9, and the serum marker CRP with radiological imaging in

Chemotherapy in conjoint aging-tumor systems: some simple models for addressing coupled aging-cancer dynamics

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Witten Tarynn M

2010-06-01

Full Text Available Abstract Background In this paper we consider two approaches to examining the complex dynamics of conjoint aging-cancer cellular systems undergoing chemotherapeutic intervention. In particular, we focus on the effect of cells growing conjointly in a culture plate as a precursor to considering the larger multi-dimensional models of such systems. Tumor cell growth is considered from both the logistic and the Gompertzian case, while normal cell growth of fibroblasts (WI-38 human diploid fibroblasts is considered as logistic only. Results We demonstrate, in a simple approach, how the interdependency of different cell types in a tumor, together with specifications of for treatment, can lead to different evolutionary patterns for normal and tumor cells during a course of therapy. Conclusions These results have significance for understanding appropriate pharmacotherapy for elderly patients who are also undergoing chemotherapy.

Vascular Endothelial-Targeted Therapy Combined with Cytotoxic Chemotherapy Induces Inflammatory Intratumoral Infiltrates and Inhibits Tumor Relapses after Surgery

Directory of Open Access Journals (Sweden)

Brendan F. Judy

2012-04-01

Full Text Available Surgery is the most effective therapy for cancer in the United States, but disease still recurs in more than 40% of patients within 5 years after resection. Chemotherapy is given postoperatively to prevent relapses; however, this approach has had marginal success. After surgery, recurrent tumors depend on rapid neovascular proliferation to deliver nutrients and oxygen. Phosphatidylserine (PS is exposed on the vascular endothelial cells in the tumor microenvironment but is notably absent on blood vessels in normal tissues. Thus, PS is an attractive target for cancer therapy after surgery. Syngeneic mice bearing TC1 lung cancer tumors were treated with mch1N11 (a novel mouse chimeric monoclonal antibody that targets PS, cisplatin (cis, or combination after surgery. Tumor relapses and disease progression were decreased 90% by combination therapy compared with a 50% response rate for cis alone (P = .02. Mice receiving postoperative mch1N11 had no wound-related complications or added systemic toxicity in comparison to control animals. Mechanistic studies demonstrated that the effects of mch1N11 were associated with a dense infiltration of inflammatory cells, particularly granulocytes. This strategy was independent of the adaptive immune system. Together, these data suggest that vascular-targeted strategies directed against exposed PS may be a powerful adjunct to postoperative chemotherapy in preventing relapses after cancer surgery.

Vascular endothelial-targeted therapy combined with cytotoxic chemotherapy induces inflammatory intratumoral infiltrates and inhibits tumor relapses after surgery.

Science.gov (United States)

Judy, Brendan F; Aliperti, Louis A; Predina, Jarrod D; Levine, Daniel; Kapoor, Veena; Thorpe, Philip E; Albelda, Steven M; Singhal, Sunil

2012-04-01

Surgery is the most effective therapy for cancer in the United States, but disease still recurs in more than 40% of patients within 5 years after resection. Chemotherapy is given postoperatively to prevent relapses; however, this approach has had marginal success. After surgery, recurrent tumors depend on rapid neovascular proliferation to deliver nutrients and oxygen. Phosphatidylserine (PS) is exposed on the vascular endothelial cells in the tumor microenvironment but is notably absent on blood vessels in normal tissues. Thus, PS is an attractive target for cancer therapy after surgery. Syngeneic mice bearing TC1 lung cancer tumors were treated with mch1N11 (a novel mouse chimeric monoclonal antibody that targets PS), cisplatin (cis), or combination after surgery. Tumor relapses and disease progression were decreased 90% by combination therapy compared with a 50% response rate for cis alone (P = .02). Mice receiving postoperative mch1N11 had no wound-related complications or added systemic toxicity in comparison to control animals. Mechanistic studies demonstrated that the effects of mch1N11 were associated with a dense infiltration of inflammatory cells, particularly granulocytes. This strategy was independent of the adaptive immune system. Together, these data suggest that vascular-targeted strategies directed against exposed PS may be a powerful adjunct to postoperative chemotherapy in preventing relapses after cancer surgery.

SARC006: Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated Chemotherapy-Naive Malignant Peripheral Nerve Sheath Tumors

Directory of Open Access Journals (Sweden)

Christine S. Higham

2017-01-01

Full Text Available Background. Worse chemotherapy response for neurofibromatosis type 1- (NF1- associated compared to sporadic malignant peripheral nerve sheath tumors (MPNST has been reported. Methods. We evaluated the objective response (OR rate of patients with AJCC Stage III/IV chemotherapy-naive NF1 MPNST versus sporadic MPNST after 4 cycles of neoadjuvant chemotherapy, 2 cycles of ifosfamide/doxorubicin, and 2 cycles of ifosfamide/etoposide. A Simon optimal two-stage design was used (target response rate 40%. Results. 34 NF1 (median age 33 years and 14 sporadic (median age 40 years MPNST patients enrolled. Five of 28 (17.9% evaluable NF1 MPNST patients had a partial response (PR, as did 4 of 9 (44.4% patients with sporadic MPNST. Stable disease (SD was achieved in 22 NF1 and 4 sporadic MPNST patients. In both strata, results in the initial stages met criteria for expansion of enrollment. Only 1 additional PR was observed in the expanded NF1 stratum. Enrollment was slower than expected and the trial closed before full accrual. Conclusions. This trial was not powered to detect differences in response rates between NF1 and sporadic MPNST. While the OR rate was lower in NF1 compared to sporadic MPNST, qualitative responses were similar, and disease stabilization was achieved in most patients.

Tumor Seeding Following Lung Radiofrequency Ablation: A Case Report

International Nuclear Information System (INIS)

Yamakado, Koichiro; Akeboshi, Masao; Nakatsuka, Atsuhiro; Takaki, Haruyuki; Takao, Motoshi; Kobayashi, Hiroyasu; Taguchi, Osamu; Takeda, Kan

2005-01-01

Lung radiofrequency (RF) ablation was performed for the treatment of a primary lung cancer measuring 2.5 cm in maximum diameter in a 78-year-old man. A contrast-enhanced computed tomography (CT) study performed 3 months after RF ablation showed incomplete ablation of the lung tumor and the appearance of a chest wall tumor 4.0 cm in maximum diameter that was considered to be the result of needle-tract seeding. RF ablation was performed for the treatment of both the lung and the chest wall tumors. Although tumor enhancement was eradicated in both of the treated tumors, follow-up CT studies revealed diffuse intra-pulmonary metastases in both lungs 2 months after the second RF session. He is currently receiving systemic chemotherapy

Monitoring tumor response to neoadjuvant chemotherapy using MRI and 18F-FDG PET/CT in breast cancer subtypes

NARCIS (Netherlands)

Schmitz, Alexander M Th; Teixeira, Suzana C; Pengel, Kenneth E; Loo, Claudette E; Vogel, Wouter V; Wesseling, Jelle; Rutgers, Emiel J Th; Valdés Olmos, Renato A; Sonke, Gabe S; Rodenhuis, Sjoerd; Vrancken Peeters, Marie Jeanne T F D; Gilhuijs, Kenneth G A

2017-01-01

PURPOSE: To explore guidelines on the use of MRI and PET/CT monitoring primary tumor response to neoadjuvant chemotherapy (NAC), taking breast cancer subtype into account. MATERIALS AND METHODS: In this prospective cohort study, 188 women were included with stages II and III breast cancer. MRI and

Chemotherapy response as a prognosticator for survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

International Nuclear Information System (INIS)

Eagan, R.T.; Fleming, T.R.; Lee, R.E.; Ingle, J.N.; Frytak, S.; Creagan, E.T.

1980-01-01

Twenty-two patients with limited unresectable squamous cell lung cancer were treated with 6 courses of combination chemotherapy consisting of cyclophosphamide, adriamycin, cisplatin, and bleomycin (CAP-Bleo) and short-course thoracic irradiation started after the first 4 weeks of chemotherapy. Of 20 patients with visible tumor who were treated with 4 weeks of chemotherapy alone, 10 (50%) had a tumor regression in that 4 week period and 10 did not. Those patients with tumor regression had significantly better progression free and overall survivals than did patients with no chemotherapy regressions (medians of 258 days vs. 136 days and 356 days vs. 150 days respectively). The original bleomycin dose had to be reduced by 50% primarily because of excessive radiation esophagitis that has not been reported with use of either the CAP regimen or bleomycin along in conjunction with thoracic irradiation. An initial chemotherapy regression seems to be a good prognosticator for progression-free and overall survival in patients with limited squamous cell lung cancer treated with combined chemotherapy and radiotherapy

The Immunological Impact of Chemotherapy on the Tumor Microenvironment of Oral Squamous Cell Carcinoma.

Science.gov (United States)

Takakura, Hiroaki; Domae, Shohei; Ono, Toshiro; Sasaki, Akira

2017-06-01

　Anticancer drugs induce cell-cycle arrest and apoptosis not only in tumor cells, but also in immune cells. However, many preclinical and clinical findings show that some chemotherapeutic agents can improve the antitumor efficacy of immunotherapy. We immunohistochemically analyzed the degree of immune cell infiltration and the relevance of programmed cell death 1 ligand-1 (PD-L1) expression in surgically resected oral squamous cell carcinoma (OSCC) specimens from patients who had undergone pretreatment with certain chemotherapies and other patients without pretreatment. We divided the patients into the group of neoadjuvant chemotherapy (NAC) patients (n=8) and the nNAC (without NAC) patient group (n=10). We observed that NAC induced infiltrations of CD4, CD8 T cells and CD56 NK cells into the tumor microenvironment. Decreased numbers of Tregs and PD-1-positive cells were observed in the NAC group. No significant difference was observed in the degree of immune-cell infiltration between the patient groups except for CD56 NK cells in the stroma and PD-1 cells in cancer nests. Eighty percent of the nNAC specimens showed intermediate-to-strong PD-L1 protein expression, whereas 75% of the NAC specimens showed down-regulation of the PD-L1 protein, indicating the effectiveness of the chemotherapeutic treatment before surgery.

Patient and tumor characteristics associated with breast cancer recurrence after complete pathological response to neoadjuvant chemotherapy.

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Ju, Na Rae; Jeffe, Donna B; Keune, Jason; Aft, Rebecca

2013-01-01

Breast cancer patients whose tumors achieve a pathological complete response (pCR) with neoadjuvant chemotherapy have a prognosis which is better than that predicted for the stage of their disease. However, within this subgroup of patients, recurrences have been observed. We sought to examine factors associated with recurrence in a population of breast cancer patients who achieved a pCR with neoadjuvant chemotherapy. A retrospective chart review was conducted of all patients with unilateral breast cancer treated with neoadjuvant chemotherapy from January 1, 2000 to December 31, 2010 at one comprehensive cancer center. A pCR was defined as no residual invasive cancer in the breast in the surgical specimen following neoadjuvant therapy. Recurrence was defined as visceral or bony reappearance of cancer after completion of all therapy. Of 818 patients who completed neoadjuvant chemotherapy, 144 (17.6 %) had pCR; six with bilateral breast cancer were excluded from further analysis. The mean time to follow-up was 47.2 months. Among the 138 patients with unilateral breast cancer, there were 14 recurrences (10.1 %). Using a binary multiple logistic regression model, examining types of chemotherapy and surgery, race, lymph node assessment, and lymph node status, breast cancer side, triple-negative status, and radiation receipt, only African-American patients (OR: 5.827, 95 % CI: 1.280-26.525; p = 0.023) were more likely to develop distant recurrence. The mean time to recurrence was 31.9 months. In our study, race was the only independent predictor of recurrence after achieving pCR with neoadjuvant chemotherapy. The reasons for this observation require further study.

Magnetic resonance imaging of white matter injury after radio- and chemotherapy

International Nuclear Information System (INIS)

Jurkiewicz, E.; Pakula-Kosciesza, I.; Bekiesinska-Figatowska, M.; Wagiel, K.; Wagiel, E.; Perek-Polnik, M.; Walecki, J.

2004-01-01

To describe MR symptomatology of radio- and chemotherapy-induced leukoencephalopathy and to assess the usefulness of 1H MRS in differential diagnosis of these lesions. The material consists of 44 patients (18 females, 26 males), aged 3-54 years, treated for brain and face tumors (29 cases), other tumors (2) and after CNS prophylaxis for acute lymphoblastic leukemia (13). 1H MRS was performed in 6 cases. Two 1,5 T and one 0,5 T scanners were used. We observed diffuse lesions, hyperintense on T2-weighted images, in the periventricular white matter and centrum semiovale in 14 cases, in 5 also in the cerebellum and brainstem, subcortical in 1. Focal lesions were found in periventricular location in 16 cases, in the corpus callosum in 1 and in 1 the foci were disseminated. No mass effect and no contrast enhancement were observed in these cases. Marked mass effect and contrast enhancement were found in 2 cases, slight mass effect without CE in 2. In these 4 cases and in other 2 with neurological symptoms, 1H MRS was performed: in 2 cases the spectrum was close to that of normal tissue, in 1 suggestive of a tumor, in 3 the spectrum was abnormal but atypical of a tumor. Follow-up studies showed regression of the lesions and of the spectral abnormalities. In 1 case necrotizing leucoencephalopathy and secondary tumor, in 7 - calcificatons, in 7 - parenchymal hematomas were found. Magnetic resonance allows detection of side effects of radio- and chemotherapy, even in asymptomatic patients. In patients with neurological signs MRI allows differentiation of chemo-, radiotherapy-induced leucoencephalopathy and neo plasmatic infiltration with high probability. 1H MRS plays an important role in differential diagnosis in unclear cases with mass effect and contrast enhancement. The results of MRI and 1H MRS should be considered in correlation with clinical findings. (author)

Chemotherapy increases long-term survival in patients with adult medulloblastoma

DEFF Research Database (Denmark)

Kocakaya, Selin; Beier, Christoph Patrick; Beier, Dagmar

2016-01-01

chemotherapy first-line survived significantly longer (mOS: 108 mo, 95% CI: 68.6-148.4) than patients treated with radiation alone (mOS: 57 mo, 95% CI: 39.6-74.4) or patients who received chemotherapy at tumor recurrence. This effect was not biased by tumor stage or decade of treatment. Importantly, (neo...... parts of treatment regimes; however, established prognostic factors and data clarifying the role of chemotherapy are missing. METHODS: We investigated 227 publications from 1969-2013, with 907 identifiable, individual patients being available for meta-analysis. Demographic data, risk stratification......)adjuvant chemotherapy also significantly increased the chance for long-term survival (>5 y) compared with radiotherapy alone or chemotherapy at tumor recurrence. CONCLUSIONS: This meta-analysis clarifies relevant prognostic factors and suggests that chemotherapy as part of first-line therapy improves overall survival...

[Cytokines in cancer chemotherapy: present state and problems in use of G- and GM-CSF for solid tumors in Japan].

Science.gov (United States)

Ogawara, M

1998-01-01

The present state and the problems of G and GM-CSF in cancer chemotherapy, especially for solid tumors in Japan, were reviewed. One of the problems is that adaptation is restricted to several tumors, and the other that recommended doses are about half or one-fourth as much as in North America or Europe. With G-CSF after dose-intensive chemotherapy in small-cell lung cancer, three studies showed G-CSF shortened the duration of neutropenia, and reduced the incidence of neutropenic fever, use of antibiotics and hospitalization, while they showed no advantages in terms of response rate and the incidence of infection-related death. Moreover, the effect on survival has not been proved. In afebrile neutropenic patients, G-CSF could accelerate recovery from neutropenia, but did not reduce the incidence of neutropenic fever. In febrile neutropenic patients with antibiotics, it could also accelerate recovery from neutropenia, but did not reduce neutropenic fever compared with no CSF except in some subsets. Our retrospective study showed the effects of G-CSF in grade 4 neutropenia were comparable with grade 3 neutropenia. The functions of neutrophils with G-CSF after chemotherapy were reported to be increased or maintained. Clinical benefits were only obtained in certain dose-intensive chemotherapy or in limited subsets. Additional clinical trials and a guideline like ASCO's should be planned.

Recurrent medulloblastoma: Frequency of tumor enhancement on Gd-DTPA MR imaging

International Nuclear Information System (INIS)

Rollins, N.; Mendelsohn, D.; Mulne, A.; Barton, R.; Diehl, J.; Reyes, N.; Sklar, F.

1990-01-01

Thirty-two children with medulloblastoma were evaluated postoperatively with conventional and gadolinium-enhanced MR imaging. Eleven patients had abnormal cranial MR studies; nine of these had recurrent tumor. In six patients recurrent tumor enhanced with Gd, while in the other three patients recurrent tumor did not enhance. The remaining two patients had areas of abnormal Gd enhancement that were caused by radiation-induced breakdown of the blood-brain barrier rather than by recurrent tumor. This study shows that not all recurrent medulloblastoma enhances and that the absence of Gd enhancement does not necessarily indicate the absence of recurrent tumor

A new survival model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing rats in the treatment of peritoneal carcinomatosis

International Nuclear Information System (INIS)

Pelz, Joerg OW; Doerfer, Joerg; Hohenberger, Werner; Meyer, Thomas

2005-01-01

Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with peritoneal carcinomatosis of colorectal origin. Animal models are important in the evaluation of new treatment modalities. The purpose of this study was to devise an experimental setting which can be routinely used for the investigation of HIPEC in peritoneal carcinomatosis. A new peritoneal perfusion system in tumor bearing rats were tested. For this purpose CC531 colon carcinoma cells were implanted intraperitoneally in Wag/Rija rats. After 10 days of tumor growth the animals were randomized into three groups of six animals each: group 1: control (n = 6), group 2: HIPEC with mitomycin C in a concentration of 15 mg/m 2 (n = 6), group III: mitomycin C i.p. as monotherapy in a concentration of 10 mg/m 2 (n = 6). After 10 days, total tumor weight and the extent of tumor spread, as classified by the modified Peritoneal Cancer Index (PCI), were assessed by autopsy of the animals. No postoperative deaths were observed. Conjunctivitis, lethargy and loss of appetite were the main side effects in the HIPEC group. No severe locoregional or systemic toxity was observed. All control animals developed massive tumor growth. Tumor load was significantly reduced in the treatment group and was lowest in group II. The combination of hyperthermia with MMC resulted in an increased tumoricidal effect in the rat model. The presented model provides an opportunity to study the mechanism and effect of hyperthermic intraperitoneal chemotherapy and new drugs for this treatment modality

Atypical choroid plexus papilloma: spontaneous resolution of diffuse leptomeningeal contrast enhancement after primary tumor removal in 2 pediatric cases.

Science.gov (United States)

Scala, Marcello; Morana, Giovanni; Milanaccio, Claudia; Pavanello, Marco; Nozza, Paolo; Garrè, Maria Luisa

2017-09-01

Atypical choroid plexus papillomas can metastasize in the form of leptomeningeal seeding. Postoperative chemotherapy is the recommended first-line treatment when gross-total removal is not achieved or in cases of disseminated disease. Here the authors report on 2 children with atypical choroid plexus papillomas and MRI findings of diffuse leptomeningeal enhancement at diagnosis, later presenting with spontaneous resolution of the leptomeningeal involvement after removal of the primary lesions. Observations in this report expand our knowledge about the natural history and biological behavior of these tumors and highlight the role of close neuroimaging surveillance in the management of atypical choroid plexus papillomas in cases with MRI evidence of diffuse leptomeningeal enhancement at presentation.

Role of MRI in osteosarcoma for evaluation and prediction of chemotherapy response: correlation with histological necrosis

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Bajpai, Jyoti; Bakhshi, Sameer [Dr. B. R. A. Institute Rotary Cancer Hospital, Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi (India); Gamnagatti, Shivanand [All India Institute of Medical Sciences, Department of Radiodiagnosis, New Delhi (India); Kumar, Rakesh; Malhotra, Arun [All India Institute of Medical Sciences, Department of Nuclear Medicine, New Delhi (India); Sreenivas, Vishnubhatla [All India Institute of Medical Sciences, Department of Biostatistics, New Delhi (India); Sharma, Mehar Chand; Safaya, Rajni [All India Institute of Medical Sciences, Department of Pathology, New Delhi (India); Khan, Shah Alam; Rastogi, Shishir [All India Institute of Medical Sciences, Department of Orthopedics, New Delhi (India)

2011-04-15

Histological necrosis, the current standard for response evaluation in osteosarcoma, is attainable after neoadjuvant chemotherapy. To establish the role of surrogate markers of response prediction and evaluation using MRI in the early phases of the disease. Thirty-one treatment-naive osteosarcoma patients received three cycles of neoadjuvant chemotherapy followed by surgery during 2006-2008. All patients underwent baseline and post-chemotherapy conventional, diffusion-weighted and dynamic contrast-enhanced MRI. Taking histological response (good response {>=}90% necrosis) as the reference standard, various parameters of MRI were compared to it. A tumor was considered ellipsoidal; volume, average tumor plane and its relative value (average tumor plane relative/body surface area) was calculated using the standard formula for ellipse. Receiver operating characteristic curves were generated to assess best threshold and predictability. After deriving thresholds for each parameter in univariable analysis, multivariable analysis was carried out. Both pre-and post-chemotherapy absolute and relative-size parameters correlated well with necrosis. Apparent diffusion coefficient did not correlate with necrosis; however, on adjusting for volume, significant correlation was found. Thus, we could derive a new parameter: diffusion per unit volume. In osteosarcoma, chemotherapy response can be predicted and evaluated by conventional and diffusion-weighted MRI early in the disease course and it correlates well with necrosis. Further, newly derived parameter diffusion per unit volume appears to be a sensitive substitute for response evaluation in osteosarcoma. (orig.)

Role of MRI in osteosarcoma for evaluation and prediction of chemotherapy response: correlation with histological necrosis

International Nuclear Information System (INIS)

Bajpai, Jyoti; Bakhshi, Sameer; Gamnagatti, Shivanand; Kumar, Rakesh; Malhotra, Arun; Sreenivas, Vishnubhatla; Sharma, Mehar Chand; Safaya, Rajni; Khan, Shah Alam; Rastogi, Shishir

2011-01-01

Histological necrosis, the current standard for response evaluation in osteosarcoma, is attainable after neoadjuvant chemotherapy. To establish the role of surrogate markers of response prediction and evaluation using MRI in the early phases of the disease. Thirty-one treatment-naive osteosarcoma patients received three cycles of neoadjuvant chemotherapy followed by surgery during 2006-2008. All patients underwent baseline and post-chemotherapy conventional, diffusion-weighted and dynamic contrast-enhanced MRI. Taking histological response (good response ≥90% necrosis) as the reference standard, various parameters of MRI were compared to it. A tumor was considered ellipsoidal; volume, average tumor plane and its relative value (average tumor plane relative/body surface area) was calculated using the standard formula for ellipse. Receiver operating characteristic curves were generated to assess best threshold and predictability. After deriving thresholds for each parameter in univariable analysis, multivariable analysis was carried out. Both pre-and post-chemotherapy absolute and relative-size parameters correlated well with necrosis. Apparent diffusion coefficient did not correlate with necrosis; however, on adjusting for volume, significant correlation was found. Thus, we could derive a new parameter: diffusion per unit volume. In osteosarcoma, chemotherapy response can be predicted and evaluated by conventional and diffusion-weighted MRI early in the disease course and it correlates well with necrosis. Further, newly derived parameter diffusion per unit volume appears to be a sensitive substitute for response evaluation in osteosarcoma. (orig.)

Antitumor efficacy of conventional anticancer drugs is enhanced by the vascular targeting agent ZD6126

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Siemann, Dietmar W.; Rojiani, Amyn M.

2002-01-01

Purpose: The present report reviews the preclinical data on combined chemotherapy/vascular targeting agent treatments. Basic principles are illustrated in studies evaluating the antitumor efficacy of the vascular targeting agent ZD6126 (N-acetylcochinol-O-phosphate) when combined with the anticancer drug cisplatin in experimental rodent (KHT sarcoma) and human renal (Caki-1) tumor models. Methods and Materials: C3H/HeJ and NCR/nu-nu mice bearing i.m. tumors were injected i.p. with ZD6126 (0-150 mg/kg) or cisplatin (0-20 mg/kg) either alone or in combination. Tumor response to treatment was assessed by clonogenic cell survival. Results: Treatment with ZD6126 was found to damage existing neovasculature, leading to a rapid vascular shutdown. Histologic evaluation showed dose-dependent morphologic damage of tumor cells within a few hours after drug exposure, followed by extensive central tumor necrosis and neoplastic cell death as a result of prolonged ischemia. ZD6126 doses that led to pathophysiologic effects also enhanced the tumor cell killing of cisplatin when administered either 24 h before or 1-24 h after chemotherapy. In both tumor models, the administration of a 150 mg/kg dose of ZD6126 1 h after a range of doses of cisplatin resulted in an increase in tumor cell kill 10-500-fold greater than that seen with chemotherapy alone. In contrast, the inclusion of the antivascular agent did not increase bone marrow stem cell toxicity associated with this anticancer drug. Conclusion: The results obtained in the KHT and Caki-1 tumor models indicate that ZD6126 effectively enhanced the antitumor effects of cisplatin therapy. These findings are representative of the marked enhancements generally observed when vascular targeting agents are combined with chemotherapy in solid tumor therapy

Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival.

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Viganò, Luca; Capussotti, Lorenzo; De Rosa, Giovanni; De Saussure, Wassila Oulhaci; Mentha, Gilles; Rubbia-Brandt, Laura

2013-11-01

We analyzed the impact of chemotherapy-related liver injuries (CALI), pathological tumor regression grade (TRG), and micrometastases on long-term prognosis in patients undergoing liver resection for colorectal metastases after preoperative chemotherapy. CALI worsen the short-term outcomes of liver resection, but their impact on long-term prognosis is unknown. Recently, a prognostic role of TRG has been suggested. Micrometastases (microscopic vascular or biliary invasion) are reduced by preoperative chemotherapy, but their impact on survival is unclear. Patients undergoing liver resection for colorectal metastases between 1998 and 2011 and treated with oxaliplatin and/or irinotecan-based preoperative chemotherapy were eligible for the study. Patients with operative mortality or incomplete resection (R2) were excluded. All specimens were reviewed to assess CALI, TRG, and micrometastases. A total of 323 patients were included. Grade 2-3 sinusoidal obstruction syndrome (SOS) was present in 124 patients (38.4%), grade 2-3 steatosis in 73 (22.6%), and steatohepatitis in 30 (9.3%). Among all patients, 22.9% had TRG 1-2 (major response), whereas 55.7% had TRG 4-5 (no response). Microvascular invasion was detected in 37.8% of patients and microscopic biliary infiltration in 5.6%.The higher the SOS grade the lower the pathological response: TRG 1-2 occurred in 16.9% of patients with grade 2-3 SOS versus 26.6% of patients with grade 0-1 SOS (P = 0.032).After a median follow-up of 36.9 months, 5-year survival was 38.6%. CALI did not negatively impact survival. Multivariate analysis showed that grade 2-3 steatosis was associated with better survival than grade 0-1 steatosis (5-year survival rate of 52.5% vs 35.2%, P = 0.002). TRG better than the percentage of viable cells stratified patient prognosis: 5-year survival rate of 60.4% in TRG 1-2, 40.2% in TRG 3, and 29.8% in TRG 4-5 (P = 0.0001). Microscopic vascular and biliary invasion negatively impacted outcome (5-year survival

Monitoring tumor response to neoadjuvant chemotherapy using MRI and 18F-FDG PET/CT in breast cancer subtypes

NARCIS (Netherlands)

Schmitz, Alexander M. Th; Teixeira, Suzana C.; Pengel, Kenneth E.; Loo, Claudette E.; Vogel, Wouter V.; Wesseling, Jelle; Rutgers, Emiel J. Th; Valdés Olmos, Renato A.; Sonke, Gabe S.; Rodenhuis, Sjoerd; Vrancken Peeters, Marie Jeanne T. F. D.; Gilhuijs, Kenneth G. A.

2017-01-01

To explore guidelines on the use of MRI and PET/CT monitoring primary tumor response to neoadjuvant chemotherapy (NAC), taking breast cancer subtype into account. In this prospective cohort study, 188 women were included with stages II and III breast cancer. MRI and 18F-FDG-PET/CT were acquired

PET imaging of 64Cu-DOTA-scFv-anti-PSMA lipid nanoparticles (LNPs): Enhanced tumor targeting over anti-PSMA scFv or untargeted LNPs

International Nuclear Information System (INIS)

Wong, Patty; Li, Lin; Chea, Junie; Delgado, Melissa K.; Crow, Desiree; Poku, Erasmus; Szpikowska, Barbara; Bowles, Nicole; Channappa, Divya; Colcher, David; Wong, Jeffrey Y.C.; Shively, John E.; Yazaki, Paul J.

2017-01-01

Introduction: Single chain (scFv) antibodies are ideal targeting ligands due to their modular structure, high antigen specificity and affinity. These monovalent ligands display rapid tumor targeting but have limitations due to their fast urinary clearance. Methods: An anti-prostate membrane antigen (PSMA) scFv with a site-specific cysteine was expressed and evaluated in a prostate cancer xenograft model by Cu-64 PET imaging. To enhance tumor accumulation, the scFv-cys was conjugated to the co-polymer DSPE-PEG-maleimide that spontaneously assembled into a homogeneous multivalent lipid nanoparticle (LNP). Results: The targeted LNP exhibited a 2-fold increase in tumor uptake compared to the scFv alone using two different thiol ester chemistries. The anti-PSMA scFv-LNP exhibited a 1.6 fold increase in tumor targeting over the untargeted LNP. Conclusions: The targeted anti-PSMA scFv-LNP showed enhanced tumor accumulation over the scFv alone or the untargeted DOTA-micelle providing evidence for the development of this system for drug delivery. Advances in knowledge and implications for patient care: Anti-tumor scFv antibody fragments have not achieved their therapeutic potential due to their fast blood clearance. Conjugation to an LNP enables multivalency to the tumor antigen as well as increased molecular size for chemotherapy drug delivery.

[A Case of Curatively Resected Ascending Colon Cancer after Long-Term Chemotherapy Found in Abdominal Trauma].

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Aomatsu, Naoki; Uchima, Yasutake; Nobori, Chihoko; Kurihara, Shigeaki; Yamakoshi, Yoshihito; Wang, En; Nagashima, Daisuke; Hirakawa, Toshiki; Iwauchi, Takehiko; Morimoto, Junya; Tei, Seika; Nakazawa, Kazunori; Takeuchi, Kazuhiro

2017-11-01

A 46-year old man presented with lower right quadrant abdominal pain caused by abdominal trauma. Abscess drainage was performed after the diagnosis of retroperitoneal abscess in the ileocecal portion of the colon. Type 2 advanced cancer was found in the cecum and ascending colon. Surgery was performed after improvement of inflammation. Considering the difficulty of curative resection for retroperitoneal invasion, we first performed ileo-transverse colon anastomosis. After surgery, the patient received FOLFOX with panitumumab(Pmab)as neoadjuvant chemotherapy. After 6 courses of this regimen, contrast enhanced computed tomography revealed shrinkage of the tumor. We performed a second surgery but the tumor was unresectable because of retroperitoneal invasion. After 47 courses of chemotherapy(5-FU plus LV with Pmab), the tumor was stable and we observed no distant metastasis. A third surgery was performed, and we were able to perform ileocecal resection including the retroperitoneum. The pathological diagnosis was pT4b(SI), pN1, ly2, V2, pPM0, pDM0, R0, pStage III a. On histological examination, the efficacy of chemotherapy was evaluated as Grade 1a. The patient received adjuvant chemotherapy with capecitabine and remains healthy without any evidence of recurrence more than 10 months after surgery.

Insulin receptor substrate 1 expression enhances the sensitivity of 32D cells to chemotherapy-induced cell death

International Nuclear Information System (INIS)

Porter, Holly A.; Carey, Gregory B.; Keegan, Achsah D.

2012-01-01

The adapters IRS1 and IRS2 link growth factor receptors to downstream signaling pathways that regulate proliferation and survival. Both suppress factor-withdrawal-induced apoptosis and have been implicated in cancer progression. However, recent studies suggest IRS1 and IRS2 mediate differential functions in cancer pathogenesis. IRS1 promoted breast cancer proliferation, while IRS2 promoted metastasis. The role of IRS1 and IRS2 in controlling cell responses to chemotherapy is unknown. To determine the role of IRS1 and IRS2 in the sensitivity of cells to chemotherapy, we treated 32D cells lacking or expressing IRS proteins with various concentrations of chemotherapeutic agents. We found that expression of IRS1, in contrast to IRS2, enhanced the sensitivity of 32D cells to chemotherapy-induced apoptosis. When IRS2 was expressed with IRS1, the cells no longer showed enhanced sensitivity. Expression of IRS1 did not alter the expression of pro- and anti-apoptotic proteins; however, 32D-IRS1 cells expressed higher levels of Annexin A2. In 32D-IRS1 cells, IRS1 and Annexin A2 were both located in cytoplasmic and membrane fractions. We also found that IRS1 coprecipitated with Annexin A2, while IRS2 did not. Decreasing Annexin A2 levels reduced 32D-IRS1 cell sensitivity to chemotherapy. These results suggest IRS1 enhances sensitivity to chemotherapy in part through Annexin A2. -- Highlights: ► IRS1 enhanced the sensitivity of 32D cells to chemotherapy-induced apoptosis. ► This sensitivity is abrogated by the expression of IRS2. ► Expressing IRS1 in 32D cells increased levels of Annexin A2. ► Both IRS1 and Annexin A2 were located in cytoplasmic and membrane fractions. ► Decreasing Annexin A2 in 32D-IRS1 cells abated their sensitivity to chemotherapy.

Update on Intra-Arterial Chemotherapy for Retinoblastoma

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Mario Zanaty

2014-01-01

Full Text Available The tools for managing retinoblastoma have been increasing in the past decade. While globe-salvage still relies heavily on intravenous chemotherapy, tumors in advanced stage that failed chemotherapy are now referred for intra-arterial chemotherapy (IAC to avoid enucleation. However, IAC still has many obstacles to overcome. We present an update on the indications, complications, limitations, success, and technical aspects of IAC. Given its safety and high efficacy, it is expected that IAC will replace conventional strategies and will become a first-line option even for tumors that are amenable for other strategies.

Phosphoinositide 3-kinase accelerates postoperative tumor growth by inhibiting apoptosis and enhancing resistance to chemotherapy-induced apoptosis. Novel role for an old enemy.

LENUS (Irish Health Repository)

Coffey, J Calvin

2012-02-03

Tumor removal remains the principal treatment modality in the management of solid tumors. The process of tumor removal may potentiate the resurgent growth of residual neoplastic tissue. Herein, we describe a novel murine model in which flank tumor cytoreduction is followed by accelerated local tumor recurrence. This model held for primary and recurrent tumors generated using a panel of human and murine (LS174T, DU145, SW480, SW640, and 3LL) cell lines and replicated accelerated tumor growth following excisional surgery. In investigating this further, epithelial cells were purified from LS174T primary and corresponding recurrent tumors for comparison. Baseline as well as tumor necrosis factor apoptosis-inducing ligand (TRAIL)-induced apoptosis were significantly reduced in recurrent tumor epithelia. Primary and recurrent tumor gene expression profiles were then compared. This identified an increase and reduction in the expression of p110gamma and p85alpha class Ia phosphoinositide 3-kinase (PI3K) subunits in recurrent tumor epithelia. These changes were further confirmed at the protein level. The targeting of PI3K ex vivo, using LY294002, restored sensitivity to TRAIL in recurrent tumor epithelia. In vivo, adjuvant LY294002 prolonged survival and significantly attenuated recurrent tumor growth by greatly enhancing apoptosis levels. Hence, PI3K plays a role in generating the antiapoptotic and chemoresistant phenotype associated with accelerated local tumor recurrence.

Change of SPARC expression after chemotherapy in gastric cancer

International Nuclear Information System (INIS)

Gao, Yong-Yin; Han, Ru-Bing; Wang, Xia; Ge, Shao-Hua; Li, Hong-Li; Deng, Ting; Liu, Rui; Bai, Ming; Zhou, Li-Kun; Zhang, Xin-Yuan; Ba, Yi; Huang, Ding-Zhi

2015-01-01

The expression of tumor biomarkers may change after chemotherapy. However, whether secreted protein acidic and rich in cysteine (SPARC) expression changes after chemotherapy in gastric cancer (GC) is unclear. This study investigated the influence of chemotherapy on SPARC expression in GC. Immunohistochemistry was used to analyze SPARC expression in 132 GC cases (including 54 cases with preoperative chemotherapy and 78 cases without preoperative chemotherapy). SPARC expression of postoperative specimens with and without preoperative chemotherapy was assessed to analyze the influence of chemotherapy on SPARC expression. SPARC was highly expressed in GC compared with the desmoplastic stroma surrounding tumor cells and noncancerous tissues. High SPARC expression was correlated with invasion depth, lymph node, and TNM stage. After chemotherapy, a lower proportion of high SPARC expression was observed in patients with preoperative chemotherapy than in the controls. For 54 patients with preoperative chemotherapy, gross type, histology, depth of invasion, lymph node, TNM stage, and SPARC expression were related to overall survival. Further multivariate analysis showed that lymph node, histology, and SPARC expression after chemotherapy were independent prognostic factors. SPARC expression may change after chemotherapy in GC. SPARC expression should be reassessed for patients with GC after chemotherapy

pH- and NIR Light-Responsive Polymeric Prodrug Micelles for Hyperthermia-Assisted Site-Specific Chemotherapy to Reverse Drug Resistance in Cancer Treatment.

Science.gov (United States)

Li, Zuhong; Wang, Haibo; Chen, Yangjun; Wang, Yin; Li, Huan; Han, Haijie; Chen, Tingting; Jin, Qiao; Ji, Jian

2016-05-01

Despite the exciting advances in cancer chemotherapy over past decades, drug resistance in cancer treatment remains one of the primary reasons for therapeutic failure. IR-780 loaded pH-responsive polymeric prodrug micelles with near infrared (NIR) photothermal effect are developed to circumvent the drug resistance in cancer treatment. The polymeric prodrug micelles are stable in physiological environment, while exhibit fast doxorubicin (DOX) release in acidic condition and significant temperature elevation under NIR laser irradiation. Phosphorylcholine-based biomimetic micellar shell and acid-sensitive drug conjugation endow them with prolonged circulation time and reduced premature drug release during circulation to conduct tumor site-specific chemotherapy. The polymeric prodrug micelles combined with NIR laser irradiation could significantly enhance intracellular DOX accumulation and synergistically induce the cell apoptosis in DOX-resistant MCF-7/ADR cells. Meanwhile, the tumor site-specific chemotherapy combined with hyperthermia effect induces significant inhibition of MCF-7/ADR tumor growth in tumor-bearing mice. These results demonstrate that the well-designed IR-780 loaded polymeric prodrug micelles for hyperthermia-assisted site-specific chemotherapy present an effective approach to reverse drug resistance. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multimodal treatment combining chemotherapy, hyperthermia and radiotherapy for ovarian cancer

International Nuclear Information System (INIS)

Nagashima, Kei

1992-01-01

There has been increasing interest in the use of heat in the treatment of cancer. Theoretically cells are the most sensitive to ionizing radiation at mitosis, whereas the cycle phase that is the most resistant to ionizing radiation namely late in the DNA. Synthetic phase (late S) is the most sensitive to hyperthermia. Hyperthermia has been reported to enhance the cytocidal effects of several active chemotherapeutic agents. When thermal potentiation of chemotherapeutic agents against malignant cells is contemplated, normal tissues have a relatively high ambient blood flow which increases in response to thermal stress, thereby dissipating heat, compared to tumors. Tumors, with relatively poor blood flow and a responsive neovasculature, are in capable of augmenting flow and acting as a heat reservoir. This is the phenomenon of a heat reservoir which is one factor to enhance the cytocidal effects of several active anticancer agents for enhancing the uptake in tumor. The importance is in the adjuvant chemotherapy treated for post operative, advanced and recurrent ovarian cancer. Heating enhances the effects of radiotherapy and chemotherapy. Thirty patients with ovarian cancer were subjected to the multidisciplinary treatment with combination of hyperthermochemotherapy and radiation. The 30 patients consisted of 18 with endometrioid adenocarcinoma and 7 with serious post operative or recurrent status. Two types of equipments with rediofrequencies of 70 MHz (BSD-1000) or 434 MHZ (TAG MED·HS 434) were used for hyperthermia. Chemotherapeutic agents such as adriamycin, cis DDP, cyclophosphamide and etoposide were injected intravenously. Arterial infusion with reservoir was very effective in advanced stage of ovarian cancer. No severe or fatal side effects were observed. Hyperthermochemotherapy is useful and effective for the postoperative management or the treatment of recurrent cancer of the ovary. (J.P.N.)

Management of CNS tumors

International Nuclear Information System (INIS)

Griem, M.L.

1987-01-01

The treatment of tumors of the CNS has undergone a number of changes based on the impact of CT. The use of intraoperative US for the establishment of tumor location and tumor histology is demonstrated. MR imaging also is beginning to make an impact on the diagnosis and treatment of tumors of the CNS. Examples of MR images are shown. The authors then discuss the important aspects of tumor histology as it affects management and newer concepts in surgery, radiation, and chemotherapy on tumor treatment. The role of intraoperative placement of radioactive sources, the utilization of heavy particle radiation therapy, and the potential role of other experimental radiation therapy techniques are discussed. The role of hyperfractionated radiation and of neutrons and x-ray in a mixed-beam treatment are discussed in perspective with standard radiation therapy. Current chemotherapy techniques, including intraarterial chemotherapy, are discussed. The complications of radiation therapy alone and in combination with chemotherapy in the management of primary brain tumors, brain metastases, and leukemia are reviewed. A summary of the current management of pituitary tumors, including secreting pituitary adenomas and chromophobe adenomas, are discussed. The treatment with heavy particle radiation, transsphenoidal microsurgical removal, and combined radiotherapeutic and surgical management are considered. Tumor metastasis management of lesions of the brain and spinal cord are considered

Inference of Tumor Evolution during Chemotherapy by Computational Modeling and In Situ Analysis of Genetic and Phenotypic Cellular Diversity

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Vanessa Almendro

2014-02-01

Full Text Available Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and posttreatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution.

Inference of tumor evolution during chemotherapy by computational modeling and in situ analysis of genetic and phenotypic cellular diversity

International Nuclear Information System (INIS)

Almendro, Vanessa; Cheng, Yu-Kang; Randles, Amanda; Itzkovitz, Shalev; Marusyk, Andriy; Ametller, Elisabet; Gonzalez-Farre, Xavier; Muñoz, Montse; Russnes, Hege G.; Helland, Åslaug; Rye, Inga H.; Borresen-Dale, Anne-Lise; Maruyama, Reo; Van Oudenaarden, Alexander; Dowsett, Mitchell; Jones, Robin L.; Reis-Filho, Jorge; Gascon, Pere; Gönen, Mithat; Michor, Franziska; Polyak, Kornelia

2014-01-01

Cancer therapy exerts a strong selection pressure that shapes tumor evolution, yet our knowledge of how tumors change during treatment is limited. Here, we report the analysis of cellular heterogeneity for genetic and phenotypic features and their spatial distribution in breast tumors pre- and post-neoadjuvant chemotherapy. We found that intratumor genetic diversity was tumor-subtype specific, and it did not change during treatment in tumors with partial or no response. However, lower pretreatment genetic diversity was significantly associated with pathologic complete response. In contrast, phenotypic diversity was different between pre- and post-treatment samples. We also observed significant changes in the spatial distribution of cells with distinct genetic and phenotypic features. We used these experimental data to develop a stochastic computational model to infer tumor growth patterns and evolutionary dynamics. Our results highlight the importance of integrated analysis of genotypes and phenotypes of single cells in intact tissues to predict tumor evolution

Chemotherapy and Radiofrequency-Induced Mild Hyperthermia Combined Treatment of Orthotopic Pancreatic Ductal Adenocarcinoma Xenografts.

Science.gov (United States)

Krzykawska-Serda, Martyna; Agha, Mahdi S; Ho, Jason Chak-Shing; Ware, Matthew J; Law, Justin J; Newton, Jared M; Nguyen, Lam; Curley, Steven A; Corr, Stuart J

2018-04-02

Patients with pancreatic ductal adenocarcinomas (PDAC) have one of the poorest survival rates of all cancers. The main reason for this is related to the unique tumor stroma and poor vascularization of PDAC. As a consequence, chemotherapeutic drugs, such as nab-paclitaxel and gemcitabine, cannot efficiently penetrate into the tumor tissue. Non-invasive radiofrequency (RF) mild hyperthermia treatment was proposed as a synergistic therapy to enhance drug uptake into the tumor by increasing tumor vascular inflow and perfusion, thus, increasing the effect of chemotherapy. RF-induced hyperthermia is a safer and non-invasive technique of tumor heating compared to conventional contact heating procedures. In this study, we investigated the short- and long-term effects (~20 days and 65 days, respectively) of combination chemotherapy and RF hyperthermia in an orthotopic PDAC model in mice. The benefit of nab-paclitaxel and gemcitabine treatment was confirmed in mice; however, the effect of treatment was statistically insignificant in comparison to saline treated mice during long-term observation. The benefit of RF was minimal in the short-term and completely insignificant during long-term observation. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Cystic craniopharyngioma: intratumoral chemotherapy with alpha interferon

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Patrícia Alessandra Dastoli

2011-02-01

Full Text Available OBJECTIVE: To assess whether the cystic craniopharyngiomas can be controlled with the use of intratumoral applications of interferon alpha. METHOD: Nineteen patients with the diagnosis of cystic craniopharyngioma were treated with intratumoral chemotherapy with interferon alpha from January 2002 to April 2006. All patients underwent placement of an intracystic catheter connected to an Ommaya reservoir. Through this reservoir were made applications during chemotherapy cycles. Each cycle corresponded to application of 3,000,000 units of interferon alpha three times per week on alternate days totalizing 36,000,000 units. Response to treatment was evaluated by calculating the tumor volume on MRI control after one, three and six months after the end of each cycle. Patients who developed worsening of symptoms or who had insignificant reduction in tumor volume during follow-up underwent repeat cycle chemotherapy. RESULTS: Four patients received four cycles of chemotherapy, three patients received three cycles, six patients received two cycles and six patients received one. The lower percentage of reduction in tumor volume was 60% and the bigger reduction was 98.37%. Eleven patients had a reduction greater than 90%. Five patients had a tumor reduction between 75 and 90% and in three patients the tumors were reduced by less than 75%. No deaths occurred during treatment and side effects of interferon alpha were well tolerated. No treatment was discontinued. Follow-up after the last application ranged from one year and five months to three years and nine months. CONCLUSION: The intratumoral chemotherapy with interferon alpha decreases the volume of cystic craniopharyngiomas and so far can be considered a new therapeutic alternative.

Quantitative contrast-enhanced CT attenuation evaluation of osseous metastases following chemotherapy

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Chang, Connie Y.; Simeone, F.J.; Torriani, Martin; Bredella, Miriam A. [Massachusetts General Hospital, Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Boston, MA (United States)

2017-10-15

Osseous metastases often undergo an osteoblastic healing response following chemotherapy. The purpose of our study was to demonstrate the quantitative CT changes in attenuation of osseous metastases before and after chemotherapy. Our study was IRB approved and HIPAA compliant. Our cohort consisted of 86 consecutive cancer patients with contrast-enhanced CTs before and 14 ± 2 (12-25) months after initiation of chemotherapy (60 ± 11 years, 36 males, 50 females). The average and maximum metastasis attenuations were measured in Hounsfield units (HU) by two readers. Treatment effects were assessed using paired t-tests and Fisher exact tests. Intraclass correlation coefficients (ICCs) were calculated. Patient records were reviewed to determine the patient's clinical status (worse, unchanged, or improved) at the time of follow-up CT. The distribution of lesion types was as follows: lytic (30/86, 35%), blastic (43/86, 50%), and mixed lytic-blastic (13/86, 15%). There was a significant increase in average and maximum CT attenuation of metastases following chemotherapy for all patients, which remained statistically significant when stratified by lesion type, clinical status (worsening or improving/stable), cancer type (breast, lung), and radiation therapy (P < 0.05). In a subgroup of patients whose osseous metastases decreased in average attenuation (14/86, 16%), more patients had a worse clinical status (11/14, 79%) (P = 0.02). ICC was almost perfect for average attenuation and substantial for maximum attenuation. Quantitative assessment of osseous metastatic disease using CT attenuation measurements demonstrated a statistically significant increase in attenuation more than 12 months after initiation of chemotherapy. (orig.)

Applications of polymeric micelles with tumor targeted in chemotherapy

International Nuclear Information System (INIS)

Ding Hui; Wang Xiaojun; Zhang Song; Liu Xinli

2012-01-01

Polymeric micelles (PMs) have gained more progress as a carrier system with the quick development of biological and nanoparticle techniques. In particular, PMs with smart targeting can deliver anti-cancer drugs directly into tumor cells at a sustained rate. PMs with core–shell structure (with diameters of 10 ∼ 100 nm) have been prepared by a variety of biodegradable and biocompatible polymers via a self-assembly process. The preparation of polymeric micelles with stimuli-responsive block copolymers or modification of target molecules on polymeric micelles’ surface are able to significantly improve the efficiency of drug delivery. Polymeric micelles, which have been considered as a novel promising drug carrier for cancer therapeutics, are rapidly evolving and being introduced in an attempt to overcome several limitations of traditional chemotherapeutics, including water solubility, tumor-specific accumulation, anti-tumor efficacy, and non-specific toxicity. This review describes the preparation of polymeric micelles and the targeted modification which greatly enhance the effects of chemotherapeutic agents.

Quantitative analysis of tumor shrinkage due to chemotherapy and its implication for radiation treatment planning in limited-stage small-cell lung cancer

International Nuclear Information System (INIS)

Xia, Bing; Wang, Jia-Zhou; Liu, Qi; Cheng, Jing-Yi; Zhu, Zheng-Fei; Fu, Xiao-Long

2013-01-01

The optimal timing of chemoradiotherapy in limited-stage small-cell lung cancer (LS-SCLC) hasn’t been established, although evidence from studies supported that patients can benefit from early radiation therapy. The purpose of this study was to quantify tumor shrinkage in response to induction chemotherapy (IC), evaluate the impact of tumor shrinkage on radiation dosimetric parameters and determine its implication for the timing of radiation therapy for patients with LS-SCLC. Twenty patients with LS-SCLC who were treated with IC followed by concomitant radiation therapy were investigated retrospectively. Ten patients received 1 cycle of IC, and 10 patients received 2 cycles of IC. Pre-IC CT imaging was coregistered with a simulation CT, and virtual radiation plans were created for pre- and post-IC thoracic disease in each case. The changes in the gross target volume (GTV), planning target volume (PTV) and dosimetric factors associated with the lungs, esophagus and heart were analyzed. The mean GTV and PTV for all of the patients decreased by 60.9% and 40.2%, respectively, which resulted in a significant reduction in the radiation exposure to the lungs, esophagus and heart. Changes in the PTV and radiation exposure of normal tissue were not significantly affected by the number of chemotherapy cycles delivered, although patients who received 2 cycles of IC had a greater decrease in GTV than those who received only 1 cycle of IC (69.6% vs. 52.1%, p = 0.273). Our data showed that targeting the tumor post-IC may reduce the radiation dose to normal tissue in patients with LS-SCLC. However, the benefit to the normal tissue was not increased by an additional cycle of IC. These findings suggest that the first cycle of chemotherapy is very important for tumor shrinkage and that initiating thoracic radiation therapy at the second cycle of chemotherapy may be a reasonable strategy for timing of radiation therapy in LS-SCLC treatment

Tumor tissue levels of Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) and outcome following adjuvant chemotherapy in premenopausal lymph node-positive breast cancer patients: A retrospective study

International Nuclear Information System (INIS)

Schrohl, Anne-Sofie; Look, Maxime P; Meijer-van Gelder, Marion E; Foekens, John A; Brünner, Nils

2009-01-01

We have previously demonstrated that high tumor tissue levels of TIMP-1 are associated with no or limited clinical benefit from chemotherapy with CMF and anthracyclines in metastatic breast cancer patients. Here, we extend our investigations to the adjuvant setting studying outcome after adjuvant chemotherapy in premenopausal lymph node-positive patients. We hypothesize that TIMP-1 high tumors are less sensitive to chemotherapy and accordingly that high tumor tissue levels are associated with shorter survival. From our original retrospectively collected tumor samples we selected a group of 525 pre-menopausal lymph node-positive patients (adjuvant treatment: CMF, 324 patients; anthracycline-based, 99 patients; no adjuvant chemotherapy, 102 patients). TIMP-1 levels were measured using ELISA in cytosolic extracts of frozen primary tumors. TIMP-1 was analyzed as a continuous variable and as a dichotomized one using the median TIMP-1 concentration as a cut point between high and low TIMP-1 groups. We analyzed the benefit of adjuvant CMF and anthracyclines in univariate and multivariable survival models; endpoints were disease-free (DFS) and overall survival (OS). In this selected cohort of high-risk patients, and in the subgroup of patients receiving no adjuvant therapy, TIMP-1 was not associated with prognosis. In the subgroup of patients treated with anthracyclines, when analyzed as a continuous variable we observed a tendency for increasing TIMP-1 levels to be associated with shorter DFS (multivariable analysis, HR 1.75, 95% CI 1.00-3.07, P = 0.05) and a significant association between increasing TIMP-1 and shorter OS in both univariate (HR 3.52, 95% CI 1.54-8.06, P = 0.003) and multivariable analyses (HR 4.19, 95% CI 1.67-10.51, P = 0.002). No statistically significant association between TIMP-1 and DFS was observed in the CMF-treated patients although high TIMP-1 was associated with shorter OS when analyzed as a dichotomized variable (HR 1.64, 95% CI 1.02-2.65, P

Prevalence of Circulating Tumor Cells After Adjuvant Chemotherapy With or Without Anthracyclines in Patients With HER2-negative, Hormone Receptor-positive Early Breast Cancer.

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Schramm, Amelie; Schochter, Fabienne; Friedl, Thomas W P; de Gregorio, Nikolaus; Andergassen, Ulrich; Alunni-Fabbroni, Marianna; Trapp, Elisabeth; Jaeger, Bernadette; Heinrich, Georg; Camara, Oumar; Decker, Thomas; Ober, Angelika; Mahner, Sven; Fehm, Tanja N; Pantel, Klaus; Fasching, Peter A; Schneeweiss, Andreas; Janni, Wolfgang; Rack, Brigitte K

2017-07-01

Use of anthracycline-based chemotherapy in patients with early breast cancer (EBC) has been well-established but is often associated with cardiotoxicity. Based on data suggesting a limited benefit of anthracyclines in human epidermal growth factor receptor 2 (HER2)-negative patients, the Simultaneous Study of Docetaxel Based Anthracycline Free Adjuvant Treatment Evaluation, as well as Life Style Intervention Strategies (SUCCESS) C study randomized patients to either anthracycline-containing or anthracycline-free chemotherapy. Given the proven prognostic value of circulating tumor cells (CTCs) in EBC, we compared the prevalence of CTCs after chemotherapy between both treatment arms for a preliminary efficacy assessment. The SUCCESS C trial (NCT00847444) is an open-label, phase III study randomizing 3547 patients with HER2-negative EBC to either 3 cycles of epirubicin, 5-fluorouracil, and cyclophosphamide followed by 3 cycles of docetaxel (FEC-DOC) or 6 cycles of docetaxel and cyclophosphamide (DOC-C). CTC status was prospectively evaluated in hormone receptor-positive patients at the time of last chemotherapy cycle using the US Food and Drug Administration-approved CellSearch System (Janssen Diagnostics). Data on CTC status were available for 1766 patients. Overall, CTCs were found in 221 (12.5%) patients. Univariate analyses revealed that presence of CTCs at time of last chemotherapy cycle was not significantly associated with tumor or patient characteristics (all P > .1). There was no significant difference with respect to presence of CTCs between patients randomized to FEC-DOC or DOC-C (11.5% vs. 13.6%; P = .18). The comparable prevalence of CTCs at the time of last chemotherapy cycle may indicate that anthracycline-free chemotherapy is equally effective to anthracycline-containing chemotherapy in HER2-negative, hormone receptor-positive EBC. However, efficacy data from the final survival analysis of SUCCESS C have to be awaited to confirm these preliminary

Change of tumor vascular reactivity during tumor growth and postchemotherapy observed by near-infrared spectroscopy

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Lee, Songhyun; Jeong, Hyeryun; Seong, Myeongsu; Kim, Jae Gwan

2017-12-01

Breast cancer is one of the most common cancers in females. To monitor chemotherapeutic efficacy for breast cancer, medical imaging systems such as x-ray mammography, computed tomography, magnetic resonance imaging, and ultrasound imaging have been used. Currently, it can take up to 3 to 6 weeks to see the tumor response from chemotherapy by monitoring tumor volume changes. We used near-infrared spectroscopy (NIRS) to predict breast cancer treatment efficacy earlier than tumor volume changes by monitoring tumor vascular reactivity during inhalational gas interventions. The results show that the amplitude of oxy-hemoglobin changes (vascular reactivity) during hyperoxic gas inhalation is well correlated with tumor growth and responded one day earlier than tumor volume changes after chemotherapy. These results may imply that NIRS with respiratory challenges can be useful in early detection of tumor and in the prediction of tumor response to chemotherapy.

Novel nitric oxide generating compound glycidyl nitrate enhances the therapeutic efficacy of chemotherapy and radiotherapy.

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Ning, Shoucheng; Bednarski, Mark; Oronsky, Bryan; Scicinski, Jan; Knox, Susan J

2014-05-09

Selective release of nitric oxide (NO) in tumors could improve the tumor blood flow and drug delivery for chemotherapeutic agents and radiotherapy, thereby increasing the therapeutic index. Glycidyl nitrate (GLYN) is a NO generating small molecule, and has ability to release NO on bioactivation in SCC VII tumor cells. GLYN-induced intracellular NO generation was significantly attenuated by NO scavenger carboxy-PTIO (cPTIO) and NAC. GLYN significantly increases tumor blood flow, but has no effect on the blood flow of normal tissues in tumor-bearing mice. When used with cisplatin, GLYN significantly increased the tumor growth inhibition effect of cisplatin. GLYN also had a modest radiosensitizing effect in vitro and in vivo. GLYN was well tolerated and there were no acute toxicities found at its effective therapeutic doses in preclinical studies. These results suggest that GLYN is a promising new drug for use with chemotherapy and radiotherapy, and provide a compelling rationale for future studies of GLYN and related compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

Subcutaneous testosterone-letrozole therapy before and concurrent with neoadjuvant breast chemotherapy: clinical response and therapeutic implications.

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Glaser, Rebecca L; York, Anne E; Dimitrakakis, Constantine

2017-07-01

Hormone receptor-positive breast cancers respond favorably to subcutaneous testosterone combined with an aromatase inhibitor. However, the effect of testosterone combined with an aromatase inhibitor on tumor response to chemotherapy was unknown. This study investigated the effect of testosterone-letrozole implants on breast cancer tumor response before and during neoadjuvant chemotherapy. A 51-year-old woman on testosterone replacement therapy was diagnosed with hormone receptor-positive invasive breast cancer. Six weeks before starting neoadjuvant chemotherapy, the patient was treated with subcutaneous testosterone-letrozole implants and instructed to follow a low-glycemic diet. Clinical status was followed. Tumor response to "testosterone-letrozole" and subsequently, "testosterone-letrozole with chemotherapy" was monitored using serial ultrasounds and calculating tumor volume. Response to therapy was determined by change in tumor volume. Cost of therapy was evaluated. There was a 43% reduction in tumor volume 41 days after the insertion of testosterone-letrozole implants, before starting chemotherapy. After the initiation of concurrent chemotherapy, the tumor responded at an increased rate, resulting in a complete pathologic response. Chemotherapy was tolerated. Blood counts and weight remained stable. There were no neurologic or cardiac complications from the chemotherapy. Cost of therapy is reported. Subcutaneous testosterone-letrozole was an effective treatment for this patient's breast cancer and did not interfere with chemotherapy. This novel combination implant has the potential to prevent side effects from chemotherapy, improve quality of life, and warrants further investigation.

Photochemical internalization enhanced macrophage delivered chemotherapy.

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Shin, Diane; Christie, Catherine; Ju, David; Nair, Rohit Kumar; Molina, Stephanie; Berg, Kristian; Krasieva, Tatiana B; Madsen, Steen J; Hirschberg, Henry

2018-03-01

Macrophage (Ma) vectorization of chemotherapeutic drugs has the advantage for cancer therapy in that it can actively target and maintain an elevated concentration of drugs at the tumor site, preventing their spread into healthy tissue. A potential drawback is the inability to deliver a sufficient number of drug-loaded Ma into the tumor, thus limiting the amount of active drug delivered. This study examined the ability of photochemical internalization (PCI) to enhance the efficacy of released drug by Ma transport. Tumor spheroids consisting of either F98 rat glioma cells or F98 cells combined with a subpopulation of empty or doxorubicin (DOX)-loaded mouse Ma (RAW264.7) were used as in vitro tumor models. PCI was performed with the photosensitizer AlPcS 2a and laser irradiation at 670 nm. RAW264.7 Ma pulsed with DOX released the majority of the incorporated DOX within two hours of incubation. PCI significantly increased the toxicity of DOX either as pure drug or derived from monolayers of DOX-loaded Ma. Significant growth inhibition of hybrid spheroids was also observed with PCI even at subpopulations of DOX-loaded Ma as low as 11% of the total initial hybrid spheroid cell number. Results show that RAW264.7 Ma, pulsed with DOX, could effectively incorporate and release DOX. PCI significantly increased the ability of both free and Ma-released DOX to inhibit the growth of tumor spheroids in vitro. The growth of F98 + DOX loaded Ma hybrid spheroids were synergistically reduced by PCI, compared to either photodynamic therapy or released DOX acting alone. Copyright © 2017 Elsevier B.V. All rights reserved.

Proteomic characterization of EL4 lymphoma-derived tumors upon chemotherapy treatment reveals potential roles for lysosomes and caspase-6 during tumor cell death in vivo.

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Kramer, David A; Eldeeb, Mohamed A; Wuest, Melinda; Mercer, John; Fahlman, Richard P

2017-06-01

The murine mouse lymphoblastic lymphoma cell line (EL4) tumor model is an established in vivo apoptosis model for the investigation of novel cancer imaging agents and immunological treatments due to the rapid and significant response of the EL4 tumors to cyclophosphamide and etoposide combination chemotherapy. Despite the utility of this model system in cancer research, little is known regarding the molecular details of in vivo tumor cell death. Here, we report the first in-depth quantitative proteomic analysis of the changes that occur in these tumors upon cyclophosphamide and etoposide treatment in vivo. Using a label-free quantitative proteomic approach a total of 5838 proteins were identified in the treated and untreated tumors, of which 875 were determined to change in abundance with statistical significance. Initial analysis of the data reveals changes that may have been predicted, such as the downregulation of ribosomes, but demonstrates the robustness of the dataset. Analysis of the dataset also reveals the unexpected downregulation of caspase-3 and an upregulation of caspase-6 in addition to a global upregulation of lysosomal proteins in the bulk of the tumor. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Insulin receptor substrate 1 expression enhances the sensitivity of 32D cells to chemotherapy-induced cell death

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Porter, Holly A.; Carey, Gregory B.; Keegan, Achsah D.

2012-01-01

The adaptors IRS1 and IRS2 link growth factor receptors to downstream signaling pathways that regulate proliferation and survival. Both suppress factor-withdrawal-induced apoptosis and have been implicated in cancer progression. However, recent studies suggest IRS1 and IRS2 mediate differential functions in cancer pathogenesis. IRS1 promoted breast cancer proliferation, while IRS2 promoted metastasis. The role of IRS1 and IRS2 in controlling cell responses to chemotherapy is unknown. To determine the role of IRS1 and IRS2 in the sensitivity of cells to chemotherapy, we treated 32D cells lacking or expressing IRS proteins with various concentrations of chemotherapeutic agents. We found that expression of IRS1, in contrast to IRS2, enhanced the sensitivity of 32D cells to chemotherapy-induced apoptosis. When IRS2 was expressed with IRS1, the cells no longer showed enhanced sensitivity. Expression of IRS1 did not alter the expression of pro- and anti-apoptotic proteins; however, 32D-IRS1 cells expressed higher levels of Annexin A2. In 32D-IRS1 cells, IRS1 and Annexin A2 were both located in cytoplasmic and membrane fractions. We also found that IRS1 coprecipitated with Annexin A2, while IRS2 did not. Decreasing Annexin A2 levels reduced 32D-IRS1 cell sensitivity to chemotherapy. These results suggest IRS1 enhances sensitivity to chemotherapy in part through Annexin A2. PMID:22652453

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

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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.

PET Imaging of 64Cu-DOTA-scFv-Anti-PSMA Lipid Nanoparticles (LNPs): Enhanced Tumor Targeting over Anti-PSMA scFv or Untargeted LNPs

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Wong, Patty; Li, Lin; Chea, Junie; Delgado, Melissa K.; Crow, Desiree; Poku, Erasmus; Szpikowska, Barbara; Bowles, Nicole; Channappa, Divya; Colcher, David; Wong, Jeffrey Y.C.; Shively, John E.; Yazaki, Paul J.

2017-01-01

Introduction Single chain (scFv) antibodies are ideal targeting ligands due to their modular structure, high antigen specificity and affinity. These monovalent ligands display rapid tumor targeting but have limitations due to their fast urinary clearance. Methods An anti-prostate membrane antigen (PSMA) scFv with a site-specific cysteine was expressed and evaluated in a prostate cancer xenograft model by Cu-64 PET imaging. To enhance tumor accumulation, the scFv-cys was conjugated to the co-polymer DSPE-PEG-maleimide that spontaneously assembled into a homogeneous multivalent lipid nanoparticle (LNP). Results The targeted LNP exhibited a 2-fold increase in tumor uptake compared to the scFv alone using two different thiol ester chemistries. The anti-PSMA scFv-LNP exhibited a 1.6 fold increase in tumor targeting over the untargeted LNP. Conclusions The targeted anti-PSMA scFv-LNP showed enhanced tumor accumulation over the scFv alone or the untargeted DOTA-micelle providing evidence for the development of this system for drug delivery. Advances in Knowledge and implications for patient care Anti-tumor scFv antibody fragments have not achieved their therapeutic potential due to their fast blood clearance. Conjugation to a LNP enables multivalency to the tumor antigen as well as increased molecular size for chemotherapy drug delivery. PMID:28126683

Benign and malignant hepatocellular tumors: evaluation of tumoral enhancement after mangafodipir trisodium injection on MR imaging

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Coffin, C.M.; Diche, T.; Mahfouz, A.E.; Alexandre, M.; Caseiro-Alves, F.; Rahmouni, A.; Vasile, N.; Mathieu, D.

1999-01-01

The aim of this work was to study the ability of mangafodipir trisodium (Mn-DPDP)-enhanced MR imaging in differentiating malignant from benign hepatocellular tumors. Eleven patients with pathologically proved hepatocellular carcinomas, six with focal nodular hyperplasias, and one with a single hepatocellular adenoma were examined by spin-echo and gradient-echo T1-weighted sequences before, 1 h after, and 24 h after intravenous injection of Mn-DPDP (5 μmol/kg). Quantitative analysis including enhancement and lesion-to-liver contrast-to-noise ratio, and qualitative analysis including the presence of a central area and a capsule were done on pre- and post-Mn-DPDP-enhanced images. Enhancement was observed in all the tumors with significant improvement (p < 0.05) in contrast-to-noise ratio 1 h after, and 24 h after intravenous injection of Mn-DPDP. There were no significant differences in the mean enhancement and the mean contrast-to-noise ratio (CNR) between benign and malignant tumors. No enhancement was seen within internal areas observed in 7 hepatocellular carcinomas, and in 5 focal nodular hyperplasias, and within capsules which were observed in 9 hepatocellular carcinomas. In our study, Mn-DPDP increased CNR of both benign and malignant tumors but did not enable differentiation between benign and malignant tumors of hepatocellular nature. (orig.)

Multispectral and phase-contrast diffuse optical tomography of breast cancer during neoadjuvant chemotherapy: a case study

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Liang, Xiaoping; Zhang, Qizhi; Staal, Stephen; Grobmyer, Stephen; Jiang, Huabei

2009-02-01

Multispectral and phase-contrast diffuse optical tomography are used to track treatment progress in a patient with locally advanced invasive carcinoma of the breast cancer during neoadjuvant chemotherapy. Two types of chemotherapy treatment including four cycles of Adriamycin/Cytoxin (AC cycles) and twelve cycles of Taxol/Herceptin (TH cycles) were applied to patient. A total of eight optical exams were performed before and within the chemotherapy. Images of tissue refractive index, and absorption and scattering coefficients, as well as oxy-hemoglobin and deoxy-hemoglobin concentrations along with scattering particle volume fraction and mean diameter of cellular components were all obtained. The tumor was identified through absorption and scattering images. Tumor shrinkage was observed during the course of chemotherapy from all the optical images. Our results show that oxy-hemoglobin, deoxy-hemoglobin and total hemoglobin in tumor decreased after chemotherapy compared to that of before chemotherapy. Significant changes in tumor refractive index along with tumor cellular morphology during the entire chemotherapy are also observed.

Biphasic pulses enhance bleomycin efficacy in a spontaneous canine genital tumor model of chemoresistance: Sticker sarcoma

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Citro Gennaro

2008-11-01

Full Text Available Abstract Sticker's sarcoma (also known as transmissible venereal tumor is a horizontally transmitted neoplasm of the dog, that is passed with coitus. It is a locally aggressive tumor with a low tendency to metastatic spread. The most common locations are the genitals, the nose, the perianal area. Standard treatment consists with chemotherapy with vincristine, however other therapies such as, cryotherapy, immunotherapy or, in selected cases, radiation therapy, have been reported. In this article we describe the outcome of a small cohort of canine patients, with chemotherapy resistant transmissible venereal tumor (TVT, treated with bleomycin selectively driven by trains of biphasic pulses (electrochemotherapy. Three canine patients, with refractory TVT, entered the study and received two sessions of ECT under sedation. The pets had local injection of bleomycin at the concentration of 1.5 mg/ml and five minutes after the chemotherapy, trains of 8 biphasic electric pulses lasting 50 + 50 μs each, with 1 ms interpulse intervals, were delivered by means of modified caliper or, for difficult districts, through paired needle electrode. All the patients responded to the treatment and are still in remission at different times. Electrochemotherapy appears as a safe and efficacious modality for the treatment of TVT and warrants further investigations.

Radio chemotherapy for uterine cervix carcinoma

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Resbeut, M.; Alzieu, C.; Gonzague-Casabianca, L.; Haie-Meder, C.

2000-01-01

Low-stage uterine cervix carcinoma can be treated by either surgery, radiation therapy or combined treatments with high cure rates ranging from 90 to 95 % for stage IB1 tumors. However, the standard treatment, combining external beam plus intracavitary radiation, fails to control the progression of the disease in 35 to 90 % of patients with locally advanced cervical cancer. No substantial improvements have been made in the treatment of these tumors in the past two decades. The addition of concurrent 5-FU in a phase III study failed to improve the results in the overall patient population, but the five-year DFS was significantly better in a subset of patients (tumor > 5 cm and IB/IIA or medial parametrial IIB disease). Concurrent chemo-radiation and adjuvant chemotherapy with epirubicin showed, in a phase III study, a significant longer DFS in patients treated with chemotherapy despite the same long-term local tumor control. After many phase II studies, five phase III studies have recently demonstrated a 40 to 60 % reduction in the relative risk of recurrence with cisplatin containing chemo-radiation. Across these studies, the risk of death was reduced by 30 to 50 %. The benefit was less clear in patients with stages III-IV tumors than in patients with lower stages associated with poor prognostic factors. Hematologic and gastrointestinal toxicity of chemo-radiation was greater than that of radiotherapy alone. However, late side effects were similar in the different treatment groups. These results must be confirmed with a longer follow-up. The importance of concurrent chemotherapy during the brachytherapy procedure should be analyzed. It has yet to be determined which chemotherapy regimen achieves the most favorable therapeutic ratio. (authors)

Non-pineal supratentorial primitive neuro-ectodermal tumors (sPNET) in teenagers and young adults: Time to reconsider cisplatin based chemotherapy after cranio-spinal irradiation?

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Biswas, Swethajit; Burke, Amos; Cherian, Sheen; Williams, Denise; Nicholson, James; Horan, Gail; Jefferies, Sarah; Williams, Michael; Earl, Helena M; Burnet, Neil G; Hatcher, Helen

2009-07-01

Supratentorial PNET (sPNET) are rare CNS tumors of embryonal origin arising in children and adults. The treatment of sPNET for all age groups at our cancer center has been based on the management of medulloblastoma (MB), involving neurosurgical debulking followed by cranio-spinal irradiation (CSI) and systemic chemotherapy. Medical records were reviewed to gather demographic and clinical data about all embryonal CNS tumors in children and adults from 2001 to 2007. Tumor pathology, clinical management and survival data were also assessed, particularly as regards those patients who received the Packer chemotherapy regimen for either sPNET or MB. Eleven patients (five children and six adults) were identified with non-pineal sPNET, three children with pineal sPNET, and 19 patients (18 children and 1 adult) with MB. There was no difference in overall survival (OS) rates between pediatric and adult sPNET. When all sPNET were compared to all MB, 5-year OS was 14% versus 73%, respectively, but was only 9% for non-pineal sPNET. When only considering those patients treated with the Packer chemotherapy regimen, the 5-year OS was 12% for sPNET versus 79% for MB. This retrospective study demonstrates that non-pineal sPNET are clinically distinct from MB and are resistant to the Packer chemotherapy regimen. We suggest that it is time to reconsider the use of this regimen in teenage and young adult non-pineal sPNET and to investigate the utility of alternative approaches. (c) 2009 Wiley-Liss, Inc.

Verapamil inhibits tumor progression of chemotherapy-resistant pancreatic cancer side population cells

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ZHAO, LU; ZHAO, YUE; SCHWARZ, BETTINA; MYSLIWIETZ, JOSEF; HARTIG, ROLAND; CAMAJ, PETER; BAO, QI; JAUCH, KARL-WALTER; GUBA, MAKUS; ELLWART, JOACHIM WALTER; NELSON, PETER JON; BRUNS, CHRISTIANE JOSEPHINE

2016-01-01

Tumor side population (SP) cells display stem-like properties that can be modulated by treatment with the calcium channel blocker verapamil. Verapamil can enhance the cytotoxic effects of chemotherapeutic drugs and multi-drug resistance by targeting the transport function of the P-glycoprotein (P-gp). This study focused on the therapeutic potential of verapamil on stem-like SP tumor cells, and further investigated its chemosensitizing effects using L3.6pl and AsPC-1 pancreatic carcinoma models. As compared to parental L3.6pl cells (0.9±0.22%), L3.6pl gemcitabine-resistant cells (L3.6plGres) showed a significantly higher percentage of SP cells (5.38±0.99%) as detected by Hoechst 33342/FACS assays. The L3.6plGres SP cells showed stable gemcitabine resistance, enhanced colony formation ability and increased tumorigenicity. Verapamil effectively inhibited L3.6plGres and AsPC-1 SP cell proliferation in vitro. A pro-apoptotic effect of verapamil was observed in L3.6pl cells, but not in L3.6plGres cells, which was linked to their differential expression of P-gp and equilibrative nucleoside transporter-1 (ENT-1). In an orthotopic pancreatic cancer mouse model, both low and high dose verapamil was shown to substantially reduce L3.6plGres-SP cell tumor growth and metastasis, enhance tumor apoptosis, and reduce microvascular density. PMID:27177126

Prognostic significance of an early decline in serum alpha-fetoprotein during chemotherapy for ovarian yolk sac tumors.

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de la Motte Rouge, Thibault; Pautier, Patricia; Genestie, Catherine; Rey, Annie; Gouy, Sébastien; Leary, Alexandra; Haie-Meder, Christine; Kerbrat, Pierre; Culine, Stéphane; Fizazi, Karim; Lhommé, Catherine

2016-09-01

The ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact. This retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan-Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively. Data on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%-93%) and 84% (95% CI: 73%-91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%-72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p<0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR=7.3, p=0.03) and an unfavorable early AFP decline (RR=16.9, p<0.01) were significant negative predictive factors for OS. An early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs. No conflict of interest. Copyright © 2016. Published by Elsevier Inc.

Effect of S-1 chemotherapy and FP chemotherapy on prognosis, imaging characteristics and serum marker levels after operation for gastric carcinoma

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Qing-Hao Gong

2016-09-01

Full Text Available Objective: To analyze the effect of S-1 chemotherapy and FP chemotherapy on prognosis, imaging characteristics and serum marker levels after operation for gastric carcinoma. Methods: A total of 68 patients with gastric cancer who underwent radical surgery were included in the study and divided into observation group and control group patients (n=34 according to random number table. Control group received FP chemotherapy, observation group received S-1 chemotherapy, and then differences in serum tumor markers, illnessrelated factors, nutrition indexes and T cell immune function values were compared between two groups. Results: After observation group received systematic chemotherapy, serum tumor markers such as MMP-9, MMP-2, MG7-Ag, TSGF, CA72-4, CA19-9, TP and DpD as well as illness-related factors such as DKK1, MK, Leptin, Exosome and OPN were all lower than those of control group (P<0.05; nutrition and cellular immune function indexes such as TP, ALB, PA, CD4+ T and CD4+ T/ CD8+ T values were higher than those of control group and CD8+ T value was lower than that of control group (P<0.05. Conclusions: S-1 chemotherapy after operation for gastric carcinoma can inhibit the tumor activity and optimize patients’ overall condition, and it has positive clinical significance.

Magnetically assisted intraperitoneal drug delivery for cancer chemotherapy.

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Shamsi, Milad; Sedaghatkish, Amir; Dejam, Morteza; Saghafian, Mohsen; Mohammadi, Mehdi; Sanati-Nezhad, Amir

2018-11-01

Intraperitoneal (IP) chemotherapy has revived hopes during the past few years for the management of peritoneal disseminations of digestive and gynecological cancers. Nevertheless, a poor drug penetration is one key drawback of IP chemotherapy since peritoneal neoplasms are notoriously resistant to drug penetration. Recent preclinical studies have focused on targeting the aberrant tumor microenvironment to improve intratumoral drug transport. However, tumor stroma targeting therapies have limited therapeutic windows and show variable outcomes across different cohort of patients. Therefore, the development of new strategies for improving the efficacy of IP chemotherapy is a certain need. In this work, we propose a new magnetically assisted strategy to elevate drug penetration into peritoneal tumor nodules and improve IP chemotherapy. A computational model was developed to assess the feasibility and predictability of the proposed active drug delivery method. The key tumor pathophysiology, including a spatially heterogeneous construct of leaky vasculature, nonfunctional lymphatics, and dense extracellular matrix (ECM), was reconstructed in silico. The transport of intraperitoneally injected magnetic nanoparticles (MNPs) inside tumors was simulated and compared with the transport of free cytotoxic agents. Our results on magnetically assisted delivery showed an order of magnitude increase in the final intratumoral concentration of drug-coated MNPs with respect to free cytotoxic agents. The intermediate MNPs with the radius range of 200-300 nm yield optimal magnetic drug targeting (MDT) performance in 5-10 mm tumors while the MDT performance remains essentially the same over a large particle radius range of 100-500 nm for a 1 mm radius small tumor. The success of MDT in larger tumors (5-10 mm in radius) was found to be markedly dependent on the choice of magnet strength and tumor-magnet distance while these two parameters were less of a concern in small tumors

Identification of colorectal cancer patients with tumors carrying the TP53 mutation on the codon 72 proline allele that benefited most from 5-fluorouracil (5-FU) based postoperative chemotherapy

International Nuclear Information System (INIS)

Godai, Ten-i; Sakuma, Yuji; Tsuchiya, Eiju; Kameda, Yoichi; Akaike, Makoto; Miyagi, Yohei; Suda, Tetsuji; Sugano, Nobuhiro; Tsuchida, Kazuhito; Shiozawa, Manabu; Sekiguchi, Hironobu; Sekiyama, Akiko; Yoshihara, Mitsuyo; Matsukuma, Shoichi

2009-01-01

Although postoperative chemotherapy is widely accepted as the standard modality for Dukes' stage C or earlier stage colorectal cancer (CRC) patients, biomarkers to predict those who may benefit from the therapy have not been identified. Previous in vitro and clinical investigations reported that CRC patients with wild-type p53 gene (TP53)-tumors benefit from 5-fluorouracil (5-FU) based chemotherapy, while those with mutated TP53-tumors do not. However, these studies evaluated the mutation-status of TP53 by immunohistochemistry with or without single-strand conformation polymorphism, and the mutation frequency was different from study to study. In addition, the polymorphic status at p53 codon 72, which results in arginine or proline residues (R72P) and is thought to influence the function of the protein significantly, was not examined. To evaluate the significance of the TP53 mutation as a molecular marker to predict the prognosis of CRC patients, especially those who received postoperative chemotherapy, we examined the mutation by direct sequencing from fresh CRC tumors and evaluated the R72P polymorphism of the mutated TP53 by a combined mutant allele- and polymorphic allele-specific polymerase chain reaction (PCR). The TP53 mutation occurred in 147 (70%) of 211 Japanese CRC tumors. The mutation was observed in 93 (63%) tumors on the R72 allele and in 54 (37%) tumors on the P72 allele. Although the alterations to TP53 have no prognostic significance for CRC patients overall, we found that Dukes' stage C CRC patients who did not receive postoperative chemotherapy and carried the mutated TP53-R72 showed significantly longer survival times than those with the mutated TP53-P72 when evaluated by overall survival (p = 0.012). Using a combined mutant allele- and polymorphic allele-specific PCR, we defined the codon 72 polymorphic status of the TP53 mutated allele in Japanese CRC patients. We raised a possibility that Dukes' stage C colorectal cancer

Chemotherapy for neuroendocrine tumors: the Beatson Oncology Centre experience.

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Hatton, M Q; Reed, N S

1997-01-01

The role of chemotherapy in malignant neuroendocrine tumours is difficult to assess because of their rarity and variation in biological behaviour. We present a retrospective review of chemotherapy given to 18 patients with metastatic and one with locally advanced neuroendocrine tumours. There were eight poorly differentiated neuroendocrine tumours, six thyroid medullary carcinomas, two phaeochromocytomas, two pancreatic islet cell tumours and one undifferentiated neuroblastoma. Four patients were given 3-weekly dacarbazine, vincristine and cyclophosphamide (DOC) chemotherapy. In eight patients, this regimen was modified by substituting the dacarbazine and cisplatin and etoposide (OPEC). A further six patients were treated with dacarbazine reintroduced into the 3-weekly regimen (DOPEC). The remaining patient received cisplatin and etoposide. There were two complete responses (both with OPEC) and eight partial responses (two with DOC, three with OPEC and three with DOPEC). Five patients had stable disease and four progressed. Four received further chemotherapy on relapse, producing one complete and one partial response. The median response duration to initial chemotherapy was 10 months (range 3-34). The median survival was 12 months (range 1-42). The main toxicity was haematological, with grade 3-4 neutropenia in 12 patients; eight suffered episodes of sepsis. One death was treatment related. Other toxicity was mild although three patients discontinued vincristine with grade 2 neurotoxicity. The response rate and side effects of these three regimens appear comparable. We conclude that, although these patient numbers are small, combination chemotherapy produces an encouraging response rate (53%; 95% CI 30-75) in malignant neuroendocrine tumours, with acceptable toxicity.

Immunogenic Chemotherapy Sensitizes Renal Cancer to Immune Checkpoint Blockade Therapy in Preclinical Models.

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Cui, Shujin

2017-07-11

BACKGROUND Renal cell carcinoma (RCC) is among the most common malignant cancers of males worldwide. For advanced RCC patients, there still is no effective therapy. Immune checkpoint blockade therapies have shown benefits for many cancers, but previous clinical trials of immune checkpoint blockade therapies in RCC patients achieved only modest results. MATERIAL AND METHODS We explored the effects of combining chemotherapy with immune checkpoint blockade therapy in RCC xenograft mouse models. We also studied the potential mechanisms by which chemotherapy might enhance the efficacy of immune checkpoint blockade therapy, both in vitro and in vivo. RESULTS Our results showed that many commonly used chemotherapy agents can induce immunogenic marker release in RCC cell lines. Importantly, the RCC xenograft mouse model mice who received the combination treatment of 5-fluorouracil (5-FU) and anti-programmed cell death-ligand 1 (PD-L1) antibodies (Abs) had longer survival times compared to those who received 5-FU or anti-PD-L1 Abs alone. Also, increased key cytokines that promote tumor immunity, such as IL-2, IFN-γ, and TNF-α, as well as tumor-infiltrating cytotoxic T cells, were also increased after the combination treatment. CONCLUSIONS We conclude that 5-FU can sensitize RCC to anti-PD-L1 treatment by releasing the immune suppression in the tumor microenvironment.

Benefit from prolonged dose-intensive chemotherapy for infants with malignant brain tumors is restricted to patients with ependymoma: a report of the Pediatric Oncology Group randomized controlled trial 9233/34.

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Strother, Douglas R; Lafay-Cousin, Lucie; Boyett, James M; Burger, Peter; Aronin, Patricia; Constine, Louis; Duffner, Patricia; Kocak, Mehmet; Kun, Larry E; Horowitz, Marc E; Gajjar, Amar

2014-03-01

The randomized controlled Pediatric Oncology Group study 9233 tested the hypothesis that dose-intensive (DI) chemotherapy would improve event-free survival (EFS) for children chemotherapy (Regimen A, n = 162) or DI chemotherapy (Regimen B, n = 166). Radiation therapy (RT) was recommended for patients with evidence of disease at completion of chemotherapy or who relapsed within 6 months of chemotherapy completion. Distributions of EFS for Regimens A and B were not significantly different (P = 0.32) with 2- and 10-year rates of 22.8% ± 3.3% and 15.4% ± 3.7%, and 27.1% ± 3.4% and 20.8% ± 3.8%, respectively. Thus, the study hypothesis was rejected. While distributions of EFS and OS were not significantly different between Regimens A and B for patients with medulloblastoma and sPNET, DI chemotherapy resulted in significantly improved EFS distribution (P = .0011) (2-year EFS rates of 42.1% vs. 19.6% with SD chemotherapy), but not OS distribution, for patients with centrally confirmed ependymoma. The degree of surgical resection affected EFS, OS or both for most tumor groups. Approximately 20%, 40% and 20% of patients with medulloblastoma, ependymoma treated with DI chemotherapy, and sPNET, respectively appear to have been cured without RT. Of 11 toxic deaths on study, 10 occurred on the DI chemotherapy arm. Prolonged dose-intensive chemotherapy given to infants with malignant brain tumors resulted in increased EFS only for patients with ependymoma.

Imatinib mesylate induces responses in patients with liver metastases from gastrointestinal stromal tumor failing intra-arterial hepatic chemotherapy

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Fiorentini Giammaria

2006-01-01

Full Text Available Background: Imatinib mesylate represents a real major paradigm shift in cancer therapy, targeting the specific molecular abnormalities, crucial in the etiology of tumor. Intra-arterial hepatic chemotherapy (IAHC followed by embolization, has been considered an interesting palliative option for patients with liver metastases from gastrointestinal stromal tumor (GIST, due to the typically hypervascular pattern of the tumor. Aims: We report our experience with IAHC followed by Imatinib mesylate, in order to show the superiority of the specific molecular approach in liver metastases from GIST. Materials and Methods: Three patients (pts with pretreated massive liver metastases from GIST, received IAHC with Epirubicin 50 mg/mq, every 3 weeks for 6 cycles. At the evidence of progression, they received Imatinib mesylate. Results: We observed progressive diseases in all cases. In 1998, one patient underwent Thalidomide at 150 mg orally, every day for 4 months, with evidence of stable disease and clinical improvement. In 2001, two patients received Imatinib mesylate at 400 mg orally, every day, with evidence of partial response lasting 18+ months and 16 months. One of them had grade 3 neutropenia, with suspension of therapy for 3 weeks. Conclusion: No patient treated with IAHC, reported objective responses, but two of them obtained partial response after the assumption of Imatinib mesylate and one showed temporary stabilization with thalidomide. Imatinib mesylate represents a new opportunity in GIST therapy, targeting the specific molecular alteration. It seems to be superior to conventional intra arterial hepatic chemotherapy.

An Immune-Modulating Diet in Combination with Chemotherapy Prevents Cancer Cachexia by Attenuating Systemic Inflammation in Colon 26 Tumor-Bearing Mice.

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Nakamura, Kentaro; Sasayama, Akina; Takahashi, Takeshi; Yamaji, Taketo

2015-01-01

Cancer cachexia is characterized by muscle wasting caused partly by systemic inflammation. We previously demonstrated an immune-modulating diet (IMD), an enteral diet enriched with immunonutrition and whey-hydrolyzed peptides, to have antiinflammatory effects in some experimental models. Here, we investigated whether the IMD in combination with chemotherapy could prevent cancer cachexia in colon 26 tumor-bearing mice. Forty tumor-bearing mice were randomized into 5 groups: tumor-bearing control (TB), low dose 5-fluorouracil (5-FU) and standard diet (LF/ST), low dose 5-FU and IMD (LF/IMD), high dose 5-FU and standard diet (HF/ST) and high dose 5-FU and IMD (HF/IMD). The ST and IMD mice received a standard diet or the IMD ad libitum for 21 days. Muscle mass in the IMD mice was significantly higher than that in the ST mice. The LF/IMD in addition to the HF/ST and HF/IMD mice preserved their body and carcass weights. Plasma prostaglandin E2 levels were significantly lower in the IMD mice than in the ST mice. A combined effect was also observed in plasma interleukin-6, glucose, and vascular endothelial growth factor levels. Tumor weight was not affected by different diets. In conclusion, the IMD in combination with chemotherapy prevented cancer cachexia without suppressing chemotherapeutic efficacy.

Endothelial Thermotolerance Impairs Nanoparticle Transport in Tumors.

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Bagley, Alexander F; Scherz-Shouval, Ruth; Galie, Peter A; Zhang, Angela Q; Wyckoff, Jeffrey; Whitesell, Luke; Chen, Christopher S; Lindquist, Susan; Bhatia, Sangeeta N

2015-08-15

The delivery of diagnostic and therapeutic agents to solid tumors is limited by physical transport barriers within tumors, and such restrictions directly contribute to decreased therapeutic efficacy and the emergence of drug resistance. Nanomaterials designed to perturb the local tumor environment with precise spatiotemporal control have demonstrated potential to enhance drug delivery in preclinical models. Here, we investigated the ability of one class of heat-generating nanomaterials called plasmonic nanoantennae to enhance tumor transport in a xenograft model of ovarian cancer. We observed a temperature-dependent increase in the transport of diagnostic nanoparticles into tumors. However, a transient, reversible reduction in this enhanced transport was seen upon reexposure to heating, consistent with the development of vascular thermotolerance. Harnessing these observations, we designed an improved treatment protocol combining plasmonic nanoantennae with diffusion-limited chemotherapies. Using a microfluidic endothelial model and genetic tools to inhibit the heat-shock response, we found that the ability of thermal preconditioning to limit heat-induced cytoskeletal disruption is an important component of vascular thermotolerance. This work, therefore, highlights the clinical relevance of cellular adaptations to nanomaterials and identifies molecular pathways whose modulation could improve the exposure of tumors to therapeutic agents. ©2015 American Association for Cancer Research.

A herbal composition (hemohim) as a complementary agent for cancer radiotherapy and chemotherapy

International Nuclear Information System (INIS)

Jo, Sung-Kee; Park, Hae-Ran; Jung, Uhee; Choi, Soo Young; Kim, Sung-Ho

2016-01-01

HemoHIM significantly reduced the damage of liver and kidney by cisplatin. In a preliminary clinical study, 85 patients, diagnosed with breast or uterine cervix cancer, were administered with HemoHIM (6 g/day) for 12 weeks during radiation and/or chemotherapy. Age-matched 209 patients were monitored as control group. In the HemoHIM group, fewer cases of severe leucopenia (<3,000 leukocytes/mm 3 ) were shown compared with the control group, and it was more evident in the breast cancer patients. In conclusion, HemoHIM may be a beneficial supplement during radiotherapy and chemotherapy for enhancing the anti-tumor efficacy and reducing the side effects

Chemotherapy-Induced Fatigue Correlates With Higher Fatigue Scores Before Treatment.

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Araújo, José Klerton Luz; Giglio, Adriana Del; Munhoz, Bruna Antenusse; Fonseca, Fernando Luiz Affonso; Cruz, Felipe Melo; Giglio, Auro Del

2017-06-01

Cancer chemotherapy can induce fatigue in about 20% to 30% of patients. So far, there is very little information as to the predictors of chemotherapy-induced fatigue (CIF). We evaluated potential predictors of CIF in a sample of patients with cancer with several types of solid tumors scheduled to receive chemotherapy according to institutional protocols. Before their first and second chemotherapy cycles, patients answered to the Brief Fatigue Inventory (BFI), Chalder, Mini Nutritional Assessment (MNA), Stress thermometer, and HADS questionnaires as well as provided blood samples for inflammatory markers. We evaluated 52 patients, 37 (71%) were female and mean age was 53 years. The most common tumors were breast cancer 21 (40%) and gastrointestinal tumors 12 (23%). Although 14 (25.2%) patients had an increase in their fatigue BFI scores equal or above 3 points from baseline, we observed no significant overall differences between BFI scores before and after chemotherapy. The only 2 factors associated with an increase of 3 points in the BFI scores after chemotherapy were race and higher baseline BFI levels. By multivariate analysis, overall BFI and Chalder scores after chemotherapy also correlated significantly with their respective baseline scores before treatment. HADS scores before treatment correlated with overall BFI scores postchemotherapy, whereas MNA scores before chemotherapy and female sex correlated with higher Chalder scores after treatment. We conclude that fatigue induced by chemotherapy is common and consistently associated with higher fatigue scores before treatment. Screening for fatigue before chemotherapy may help to identify patients who are prone to develop CIF.

Relations between the distribution of signal strength on dynamic MRI imaging and the effect of primary systemic chemotherapy on breast cancer

International Nuclear Information System (INIS)

Ohta, Koji; Endo, Naoki; Miyanaga, Tamon; Hosokawa, Osamu; Takeda, Takayuki; Kaizaki, Yasuharu

2009-01-01

The subjects were 24 patients in whom MRI was performed before and after primary system chemotherapy (PSC). We investigated the pattern of contrast enhancement with respect to treatment responses. We prepared the time-signal intensity in each region of interest (ROI) (small ROI), established by dividing the maximum cut surface of each tumor into 9, and then subdividing them, and examined the distribution of enhancement. We counted small ROIs showing early enhancement and late washout per lesion. Counts were plotted on the longitudinal axis, and the tumor reduction rate on the transverse axis based on data for all tumors. These were also evaluated with respect to subtypes. The complete response (CR) group showed early enhancement and late washout. In addition, the small ROI count was correlated with the tumor reduction rate only in the luminal group. In this group, treatment responses may have more strongly depended on the intra-tumoral vascular density and permeability, because anticancer agent sensitivity was low. (author)

Investigation of Effect of Nutritional Drink on Chemotherapy-Induced Mucosal Injury and Tumor Growth in an Established Animal Model

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Eduardo Schiffrin

2013-09-01

Full Text Available Chemotherapy-induced mucositis represents a significant burden to quality of life and healthcare costs, and may be improved through enhanced nutritional status. We first determined the safety of two nutritional drinks (plus placebo, and then potential gut protection in tumor-bearing rats in a model of methotrexate-induced mucositis. In study 1, animals were fed one of two test diets (or placebo or control chow pellets for a total of 60 days and were monitored daily. All diets were found to be safe to administer. In study 2, after seven days of receiving diets, a Dark Agouti Mammary Adenocarcinoma (DAMA was transplanted subcutaneously. Ten days after starting diets, animals had 2 mg/kg intramuscular methotrexate administered on two consecutive days; after this time, all animals were given soaked chow. Animals were monitored daily for changes in bodyweight, tumor burden and general health. Animals were killed 10, 12 and 16 days after initially starting diets, and tissues were collected at necropsy. In study 1, animals receiving diets had gained 0.8% and 10.8% of their starting bodyweight after 60 days, placebo animals 4.4%, and animals fed on standard chow had gained 15.1%. In study 2, there was no significant influence of test diet on bodyweight, organ weight, tumor burden or biochemical parameters. Only animals treated with MTX exhibited diarrhea, although animals receiving Diet A and Diet C showed a non-significant increase in incidence of diarrhea. Administration of these nutritional drinks did not improve symptoms of mucositis.

Inhibition of colon cancer growth by methylselenocysteine-induced angiogenic chemomodulation is influenced by histologic characteristics of the tumor.

Science.gov (United States)

Bhattacharya, Arup; Tóth, Károly; Sen, Arindam; Seshadri, Mukund; Cao, Shousong; Durrani, Farukh A; Faber, Erik; Repasky, Elizabeth A; Rustum, Youcef M

2009-07-01

Despite an armamentarium that is wide in range, scope of action, and target, chemotherapy has limited success in colorectal cancer (CRC). Novel approaches are needed to overcome tumor barriers to chemotherapy that includes an abnormal tumor vasculature constituting a poor drug delivery system. We have previously shown that 5-methylselenocysteine (MSC) enhances therapeutic efficacy of irinotecan in various human tumor xenografts. We have recently demonstrated that MSC through vascular normalization leads to better tumor vascular function in vivo. In this study, we examined the role of MSC on tumor vasculature, interstitial fluid pressure (IFP) and drug delivery in 2 histologically distinct CRC xenografts, HCT-8 (uniformly poorly differentiated) and HT-29 (moderately differentiated tumor with avascular glandular regions). The presence of specific histologic structures as a barrier to therapy in these xenografts and their clinical relevance was studied using tissue microarray of human surgical samples of CRC. MSC led to a significant tumor growth inhibition, a reduced microvessel density, and a more normalized vasculature in both colorectal xenografts. While IFP was found to be significantly improved in HCT-8, an improved intratumoral doxorubicin delivery seen in both xenografts could explain the observed increase in therapeutic efficacy. Differentiated, glandular, avascular and hypoxic regions that contribute to tumor heterogeneity in HT-29 were also evident in the majority of surgical samples of CRC. Such regions constitute a physical barrier to chemotherapy and can confer drug resistance. Our results indicate that MSC could enhance chemotherapeutic efficacy in human CRC, especially in CRC with few or no hypoxic regions.

Three-dimensional evaluation of chemotherapy response in malignant pleural mesothelioma

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Ak, Guntulu [Department of Chest Disease, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey)], E-mail: guntuluak@yahoo.com; Metintas, Muzaffer [Department of Chest Disease, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey); Metintas, Selma [Department of Public Health, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey); Yildirim, Huseyin [Department of Chest Disease, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey); Ozkan, Ragip [Department of Radiology, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey); Ozden, Hilmi [Department of Anatomy, Eskisehir Osmangazi University, Medical Faculty, Eskisehir (Turkey)

2010-04-15

Objectives: Measurement of tumor response to chemotherapy in malignant pleural mesothelioma (MPM) is problematic because of non-spherical tumor growth patterns and difficulty in choosing target lesion. In this study, we aimed to determine the effectiveness of tumor volume measurement for evaluating chemotherapy response. Methods: Fifty-seven MPM patients were included. Chemotherapy responses were evaluated by computed tomography (CT) using volumetric method, World Health Organization (WHO), and modified Response Evaluation Criteria in Solid Tumor (RECIST). The tumor volume was measured using the Cavalieri principle of stereological approaches. Results: According to the volumetric method, median survival was 10.0 months for progressive disease (PD), 14.0 months for stable disease (SD) and 16.0 months for objective response (OR). According to the WHO method, median survival was 11.3, 14.0, and 13.0 months, respectively. For modified RECIST, median survival was 10.0, 14.0, and 14.0 months, respectively. The correspondence between the WHO and modified RECIST methods was substantial (K = 0.66), as was that between the volumetric and WHO methods (K = 0.64); however the correspondence between the volumetric and modified RECIST methods was only moderate (K = 0.52). Conclusions: The most suitable chemotherapy response measurement technique is the volumetric method because of non-spherical tumor growth patterns in MPM. However, larger studies should be performed to better establish the suitability of this method. We recommend our method for determining the chemotherapy response in mesothelioma cases. However, modified RECIST criteria can also be applied due to favourable prediction of survival, ease of application, and moderate correspondence with the volumetric method.

Tumor suppressors: enhancers or suppressors of regeneration?

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Pomerantz, Jason H.; Blau, Helen M.

2013-01-01

Tumor suppressors are so named because cancers occur in their absence, but these genes also have important functions in development, metabolism and tissue homeostasis. Here, we discuss known and potential functions of tumor suppressor genes during tissue regeneration, focusing on the evolutionarily conserved tumor suppressors pRb1, p53, Pten and Hippo. We propose that their activity is essential for tissue regeneration. This is in contrast to suggestions that tumor suppression is a trade-off for regenerative capacity. We also hypothesize that certain aspects of tumor suppressor pathways inhibit regenerative processes in mammals, and that transient targeted modification of these pathways could be fruitfully exploited to enhance processes that are important to regenerative medicine. PMID:23715544

Recent Developments in Active Tumor Targeted Multifunctional Nanoparticles for Combination Chemotherapy in Cancer Treatment and Imaging

Science.gov (United States)

Glasgow, Micah D. K.; Chougule, Mahavir B.

2016-01-01

Nanotechnology and combination therapy are two major fields that show great promise in the treatment of cancer. The delivery of drugs via nanoparticles helps to improve drug’s therapeutic effectiveness while reducing adverse side effects associated with high dosage by improving their pharmacokinetics. Taking advantage of molecular markers over-expressing on tumor tissues compared to normal cells, an “active” molecular marker targeted approach would be beneficial for cancer therapy. These actively targeted nanoparticles would increase drug concentration at the tumor site, improving efficacy while further reducing chemo-resistance. The multidisciplinary approach may help to improve the overall efficacy in cancer therapy. This review article summarizes recent developments of targeted multifunctional nanoparticles in the delivery of various drugs for a combinational chemotherapy approach to cancer treatment and imaging. PMID:26554150

Prolonged response without prolonged chemotherapy: a lesson from PCV chemotherapy in low-grade gliomas

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Peyre, Matthieu; Cartalat-Carel, Stéphanie; Meyronet, David; Ricard, Damien; Jouvet, Anne; Pallud, Johan; Mokhtari, Karima; Guyotat, Jacques; Jouanneau, Emmanuel; Sunyach, Marie-Pierre; Frappaz, Didier; Honnorat, Jérôme; Ducray, François

2010-01-01

Previous studies with temozolomide suggest that a prolonged duration of chemotherapy is important for treating low-grade gliomas (LGGs). PCV (procarbazine, CCNU, vincristine) chemotherapy has demonstrated efficacy in treating LGGs, but this therapy cannot be used for a prolonged period because of the cumulative toxicity. The aim of the present study was to evaluate the impact of first-line PCV chemotherapy on LGGs growth kinetics. The mean tumor diameter (MTD) of 21 LGGs was measured on serial magnetic resonance images before (n=13), during, and after PCV onset (n=21). During PCV treatment, a decrease in the MTD was observed in all patients. After PCV discontinuation, an ongoing decrease in MTD was observed in 20 of the 21 patients. Median duration of the MTD decrease was 3.4 years (range, 0.8–7.7) after PCV onset and 2.7 years (range, 0–7) after the end of PCV treatment with 60% of LGGs, demonstrating an ongoing and prolonged (>2 years) response despite chemotherapy no longer being administered. According to McDonald's criteria, the rates of partial and minor responses were 5% and 38% at the end of PCV but 38% and 42% at the time of maximal MTD decrease, which occurred after a median period of 3.4 years after PCV onset. These results challenge the idea that a prolonged duration of chemotherapy is necessary for treating LGGs and raise the issue of understanding the mechanisms involved in the persistent tumor volume decrease once chemotherapy is terminated. PMID:20488959

Identification of activated enhancers and linked transcription factors in breast, prostate, and kidney tumors by tracing enhancer networks using epigenetic traits.

Science.gov (United States)

Rhie, Suhn Kyong; Guo, Yu; Tak, Yu Gyoung; Yao, Lijing; Shen, Hui; Coetzee, Gerhard A; Laird, Peter W; Farnham, Peggy J

2016-01-01

Although technological advances now allow increased tumor profiling, a detailed understanding of the mechanisms leading to the development of different cancers remains elusive. Our approach toward understanding the molecular events that lead to cancer is to characterize changes in transcriptional regulatory networks between normal and tumor tissue. Because enhancer activity is thought to be critical in regulating cell fate decisions, we have focused our studies on distal regulatory elements and transcription factors that bind to these elements. Using DNA methylation data, we identified more than 25,000 enhancers that are differentially activated in breast, prostate, and kidney tumor tissues, as compared to normal tissues. We then developed an analytical approach called Tracing Enhancer Networks using Epigenetic Traits that correlates DNA methylation levels at enhancers with gene expression to identify more than 800,000 genome-wide links from enhancers to genes and from genes to enhancers. We found more than 1200 transcription factors to be involved in these tumor-specific enhancer networks. We further characterized several transcription factors linked to a large number of enhancers in each tumor type, including GATA3 in non-basal breast tumors, HOXC6 and DLX1 in prostate tumors, and ZNF395 in kidney tumors. We showed that HOXC6 and DLX1 are associated with different clusters of prostate tumor-specific enhancers and confer distinct transcriptomic changes upon knockdown in C42B prostate cancer cells. We also discovered de novo motifs enriched in enhancers linked to ZNF395 in kidney tumors. Our studies characterized tumor-specific enhancers and revealed key transcription factors involved in enhancer networks for specific tumor types and subgroups. Our findings, which include a large set of identified enhancers and transcription factors linked to those enhancers in breast, prostate, and kidney cancers, will facilitate understanding of enhancer networks and mechanisms

Distribution of 99Tcm-rh-Annexin V and its relationship with expression of survivin and Caspase-3 in tumors after a single dose of chemotherapy

International Nuclear Information System (INIS)

Zhang Xin; Zhang Yanjun; Tao Li; Zhu Yi; Yang Chun; Li Yaming; Zhang Jianying; Zhao Zhenzhen; Ji Xiaopeng; Zhao Ming; Tian Aijuan

2008-01-01

Objective: Recently, molecular imaging for detecting cellular apoptosis is developing rapidly. The aim of the study was to determine the effectiveness of imaging with 99 Tc m labelled recombinant human Annexin V ( 99 Tc m -rh-Annexin V) as a reflection of apoptosis in tumor, and related its distribution with expression of Survivin and Caspase-3 after a single dose of chemotherapy. Methods: Eight days after being inoculated with allogenic hepatoma cells (Hca-F25) into right axillary fossa, the mice (purebred 615) were randomly divided into two groups (control group A, n=9; and treated group B, n=10). Group B was received a single dose of chemotherapy intraperitoneally (cyclophosphamide, 150 mg/kg). Groups A and B were given 99 Tc m -rh-AnnexinV (3.7 MBq·0.5 μg -1 per mouse) intravenously 20 h later. Four hours after 99 Tc m -rh-Annexin V injection, the animals were imaged and sacrificed, and the tumor samples were weighed and the radioactivity was determined in a well-counter. The accumulation of 99 Tc m -rh-Annexin V in tumor was expressed as the percentage activity of injection dose per gram of tissue (% ID/g). Tumor cell apoptosis was examined by terminal deoxynueleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) method, and the expression of Survivin and Caspase-3 in tumor were determined with immunohistochemical method. SPSS 10.0 was used for data analysis. Results: Single dose chemotherapy tsignificantly increased the tumor uptake of 99 Tc m -rh-Annexin V [(0.478 ± 0.123)% ID/g vs (0.332 ± 0.061)% ID/g] and the positive number of TUNEL [(18.030 ± 5.600) cells/field vs (6.744 ± 2.325) cells/field], as well as the expression of Caspase-3 [(3.266 ± 0.482)% vs (2.387 ± 0.387)%, F was 10.502, 31.507, 18.971, respectively, all P 99 Tc m -rh-Annexin V correlated positively well with the expression of Caspase-3 and negatively with the expression of Survivin (P 99 Tc m -rh-Annexin V can not only reflect the extent of apoptosis

Natural Killer Cell Response to Chemotherapy-Stressed Cancer Cells: Role in Tumor Immunosurveillance

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Alessandra Zingoni

2017-09-01

Full Text Available Natural killer (NK cells are innate cytotoxic lymphoid cells that actively prevent neoplastic development, growth, and metastatic dissemination in a process called cancer immunosurveillance. An equilibrium between immune control and tumor growth is maintained as long as cancer cells evade immunosurveillance. Therapies designed to kill cancer cells and to simultaneously sustain host antitumor immunity are an appealing strategy to control tumor growth. Several chemotherapeutic agents, depending on which drugs and doses are used, give rise to DNA damage and cancer cell death by means of apoptosis, immunogenic cell death, or other forms of non-apoptotic death (i.e., mitotic catastrophe, senescence, and autophagy. However, it is becoming increasingly clear that they can trigger additional stress responses. Indeed, relevant immunostimulating effects of different therapeutic programs include also the activation of pathways able to promote their recognition by immune effector cells. Among stress-inducible immunostimulating proteins, changes in the expression levels of NK cell-activating and inhibitory ligands, as well as of death receptors on tumor cells, play a critical role in their detection and elimination by innate immune effectors, including NK cells. Here, we will review recent advances in chemotherapy-mediated cellular stress pathways able to stimulate NK cell effector functions. In particular, we will address how these cytotoxic lymphocytes sense and respond to different types of drug-induced stresses contributing to anticancer activity.

Clinical applicability of determination of serum tumor markers (CEA, CA15-3 and CA125) levels changes for assessment of efficacy of chemotherapy in patients with breast cancer

International Nuclear Information System (INIS)

Xu Junying; Liu Chaoying; Li Jiang; Hu Hong; Wang Runjie

2009-01-01

Objective: To study the usefulness of monitoring changes of serum levels of tumor markers (CEA, CA15-3 and CA125) for assessment of efficacy of chemotherapy in patients with breast cancer. Methods: Serum CEA, CA15-3 and CA125 levels were measured with CLIA three days before beginning 1st course of appropriate chemotherapy and 3 weeks after completing 2nd course of treatment in 45 patients with advanced breast cancer (TNM stage III, n=20, stage IV n=25). Results: Expressed as CR, PR, SD and PD as defined by the changes of serum tumor markers levels (according to Bac D.J. et al) were compared with clinically observed ones (WHO standard). The serum levels of Cea, CA15-3 decreased markedly in the CR and PR groups of patients but increased markedly in PD patients (P 0.05). The coincidence rate between the results observed clinically and results derived from tumor marker changes was 50.0% for CEA, 55.6% for CA15-3, 31.1% for CA125 and 73% for three markers combined. Conclusion: Combined determination of the changes of serum levels of three tumor marker would help to make a reasonably satisfactory assessment of efficacy of chemotherapy in patients with breast cancer. (authors)

Dynamic Contrast-Enhanced Ultrasound of Colorectal Liver Metastases as an Imaging Modality for Early Response Prediction to Chemotherapy

DEFF Research Database (Denmark)

Mogensen, Marie Benzon; Hansen, Martin Lundsgaard; Henriksen, Birthe Merete

2017-01-01

Our aim was to investigate whether dynamic contrast-enhanced ultrasound (DCE-US) can detect early changes in perfusion of colorectal liver metastases after initiation of chemotherapy. Newly diagnosed patients with colorectal cancer with liver metastases were enrolled in this explorative prospective...... study. Patients were treated with capecitabine or 5-fluorouracil-based chemotherapy with or without bevacizumab. DCE-US was performed before therapy (baseline) and again 10 days after initiation of treatment. Change in contrast-enhancement in one liver metastasis (indicator lesion) was measured....... Treatment response was evaluated with a computed tomography (CT) scan after three cycles of treatment and the initially observed DCE-US change of the indicator lesion was related to the observed CT response. Eighteen patients were included. Six did not complete three series of chemotherapy...

Therapeutic effects of microbubble added to combined high-intensity focused ultrasound and chemotherapy in a pancreatic cancer xenograft model

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Yu, Mi Hye [Dept. of Radiology, Konkuk University Medical Center, Seoul (Korea, Republic of); Lee, Jae Young; Kim, Bo Ram; Park, Eun Joo; Kim, Hoe Suk; Han, Joon Koo [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Hae Ri [Dept. of Pre-Dentistry, Gangneung-Wonju National University College of Dentistry, Gangneung (Korea, Republic of); Choi, Byung Ihn [Dept. of Radiology, Chung-Ang University Hospital, Seoul (Korea, Republic of)

2016-09-15

To investigate whether high-intensity focused ultrasound (HIFU) combined with microbubbles enhances the therapeutic effects of chemotherapy. A pancreatic cancer xenograft model was established using BALB/c nude mice and luciferase-expressing human pancreatic cancer cells. Mice were randomly assigned to five groups according to treatment: control (n = 10), gemcitabine alone (GEM; n = 12), HIFU with microbubbles (HIFU + MB, n = 11), combined HIFU and gemcitabine (HIGEM; n = 12), and HIGEM + MB (n = 13). After three weekly treatments, apoptosis rates were evaluated using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay in two mice per group. Tumor volume and bioluminescence were monitored using high-resolution 3D ultrasound imaging and in vivo bioluminescence imaging for eight weeks in the remaining mice. The HIGEM + MB group showed significantly higher apoptosis rates than the other groups (p < 0.05) and exhibited the slowest tumor growth. From week 5, the tumor-volume-ratio relative to the baseline tumor volume was significantly lower in the HIGEM + MB group than in the control, GEM, and HIFU + MB groups (p < 0.05). Despite visible distinction, the HIGEM and HIGEM + MB groups showed no significant differences. High-intensity focused ultrasound combined with microbubbles enhances the therapeutic effects of gemcitabine chemotherapy in a pancreatic cancer xenograft model.

Therapeutic Effects of Microbubbles Added to Combined High-Intensity Focused Ultrasound and Chemotherapy in a Pancreatic Cancer Xenograft Model

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Yu, Mi Hye [Department of Radiology, Konkuk University Medical Center, Seoul 05030 (Korea, Republic of); Lee, Jae Young [Department of Radiology, Seoul National University Hospital, Seoul 03080 (Korea, Republic of); Kim, Hae Ri [Department of Pre-Dentistry, Gangneung-Wonju National University College of Dentistry, Gangneung 25457 (Korea, Republic of); Kim, Bo Ram; Park, Eun-Joo; Kim, Hoe Suk; Han, Joon Koo [Department of Radiology, Seoul National University Hospital, Seoul 03080 (Korea, Republic of); Choi, Byung Ihn [Department of Radiology, Chung-Ang University Hospital, Seoul 06973 (Korea, Republic of)

2016-11-01

To investigate whether high-intensity focused ultrasound (HIFU) combined with microbubbles enhances the therapeutic effects of chemotherapy. A pancreatic cancer xenograft model was established using BALB/c nude mice and luciferase-expressing human pancreatic cancer cells. Mice were randomly assigned to five groups according to treatment: control (n = 10), gemcitabine alone (GEM; n = 12), HIFU with microbubbles (HIFU + MB, n = 11), combined HIFU and gemcitabine (HIGEM; n = 12), and HIGEM + MB (n = 13). After three weekly treatments, apoptosis rates were evaluated using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay in two mice per group. Tumor volume and bioluminescence were monitored using high-resolution 3D ultrasound imaging and in vivo bioluminescence imaging for eight weeks in the remaining mice. The HIGEM + MB group showed significantly higher apoptosis rates than the other groups (p < 0.05) and exhibited the slowest tumor growth. From week 5, the tumor-volume-ratio relative to the baseline tumor volume was significantly lower in the HIGEM + MB group than in the control, GEM, and HIFU + MB groups (p < 0.05). Despite visible distinction, the HIGEM and HIGEM + MB groups showed no significant differences. High-intensity focused ultrasound combined with microbubbles enhances the therapeutic effects of gemcitabine chemotherapy in a pancreatic cancer xenograft model.

Ablation of EIF5A2 induces tumor vasculature remodeling and improves tumor response to chemotherapy via regulation of matrix metalloproteinase 2 expression.

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Wang, Feng-Wei; Cai, Mu-Yan; Mai, Shi-Juan; Chen, Jie-Wei; Bai, Hai-Yan; Li, Yan; Liao, Yi-Ji; Li, Chang-Peng; Tian, Xiao-Peng; Kung, Hsiang-Fu; Guan, Xin-Yuan; Xie, Dan

2014-08-30

Hepatocellular carcinoma (HCC) is a highly vascularized tumor with poor clinical outcome. Our previous work has shown that eukaryotic initiation factor 5A2 (EIF5A2) over-expression enhances HCC cell metastasis. In this study, EIF5A2 was identified to be an independent risk factor for poor disease-specific survival among HCC patients. Both in vitro and in vivo assays indicated that ablation of endogenous EIF5A2 inhibited tumor angiogenesis by reducing matrix metalloproteinase 2 (MMP-2) expression. Given that MMP-2 degrades collagen IV, a main component of the vascular basement membrane (BM), we subsequently investigated the effect of EIF5A2 on tumor vasculature remodeling using complementary approaches, including fluorescent immunostaining, transmission electron microscopy, tumor perfusion assays and tumor hypoxia assays. Taken together, our results indicate that EIF5A2 silencing increases tumor vessel wall continuity, increases blood perfusion and improves tumor oxygenation. Additionally, we found that ablation of EIF5A2 enhanced the chemosensitivity of HCC cells to 5-Fluorouracil (5-FU). Finally, we demonstrated that EIF5A2 might exert these functions by enhancing MMP-2 activity via activation of p38 MAPK and JNK/c-Jun pathways. This study highlights an important role of EIF5A2 in HCC tumor vessel remodeling and indicates that EIF5A2 represents a potential therapeutic target in the treatment of HCC.

Utilization of special computerized tomography and nuclear medicine techniques for quality control and for the optimization of combined precision chemotherapy and precision radiation therapy

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Wiley, A.L. Jr.; Wirtanen, G.W.; Chien, I.-C.

1984-01-01

A combination of precision (selective, intra-arterial) chemotherapy and precision radiotherapy can be used for advanced pancreatic, biliary tract, and sarcomatous malignancies. There were some remarkable responses, but also a few poor responses and even some morbidity. Accordingly, methods are developed of pre-selecting those patients whose tumors are likely to respond to such therapy, as well as methods for improving the therapeutic ratio by the rational optimization of combined therapy. Specifically, clinical tumor blood flow characteristics (monitored with nuclear medicine techniques) may provide useful criteria for such selection. The authors also evaluate qualitatively the drug distribution or exposure space with specialized color-coded computerized tomography images, which demonstrate spatially dependent enhancement of intra-arterial contrast in tumor and in adjacent normal tissues. Such clinical data can improve the quality control aspects of intra-arterial chemotherapy administration, as well as the possibility of achievement of a significant therapeutic ratio by the integration of precision chemotherapy and precision radiation therapy. (Auth.)

Effect of chemotherapy and immunotherapy on tumor-specific immunity in melanoma.

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Mitchell, M S; Mokyr, M B; Davis, J M

1977-01-01

The effects of chemotherapy, with nitrosoureas or dimethyl-triazeno-imidazole-carboxamide (DTIC), or immunotherapy with Bacillus Calmette-Guérin (BCG), on cell-mediated immunity (CMI), and serum blocking factor (BF) to melanoma cells were studied in 23 patients. Studies were performed with autologous or allogenic melanoma target cells obtained from recent biopsy, in 16 mm diameter plastic wells. Assays for lymphocyte-mediated cytotoxicity and BF were performed at weekly intervals over the course of 3-4 mo, with some studies extending beyond 3 yr. The specificity of cytotoxicity was good with these methods. Nine patients given nitrosoureas, predominantly methyl-chloroethyl-cyclohexyl-nitrosourea, showed a transient decline in CMI from 42.2 to 14% 3 wk after administration of a single dose of the agent, with a rapid recovery within 1 week. 10 patients given 5-day courses of DTIC at 3-wk intervals showed no decline in CMI after two courses, and 7 of the 10 had no decline even after three courses. Three of the four patients who achieved a remission lost BF previously present: BF reappeared in both patients studied during a subsequent relapse. BCG intradermally or intralesionally elevated CMI within 2 mo after initiation of therapy, but despite continuation of the injections CMI returned to base line in all but two of the nine patients studied. These results indicate that chemotherapy for melanoma with nitrosoureas or DTIC at these schedules is not profoundly immunosuppressive towards tumor-specific immunity, as measured by our procedures. Putative immunotherapy with BCG at these schedules was likewise only transiently stimulatory. PMID:863999

Fish oil mitigates myosteatosis and improves chemotherapy efficacy in a preclinical model of colon cancer.

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Alaa A Almasud

Full Text Available This study aimed to assess whether feeding a diet containing fish oil was efficacious in reducing tumor- and subsequent chemotherapy-associated myosteatosis, and improving tumor response to treatment.Female Fischer 344 rats were fed either a control diet for the entire study (control, or switched to a diet containing fish oil (2.0 g /100 g of diet one week prior to tumor implantation (long term fish oil or at the start of chemotherapy (adjuvant fish oil. Chemotherapy (irinotecan plus 5-fluorouracil was initiated 2 weeks after tumor implantation (cycle-1 and 1 week thereafter (cycle-2. Reference animals received no tumor or treatment and only consumed the control diet. All skeletal muscle measures were conducted in the gastrocnemius. To assess myosteatosis, lipids were assessed histologically by Oil Red O staining and total triglyceride content was quantified by gas chromatography. Expression of adipogenic transcription factors were assessed at the mRNA level by real-time RT-PCR.Feeding a diet containing fish oil significantly reduced tumor- and subsequent chemotherapy-associated increases in skeletal muscle neutral lipid (p<0.001 and total triglyceride content (p<0.03, and expression of adipogenic transcription factors (p<0.01 compared with control diet fed animals. The adjuvant fish oil diet was as effective as the long term fish oil diet in mitigating chemotherapy-associated skeletal muscle fat content, and in reducing tumor volume during chemotherapy compared with control fed animals (p<0.01.Long term and adjuvant fish oil diets are equally efficacious in reducing chemotherapy-associated myosteatosis that may be occurring by reducing expression of transcription factors involved in adipogenesis/lipogenesis, and improving tumor-response to chemotherapy in a neoplastic model.

Hepatic lesions that mimic metastasis on radiological imaging during chemotherapy for gastrointestinal malignancy: Recent updates

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You, Sung Hye; Park, Beom Jin; Kim, Yeul Hong [Anam Hospital, Korea University College of Medicine, Seoul (Korea, Republic of)

2017-06-15

During chemotherapy in patients with gastrointestinal malignancy, the hepatic lesions may occur as chemotherapy-induced lesions or tumor-associated lesions, with exceptions for infectious conditions and other incidentalomas. Focal hepatic lesions arising from chemotherapy-induced hepatopathies (such as chemotherapy-induced sinusoidal injury and steatosis) and tumor-associated eosinophilic abscess should be considered a mimicker of metastasis in patients with gastrointestinal malignancy. Accumulating evidence suggests that chemotherapy for gastrointestinal malignancy in the liver has roles in both the therapeutic effects for hepatic metastasis and injury to the non-tumor bearing hepatic parenchyma. In this article, we reviewed the updated concept of chemotherapy-induced hepatopathies and tumor-associated eosinophilic abscess in the liver, focusing on the pathological and radiological findings. Awareness of the causative chemo-agent, pathophysiology, and characteristic imaging findings of these mimickers is critical for accurate diagnosis and avoidance of unnecessary exposure of the patient to invasive tissue-based diagnosis and operation.

Nitrosourea-based chemotherapy for low grade gliomas failing initial treatment with temozolomide.

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Kaloshi, Gentian; Sierra del Rio, Monica; Ducray, François; Psimaras, Dimitri; Idbaih, Ahmed; Laigle-Donadey, Florence; Taillibert, Sophie; Houillier, Caroline; Dehais, Caroline; Omuro, Antonio; Sanson, Marc; Delattre, Jean-Yves; Hoang-Xuan, Khe

2010-12-01

There is a growing evidence of using Temozolomide as upfront therapy for progressive low grade gliomas. No data exist on the efficacy of nitrosoureas as an alternative to radiotherapy in those patients who progress after Temozolomide. We retrospectively reviewed 30 patients with median age of 46 years. Twenty-one patients had pure oligodendrogliomas. Thirteen patients had a non-enhancing tumor at progression after Temozolomide. The chromosomes 1p/19q were co-deleted in 5 cases and retained in 10 cases. Response rate was 10% (3 minor responses achieved in non-enhancing tumors). Tolerance was acceptable (17% grade III and IV myelosupression). Median PFS was 6.5 months. Median OS from start of salvage treatment was 23.4 months. Tumors without contrast enhancement demonstrated a better prognosis than those with contrast enhancement both in term of PFS (P = 0.0003) and OS (P = 0.0006). Chromosomes 1p/19q codeletion was not predictive for objective response to salvage treatment but correlated with a better PFS (P = 0.02). In conclusion, salvage NU chemotherapy provide disappointing results in TMZ-pretreated low grade gliomas (LGG), which should be treated in priority by conventional radiotherapy especially in LGG that display contrast enhancement at progression.

Tumor targeting using liposomal antineoplastic drugs

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Jörg Huwyler

2008-03-01

Full Text Available Jörg Huwyler1, Jürgen Drewe2, Stephan Krähenbühl21University of Applied Sciences Northwestern Switzerland, Institute of Pharma Technology, Muttenz, Switzerland; 2Department of Research and Division of Clinical Pharmacology, University Hospital Basel, Basel, SwitzerlandAbstract: During the last years, liposomes (microparticulate phospholipid vesicles have beenused with growing success as pharmaceutical carriers for antineoplastic drugs. Fields of application include lipid-based formulations to enhance the solubility of poorly soluble antitumordrugs, the use of pegylated liposomes for passive targeting of solid tumors as well as vector-conjugated liposomal carriers for active targeting of tumor tissue. Such formulation and drug targeting strategies enhance the effectiveness of anticancer chemotherapy and reduce at the same time the risk of toxic side-effects. The present article reviews the principles of different liposomal technologies and discusses current trends in this field of research.Keywords: tumor targeting, antineoplastic drugs, liposomes, pegylation, steric stabilization, immunoliposomes

Non-invasive thermal IR detection of breast tumor development in vivo

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Case, Jason R.; Young, Madison A.; Dréau, D.; Trammell, Susan R.

2015-03-01

Lumpectomy coupled with radiation therapy and/or chemotherapy comprises the treatment of breast cancer for many patients. We are developing an enhanced thermal IR imaging technique that can be used in real-time to guide tissue excision during a lumpectomy. This novel enhanced thermal imaging method is a combination of IR imaging (8- 10 μm) and selective heating of blood (~0.5 °C) relative to surrounding water-rich tissue using LED sources at low powers. Post-acquisition processing of these images highlights temporal changes in temperature and is sensitive to the presence of vascular structures. In this study, fluorescent and enhanced thermal imaging modalities were used to estimate breast cancer tumor volumes as a function of time in 19 murine subjects over a 30-day study period. Tumor volumes calculated from fluorescent imaging follow an exponential growth curve for the first 22 days of the study. Cell necrosis affected the tumor volume estimates based on the fluorescent images after Day 22. The tumor volumes estimated from enhanced thermal imaging show exponential growth over the entire study period. A strong correlation was found between tumor volumes estimated using fluorescent imaging and the enhanced IR images, indicating that enhanced thermal imaging is capable monitoring tumor growth. Further, the enhanced IR images reveal a corona of bright emission along the edges of the tumor masses. This novel IR technique could be used to estimate tumor margins in real-time during surgical procedures.

[Oral complications of chemotherapy of malignant neoplasms].

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Obralić, N; Tahmiscija, H; Kobaslija, S; Beslija, S

1999-01-01

Function and integrity disorders of the oral cavity fall into the most frequent complication of the chemotherapy of leucemias, malignant lymphomas and solid tumors. Complications associated with cancer chemotherapy can be direct ones, resulting from the toxic action of antineoplastic agents on the proliferative lining of the mouth, or indirect, as a result of myelosuppression and immunosuppression. The most frequent oral complications associated with cancer chemotherapy are mucositis, infection and bleeding. The principles of prevention and management of oral complications during cancer chemotherapy are considered in this paper.

Eradication of breast cancer with bone metastasis by autologous formalin-fixed tumor vaccine (AFTV) combined with palliative radiation therapy and adjuvant chemotherapy: a case report.

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Kuranishi, Fumito; Ohno, Tadao

2013-06-04

Skeletal metastasis of breast carcinoma is refractory to intensive chemo-radiation therapy and therefore is assumed impossible to cure. Here, we report an advanced case of breast cancer with vertebra-Th7 metastasis that showed complete response to combined treatments with formalin-fixed autologous tumor vaccine (AFTV), palliative radiation therapy with 36 Gy, and adjuvant chemotherapy with standardized CEF (cyclophosphamide, epirubicin, and 5FU), zoledronic acid, and aromatase inhibitors following mastectomy for the breast tumor. The patient has been disease-free for more than 4 years after the mammary surgery and remains well with no evidence of metastasis or local recurrence. Thus, a combination of AFTV, palliative radiation therapy, and adjuvant chemotherapy may be an effective treatment for this devastating disease.

Treatment of cancer chemotherapy-induced toxicity with the pineal hormone melatonin.

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Lissoni, P; Tancini, G; Barni, S; Paolorossi, F; Ardizzoia, A; Conti, A; Maestroni, G

1997-03-01

Experimental data have suggested that the pineal hormone melatonin (MLT) may counteract chemotherapy-induced myelosuppression and immunosuppression. In addition, MLT has been shown to inhibit the production of free radicals, which play a part in mediating the toxicity of chemotherapy. A study was therefore performed in an attempt to evaluate the influence of MLT on chemotherapy toxicity. The study involved 80 patients with metastatic solid tumors who were in poor clinical condition (lung cancer: 35; breast cancer: 31; gastrointestinal tract tumors: 14). Lung cancer patients were treated with cisplatin and etoposide, breast cancer patients with mitoxantrone, and gastrointestinal tract tumor patients with 5-fluorouracil plus folates. Patients were randomised to receive chemotherapy alone or chemotherapy plus MLT (20 mg/day p.o. in the evening). Thrombocytopenia was significantly less frequent in patients concomitantly treated with MLT. Malaise and asthenia were also significantly less frequent in patients receiving MLT. Finally, stomatitis and neuropathy were less frequent in the MLT group, albeit without statistically significant differences. Alopecia and vomiting were not influenced by MLT. This pilot study seems to suggest that the concomitant administration of the pineal hormone MLT during chemotherapy may prevent some chemotherapy-induced side-effects, particularly myelosuppression and neuropathy. Evaluation of the impact of MLT on chemotherapy efficacy will be the aim of future clinical investigations.

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

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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.

Treatment-independent miRNA signature in blood of wilms tumor patients

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Schmitt Jana

2012-08-01

Full Text Available Abstract Background Blood-born miRNA signatures have recently been reported for various tumor diseases. Here, we compared the miRNA signature in Wilms tumor patients prior and after preoperative chemotherapy according to SIOP protocol 2001. Results We did not find a significant difference between miRNA signature of both groups. However both, Wilms tumor patients prior and after chemotherapy showed a miRNA signature different from healthy controls. The signature of Wilms tumor patients prior to chemotherapy showed an accuracy of 97.5% and of patients after chemotherapy an accuracy of 97.0%, each as compared to healthy controls. Conclusion Our results provide evidence for a blood-born Wilms tumor miRNA signature largely independent of four weeks preoperative chemotherapy treatment.

Resistance to antitumor chemotherapy due to bounded-noise-induced transitions

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D'Onofrio, Alberto; Gandolfi, Alberto

2010-12-01

Tumor angiogenesis is a landmark of solid tumor development, but it is also directly relevant to chemotherapy. Indeed, the density and quality of neovessels may influence the effectiveness of therapies based on blood-born agents. In this paper, first we define a deterministic model of antiproliferative chemotherapy in which the drug efficacy is a unimodal function of vessel density, and then we show that under constant continuous infusion therapy the tumor-vessel system may be multistable. However, the actual drug concentration profiles are affected by bounded even if possibly large fluctuations. Through numerical simulations, we show that the tumor volume may undergo transitions to the higher equilibrium value induced by the bounded noise. In case of periodically delivered boli-based chemotherapy, we model the fluctuations due to time variability of both the drug clearance rate and the distribution volume, as well as those due to irregularities in drug delivery. We observed noise-induced transitions also in case of periodic delivering. By applying a time dense scheduling with constant average delivered drug (metronomic scheduling), we observed an easier suppression of the transitions. Finally, we propose to interpret the above phenomena as an unexpected non-genetic kind of resistance to chemotherapy.

Correlation between apparent diffusion coefficient and histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy.

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Wang, Jifei; Sun, Meili; Liu, Dawei; Hu, Xiaoshu; Pui, Margaret H; Meng, Quanfei; Gao, Zhenhua

2017-08-01

Background Neoadjuvant chemotherapy has made limb-salvage surgery possible for the patients with osteosarcoma. Diffusion-weighted magnetic resonance imaging (DWI) has been used to monitor chemotherapy response. Purpose To correlate the apparent diffusion coefficient (ADC) values with histopathology subtypes of osteosarcoma after neoadjuvant chemotherapy. Material and Methods Twelve patients with osteoblastic (n = 7), chondroblastic (n = 4), and fibroblastic (n = 1) osteosarcomas underwent post-chemotherapy DWI before limb-salvage surgery. ADCs corresponding to 127 histological tissue samples from the 12 resected specimens were compared to histological features. Results The mean ADC value of non-cartilaginous viable tumor (38/91, ADC = 1.22 ± 0.03 × 10 -3  mm 2 /s) was significantly ( P  0.05) different between viable cartilaginous tumor and cystic/hemorrhagic necrosis. Conclusion DWI allows assessment of tumor necrosis after neoadjuvant chemotherapy by ADC differences between viable tumor and necrosis in fibroblastic and osteoblastic osteosarcomas whereas viable chondroblastic osteosarcoma has high ADC and cannot be distinguished reliably from necrosis.

Contrast-enhanced spectral mammography in neoadjuvant chemotherapy monitoring: a comparison with breast magnetic resonance imaging.

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Iotti, Valentina; Ravaioli, Sara; Vacondio, Rita; Coriani, Chiara; Caffarri, Sabrina; Sghedoni, Roberto; Nitrosi, Andrea; Ragazzi, Moira; Gasparini, Elisa; Masini, Cristina; Bisagni, Giancarlo; Falco, Giuseppe; Ferrari, Guglielmo; Braglia, Luca; Del Prato, Alberto; Malavolti, Ivana; Ginocchi, Vladimiro; Pattacini, Pierpaolo

2017-09-11

Neoadjuvant-chemotherapy (NAC) is considered the standard treatment for locally advanced breast carcinomas. Accurate assessment of disease response is fundamental to increase the chances of successful breast-conserving surgery and to avoid local recurrence. The purpose of this study was to compare contrast-enhanced spectral mammography (CESM) and contrast-enhanced-MRI (MRI) in the evaluation of tumor response to NAC. This prospective study was approved by the institutional review board and written informed consent was obtained. Fifty-four consenting women with breast cancer and indication of NAC were consecutively enrolled between October 2012 and December 2014. Patients underwent both CESM and MRI before, during and after NAC. MRI was performed first, followed by CESM within 3 days. Response to therapy was evaluated for each patient, comparing the size of the residual lesion measured on CESM and MRI performed after NAC to the pathological response on surgical specimens (gold standard), independently of and blinded to the results of the other test. The agreement between measurements was evaluated using Lin's coefficient. The agreement between measurements using CESM and MRI was tested at each step of the study, before, during and after NAC. And last of all, the variation in the largest dimension of the tumor on CESM and MRI was assessed according to the parameters set in RECIST 1.1 criteria, focusing on pathological complete response (pCR). A total of 46 patients (85%) completed the study. CESM predicted pCR better than MRI (Lin's coefficient 0.81 and 0.59, respectively). Both methods tend to underestimate the real extent of residual tumor (mean 4.1mm in CESM, 7.5mm in MRI). The agreement between measurements using CESM and MRI was 0.96, 0.94 and 0.76 before, during and after NAC respectively. The distinction between responders and non-responders with CESM and MRI was identical for 45/46 patients. In the assessment of CR, sensitivity and specificity were 100% and

pH-Responsive Magnetic Mesoporous Silica-Based Nanoplatform for Synergistic Photodynamic Therapy/Chemotherapy.

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Tang, Xiang-Long; Jing, Feng; Lin, Ben-Lan; Cui, Sheng; Yu, Ru-Tong; Shen, Xiao-Dong; Wang, Ting-Wei

2018-05-02

By overcoming drug resistance and subsequently enhancing the treatment, the combination therapy of photodynamic therapy (PDT) and chemotherapy has promising potential for cancer treatment. However, the major challenge is how to establish an advanced nanoplatform that can be efficiently guided to tumor sites and can then stably release both chemotherapy drugs and a photosensitizer simultaneously and precisely. In this study, which considered the possibility and targeting efficiency of a magnetic targeting strategy, a novel Fe 3 O 4 @mSiO 2 (DOX)@HSA(Ce6) nanoplatform was successfully built; this platform could be employed as an efficient synergistic antitumor nanoplatform with magnetic guidance for highly specific targeting and retention. Doxorubicin (DOX) molecules were loaded into mesoporous silica with high loading capability, and the mesoporous channels were blocked by a polydopamine coating. Human serum albumin (HSA) was conjugated to the outer surface to increase the biocompatibility and blood circulation time, as well as to provide a vehicle for loading photosensitizer chlorin e6 (Ce6). The sustained release of DOX under acidic conditions and the PDT induced by red light exerted a synergistic inhibitory effect on glioma cells. Our experiments demonstrated that the pH-responsive Fe 3 O 4 @mSiO 2 (DOX)@HSA(Ce6) nanoplatform was guided to the tumor region by magnetic targeting and that the nanoplatform suppressed glioma tumor growth efficiently, implying that the system is a highly promising photodynamic therapy/chemotherapy combination nanoplatform with synergistic effects for cancer treatment.

Chemotherapy-enhanced inflammation may lead to the failure of therapy and metastasis

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Vyas D

2014-06-01

Full Text Available Dinesh Vyas, Gieric Laput, Arpitak K Vyas College of Human Medicine, Michigan State University, East Lansing, MI, USA Abstract: The lack of therapy and the failure of existing therapy has been a challenge for clinicians in treating various cancers. Doxorubicin, 5-fluorouracil, cisplatin, and paclitaxel are the first-line therapy in various cancers; however, toxicity, resistance, and treatment failure limit their clinical use. Their status leads us to discover and investigate more targeted therapy with more efficacy. In this article, we dissect literature from the patient perspective, the tumor biology perspective, therapy-induced metastasis, and cell data generated in the laboratory. Keywords: chemotherapy, cancer, inflammation

Childhood kidney tumors - the relevance of imaging

International Nuclear Information System (INIS)

Schenk, J.-P.; Schrader, C.; Ley, S.; Troeger, J.; Guenther, P.; Furtwaengler, R.; Graf, N.; Leuschner, I.; Edelhaeuser, M.

2005-01-01

Kidney tumors represent 6.2% of malignant tumors in children. History, clinical course and radiological findings are necessary elements in the differential diagnosis of the different renal tumors. In the case of nephroblastoma, chemotherapy is based solely on the radiological diagnosis without prior histology. In therapy-optimizing studies of the Society of Pediatric Oncology and Hematology, preoperative chemotherapy is performed. Therapy monitoring is performed in the course of and after preoperative chemotherapy to verify tumor response. Radiological staging plays a significant role in deciding on further treatment and in operative planning. Three-dimensional visualization of the abdominal situs can assist preoperative planning. In summary, diagnostic imaging in renal tumors in children plays a role in differential diagnosis, staging, monitoring of therapy, and surgical planning. (orig.) [de

Contrast-enhanced fast fluid-attenuated inversion recovery MR imaging in patients with brain tumors

International Nuclear Information System (INIS)

Kim, Chan Kyo; Na, Dong Gyu; Ryoo, Wook Jae; Byun Hong Sik; Yoon, Hye Kyung; Kim, Jong hyun

2000-01-01

To assess the feasibility of contrast-enhanced fast fluid-attenuated inversion recovery (fast FLAIR) MR imaging in patients with brain tumors. This study involved 31 patients with pathologically proven brain tumors and nine with clinically diagnosed metastases. In all patients, T2-weighted, fast FLAIR, images were visual contrast-enhanced T1-weighted MR images were obtained. Contrast-enhanced fast FLAIR images were visually compared with other MR sequences in terms of tumor conspicuity. In order to distinguish tumor and surrounding edema, contrast-enhanced fast FLAIR images were compared with fast FLAIR and T2-weighted images. The tumor-to- white matter contrast-to-noise ratios (CNRs), as demonstrated by T2-weighted, fast FLAIR, contrast-enhanced fast FLAIR and contrast-enhanced T1-weighted imaging, were quantitatively assessed and compared. For the visual assessment of tumor conspicuity, contrast-enhanced fast FLAIR image imaging superior to fast FLAIR in 60% of cases (24/40), and superior to T2-weighted in 70% (28/40). Contrast-enhanced fast FLAIR imaging was inferior to contrast-enhanced T1-weighted in 58% of cases (23/40). For distinguishing between tumor and surrounding edema, contrast-enhanced fast FLAIR imaging was superior to fast FLAIR or T2-weighted in 22 of 27 tumors with peritumoral edema (81%). Quantitatively, CNR was the highest on contrast-enhanced fast FLAIR image and the lowest on fast FLAIR. For the detection of leptomeningeal metastases, contrast-enhanced fast FLAIR was partially superior to contrast-enhanced T1-weighted imaging in two of three high-grade gliomas. Although contrast-enhanced fast FLAIR imaging should not be seen as a replacement for conventional modalities, it provides additional informaton for assessment of the extent of glial cell tumors and leptomeningeal metastases in patients with brain tumors. (author)

Benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer.

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Teufel, Andreas; Gerken, Michael; Hartl, Janine; Itzel, Timo; Fichtner-Feigl, Stefan; Stroszczynski, Christian; Schlitt, Hans Jürgen; Hofstädter, Ferdinand; Klinkhammer-Schalke, Monika

2015-05-20

Colorectal cancer is the third most common cancer and a major cause of morbidity and mortality worldwide. Adjuvant chemotherapy is considered the standard of care in patients with UICC stage III colon cancer after R0 resection. Adjuvant therapy was not shown to be beneficial in patients with UICC stage II colon cancer. However, there is an ongoing discussion as to whether adjuvant chemotherapy may be beneficial for a subgroup of UICC II patients in a "high-risk situation" (such as T4). We investigated a Bavarian population-based (2.1 million inhabitants) cohort of 1937 patients with UICC II CRC treated between 2002 and 2012 in regard of the benefit of adjuvant chemotherapy for large (T4) tumors. Patients older than 80 years of age were excluded. Of 1937 patients, 240 had a T4 tumor (12%); 77 of all T4 patients received postoperative chemotherapy (33%). Kaplan-Meier analysis and Cox regression models were used for survival analyses. Patients with a T4 tumor who received postoperative chemotherapy had a highly significant survival benefit in respect of overall survival (pbenefit from adjuvant treatment. Chemotherapy, age at diagnosis, and tumor grading remained independent risk factors in the multivariate cox regression analysis. Our retrospective study demonstrated the significant benefit of adjuvant chemotherapy in the T4 subgroup of patients with UICC II colon cancer. Our data suggest that adjuvant chemotherapy should be seriously considered in these patients.

Prostatic stromal sarcoma in an adolescent: the role of chemotherapy

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Elena Cavaliere

2014-12-01

Full Text Available Prostatic stromal sarcoma (PSS is a rare tumor that normally occurs in adult age. Its management relies mainly on surgery. We report the first case of PSS occurring in an adolescent. There was evidence of a good response to chemotherapy including ifosfamide, doxorubicin, vincristine and actinomycin-D, although the final outcome was dismal. A review of the English literature revealed 14 additional patients with PSS treated with chemotherapy: tumor shrinkage was reported in 4 of the 6 evaluable patients. Patients with PSS may benefit from the use of chemotherapy in combination with early aggressive local treatment.

Soft Tissue Sarcoma Response to Two Cycles of Neoadjuvant Chemotherapy: A Multireader Analysis of MRI Findings and Agreement with RECIST Criteria and Change in SUVmax.

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Favinger, Jennifer L; Hippe, Daniel S; Davidson, Darin J; Elojeimy, Saeed; Roth, Eira S; Lindberg, Antoinette W; Ha, Alice S

2018-04-01

When soft tissue sarcomas are treated with neoadjuvant chemotherapy, the number of cycles of chemotherapy is usually dependent on the tumor's initial response. Popular methods to assess tumor response include Response Evaluation Criteria in Solid Tumors (RECIST) criteria, which rely solely on tumor size, and maximum standardized uptake value (SUVmax) reduction in positron emission tomography (PET), which requires an expensive and high radiation test. We hypothesized that contrast-enhanced magnetic resonance imaging (MRI) may offer a good alternative by providing additional information beyond tumor size. Following IRB approval, a retrospective review identified patients with soft tissue sarcomas who underwent both PET and MRI before and after two cycles of neoadjuvant chemotherapy. Five readers independently examined the MRI exams for: changes in size, T2 or T1 signal, necrosis and degree of enhancement. Readers then made a subjective binary assessment of tumor response to therapy. Each reader repeated the anonymized randomized reading at least 2 weeks apart. 18 F-FDG PET exams were interpreted by a nuclear medicine specialist. The maximum standardized uptake values (SUVmax) for pre and post-chemotherapy exams were compared. Intra- and inter-reader agreement was assessed using Cohen's kappa and Light's kappa, respectively. . Twenty cases were selected for this multireader study, of which 9 (45%) were responders and 11 were nonresponders by SUVmax. Using all MRI criteria, 43% were classified as responders based on MRI and 1.5% were classified as responders by RECIST criteria. Using PET as the reference, the sensitivity and the specificity of the MRI diagnosis for response using all findings were 50% and 63%, respectively. There was fair to moderate intrareader (kappa = 0.37) and inter-reader (kappa = 0.48) agreement for the MRI diagnosis of response. None of the individual MRI signal characteristics were significantly different between the PET responders and

Tumor-Triggered Geometrical Shape Switch of Chimeric Peptide for Enhanced in Vivo Tumor Internalization and Photodynamic Therapy.

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Han, Kai; Zhang, Jin; Zhang, Weiyun; Wang, Shibo; Xu, Luming; Zhang, Chi; Zhang, Xianzheng; Han, Heyou

2017-03-28

Geometrical shape of nanoparticles plays an important role in cellular internalization. However, the applicability in tumor selective therapeutics is still scarcely reported. In this article, we designed a tumor extracellular acidity-responsive chimeric peptide with geometrical shape switch for enhanced tumor internalization and photodynamic therapy. This chimeric peptide could self-assemble into spherical nanoparticles at physiological condition. While at tumor extracellular acidic microenvironment, chimeric peptide underwent detachment of acidity-sensitive 2,3-dimethylmaleic anhydride groups. The subsequent recovery of ionic complementarity between chimeric peptides resulted in formation of rod-like nanoparticles. Both in vitro and in vivo studies demonstrated that this acidity-triggered geometrical shape switch endowed chimeric peptide with accelerated internalization in tumor cells, prolonged accumulation in tumor tissue, enhanced photodynamic therapy, and minimal side effects. Our results suggested that fusing tumor microenvironment with geometrical shape switch should be a promising strategy for targeted drug delivery.

In vivo targeting of dead tumor cells in a murine tumor model using a monoclonal antibody specific for the La autoantigen.

Science.gov (United States)

Al-Ejeh, Fares; Darby, Jocelyn M; Pensa, Katherine; Diener, Kerrilyn R; Hayball, John D; Brown, Michael P

2007-09-15

To investigate the potential of the La-specific monoclonal antibody (mAb) 3B9 as an in vivo tumor-targeting agent. The murine EL4 lymphoma cell line was used for in vitro studies and the EL4 model in which apoptosis was induced with cyclophosphamide and etoposide was used for in vivo studies. In vitro studies compared 3B9 binding in the EL4 cell with that in its counterpart primary cell type of the thymocyte. For in vivo studies, 3B9 was intrinsically or extrinsically labeled with carbon-14 or 1,4,7,10-tetra-azacylododecane-N,N',N'',N''''-tetraacetic acid-indium-111, respectively, and biodistribution of the radiotracers was investigated in EL4 tumor-bearing mice, which were treated or not with chemotherapy. La-specific 3B9 mAb bound EL4 cells rather than thymocytes, and binding was detergent resistant. 3B9 binding to dead EL4 cells in vitro was specific, rapid, and saturable. Significantly, more 3B9 bound dead EL4 tumor explant cells after host mice were treated with chemotherapy, which suggested that DNA damage induced 3B9 binding. Tumor binding of 3B9 in vivo was antigen specific and increased significantly after chemotherapy. Tumor accumulation of 3B9 peaked at approximately 50% of the injected dose per gram of tumor 72 h after chemotherapy and correlated with increased tumor cell death. Tumor/organ ratios of 3B9 biodistribution, which included the tumor/blood ratio, exceeded unity 48 or more hours after chemotherapy. La-specific mAb selectively targeted dead tumor cells in vivo, and targeting was augmented by cytotoxic chemotherapy. This novel cell death radioligand may be useful both for radioimmunoscintigraphy and radioimmunotherapy.

Benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer

International Nuclear Information System (INIS)

Teufel, Andreas; Gerken, Michael; Hartl, Janine; Itzel, Timo; Fichtner-Feigl, Stefan; Stroszczynski, Christian; Schlitt, Hans Jürgen; Hofstädter, Ferdinand; Klinkhammer-Schalke, Monika

2015-01-01

Colorectal cancer is the third most common cancer and a major cause of morbidity and mortality worldwide. Adjuvant chemotherapy is considered the standard of care in patients with UICC stage III colon cancer after R0 resection. Adjuvant therapy was not shown to be beneficial in patients with UICC stage II colon cancer. However, there is an ongoing discussion as to whether adjuvant chemotherapy may be beneficial for a subgroup of UICC II patients in a “high-risk situation” (such as T4). We investigated a Bavarian population-based (2.1 million inhabitants) cohort of 1937 patients with UICC II CRC treated between 2002 and 2012 in regard of the benefit of adjuvant chemotherapy for large (T4) tumors. Patients older than 80 years of age were excluded. Of 1937 patients, 240 had a T4 tumor (12 %); 77 of all T4 patients received postoperative chemotherapy (33 %). Kaplan-Meier analysis and Cox regression models were used for survival analyses. Patients with a T4 tumor who received postoperative chemotherapy had a highly significant survival benefit in respect of overall survival (p < 0.001) and recurrence-free survival (p = 0.008). However, no difference was observed between oxaliplatin-containing and non-oxaliplatin-containing treatment regimens. G2 and G3 tumors were found to particularly benefit from adjuvant treatment. Chemotherapy, age at diagnosis, and tumor grading remained independent risk factors in the multivariate cox regression analysis. Our retrospective study demonstrated the significant benefit of adjuvant chemotherapy in the T4 subgroup of patients with UICC II colon cancer. Our data suggest that adjuvant chemotherapy should be seriously considered in these patients. The online version of this article (doi:10.1186/s12885-015-1404-9) contains supplementary material, which is available to authorized users

Local recurrence and distant metastasis of supratentorial primitive neuro-ectodermal tumor in an adult patient successfully treated with intensive induction chemotherapy and maintenance temozolomide

NARCIS (Netherlands)

Terheggen, F.; Troost, D.; Majoie, C. B.; Leenstra, S.; Richel, D. J.

2007-01-01

Supratentorial primitive neuro-ectodermal tumors (PNET) in adults are very rare. Extraneural metastasis are unusual and the optimal palliative chemotherapy regimen is not established. We present a 26-year-old patient with local recurrence and distant metastasis of supratentorial PNET successfully

Brain Tumors (For Parents)

Science.gov (United States)

... Staying Safe Videos for Educators Search English Español Brain Tumors KidsHealth / For Parents / Brain Tumors What's in ... radiation therapy or chemotherapy, or both. Types of Brain Tumors There are many different types of brain ...

Retrospective analysis of chronomodulated chemotherapy versus conventional chemotherapy with paclitaxel, carboplatin, and 5-fluorouracil in patients with recurrent and/or metastatic head and neck squamous cell carcinoma

Directory of Open Access Journals (Sweden)

Chen D

2013-10-01

Full Text Available Dan Chen, Jue Cheng, Kai Yang, Yue Ma, Fang Yang Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China Background: Chronomodulated chemotherapy has emerged as a new therapy as a result of recent studies focusing on the biological clock. It has been demonstrated that combination chronomodulated chemotherapy of platinum-based drugs and 5-fluorouracil (5-Fu can significantly improve efficacy and reduce the incidence of adverse events in patients with metastatic colorectal cancer, as compared with conventional chemotherapy. However, the results may be different in different tumors. Recurrent and metastatic head and neck squamous cell carcinoma (HNSCC is very difficult to treat, with an extremely unfavorable prognosis. So far, no report is available on chronomodulated chemotherapy for HNSCC. Methods: Retrospective analyses were made on 49 patients with local recurrent and/or metastatic HNSCC who underwent palliative treatments with paclitaxel, carboplatin, and 5-Fu. The patients were divided into a chronomodulated chemotherapy group (28 patients and a conventional chemotherapy group (21 patients according to their administration times. The two groups were compared for tumor objective response rate, overall survival (OS, progression-free survival (PFS, and the incidence of adverse events. Results: The tumor objective response rate and patients' OS were significantly higher and longer in the chronomodulated chemotherapy group than in the conventional chemotherapy group (71.43% versus 42.86%, respectively, P0.05. The global incidence of adverse events in the chronomodulated chemotherapy group was significantly lower than that in the conventional chemotherapy group (46.43% versus 76.19%, P<0.05, with significantly lower incidence of grade 3–4 adverse events (7.14% versus 33.33%, P<0.05. Conclusion: Chronomodulated chemotherapy with paclitaxel, carboplatin, and

Sonoporation enhances liposome accumulation and penetration in tumors with low EPR.

Science.gov (United States)

Theek, Benjamin; Baues, Maike; Ojha, Tarun; Möckel, Diana; Veettil, Seena Koyadan; Steitz, Julia; van Bloois, Louis; Storm, Gert; Kiessling, Fabian; Lammers, Twan

2016-06-10

The Enhanced Permeability and Retention (EPR) effect is a highly variable phenomenon. To enhance EPR-mediated passive drug targeting to tumors, several different pharmacological and physical strategies have been evaluated over the years, including e.g. TNFα-treatment, vascular normalization, hyperthermia and radiotherapy. Here, we systematically investigated the impact of sonoporation, i.e. the combination of ultrasound (US) and microbubbles (MB), on the tumor accumulation and penetration of liposomes. Two different MB formulations were employed, and their ability to enhance liposome accumulation and penetration was evaluated in two different tumor models, which are both characterized by relatively low levels of EPR (i.e. highly cellular A431 epidermoid xenografts and highly stromal BxPC-3 pancreatic carcinoma xenografts). The liposomes were labeled with two different fluorophores, enabling in vivo computed tomography/fluorescence molecular tomography (CT-FMT) and ex vivo two-photon laser scanning microscopy (TPLSM). In both models, in spite of relatively high inter- and intra-individual variability, a trend towards improved liposome accumulation and penetration was observed. In treated tumors, liposome concentrations were up to twice as high as in untreated tumors, and sonoporation enhanced the ability of liposomes to extravasate out of the blood vessels into the tumor interstitium. These findings indicate that sonoporation may be a useful strategy for improving drug targeting to tumors with low EPR. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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.

High-resolution blood-pool-contrast-enhanced MR angiography in glioblastoma: tumor-associated neovascularization as a biomarker for patient survival. A preliminary study

Energy Technology Data Exchange (ETDEWEB)

Puig, Josep; Blasco, Gerard; Remollo, Sebastian; Hernandez, David; Pedraza, Salvador [Hospital Universitari Dr Josep Trueta, Research Unit of Diagnostic Imaging Institute (IDI), Department of Radiology [Girona Biomedical Research Institute] IDIBGI, Girona (Spain); Daunis-i-Estadella, Josep; Mateu, Gloria [University of Girona, Department of Computer Science, Applied Mathematics and Statistics, Girona (Spain); Alberich-Bayarri, Angel [La Fe Polytechnics and University Hospital, Biomedical Imaging Research Group (GIBI230), La Fe Health Research Institute, Valencia (Spain); Essig, Marco [University of Manitoba, Department of Radiology, Winnipeg (Canada); Jain, Rajan [NYU School of Medicine, Division of Neuroradiology, Department of Radiology, New York, NY (United States); Puigdemont, Montserrat [Hospital Universitari Dr Josep Trueta, Catalan Institute of Oncology (ICO), Hospital Cancer Registry, Girona (Spain); Sanchez-Gonzalez, Javier [Philips Healthcare Iberica, Madrid (Spain); Wintermark, Max [Stanford University, Department of Radiology, Neuroradiology Division, Palo Alto, CA (United States)

2016-01-15

The objective of the study was to determine whether tumor-associated neovascularization on high-resolution gadofosveset-enhanced magnetic resonance angiography (MRA) is a useful biomarker for predicting survival in patients with newly diagnosed glioblastomas. Before treatment, 35 patients (25 men; mean age, 64 ± 14 years) with glioblastoma underwent MRI including first-pass dynamic susceptibility contrast (DSC) perfusion and post-contrast T1WI sequences with gadobutrol (0.1 mmol/kg) and, 48 h later, high-resolution MRA with gadofosveset (0.03 mmol/kg). Volumes of interest for contrast-enhancing lesion (CEL), non-CEL, and contralateral normal-appearing white matter were obtained, and DSC perfusion and DWI parameters were evaluated. Prognostic factors were assessed by Kaplan-Meier survival and Cox proportional hazards model. Eighteen (51.42 %) glioblastomas were hypervascular on high-resolution MRA. Hypervascular glioblastomas were associated with higher CEL volume and lower Karnofsky score. Median survival rates for patients with hypovascular and hypervascular glioblastomas treated with surgery, radiotherapy, and chemotherapy were 15 and 9.75 months, respectively (P < 0.001). Tumor-associated neovascularization was the best predictor of survival at 5.25 months (AUC = 0.794, 81.2 % sensitivity, 77.8 % specificity, 76.5 % positive predictive value, 82.4 % negative predictive value) and yielded the highest hazard ratio (P < 0.001). Tumor-associated neovascularization detected on high-resolution blood-pool-contrast-enhanced MRA of newly diagnosed glioblastoma seems to be a useful biomarker that correlates with worse survival. (orig.)

Adjuvant chemo- and radiotherapy in gastrointestinal tumors

International Nuclear Information System (INIS)

Sendler, A.; Feldmann, H.J.; Fink, U.; Molls, M.; Siewert, J.R.

1995-01-01

In modern surgical oncology, adjuvant therapies are important complementary strategies. In local advanced carcinomas of the gastrointestinal tract, 5-year survival data are still disappointing despite standardized surgery. In this context, it has to be differentiated between adjuvant therapy following complete tumor exstirpation (so-called UICC R 0 resection) and additive therapies following incomplete tumor resections (UICC R 1 or R 2 resection). Modalities in the adjuvant setting are chemotherapy, radiotherapy or the combined radio-/chemotherapy. In esophageal and gastric cancer there is up to now no benefit of postoperative adjuvant therapy. In pancreatic cancer, there are studies indicating a benefit of combined radio-/chemotherapy after complete tumor resection. A standard adjuvant chemotherapeutic treatment is proven in colon cancer stage III (Dukes C) with levamisole and 5-FU. Completely resected rectal carcinoma should be treated postoperatively with combined radio-/chemotherapy. In the common clinical or practical setting, adjuvant therapy is indicated only in locally advanced gastrointestinal tumors following R 0 resection. Postoperative therapy following incomplete tumor resection has its reason only in a palliative intention. (orig.) [de

In vivo synergistic cytogenetic effects of aminophylline on lymphocyte cultures from patients with lung cancer undergoing chemotherapy

International Nuclear Information System (INIS)

Mylonaki, Effie; Manika, Katerina; Zarogoulidis, Paul; Domvri, Kalliopi; Voutsas, Vasilis; Zarogoulidis, Kostas; Mourelatos, Dionysios

2012-01-01

Highlights: ► SCEs in vivo, a possible predictor of tumor chemoresponse. ► In vivo exposure to combined treatment, applying the SCE assay. ► Aminophylline enhances DNA instability induced by chemotherapy in vivo. ► In vivo synergistic effect of Aminophylline with the chemotherapeutic agents. - Abstract: Background: The anti-cancer and cytogenetic effects of aminophylline (AM) have been demonstrated in several clinical trials. The aim of the present study was to investigate the in vivo cytogenetic effects of AM in newly diagnosed patients with small cell (SCLC) and non-small cell lung cancer (NSCLC), receiving chemotherapy for the first time. Methods: Sister chromatid exchanges (SCEs) and proliferation rate index (PRI) were evaluated in peripheral blood lymphocyte cultures from six patients with SCLC and six patients with NSCLC after the in vitro addition of AM and after the in vivo administration of AM in patients receiving chemotherapy. Results: The in vitro addition of AM significantly increased SCEs only in SCLC patients (p 0.05). Conclusions: These observations suggest that AM enhances the results of concurrently administered chemotherapy by synergistically increasing its cytogenetic effects in patients with lung cancer

3D tumor tissue analogs and their orthotopic implants for understanding tumor-targeting of microenvironment-responsive nanosized chemotherapy and radiation.

Science.gov (United States)

Sethi, Pallavi; Jyoti, Amar; Swindell, Elden P; Chan, Ryan; Langner, Ulrich W; Feddock, Jonathan M; Nagarajan, Radhakrishnan; O'Halloran, Thomas V; Upreti, Meenakshi

2015-11-01

An appropriate representation of the tumor microenvironment in tumor models can have a pronounced impact on directing combinatorial treatment strategies and cancer nanotherapeutics. The present study develops a novel 3D co-culture spheroid model (3D TNBC) incorporating tumor cells, endothelial cells and fibroblasts as color-coded murine tumor tissue analogs (TTA) to better represent the tumor milieu of triple negative breast cancer in vitro. Implantation of TTA orthotopically in nude mice, resulted in enhanced growth and aggressive metastasis to ectopic sites. Subsequently, the utility of the model is demonstrated for preferential targeting of irradiated tumor endothelial cells via radiation-induced stromal enrichment of galectin-1 using anginex conjugated nanoparticles (nanobins) carrying arsenic trioxide and cisplatin. Demonstration of a multimodal nanotherapeutic system and inclusion of the biological response to radiation using an in vitro/in vivo tumor model incorporating characteristics of tumor microenvironment presents an advance in preclinical evaluation of existing and novel cancer nanotherapies. Existing in-vivo tumor models are established by implanting tumor cells into nude mice. Here, the authors described their approach 3D spheres containing tumor cells, enodothelial cells and fibroblasts. This would mimic tumor micro-environment more realistically. This interesting 3D model should reflect more accurately tumor response to various drugs and would enable the design of new treatment modalities. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Copy number aberrations landscape of a breast tumor, connection with the efficiency of neoadjuvant chemotherapy

Science.gov (United States)

Ibragimova, M. K.; Tsyganov, M. M.; Slonimskaya, E. M.; Litviakov, N. V.

2017-09-01

The research involved 80 patients diagnosed with breast cancer (BC). Each patient had their tumor biopsy material sampled before their treatment. We studied the tumor tissue using the CytoScan HD Array (Affymetrix, USA) microarray to evaluate the CNA landscape. We studied the frequency of segmental and numerical CNA occurrence, their association with the efficiency of neoadjuvant chemotherapy (NAC). We found that the biggest number of amplifications (with frequency over 60%) were found on in the following locuses; 1q32.1 1q32.3, 1q42.13, 1q42.2, 1q43. The biggest frequency of deletions (more than in 58% of the patients) was found in these locuses: 16q21, 16q23.2, 16q23.3, 17p12, 17p13.1. However, we found the locuses with full absence of segmental chromosome anomalies. We observed trisomy most frequently in the 7, 8, 12, and 17 chromosomes, and monosomy in the 3, 4, 9, 11, 18, and X-chromosomes. We demonstrated the connection between the high frequency of cytobands with CNA in the patients' tumors and the efficiency of NAC. We also identified the cytobands, whose CNA are linked to the response to NAC.

Tumor response and survival in patients with advanced non-small-cell lung cancer: the predictive value of chemotherapy-induced changes in fibrinogen

International Nuclear Information System (INIS)

Zhao, Jun; Zheng, Shuang; Zhou, Qiyin; Li, Heming; Liu, Yunpeng; Qu, Xiujuan; Zhao, Mingfang; Jin, Bo; Yu, Ping; Hu, Xuejun; Teng, Yuee; Zhang, Jingdong; Luo, Ying; Zhang, Lingyun

2012-01-01

Hyperfibrinogenemia is a common problem associated with various carcinomas, and is accompanied by hypercoagulablity. In advanced non-small-cell lung cancer (NSCLC) it remains unclear whether or not chemotherapy-induced changes in fibrinogen level relate to chemotherapeutic response and prognosis. The purposes of this study were to: 1) analyze the association between chemotherapy-induced changes in plasma fibrinogen level and the chemotherapeutic response after the first two courses of standard first-line platinum-based chemotherapy; and 2) evaluate the prognostic significance of the basal plasma fibrinogen level in patients with advanced NSCLC. In this retrospective study, the data from 160 patients with advanced NSCLC were collected. The association between the changes in fibrinogen and the response to chemotherapy, or between the pre-and post-chemotherapy fibrinogen levels and patient clinical characteristics, were analyzed using SPSS software. In addition, the prognostic value of pre-chemotherapy fibrinogen levels was assessed. The median pre-chemotherapy plasma fibrinogen level was 4.4 g/L. Pre-chemotherapy plasma fibrinogen levels correlated significantly with gender (p = 0.041). Post-chemotherapy plasma fibrinogen levels correlated with gender (p = 0.023), age (p = 0.018), ECOG (p = 0.002) and tumor response (p = 0.049). Plasma fibrinogen levels markedly decreased after chemotherapy in 98 (61.25 %) patients with pre-chemotherapy hyperfibrinogenemia (p = 0.008); and in this population there was a significant link between the decrease in fibrinogen level, and initial partial response (PR; p = 0.017) and stable disease (SD; p = 0.031). Univariate and multivariate analysis revealed that higher levels of fibrinogen (≥4.4 g/L) and ECOG 1 were positively associated with shorter overall survival (OS). CEA and CA125 also decreased significantly (p =0.015, p =0.000) in DCR group after chemotherapy. This study showed that the reduction in plasma fibrinogen levels

Usefulness of superparamagnetic iron oxide particle (AMI-25) enhanced MR imaging for the diagnosis of liver tumors

International Nuclear Information System (INIS)

Hirohashi, Shinji; Hirohashi, Rina; Uchida, Hideo; Kachi, Kenji; Ohtomo, Kuni; Uchiyama, Gyou; Niitsu, Mamoru; Itai, Yuji.

1994-01-01

The purpose of this study was to clarify the usefulness of SPIO-enhanced MRI in the diagnosis of liver tumors in comparison with contrast enhanced CT. The subjects were forty patients with 154 nodules in the liver. We compared SPIO-enhanced MRI with contrast-enhanced CT in terms of tumor-liver contrast and detectability of liver tumors. In terms of tumor liver contrast, SPIO-enhanced MRI was equal or superior to contrast-enhanced CT in 82% of cases. In the detectability of liver tumor, SPIO-enhanced MRI detected more tumors than contrast-enhanced CT, especially small tumors. Tumors undetected by SPIO-enhanced MRI that were detected by contrast-enhanced CT and/or plain MRI were adenomatous hyperplasia and inflammatory pseudotumor according to fine needle biopsy. There were no severe complications of SPIO-enhanced MRI. In conclusion, SPIO-enhanced MRI will be more useful than contrast-enhanced CT in the diagnosis of liver tumors. SPIO-enhanced MRI may be a promising diagnostic method for the detection of hepatic tumors, especially small ones. (author)

Risk factors for positive margins in conservative surgery for breast cancer after neoadjuvant chemotherapy.

Science.gov (United States)

Bouzón, Alberto; Acea, Benigno; García, Alejandra; Iglesias, Ángela; Mosquera, Joaquín; Santiago, Paz; Seoane, Teresa

2016-01-01

Breast conservative surgery after neoadjuvant chemotherapy intends to remove any residual tumor with negative margins. The purpose of this study was to analyze the preoperative clinical-pathological factors influencing the margin status after conservative surgery in breast cancer patients receiving neoadjuvant chemotherapy. A retrospective study of 91 breast cancer patients undergoing neoadjuvant chemotherapy (92 breast lesions) during the period 2006 to 2013. A Cox regression analysis to identify baseline tumor characteristics associated with positive margins after breast conservative surgery was performed. Of all cases, 71 tumors were initially treated with conservative surgery after neoadjuvant chemotherapy. Pathologic exam revealed positive margins in 16 of the 71 cases (22.5%). The incidence of positive margins was significantly higher in cancers with initial size >5cm (P=.021), in cancers with low tumor grade (P=.031), and in patients with hormone receptor-positive cancer (P=.006). After a median follow-up of 45.2 months, 7 patients of the 71 treated with conservative surgery had disease recurrence (9.8%). There was no significant difference in terms of disease-free survival according to the margin status (P=.596). A baseline tumor size >5cm, low tumor grade and hormone receptor-positive status increase the risk for surgical margin involvement in breast conservative surgery after neoadjuvant chemotherapy. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Success of Chemotherapy in Soft Matter

OpenAIRE

Trifonova, I.; Kurteva, G.; Stefanov, S. Z.

2014-01-01

The success of chemotharapy in soft matter as a survival is found in the paper. Therefore, it is found the analogous tumor stretching force in soft matter; ultrasonography is performed for this tumor; restoration in soft matter with such a tumor is found; Bayes estimate of the probability of chemotherapy success is derived from the transferred chemical energy and from soft matter entropy; survival probability is juxtaposed to this probability of success.

Treatment of dogs with oral melanoma by hypofractionated radiation therapy and platinum-based chemotherapy (1987-1997).

Science.gov (United States)

Freeman, Kim P; Hahn, Kevin A; Harris, F Dee; King, Glen K

2003-01-01

This retrospective study in 39 dogs with incompletely resected oral melanoma examined the efficacy of hypofractionated radiation therapy and platinum-containing chemotherapy. All dogs were completely staged, with the majority of dogs classified as stage 1. Dogs received 6 weekly fractions of 6-gray (Gy) megavoltage irradiation with a cobalt-60 unit or a 4-MeV (megaelectron volts) linear accelerator. Dogs received cisplatin (10-30 mg/m2 IV) or carboplatin (90 mg/m2 IV) chemotherapy 60 minutes before radiation delivery. Durations of local control, metastasis-free survival time, and overall survival time were recorded. By the Kaplan-Meier method, 15% of the dogs had local recurrence within a median time of 139 days. Fifty-one percent of the dogs developed metastatic disease within a median time of 311 days (range, 24-2, 163 days). Median survival time for all 39 dogs was 363 days. The combined use of chemotherapy and radiation therapy in this protocol provided local control consistent with previous studies. Low-dose chemotherapy was used with the intent of enhancing radiation therapy for the local control of an incompletely excised tumor. Survival times were longer than previously reported for dogs with oral malignant melanoma. Additional studies are required to determine whether these results were due to the effects of chemotherapy on microscopic disease or the enhanced local control provided by chemoradiation therapy.

Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients.

Science.gov (United States)

Besser, Michal J; Shapira-Frommer, Ronnie; Treves, Avraham J; Zippel, Dov; Itzhaki, Orit; Schallmach, Ester; Kubi, Adva; Shalmon, Bruria; Hardan, Izhar; Catane, Raphael; Segal, Eran; Markel, Gal; Apter, Sara; Nun, Alon Ben; Kuchuk, Iryna; Shimoni, Avichai; Nagler, Arnon; Schachter, Jacob

2009-05-01

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) and high-dose interleukin-2 (IL-2), after nonmyeloablative chemotherapy, has been shown to result in tumor regression in half of refractory metastatic melanoma patients. In the present study, we describe 2 separate clinical protocols. Twelve patients were treated with "Selected"-TIL, as previously reported and 8 patients with the modified version of "Young"-TIL. Selected-TIL protocol required the establishment of multiple T-cell cultures from 1 patient and in vitro selection of cultures secreting interferon-gamma upon antigenic stimulation. In contrast, Young-TIL are minimally cultured T cells with superior in vitro features that do not require further selection. Two of 12 Selected-TIL patients experienced objective clinical responses (1 complete response, 1 partial response). Out of 8 treated Young-TIL patients, 1 experienced complete response, 2 partial response, and 4 patients had disease stabilization. Twenty-one of 33 enrolled Selected-TIL patients were excluded from the protocol, mainly as cultures failed the interferon-gamma selection criteria or due to clinical deterioration, compared with only 3 Young-TIL patients. Expected bone marrow suppression and high-dose IL-2 toxicity were transient. There was no treatment-related mortality. This study vindicates the feasibility and effectiveness of TIL technology and calls for further efforts to implement and enhance this modality. The use of minimally cultured, unselected Young-TIL enables the treatment of most enrolled patients. Although the cohort of Young-TIL patients treated so far is rather small and the follow-up short, the response rate is encouraging.

Neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer with variant histology.

Science.gov (United States)

Vetterlein, Malte W; Wankowicz, Stephanie A M; Seisen, Thomas; Lander, Richard; Löppenberg, Björn; Chun, Felix K-H; Menon, Mani; Sun, Maxine; Barletta, Justine A; Choueiri, Toni K; Bellmunt, Joaquim; Trinh, Quoc-Dien; Preston, Mark A

2017-11-15

Neoadjuvant chemotherapy in pure urothelial bladder cancer provides a significant survival benefit. However, to the authors' knowledge, it is unknown whether this benefit persists in histological variants. The objective of the current study was to assess the effect of neoadjuvant chemotherapy on the probability of non-organ-confined disease and overall survival after radical cystectomy (RC) in patients with histological variants. Querying the National Cancer Data Base, the authors identified 2018 patients with histological variants who were undergoing RC for bladder cancer between 2003 and 2012. Variants were categorized as micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, neuroendocrine tumors, and other histology. Logistic regression models estimated the odds of non-organ-confined disease at the time of RC for each histological variant, stratified by the receipt of neoadjuvant chemotherapy. Cox regression models were used to examine the effect of neoadjuvant chemotherapy on overall mortality in each variant subgroup. Patients with neuroendocrine tumors (odds ratio [OR], 0.16; 95% confidence interval [95% CI], 0.08-0.32 [Pchemotherapy. An overall survival benefit for neoadjuvant chemotherapy was only found in patients with neuroendocrine tumors (hazard ratio, 0.49; 95% CI, 0.33-0.74 [P=.001]). Patients with neuroendocrine tumors benefit from neoadjuvant chemotherapy, as evidenced by better overall survival and lower rates of non-organ-confined disease at the time of RC. For tumors with micropapillary differentiation, sarcomatoid differentiation, or adenocarcinoma, neoadjuvant chemotherapy decreased the frequency of non-organ-confined disease at the time of RC. However, this favorable effect did not translate into a statistically significant overall survival benefit for these patients, potentially due to the aggressive tumor biology. Cancer 2017;123:4346-55. © 2017 American Cancer Society. © 2017 American Cancer Society.

Radiation as an inducer of in-situ autologous vaccine in the treatment of solid tumors

International Nuclear Information System (INIS)

Ahmed, Mansoor M.

2013-01-01

Radiation therapy (RT) is conventionally used for local tumor control. Although local control of the primary tumor can prevent the development of subsequent systemic metastases, tumor irradiation is not effective in controlling pre-existing systemic disease. The concept of radiation-enhanced antigen presentation and immunomodulation allows the harnessing of tumor cell death induced by radiation as a potential source of tumor antigens for immunotherapy. Immunomodulation using RT is a novel strategy of in situ tumor vaccination where primary tumor irradiation can contribute to the control of pre-existing systemic metastatic disease. The absence of systemic immunosuppression (often associated with chemotherapy) and the generally lower toxicity makes radiation a desirable adjuvant regimen for immunotherapy and tumor vaccination strategies. Increased understanding of tumor immunology and the biology of radiation-mediated immune modulation should enhance the efficacy of combining these therapeutic modalities. Here we aim to provide an overview of the biology of radiation-induced immune modulation. (author)

Cell structure and function and response to chemotherapy in tumors heterotransplanted into the subrenal capsule of mice and rats.

Science.gov (United States)

Stenbäck, F; Kangas, L; Wasenius, V M

1985-12-01

Specimens from 16 freshly biopsied human tumors, two mammary adenocarcinomas, ten ovarian adenocarcinomas, two squamous cell carcinomas, one malignant histiocytoma and one chondrosarcoma of the bone, two human ovarian adenocarcinomas established by transplantation into nude mice and two adenocarcinomas induced in rat mammary gland were transplanted under the renal capsule of 510 normal immunocompetent mice and 180 rats and the effects of chemotherapy were evaluated. The results showed successful transplantation of all types of tumors in both animal species. Morphological analysis revealed preserved glandular structures with surface microvilli, mucin and CEA production and partially preserved basement membranes. Treatment with cyclophosphamide, vinblastine, adriamycin and cisplatin caused cell shrinkage, degradation and partial or total disappearance of the tumor cells. Vascularization was distinct in all specimens. A cellular infiltrate was found frequently but not consistently. A common end stage was a fibrotic scar with no cellular activity, occasionally giving a misleading impression of a growing tumor on gross observation. The results were obtained rapidly and suggest that the subrenal capsule assay would be useful for evaluating the sensitivity of human tumors to therapeutic manipulation, but needs supplementary histological examination.

Combined radiotherapy and chemotherapy for head and neck cancer

International Nuclear Information System (INIS)

Inuyama, Yukio; Fujii, Masato; Tanaka, Juichi; Takaoka, Tetsuro; Hosoda, Hyonosuke; Kawaura, Mitsuhiro; Toji, Masao

1988-01-01

There are 4 modalities of combined radiotherapy and chemotherapy which include (1) concurrent radiotherapy and chemotherapy, (2) sequential use of radiotherapy and chemotherapy (pre-radiation chemotherapy), (3) pre-radiation chemotherapy followed by concurrent radiation and chemotherapy, and (4) alternating use of radiotherapy and chemotherapy based upon Looney's hypothesis. We studied concurrent use of radiotherapy and UFT by means of animal experimentation and clinical trials. The results obtained revealed that UFT was a most suitable agent together with 5-fluorouracil for concurrent application of radiotherapy and chemotherapy. Neo-adjuvant chemotherapy including pre-radiation chemotherapy was also studied in cases of maxillary sinus carcinoma and nasopharyngeal carcinoma. From the results, it seemed desirable to use cisplatin and bleomycin analogs sequentially in combined chemotherapy and radiotherapy. Neo-adjuvant chemotherapy should be studied successively to improve local tumor control rates and prevent distant metastases. For future perspectives, new trials of alternating radiotherapy and chemotherapy based upon Looney's hypothesis seem necessary. (author)

Tungsten Targets the Tumor Microenvironment to Enhance Breast Cancer Metastasis

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Bolt, Alicia M.; Sabourin, Valérie; Molina, Manuel Flores; Police, Alice M.; Negro Silva, Luis Fernando; Plourde, Dany; Lemaire, Maryse; Ursini-Siegel, Josie; Mann, Koren K.

2015-01-01

The number of individuals exposed to high levels of tungsten is increasing, yet there is limited knowledge of the potential human health risks. Recently, a cohort of breast cancer patients was left with tungsten in their breasts following testing of a tungsten-based shield during intraoperative radiotherapy. While monitoring tungsten levels in the blood and urine of these patients, we utilized the 66Cl4 cell model, in vitro and in mice to study the effects of tungsten exposure on mammary tumor growth and metastasis. We still detect tungsten in the urine of patients’ years after surgery (mean urinary tungsten concentration at least 20 months post-surgery = 1.76 ng/ml), even in those who have opted for mastectomy, indicating that tungsten does not remain in the breast. In addition, standard chelation therapy was ineffective at mobilizing tungsten. In the mouse model, tungsten slightly delayed primary tumor growth, but significantly enhanced lung metastasis. In vitro, tungsten did not enhance 66Cl4 proliferation or invasion, suggesting that tungsten was not directly acting on 66Cl4 primary tumor cells to enhance invasion. In contrast, tungsten changed the tumor microenvironment, enhancing parameters known to be important for cell invasion and metastasis including activated fibroblasts, matrix metalloproteinases, and myeloid-derived suppressor cells. We show, for the first time, that tungsten enhances metastasis in an animal model of breast cancer by targeting the microenvironment. Importantly, all these tumor microenvironmental changes are associated with a poor prognosis in humans. PMID:25324207

Cost-effectiveness analysis of optimal strategy for tumor treatment

International Nuclear Information System (INIS)

Pang, Liuyong; Zhao, Zhong; Song, Xinyu

2016-01-01

We propose and analyze an antitumor model with combined immunotherapy and chemotherapy. Firstly, we explore the treatment effects of single immunotherapy and single chemotherapy, respectively. Results indicate that neither immunotherapy nor chemotherapy alone are adequate to cure a tumor. Hence, we apply optimal theory to investigate how the combination of immunotherapy and chemotherapy should be implemented, for a certain time period, in order to reduce the number of tumor cells, while minimizing the implementation cost of the treatment strategy. Secondly, we establish the existence of the optimality system and use Pontryagin’s Maximum Principle to characterize the optimal levels of the two treatment measures. Furthermore, we calculate the incremental cost-effectiveness ratios to analyze the cost-effectiveness of all possible combinations of the two treatment measures. Finally, numerical results show that the combination of immunotherapy and chemotherapy is the most cost-effective strategy for tumor treatment, and able to eliminate the entire tumor with size 4.470 × 10"8 in a year.

Diagnostic value of dynamic contrast-enhanced MRI for submucosal palatal tumors

International Nuclear Information System (INIS)

Matsuzaki, Hidenobu; Yanagi, Yoshinobu; Hara, Marina; Katase, Naoki; Hisatomi, Miki; Unetsubo, Teruhisa; Konouchi, Hironobu; Takenobu, Toshihiko

2012-01-01

Objectives: To evaluate the diagnostic value of dynamic contrast-enhanced MRI (DCE-MRI) for differentiating between benign and malignant tumors in the palate. Materials and methods: 26 patients with submucosal palatal tumors were preoperatively examined using DCE-MRI. Their maximum contrast index (CImax), time of CImax (Tmax), and washout ratios (WR300 and WR600) were determined from contrast index curves. The submucosal palatal tumors were divided into two groups according to their Tmax values: the early enhancement group (Tmax 2 = 0.92, P < 0.001). Conclusions: Tmax is a useful parameter for distinguishing between benign and malignant submucosal palatal tumors.

Current status of secondary leukemia following cancer chemotherapy and/or radiotherapy

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Kawashima, Kohei; Nagura, Ei-ichi.

1990-01-01

As part of a study on hematopoietic effects of A-bombing, a nationwide questionnaire survey was made in 1,487 facilities to analyze secondary leukemia. A total of 232 patients, who were reported to have developed secondary hematopoietic or solid tumor, were eligible for this study. For 62 each evaluable male and female patients, the most common primary solid cancer was gastric cancer (27/62) for men; and breast cancer (25/62) and urinary cancer (27/62) for women. Of a total of 124 patients, 73 (59%) developed acute leukemia as secondary hematopoietic tumor, 53 of whom had underwent chemotherapy and/or radiotherapy for primary cancer. For primary hematopoietic tumor seen in 90 patients, non-Hodgkin's disease was the most common (38%, 34/90), followed by multiple myeloma (20%, 18/90). Of a total of 155 patients developing secondary hematopoietic tumor, 111 had received chemotherapy and/or radiotherapy. Chemotherapy or radiotherapy for primary cancer may have the potential risk for developing secondary cancer. (N.K.)

Malignant renal tumors in pediatrics

International Nuclear Information System (INIS)

Pena, C.; Torterolo, J.; Irigoyen, B.; Bel, M.; Elias, E.

2004-01-01

Introduction: Professionals who work in pediatric oncology, we see childhood cancer as a common disease, but in fact constitutes about 2% of all cancers diagnosed worldwide. Wilms tumor accounts for 6% of all childhood tumors and presentation bilateral accounts for 4-6% of all Wilms tumors diagnosed. Theoretical Framework: In the period between the year 1994-2003 period were attended in the Pediatric Hematology-Oncology Center, a total of 29 cases of malignant renal tumors, corresponding to 86% (25 cases) to Wilms tumor or nephroblastoma tumor. The Wilms is of embryonic origin, capable of metastatic spread, (85% lungs 15% liver). Very sensitive to chemotherapy and radiotherapy, which confers high cure rates (85%); having a multidisciplinary treatment model, combining surgery, chemotherapy, and radiotherapy. The role of nursing in comprehensive cancer care child is essential in the prevention and early detection of side effects or complications. Case report: S.D. currently 10 years old. In 10/1994, at 8 months of age, was diagnosed with bilateral Wilms tumor. On admission her weight was 8200gr with abdominal circumference 50cm. Conducted pre-operative MDT and 02/1995 nephrectomy of the left kidney and right kidney lumpectomy (tumor nodule 420gr. and a 250gr.). MDT begins in 03/1995 01/1996 ending. 09/2003 with abdominal pain and vomiting, and kidney failure. 10/2003 lumpectomy biopsy (sclerotic nodule associated with maturation nephroblastoma). Currently severe renal insufficiency plan enters dialysis. Nursing process: Objectives: 1) To prepare the child and family to the side effects and possible complications of chemotherapy and / or radiotherapy 2) Prevent and minimize related complications tumor and / or treatment. Care Plan comprises four stages: A) rating and customer income. B) Implement care chemotherapy C) post-operative Care D) Implement radiation care

Evaluation of static and dynamic MRI for assessing response of bone sarcomas to preoperative chemotherapy: Correlation with histological necrosis

International Nuclear Information System (INIS)

Amit, Priyadarshi; Malhotra, Atul; Kumar, Rahul; Kumar, Lokesh; Patro, Dilip Kumar; Elangovan, Sundar

2015-01-01

Preoperative chemotherapy plays a key role in management of bone sarcomas. Postoperative evaluation of histological necrosis has been the gold standard method of assessing response to preoperative chemotherapy. This study was done to evaluate the efficacy of static and dynamic magnetic resonance imaging (MRI) for assessing response preoperatively. Our study included 14 patients (12 osteosarcomas and 2 malignant fibrous histiocytomas) with mean age of 21.8 years, treated with preoperative chemotherapy followed by surgery. They were evaluated with static and dynamic MRI twice, before starting chemotherapy and again prior to surgery. Change in tumor volume and slope of signal intensity - time curve were calculated and correlated with percentage of histological necrosis using Pearson correlation test. The change in dynamic MRI slope was significant (P = 0.001). Also, ≥60% reduction in slope of the curve proved to be an indicator of good histological response [positive predictive value (PPV) =80%]. Change in tumor volume failed to show significant correlation (P = 0.071). Although it showed high negative predictive value (NPV = 85.7%), PPV was too low (PPV = 57.14%). Dynamic MRI correctly predicts histological necrosis after administration of preoperative chemotherapy to bone sarcomas. Hence, it can be used as a preoperative indicator of response to neoadjuvant chemotherapy. On the other hand, volumetric assessment by static MRI is not an effective predictor of histological necrosis. This study proves the superiority of dynamic contrast-enhanced study over volumetric study by MRI

[Actual questions about the prevention of venous thromboembolism in cancer patients receiving chemotherapy].

Science.gov (United States)

Losonczy, Hajna; Nagy, Ágnes; Tar, Attila

2016-02-07

Cancer patients have a 2-7 fold increased risk of venous thromboembolism compared with the general population and, since 1990, this is associated with significant morbidity and mortality. This review summarizes the current knowledge on venous thromboembolism and cancer. Notably, the risk of venous thromboembolism varies depending on the type and stage of cancer. For instance, pancreatic and brain cancer patients have a higher risk of venous thromboembolism than breast and prostate cancer patients. Moreover, patients with metastatic disease have a higher risk than those with localized tumors. Tumor-derived procoagulant factors, cytokines and growth factors may directly and indirectly enhance venous thromboembolism. Chemotherapy produces ~6,5 fold increase in venous thromboembolism incidence in cancer patients compared to the general population. Prevention of this complication is challenging. The authors review the development of guidelines concerning venous thromboembolism prevention in hospitalized and also in ambulatory cancer patients treated with chemotherapy. Current guidelines recommend the use of low-molecular-weight heparin. Understanding the underlying mechanisms may allow the development of new therapies to safely prevent venous thromboembolism in cancer patients.

Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

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Guilherme Freire Angotti Carrara

Full Text Available OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04. A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01. CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors.

Hypoxia-activated pro-drug TH-302 exhibits potent tumor suppressive activity and cooperates with chemotherapy against osteosarcoma.

Science.gov (United States)

Liapis, Vasilios; Labrinidis, Agatha; Zinonos, Irene; Hay, Shelley; Ponomarev, Vladimir; Panagopoulos, Vasilios; DeNichilo, Mark; Ingman, Wendy; Atkins, Gerald J; Findlay, David M; Zannettino, Andrew C W; Evdokiou, Andreas

2015-02-01

Tumor hypoxia is a major cause of treatment failure for a variety of malignancies. However, tumor hypoxia also offers treatment opportunities, exemplified by the development compounds that target hypoxic regions within tumors. TH-302 is a pro-drug created by the conjugation of 2-nitroimidazole to bromo-isophosphoramide (Br-IPM). When TH-302 is delivered to regions of hypoxia, Br-IPM, the DNA cross linking toxin, is released. In this study we assessed the cytotoxic activity of TH-302 against osteosarcoma cells in vitro and evaluated its anticancer efficacy as a single agent, and in combination with doxorubicin, in an orthotopic mouse model of human osteosarcoma (OS). In vitro, TH-302 was potently cytotoxic to osteosarcoma cells selectively under hypoxic conditions, whereas primary normal human osteoblasts were protected. Animals transplanted with OS cells directly into their tibiae and left untreated developed mixed osteolytic/osteosclerotic bone lesions and subsequently developed lung metastases. TH-302 reduced tumor burden in bone and cooperated with doxorubicin to protect bone from osteosarcoma induced bone destruction, while it also reduced lung metastases. TH-302 may therefore be an attractive therapeutic agent with strong activity as a single agent and in combination with chemotherapy against OS. Crown Copyright © 2014. Published by Elsevier Ireland Ltd. All rights reserved.

Chemo-radiotherapy for malignant brain tumors

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Kochi, Masato; Ushio, Yukitaka [Kumamoto Univ. (Japan). School of Medicine

2002-05-01

Malignant gliomas: Randomized clinical trials conducted in the USA showed that radiotherapy plus chemotherapy with nitrosoureas offered a long-term survival advantage to patients younger than 60 years old with malignant gliomas. Combination chemotherapy, such as procarbazine/CCNU/vincristine (PCV) must be tested further, and intra-arterial chemotherapy with nitrosoureas offered no survival advantage. Combination chemotherapy with PCV showed efficacy for patients with anaplastic oligodendroglioma and anaplastic oligoastrocytoma. Medulloblastoma: The addition of chemotherapy to radiotherapy improved the survival of patients with poor risk medulloblastoma, and may reduce the required craniospinal radiation dose in patients with good risk medulloblastoma. Primary CNS lymphoma (PCNSL): Combination of chemotherapy with high-dose MTX and radiotherapy improved survival of patients with PCNSL; however, the neurotoxicity produced by this treatment modality is a serious problem in older patients. Intracranial germ cell tumors: The addition of chemotherapy to radiotherapy may produce long term survival with good quality of life in patients with germinoma. Neoadjuvant therapy consisting of chemotherapy and radiotherapy followed by complete surgical excision improved survival of patients with intracranial nongerminomatous germ cell tumors. (author)

Chemo-radiotherapy for malignant brain tumors

International Nuclear Information System (INIS)

Kochi, Masato; Ushio, Yukitaka

2002-01-01

Malignant gliomas: Randomized clinical trials conducted in the USA showed that radiotherapy plus chemotherapy with nitrosoureas offered a long-term survival advantage to patients younger than 60 years old with malignant gliomas. Combination chemotherapy, such as procarbazine/CCNU/vincristine (PCV) must be tested further, and intra-arterial chemotherapy with nitrosoureas offered no survival advantage. Combination chemotherapy with PCV showed efficacy for patients with anaplastic oligodendroglioma and anaplastic oligoastrocytoma. Medulloblastoma: The addition of chemotherapy to radiotherapy improved the survival of patients with poor risk medulloblastoma, and may reduce the required craniospinal radiation dose in patients with good risk medulloblastoma. Primary CNS lymphoma (PCNSL): Combination of chemotherapy with high-dose MTX and radiotherapy improved survival of patients with PCNSL; however, the neurotoxicity produced by this treatment modality is a serious problem in older patients. Intracranial germ cell tumors: The addition of chemotherapy to radiotherapy may produce long term survival with good quality of life in patients with germinoma. Neoadjuvant therapy consisting of chemotherapy and radiotherapy followed by complete surgical excision improved survival of patients with intracranial nongerminomatous germ cell tumors. (author)

Evaluation of recent curative effect of chemotherapy on hepatocellular carcinoma with MSCT

International Nuclear Information System (INIS)

Zhao Jing; Zheng Keguo

2009-01-01

Objective: To study the value of MSCT in evaluating the recent curative effect of hepatocellular carcinoma (HCC) after the chemotherapy with Oxaliplatin combined with 5-FU and Folinic Acid. Methods: 6 cases with HCC or post hepatectomy metastasis HCC confirmed by pathohistology underwent chemotherapy with Oxaliplatin combined with 5-FU and Folinic Acid. MultiSpiral Computed Tomography was used to determine the target lesions before and after the chemotherapy. The size of the target lesions before the chemotherapy was refer as the basic value (x0), and that after the chemotherapy was regarded as the observed value (y1). The theoretic value was obtained based on tumor growth dynamics mathematic model y2(x)=X 0 2 t/3td . Results: Before and after the first chemotherapy or between the consecutive chemotherapy cycles, the target lesions could be follow-up one by one with MSCT. There was significant statistical difference between observed increase size and theoretical increase size, P=0.0442. Conclusion: Tumor growth velocity can be effectively controlled with this chemotherapy plan, and MSCT may used to be an objective tool to evaluate the recent curative effect of chemotherapy on hepatocellular carcinoma. (authors)

Primary Carcinosarcoma of Ovary an Unusual Tumor Case Report ...

African Journals Online (AJOL)

radiotherapy and chemotherapy or chemotherapy alone.[2]. These tumors are .... stage of disease.[6]. The adverse prognostic factors as enumerated by various ... The effect of epithelial and stromal tumor components on. FIGO stages III and IV ...

Neoadjuvant chemotherapy in locally advanced colon cancer

DEFF Research Database (Denmark)

Jakobsen, Anders; Andersen, Fahimeh; Fischer, Anders

2015-01-01

BACKGROUND: Neoadjuvant chemotherapy has proven valuable in several tumors, but it has not been elucidated in colon cancer. The present phase II trial addressed the issue in high-risk patients selected by computed tomography (CT) scan. MATERIAL AND METHODS: Patients with resectable colon cancer...... 32% (p = 0.005) translating into a three-year DFS of 94% versus 63% (p = 0.005). CONCLUSION: Neoadjuvant chemotherapy in colon cancer is feasible and the results suggest that a major part of the patients can be spared adjuvant chemotherapy. Validation in a randomized trial is warranted....