• Immune microenvironment
• Immunotherapy
• Low-dose radiotherapy
• Radiotherapy
• Small cell lung cancer

• Animals
• Humans
• Combined Modality Therapy/methods
• Immune Checkpoint Inhibitors/pharmacology
• Immune Checkpoint Inhibitors/therapeutic use
• Immunotherapy/methods
• Lung Neoplasms/immunology
• Lung Neoplasms/pathology
• Lung Neoplasms/therapy
• Small Cell Lung Carcinoma/immunology
• Small Cell Lung Carcinoma/pathology
• Small Cell Lung Carcinoma/therapy
• Tumor Microenvironment/drug effects
• Tumor Microenvironment/immunology
• Tumor Microenvironment/radiation effects

• Bystander Effect/radiation effects
• Humans
• Animals
• Cell Communication/radiation effects
• Oxidative Stress/radiation effects

• consolidative thoracic radiotherapy
• extensive-stage small-cell lung cancer
• immunotherapy
• prophylactic cranial irradiation
• radiotherapy

• Humans
• Quality of Life
• Superior Vena Cava Syndrome
• Immunotherapy
• Small Cell Lung Carcinoma/radiotherapy
• Brain Neoplasms/radiotherapy
• Lung Neoplasms/radiotherapy

• Humans
• Small Cell Lung Carcinoma
• Lung Neoplasms
• Immune Checkpoint Inhibitors/therapeutic use
• Immunotherapy/methods
• Combined Modality Therapy

• PD-(L)1
• biomarkers
• drug conjugates
• immune checkpoint inhibitors
• small cell lung cancer

• Humans
• Small Cell Lung Carcinoma/drug therapy
• Receptors, Chimeric Antigen/therapeutic use
• Immunotherapy
• Lung Neoplasms/drug therapy
• Immunologic Factors/therapeutic use
• Radiation, Ionizing

• LC-MS
• autoradiography
• capecitabine
• gemcitabine
• pancreatic cancer

• Animals
• Autoradiography
• Capecitabine
• Disease Models, Animal
• Humans
• Mice
• Pancreatic Neoplasms/drug therapy
• Prodrugs

• P30 CA008748 NCI NIH HHS
• R01 CA194321 NCI NIH HHS
• U54 OD020355 NIH HHS
• Memorial Sloan Kettering Cancer Center
• Leona M. and Harry B. Helmsley Charitable Trust

• CTLA-4
• Durvalumab
• Immunotherapy
• PDL-1
• Solid tumor
• Tremelimumab

• Adult
• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized/therapeutic use
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Humans
• Neoplasms/drug therapy

• Fondo di Ateneo per la Ricerca 2020 from the University of Sassari, Italy
• Università degli Studi di Sassari

• Antibody-targeted therapy
• Cachexia
• Immunotherapy
• Metastasis
• Mouse model
• Pancreatic cancer
• Parabiosis
• Targeted therapy
• Vaccine

The radiosensitising effect of the poly(ADP-ribose) polymerase inhibitor olaparib on tumours has been reported. However, its effect on normal tissues in combination with radiation has not been well studied. Herein, we investigated the therapeutic index of olaparib combined with hemithoracic radiation in a urethane-induced mouse lung cancer model.

To assess tolerability, A/J mice were treated with olaparib plus whole thorax radiation (13 Gy), body weight changes were monitored and normal tissue effects were assessed by histology. In anti-tumour (intervention) studies, A/J mice were injected with urethane to induce lung tumours, and were then treated with olaparib alone, left thorax radiation alone or the combination of olaparib plus left thorax radiation at 8 weeks (early intervention) or 18 weeks (late intervention) after urethane injection. Anti-tumour efficacy and normal tissue effects were assessed by visual inspection, magnetic resonance imaging and histology.

Enhanced body weight loss and oesophageal toxicity were observed when olaparib was combined with whole thorax but not hemithorax radiation. In both the early and late intervention studies, olaparib increased the anti-tumour effects of hemithoracic irradiation without increasing lung toxicity.

The addition of olaparib increased the therapeutic index of hemithoracic radiation in a mouse model of lung cancer.

Immune checkpoint blockade (ICB) targeting programmed cell death protein 1 and cytotoxic T lymphocyte-associated protein 4 has achieved modest clinical activity as salvage therapy in relapsed small cell lung cancer (SCLC). We conducted this signal-finding study to assess the efficacy of ICB with or without radiation in relapsed SCLC.

Patients with relapsed SCLC and ≤2 previous lines of therapy were randomized to (1) arm A: durvalumab (D) 1500 mg/tremelimumab (T) 75 mg (intravenously every 4 weeks without stereotactic body radiation therapy (SBRT)) or (2) arm B: immune-sensitizing SBRT to one selected tumor site (9 Gy × 3 fractions) followed by D/T. Treatment continued until progression or a maximum of 12 months. The co-primary endpoints of the study were overall response rate (ORR) and progression-free survival (PFS). We evaluated circulating lymphocyte repertoire in serial peripheral blood samples and tumor infiltrating lymphocytes (TILs) from on-treatment biopsies as pharmacodynamic markers.

Eighteen patients were randomized to arms A and B (n=9 each): median age 70 years; 41.2% women. The median PFS and ORR were 2.1 months and 0% in arm A and 3.3 months and 28.6% in arm B. The median overall survival (OS) was 2.8 months in arm A and 5.7 months in arm B (p=0.3772). Pooled efficacy of D/T±SBRT in 15 Response evaluation criteria in solid tumors (RECIST) evaluable patients across both arms showed the best ORR in terms of partial response in 13.3%, stable disease in 26.6% and progressive disease in 60.0%; the overall median PFS and OS were 2.76 and 3.9 months. The most common adverse events were grade 1 fatigue (66%) and grade 1 elevated amylase (56%) in arm A, and grade 1 fatigue (56%) and pain (44%) in arm B. There was a significant increase in activated CD8(+)ICOS+ T cells (p=0.048) and a reduction in naïve T cells (p=0.0454) in peripheral blood following treatment, along with a significant amount of activated CD8+ICOS+ T cells in TILs from responders.

The D/T combination with and without SBRT was safe but did not show sufficient efficacy signal in relapsed SCLC. Changes in peripheral blood lymphocyte and TILs were consistent with an immunologic response.

Trial registration number NCT02701400.

• clinical trials
• immunotherapy
• lung neoplasms
• phase II as topic
• programmed cell death 1 receptor
• radioimmunotherapy

Recently, modern therapies involving immune checkpoint inhibitors, cytokines, and oncolytic virus have been developed. Because of the limited treatment effect of modern therapy alone, the immunostimulatory effect of radiotherapy attracted increasing attention. The combined use of radiotherapy and modern therapy has been examined clinically and non-clinically, and its effectiveness has been confirmed recently. Because melanomas have high immunogenicity, better therapeutic outcomes are desired when using immunotherapy. However, sufficient therapeutic effects have not yet been achieved. Thus far, radiotherapy has been used only for local control of tumors. Although extremely rare, radiotherapy has also been reported for systemic control, i.e., abscopal effect. This is thought to be due to an antitumor immune response. Therefore, we herein summarize past information on not only the mechanism of immune effects on radiotherapy but also biomarkers reported in case reports on abscopal effects. We also reviewed the animal model suitable for evaluating abscopal effects. These results pave the way for further basic research or clinical studies on new treatment methods for melanoma. Currently, palliative radiation is administered to patients with metastatic melanoma for local control. If it is feasible to provide both systemic and local control, the treatment benefit for the patients is very large.

• abscopal effect
• immunotherapy
• melanoma
• radioimmunotherapy
• radiotherapy

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with an overall 5-year survival rate of 9.3%, and this malignancy is expected to become the second leading cause of cancer-related death by 2030. Gemcitabine resistance develops within weeks of PDAC patient’s chemotherapeutic initiation. Statins, including pitavastatin, have been indicated to have anticancer effects in numerous human cancer cell lines. Thus, in this study, we hypothesized that a combination of gemcitabine and pitavastatin may have a greater anticancer effect than gemcitabine alone on the human pancreatic carcinoma cell line MIA PaCa-2.

The anticancer effects of gemcitabine with pitavastatin were evaluated using human MIA PaCa-2 cell line in vitro and in vivo Balb/c murine xenograft tumor model. Cell viability was assessed with CCK-8, and cell migration was stained by crystal violet. Cell cycle distribution, apoptosis and mitochondrial membrane potential were examined by flow cytometry. Activation of drug transporters (hENTs, hCNTs), intracellular drug activating (dCK) and inhibition of inactivating enzymes (RRMs) pathways were assessed by Western blotting analysis. Molecular mechanisms and signaling pathways of apoptosis, necrosis and autophagy also were assessed by Western blotting.

We observed that gemcitabine and pitavastatin synergistically suppressed the proliferation of MIA PaCa-2 cells through causing sub-G1 and S phase cell cycle arrest. Activation of apoptosis/necrosis was confirmed by annexin V/propidium iodide double staining, which showed increasing levels of active caspase 3, cleaved poly(ADP-ribose) polymerase and the RIP1–RIP3–MLKL complex. Moreover, gemcitabine–pitavastatin-mediated S phase arrest downregulated cyclin A2/CDK2 and upregulated p21/p27 in MIA PaCa-2 cells. Furthermore, this combination improved drug cellular metabolism pathway, mitochondria function and activated autophagy as part of the cell death mechanism. In vivo, gemcitabine-pitavastatin effectively inhibited tumor growth in a nude mouse mode of Mia PaCa-2 xenografts without observed adverse effect.

Combined gemcitabine–pitavastatin may be an effective novel treatment option for pancreatic cancer.

• MIA PaCa-2
• gemcitabine
• pancreatic cancer
• pitavastatin
• synergistic anticancer

• Limited stage
• immunotherapy
• prophylactic cranial irradiation (PCI)
• small cell lung cancer (SCLC)

• 5-fluorouracil
• adjuvant
• advanced
• cancer
• capecitabine
• chemotherapy
• gemcitabine
• pancreas
• pancreatic

• Adjuvant
• Checkpoint inhibitors
• Neoadjuvant
• Non-small cell lung cancer

• abscopal effect
• anti-tumor immunity
• immunogenic cell death
• radiotherapy

• chemoradiation
• durvalumab
• immunotherapy
• maintenance therapy
• non-small-cell lung cancer
• staging
• surgery-ineligible

Capecitabine, an oral prodrug of 5-FU, has been approved by the FDA for use in patients with breast and colon cancers. In addition, capecitabine is commonly used in patients with other malignancies such as pancreatic, gastroesophageal, and hepatobiliary tract cancers. Though cerebellar toxicity is a rare but well-known side effect of intravenous 5-FU therapy, peripheral neuropathy with capecitabine has only been described in rare cases. In this case report, we describe a 79-year-old patient with locally advanced adenocarcinoma of the pancreas undergoing chemoradiation therapy with capecitabine who developed peripheral sensorimotor neuropathy. To the best of our knowledge, this is the first patient in the literature who was found to have two mutations (2R) of a 28 base-pair tandem repeat in the 5’ promoter enhancer region (5’-TSER) on both alleles (2R/2R) of thymidylate synthetase (TYMS) gene, possibly responsible for the neurotoxicity.

• 5-fluorouracil
• capecitabine
• dihydropyrimidine dehydrogenase (dpd)
• foot drop
• peripheral neuropathy
• pharmacogenetics
• thymidylate synthase (ts)

A perioperative multimodal strategy including combination chemotherapy and radiotherapy, in addition to surgical resection, has been acknowledged to improve patient prognosis. However chemotherapy has not been actively applied as an immunomodulating modality because of concerns about various immunosuppressive effects. It has recently been shown that certain chemotherapeutic agents could modify tumor microenvironment and host immune responses through several underlying mechanisms such as immunogenic cell death, local T-cell infiltration and also the eradication of immune-suppressing regulatory cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells. With the better understanding of the cell components in the tumor microenvironment and the effect of chemotherapy to improve tumor microenvironment, it has been gradually clear that the chemotherapeutic agents is two-edged sword to have both immune promoting and suppressing effects. The cellular components of the tumor microenvironment include infiltrating T lymphocytes, dendritic cells, regulatory T cells, tumor associated macrophages, myeloid derived suppressor cells and cancer associated fibroblasts. Based on the better understanding of tumor microenvironment following chemotherapy, the treatment protocol could be modified as personalized medicine and the prognosis of pancreas cancer would be more improved utilizing multimodal chemotherapy. Here we review the recent advances of chemotherapy to improve tumor microenvironment of pancreatic cancer, introducing the unique feature of tumor microenvironment of pancreatic cancer, interaction between anti-cancer reagents and these constituting cells and future prospects.

• Pancreas cancer
• Microenvironment
• Chemotherapy
• Immune cells
• Immunomodulation

Cyclooxygenase-2 (COX-2) is an inducible form of the enzyme that catalyses the synthesis of prostanoids, including prostaglandin E2 (PGE₂), a major mediator of inflammation and angiogenesis. COX-2 is overexpressed in cancer cells and is associated with progressive tumour growth, as well as resistance of cancer cells to conventional chemotherapy and radiotherapy. These therapies are often delivered in multiple doses, which are spaced out to allow the recovery of normal tissues between treatments. However, surviving cancer cells also proliferate during treatment intervals, leading to repopulation of the tumour and limiting the effectiveness of the treatment. Tumour cell repopulation is a major cause of treatment failure. The central dogma is that conventional chemotherapy and radiotherapy selects resistant cancer cells that are able to reinitiate tumour growth. However, there is compelling evidence of an active proliferative response, driven by increased COX-2 expression and downstream PGE₂ release, which contribute to the repopulation of tumours and poor patient outcome. In this review, we will examine the evidence for a role of COX-2 in cancer stem cell biology and as a mediator of tumour repopulation that can be molecularly targeted to overcome resistance to therapy.

• Immune checkpoint
• Inflammation
• Pancreatic adenocarcinoma
• Randomized clinical trial
• Therapeutic anticancer target

• Adenocarcinoma/immunology
• Adenocarcinoma/therapy
• Antibodies, Monoclonal/therapeutic use
• Cancer Vaccines/metabolism
• Combined Modality Therapy
• Humans
• Immunotherapy/methods
• Inflammation/drug therapy
• Interleukin-6/metabolism
• Janus Kinases/metabolism
• NF-kappa B/metabolism
• Pancreatic Neoplasms/immunology
• Pancreatic Neoplasms/therapy
• Randomized Controlled Trials as Topic
• Receptors, Interleukin-8B/metabolism
• Signal Transduction
• T-Lymphocytes, Cytotoxic/metabolism

The NovoTTF-100A is a device that emits alternating electric fields and it is approved for the treatment of recurrent glioblastoma. It works by perturbing tumor cells during mitosis as they enter anaphase leading to aneuploidy, asymmetric chromosome segregation and cell death with evidence of increased immunogenicity. Clinical trial data have shown equivalent efficacy when compared to salvage chemotherapies in recurrent disease. Responders were found to have had a lower dexamethasone usage and a higher rate of prior low-grade histology. We treated a series of patients with NovoTTF-100A and bevacizumab alone (n = 34) or in combination with a regimen consisting of 6-thioguanine, lomustine, capecitabine, and celecoxib (TCCC) (n = 3). Compared to the former cohort, the latter cohort exhibited a trend for prolonged overall survival, median 4.1 (0.3–22.7) months versus 10.3 (7.7–13.6) months respectively (P = 0.0951), with one experiencing an objective response with a 50% reduction in tumor size on magnetic resonance imaging despite possessing a larger tumor size at baseline and more severe neurologic dysfunction than the median for either group. These observations illustrate the possibility of improving survival and achieving a response in patients with end-stage recurrent glioblastoma by biasing the tumor toward anti-tumor immunologic response with a combination of NovoTTF-100A and TCCC, as well as the continuation of bevacizumab in order to limit dexamethasone use due to its global immunosuppressive effect on the patient.

• Bevacizumab
• NovoTTF-100A
• chemotherapy
• glioblastoma

• capecitabine (Xeloda)
• pancreatic cancer
• radiotherapy
• thymidine phosphorylase

The abscopal effect has previously been described in various tumors and is associated with radiation therapy and hyperthermia, with possible underlying mechanisms explaining each observed case. In the present study, we aimed to investigate the antitumor effects of magnet-mediated hyperthermia on Walker-256 carcinosarcomas in rats at two different temperature ranges (42–46°C and 50–55°C). We also aimed to identify whether a higher therapeutic temperature of magnetic-mediated hyperthermia improves the abscopal antitumor effects, where localised irradiation of the tumor causes not only the irradiated tumor to shrink, but also tumors located far from the area of irradiation. Following induction of carcinosarcoma in both sides of the body, magnet-mediated hyperthermia was applied to one side only, leaving the other side as a control. The changes in tumor growth were observed. Our results demonstrated that magnet-mediated hyperthermia at a higher temperature inhibited the growth of carcinosarcoma at the site of treatment. Furthermore, the growth of the carcinosarcoma on the untreated side was also inhibited. The expression levels of proliferating cell nuclear antigen were decreased in the hyperthermia group, which was more significant in the higher temperature test group. Flow cytometric analysis showed an increased number of CD4- and CD8-positive T cells, and enzyme-linked immunosorbent assay showed increased levels of interferon-γ and interleukin-2 in the higher temperature group. These results suggested that magnet-mediated hyperthermia at a higher temperature (50–55°C) can improve the abscopal antitumor effects and stimulate a greater endogenous immune response in carcinosarcoma-bearing rats.

• Walker-256 carcinosarcoma
• abscopal effect
• magnet-mediated hyperthermia
• temperature
• tumor immunity

• Animals
• Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Antineoplastic Combined Chemotherapy Protocols/toxicity
• Capecitabine
• Carcinoma, Pancreatic Ductal/drug therapy
• Carcinoma, Pancreatic Ductal/enzymology
• Cell Line, Tumor
• Cytidine Deaminase/metabolism
• Deoxycytidine/administration & dosage
• Deoxycytidine/analogs & derivatives
• Disease Models, Animal
• Drug Screening Assays, Antitumor
• Fluorouracil/administration & dosage
• Fluorouracil/analogs & derivatives
• Mice
• Mice, Transgenic
• Neoplasm Transplantation
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/enzymology
• Prodrugs/administration & dosage
• Tissue Distribution
• Gemcitabine

• 15678 Cancer Research UK
• C96/A8333 Cancer Research UK

• fractionated radiotherapy
• pptp
• preclinical testing
• rhabdomyosarcoma
• xenograft

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols/therapeutic use
• Capecitabine
• Carcinoma, Pancreatic Ductal/drug therapy
• Carcinoma, Pancreatic Ductal/mortality
• Carcinoma, Pancreatic Ductal/secondary
• Chemotherapy, Adjuvant
• Combined Modality Therapy
• Deoxycytidine/administration & dosage
• Deoxycytidine/analogs & derivatives
• Female
• Fluorouracil/administration & dosage
• Fluorouracil/analogs & derivatives
• Follow-Up Studies
• Humans
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Recurrence, Local/drug therapy
• Neoplasm Recurrence, Local/mortality
• Neoplasm Recurrence, Local/pathology
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/pathology
• Pancreaticoduodenectomy
• Radiotherapy, Adjuvant
• Retrospective Studies
• Survival Rate
• Treatment Outcome
• Gemcitabine

• R01 CA104900 NCI NIH HHS

• Molecular targets
• Novel agents
• Pancreatic ductal carcinoma
• Pharmacogenetics

Potentiation of anticancer activity of capecitabine is required to improve its therapeutic index. In colorectal cancer (CRC) cells, we evaluated whether the histone deacetylase-inhibitor vorinostat may induce synergistic antitumour effects in combination with capecitabine by modulating the expression of thymidine phosphorylase (TP), a key enzyme in the conversion of capecitabine to 5-florouracil (5-FU), and thymidylate synthase (TS), the target of 5-FU.

Expression of TP and TS was measured by real-time PCR, western blotting and immunohistochemistry. Knockdown of TP was performed by specific small interfering RNA. Antitumour activity of vorinostat was assessed in vitro in combination with the capecitabine active metabolite deoxy-5-fluorouridine (5′-DFUR) according to the Chou and Talay method and by evaluating apoptosis as well as in xenografts-bearing nude mice in combination with capecitabine.

Vorinostat induced both in vitro and in vivo upregulation of TP as well as downregulation of TS in cancer cells, but not in ex vivo treated peripheral blood lymphocytes. Combined treatment with vorinostat and 5′-DFUR resulted in a synergistic antiproliferative effect and increased apoptotic cell death in vitro. This latter effect was impaired in cells where TP was knocked. In vivo, vorinostat plus capecitabine potently inhibited tumour growth, increased apoptosis and prolonged survival compared with control or single-agent treatments.

Overall, this study suggests that the combination of vorinostat and capecitabine is an innovative antitumour strategy and warrants further clinical evaluation for the treatment of CRC.

• Adenocarcinoma/drug therapy
• Adenocarcinoma/pathology
• Adenocarcinoma/radiotherapy
• Aged
• Aged, 80 and over
• Antimetabolites, Antineoplastic/therapeutic use
• Capecitabine
• Combined Modality Therapy
• Deoxycytidine/analogs & derivatives
• Deoxycytidine/therapeutic use
• Disease Progression
• Female
• Fluorouracil/analogs & derivatives
• Fluorouracil/therapeutic use
• Humans
• Male
• Maximum Tolerated Dose
• Middle Aged
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/radiotherapy
• Prodrugs/therapeutic use
• Prospective Studies
• Radiotherapy Dosage
• Survival Rate
• Treatment Outcome

• C1467/A7286 Department of Health

• Adult
• Aged
• Antimetabolites, Antineoplastic/administration & dosage
• Antimetabolites, Antineoplastic/adverse effects
• Antimetabolites, Antineoplastic/therapeutic use
• Capecitabine
• Combined Modality Therapy
• Deoxycytidine/administration & dosage
• Deoxycytidine/adverse effects
• Deoxycytidine/analogs & derivatives
• Deoxycytidine/therapeutic use
• Disease Progression
• Disease-Free Survival
• Drug Administration Schedule
• Female
• Fluorouracil/administration & dosage
• Fluorouracil/adverse effects
• Fluorouracil/analogs & derivatives
• Fluorouracil/therapeutic use
• Humans
• Male
• Middle Aged
• Neoplasm Invasiveness
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/pathology
• Pancreatic Neoplasms/radiotherapy
• Radiotherapy Dosage

• Animals
• Antineoplastic Agents/administration & dosage
• Bystander Effect/immunology
• Bystander Effect/radiation effects
• Combined Modality Therapy
• Granulocyte-Macrophage Colony-Stimulating Factor/administration & dosage
• Humans
• Immune System/radiation effects
• Immunotherapy
• Neoplasms/genetics
• Neoplasms/immunology
• Neoplasms/radiotherapy
• Neoplasms/therapy
• Rodentia
• Signal Transduction/immunology
• Signal Transduction/radiation effects

• P30 CA016087 NCI NIH HHS
• R01 CA113851 NCI NIH HHS
• 5P30CA016087-27 NCI NIH HHS

• Aged
• Antimetabolites, Antineoplastic/adverse effects
• Antimetabolites, Antineoplastic/therapeutic use
• Capecitabine
• Combined Modality Therapy
• Deoxycytidine/adverse effects
• Deoxycytidine/analogs & derivatives
• Deoxycytidine/therapeutic use
• Dihydrouracil Dehydrogenase (NADP)/analysis
• Dihydrouracil Dehydrogenase (NADP)/genetics
• Dihydrouracil Dehydrogenase (NADP)/metabolism
• Female
• Fluorouracil/adverse effects
• Fluorouracil/analogs & derivatives
• Fluorouracil/therapeutic use
• Humans
• Male
• Middle Aged
• Pancreatic Neoplasms/drug therapy
• Pancreatic Neoplasms/mortality
• Pancreatic Neoplasms/radiotherapy
• Pancreatic Neoplasms/therapy
• RNA, Messenger/analysis
• RNA, Messenger/metabolism
• Survival Rate
• Thrombocytopenia/chemically induced
• Thymidine Phosphorylase/analysis
• Thymidine Phosphorylase/genetics
• Thymidine Phosphorylase/metabolism
• Treatment Outcome
• Tumor Necrosis Factor-alpha/analysis
• Tumor Necrosis Factor-alpha/genetics
• Tumor Necrosis Factor-alpha/metabolism
• Up-Regulation

• 1 P20 CA101955-01 NCI NIH HHS

• Animals
• Antimetabolites, Antineoplastic/pharmacology
• Apoptosis/drug effects
• Cell Cycle/drug effects
• Cell Proliferation/drug effects
• Colorectal Neoplasms/drug therapy
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/pathology
• Drug Resistance, Neoplasm
• Female
• Fluorouracil/pharmacology
• Humans
• In Vitro Techniques
• Liposomes
• Mice
• Mice, Nude
• Thymidylate Synthase/antagonists & inhibitors
• Tumor Cells, Cultured/drug effects